Tara Haelle

PHILADELPHIA – Both a pelvic yoga program and a general physical conditioning program for incontinence led to improvements in women’s incontinence, according to a study presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

“As clinicians, we’re usually focused on treatments that we ourselves can prescribe, perform, or administer. We’re not as good as recommending or supporting treatment or management strategies that don’t rely on costly or intensive visits with clinical specialists,” lead author Alison Huang, MD, MAS, a professor of medicine at the University of California, San Francisco, said in an interview.

“But our findings suggest that women who try pelvic yoga as a complementary management strategy for genitourinary conditions like urinary incontinence that often emerge in midlife are likely to experience substantial improvement in their genitourinary symptoms and function,” Dr. Huang said. “Some of these improvements may be shared with other forms of low-impact physical movement or exercise.”

The 240 participants from communities around three Northern California sites ranged in age from 45 to 90 years old, with an average age of 62, and all had at least daily urgency, stress, or mixed-type urinary incontinence. While most were White women, 40% identified as racial/ethnic minorities, including 14% Hispanic, 6% Black, 16% Asian American, and 4% multiracial.

Participants needed to be able to walk two blocks on level ground and get from a supine to a standing position on their own, but they should not have recently participated in any organized yoga or physical conditioning exercise classes. They also needed to forgo behavioral, invasive, or pharmacologic treatments for urinary incontinence for at least 3 months. The trial ran from 2019 to 2022, with most women completing the 3-month program virtually once the pandemic began.

The 121 women randomly assigned to the pelvic yoga program had twice-weekly group instruction by trained yoga instructors and once-weekly individual practice. The practice focused on 16 standard Hatha yoga poses in standing, seated, supine, and prone positions with an emphasis on precise alignment of their postures during each pose. Yoga props, such as blocks, straps, or bolsters, were available to minimize risk of injury and to accommodate women with less flexibility.

The 119 women randomly assigned to the physical conditioning group spent the same amount of group and individual class time on skeletal muscle stretching and strengthening exercises. These exercises focused on strengthening and stretching exercises for the upper and lower extremities in standing, sitting, or supine positions. The only props needed were exercise straps and handles and an exercise mat, and the program was designed to be safe and feasible for women across all ages.

Both groups received standard self-management pamphlets describing pelvic floor muscle exercises and recommendations on timed urination and urging suppression. After early dropouts from both arms, 107 women remained for analysis in the pelvic yoga group, and 113 women remained for analysis in the physical conditioning group.

Researchers assessed participants’ genitourinary quality of life at baseline and after 3 months using the Urogenital Distress Inventory-6 (UDI-6), Incontinence Impact Questionnaire (IIQ), and Patient Perception of Bladder Condition (PPBC). At baseline, the women’s average scores were 38.8 on the UDI-6, 101 on the IIQ, and 3.4 on the PPBC.

About one-third of the women in both groups attended all 24 group classes, and 57% of women in both groups attended 20-23 classes. In addition, 65% of the women in the pelvic yoga group and 73% of the women in the physical conditioning group completed all of the recommended additional hours of individual practice. Only 15% of pelvic yoga participants and 9% of physical conditioning participants completed less than 80% of the recommended individual practice hours. No differences in participation between the groups were statistically significant.

“Over 3 months, scores on all genitourinary quality of life measures improved by more than the minimum important difference thresholds in the pelvic yoga group,” the researchers reported, but only the UDI-6 score improved significantly – albeit still modestly – in the pelvic yoga group, compared with the physical conditioning group. Average scores improved 18.9 points in the pelvic yoga group and 13.1 points in the physical conditioning group (5.8-point difference; P = .02).

The scores on the IIQ improved an average 38.5 points in the pelvic yoga group and 31.4 points in the physical conditioning group (P = .48). PPBC scores improved 0.7 points in both groups.

“While yoga may offer benefits for genitourinary quality of life, it may not offer superior benefits compared to equivalent-time practice of other activities that improve general physical function,” Dr. Huang told attendees.

“The bottom line is that physical activity toward incontinence is a helpful technique,” Stephanie Faubion, MD, MBA, director for Mayo Clinic’s Center for Women’s Health and medical director for the Menopause Society, said in an interview regarding the findings. Urinary incontinence is under-recognized, Dr. Faubion said, “because women are embarrassed, so they don’t bring it up, so it doesn’t get managed.” But it’s a common problem, so clinicians need to ask patients about it, she said.

“We should realize that, in midlife and older age, genitourinary health is often connected to overall health,” Dr. Huang said in an interview. “We shouldn’t focus exclusively on treatments that are directed solely at the genital or lower urinary tract organs or tissues. We should consider the ways in which women’s urinary and sexual function are influenced by other aspects of their physical and cognitive health.”

The research was funded by the National Institutes of Health. Dr. Huang and Dr. Faubion had no disclosures.

PHILADELPHIA – Both a pelvic yoga program and a general physical conditioning program for incontinence led to improvements in women’s incontinence, according to a study presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

“As clinicians, we’re usually focused on treatments that we ourselves can prescribe, perform, or administer. We’re not as good as recommending or supporting treatment or management strategies that don’t rely on costly or intensive visits with clinical specialists,” lead author Alison Huang, MD, MAS, a professor of medicine at the University of California, San Francisco, said in an interview.

“But our findings suggest that women who try pelvic yoga as a complementary management strategy for genitourinary conditions like urinary incontinence that often emerge in midlife are likely to experience substantial improvement in their genitourinary symptoms and function,” Dr. Huang said. “Some of these improvements may be shared with other forms of low-impact physical movement or exercise.”

The 240 participants from communities around three Northern California sites ranged in age from 45 to 90 years old, with an average age of 62, and all had at least daily urgency, stress, or mixed-type urinary incontinence. While most were White women, 40% identified as racial/ethnic minorities, including 14% Hispanic, 6% Black, 16% Asian American, and 4% multiracial.

Participants needed to be able to walk two blocks on level ground and get from a supine to a standing position on their own, but they should not have recently participated in any organized yoga or physical conditioning exercise classes. They also needed to forgo behavioral, invasive, or pharmacologic treatments for urinary incontinence for at least 3 months. The trial ran from 2019 to 2022, with most women completing the 3-month program virtually once the pandemic began.

The 121 women randomly assigned to the pelvic yoga program had twice-weekly group instruction by trained yoga instructors and once-weekly individual practice. The practice focused on 16 standard Hatha yoga poses in standing, seated, supine, and prone positions with an emphasis on precise alignment of their postures during each pose. Yoga props, such as blocks, straps, or bolsters, were available to minimize risk of injury and to accommodate women with less flexibility.

The 119 women randomly assigned to the physical conditioning group spent the same amount of group and individual class time on skeletal muscle stretching and strengthening exercises. These exercises focused on strengthening and stretching exercises for the upper and lower extremities in standing, sitting, or supine positions. The only props needed were exercise straps and handles and an exercise mat, and the program was designed to be safe and feasible for women across all ages.

Both groups received standard self-management pamphlets describing pelvic floor muscle exercises and recommendations on timed urination and urging suppression. After early dropouts from both arms, 107 women remained for analysis in the pelvic yoga group, and 113 women remained for analysis in the physical conditioning group.

Researchers assessed participants’ genitourinary quality of life at baseline and after 3 months using the Urogenital Distress Inventory-6 (UDI-6), Incontinence Impact Questionnaire (IIQ), and Patient Perception of Bladder Condition (PPBC). At baseline, the women’s average scores were 38.8 on the UDI-6, 101 on the IIQ, and 3.4 on the PPBC.

About one-third of the women in both groups attended all 24 group classes, and 57% of women in both groups attended 20-23 classes. In addition, 65% of the women in the pelvic yoga group and 73% of the women in the physical conditioning group completed all of the recommended additional hours of individual practice. Only 15% of pelvic yoga participants and 9% of physical conditioning participants completed less than 80% of the recommended individual practice hours. No differences in participation between the groups were statistically significant.

“Over 3 months, scores on all genitourinary quality of life measures improved by more than the minimum important difference thresholds in the pelvic yoga group,” the researchers reported, but only the UDI-6 score improved significantly – albeit still modestly – in the pelvic yoga group, compared with the physical conditioning group. Average scores improved 18.9 points in the pelvic yoga group and 13.1 points in the physical conditioning group (5.8-point difference; P = .02).

The scores on the IIQ improved an average 38.5 points in the pelvic yoga group and 31.4 points in the physical conditioning group (P = .48). PPBC scores improved 0.7 points in both groups.

“While yoga may offer benefits for genitourinary quality of life, it may not offer superior benefits compared to equivalent-time practice of other activities that improve general physical function,” Dr. Huang told attendees.

“The bottom line is that physical activity toward incontinence is a helpful technique,” Stephanie Faubion, MD, MBA, director for Mayo Clinic’s Center for Women’s Health and medical director for the Menopause Society, said in an interview regarding the findings. Urinary incontinence is under-recognized, Dr. Faubion said, “because women are embarrassed, so they don’t bring it up, so it doesn’t get managed.” But it’s a common problem, so clinicians need to ask patients about it, she said.

“We should realize that, in midlife and older age, genitourinary health is often connected to overall health,” Dr. Huang said in an interview. “We shouldn’t focus exclusively on treatments that are directed solely at the genital or lower urinary tract organs or tissues. We should consider the ways in which women’s urinary and sexual function are influenced by other aspects of their physical and cognitive health.”

The research was funded by the National Institutes of Health. Dr. Huang and Dr. Faubion had no disclosures.

PHILADELPHIA – Both a pelvic yoga program and a general physical conditioning program for incontinence led to improvements in women’s incontinence, according to a study presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

“As clinicians, we’re usually focused on treatments that we ourselves can prescribe, perform, or administer. We’re not as good as recommending or supporting treatment or management strategies that don’t rely on costly or intensive visits with clinical specialists,” lead author Alison Huang, MD, MAS, a professor of medicine at the University of California, San Francisco, said in an interview.

“But our findings suggest that women who try pelvic yoga as a complementary management strategy for genitourinary conditions like urinary incontinence that often emerge in midlife are likely to experience substantial improvement in their genitourinary symptoms and function,” Dr. Huang said. “Some of these improvements may be shared with other forms of low-impact physical movement or exercise.”

The 240 participants from communities around three Northern California sites ranged in age from 45 to 90 years old, with an average age of 62, and all had at least daily urgency, stress, or mixed-type urinary incontinence. While most were White women, 40% identified as racial/ethnic minorities, including 14% Hispanic, 6% Black, 16% Asian American, and 4% multiracial.

Participants needed to be able to walk two blocks on level ground and get from a supine to a standing position on their own, but they should not have recently participated in any organized yoga or physical conditioning exercise classes. They also needed to forgo behavioral, invasive, or pharmacologic treatments for urinary incontinence for at least 3 months. The trial ran from 2019 to 2022, with most women completing the 3-month program virtually once the pandemic began.

The 121 women randomly assigned to the pelvic yoga program had twice-weekly group instruction by trained yoga instructors and once-weekly individual practice. The practice focused on 16 standard Hatha yoga poses in standing, seated, supine, and prone positions with an emphasis on precise alignment of their postures during each pose. Yoga props, such as blocks, straps, or bolsters, were available to minimize risk of injury and to accommodate women with less flexibility.

The 119 women randomly assigned to the physical conditioning group spent the same amount of group and individual class time on skeletal muscle stretching and strengthening exercises. These exercises focused on strengthening and stretching exercises for the upper and lower extremities in standing, sitting, or supine positions. The only props needed were exercise straps and handles and an exercise mat, and the program was designed to be safe and feasible for women across all ages.

Both groups received standard self-management pamphlets describing pelvic floor muscle exercises and recommendations on timed urination and urging suppression. After early dropouts from both arms, 107 women remained for analysis in the pelvic yoga group, and 113 women remained for analysis in the physical conditioning group.

Researchers assessed participants’ genitourinary quality of life at baseline and after 3 months using the Urogenital Distress Inventory-6 (UDI-6), Incontinence Impact Questionnaire (IIQ), and Patient Perception of Bladder Condition (PPBC). At baseline, the women’s average scores were 38.8 on the UDI-6, 101 on the IIQ, and 3.4 on the PPBC.

About one-third of the women in both groups attended all 24 group classes, and 57% of women in both groups attended 20-23 classes. In addition, 65% of the women in the pelvic yoga group and 73% of the women in the physical conditioning group completed all of the recommended additional hours of individual practice. Only 15% of pelvic yoga participants and 9% of physical conditioning participants completed less than 80% of the recommended individual practice hours. No differences in participation between the groups were statistically significant.

“Over 3 months, scores on all genitourinary quality of life measures improved by more than the minimum important difference thresholds in the pelvic yoga group,” the researchers reported, but only the UDI-6 score improved significantly – albeit still modestly – in the pelvic yoga group, compared with the physical conditioning group. Average scores improved 18.9 points in the pelvic yoga group and 13.1 points in the physical conditioning group (5.8-point difference; P = .02).

The scores on the IIQ improved an average 38.5 points in the pelvic yoga group and 31.4 points in the physical conditioning group (P = .48). PPBC scores improved 0.7 points in both groups.

“While yoga may offer benefits for genitourinary quality of life, it may not offer superior benefits compared to equivalent-time practice of other activities that improve general physical function,” Dr. Huang told attendees.

“The bottom line is that physical activity toward incontinence is a helpful technique,” Stephanie Faubion, MD, MBA, director for Mayo Clinic’s Center for Women’s Health and medical director for the Menopause Society, said in an interview regarding the findings. Urinary incontinence is under-recognized, Dr. Faubion said, “because women are embarrassed, so they don’t bring it up, so it doesn’t get managed.” But it’s a common problem, so clinicians need to ask patients about it, she said.

“We should realize that, in midlife and older age, genitourinary health is often connected to overall health,” Dr. Huang said in an interview. “We shouldn’t focus exclusively on treatments that are directed solely at the genital or lower urinary tract organs or tissues. We should consider the ways in which women’s urinary and sexual function are influenced by other aspects of their physical and cognitive health.”

The research was funded by the National Institutes of Health. Dr. Huang and Dr. Faubion had no disclosures.

PHILADELPHIA – Women with obesity experience greater menopausal symptoms but substantially less relief from hormone therapy (HT) than women without obesity, according to a small, retrospective study presented at the annual meeting of the Menopause Society (formerly the North American Menopause Society).

More than 40% of women over age 40 in the United States have obesity, presenter Anita Pershad, MD, an ob.gyn. medical resident at Eastern Virginia Medical School, Norfolk, told attendees. Yet most of the large-scale studies investigating perimenopausal and postmenopausal hormone therapy included participants without major medical comorbidities, so little data exist on how effectively HT works in women with these comorbidities, she said

“The main takeaway of our study is that obesity may worsen a woman’s menopausal symptoms and limit the amount of relief she gets from hormone therapy,” Dr. Pershad said in an interview. “It remains unclear if hormone therapy is less effective in women with obesity overall, or if the expected efficacy can be achieved with alternative design and administration routes. A potential mechanism of action for the observed decreased effect could be due to adipose tissue acting as a heat insulator, promoting the effects of vasomotor symptoms.”

Dr. Pershad and her colleagues conducted a retrospective review of the medical records of 119 patients who presented to a menopause clinic at a Midsouth urban academic medical center between July 2018 and December 2022. Obesity was defined as having a body mass index (BMI) of 30 kg/m² or greater.

The patients with and without obesity were similar in terms of age, duration of menopause, use of hormone therapy, and therapy acceptance, but patients with obesity were more likely to identify themselves as Black (71% vs. 40%). Women with obesity were also significantly more likely than women without obesity to report vasomotor symptoms (74% vs. 45%, P = .002), genitourinary/vulvovaginal symptoms (60% vs. 21%, P < .001), mood disturbances (11% vs. 0%, P = .18), and decreased libido (29% vs. 11%, P = .017).

There were no significant differences in comorbidities between women with and without obesity, and among women who received systemic or localized HT, the same standard dosing was used for both groups.

Women with obesity were much less likely to see a satisfying reduction in their menopausal symptoms than women without obesity (odds ratio 0.07, 95% confidence interval, 0.01-0.64; P = .006), though the subgroups for each category of HT were small. Among the 20 women receiving systemic hormone therapy, only 1 of the 12 with obesity (8.3%) reported improvement in symptoms, compared with 7 of the 8 women without obesity (88%; P = .0004). Among 33 women using localized hormone therapy, 46% of the 24 women with obesity vs. 89% of the 9 women without obesity experienced symptom improvement (P = .026).

The proportions of women reporting relief from only lifestyle modifications or from nonhormonal medications, such as SSRIs/SNRIs, trazodone, and clonidine, were not statistically different. There were 33 women who relied only on lifestyle modifications, with 31% of the 16 women with obesity and 59% of the 17 women without obesity reporting improvement in their symptoms (P = .112). Similarly, among the 33 women using nonhormonal medications, 75% of the 20 women with obesity and 77% of the 13 women without obesity experienced relief (P = .9).
 

Women with obesity are undertreated

Dr. Pershad emphasized the need to improve care and counseling for diverse patients seeking treatment for menopausal symptoms.

“More research is needed to examine how women with medical comorbidities are uniquely impacted by menopause and respond to therapies,” Dr. Pershad said in an interview. “This can be achieved by actively including more diverse patient populations in women’s health studies, burdened by the social determinants of health and medical comorbidities such as obesity.”

Faubian_Stephanie_S_MN_web.jpg

Stephanie S. Faubion, MD, MBA, director for Mayo Clinic’s Center for Women’s Health, Rochester, Minn., and medical director for The Menopause Society, was not surprised by the findings, particularly given that women with obesity tend to have more hot flashes and night sweats as a result of their extra weight. However, dosage data was not adjusted for BMI in the study and data on hormone levels was unavailable, she said, so it’s difficult to determine from the data whether HT was less effective for women with obesity or whether they were underdosed.

“I think women with obesity are undertreated,” Dr. Faubion said in an interview. “My guess is people are afraid. Women with obesity also may have other comorbidities,” such as hypertension and diabetes, she said, and “the greater the number of cardiovascular risk factors, the higher risk hormone therapy is.” Providers may therefore be leery of prescribing HT or prescribing it at an appropriately high enough dose to treat menopausal symptoms.

Common practice is to start patients at the lowest dose and titrate up according to symptoms, but “if people are afraid of it, they’re going to start the lowest dose” and may not increase it, Dr. Faubion said. She noted that other nonhormonal options are available, though providers should be conscientious about selecting ones whose adverse events do not include weight gain.

Although the study focused on an understudied population within hormone therapy research, the study was limited by its small size, low overall use of hormone therapy, recall bias, and the researchers’ inability to control for other medications the participants may have been taking.

Dr. Pershad said she is continuing research to try to identify the mechanisms underlying the reduced efficacy in women with obesity.

The research did not use any external funding. Dr. Pershad had no industry disclosures, but her colleagues reported honoraria from or speaking for TherapeuticsMD, Astella Pharma, Scynexis, Pharmavite, and Pfizer. Dr. Faubion had no disclosures.

PHILADELPHIA – Women with obesity experience greater menopausal symptoms but substantially less relief from hormone therapy (HT) than women without obesity, according to a small, retrospective study presented at the annual meeting of the Menopause Society (formerly the North American Menopause Society).

More than 40% of women over age 40 in the United States have obesity, presenter Anita Pershad, MD, an ob.gyn. medical resident at Eastern Virginia Medical School, Norfolk, told attendees. Yet most of the large-scale studies investigating perimenopausal and postmenopausal hormone therapy included participants without major medical comorbidities, so little data exist on how effectively HT works in women with these comorbidities, she said

“The main takeaway of our study is that obesity may worsen a woman’s menopausal symptoms and limit the amount of relief she gets from hormone therapy,” Dr. Pershad said in an interview. “It remains unclear if hormone therapy is less effective in women with obesity overall, or if the expected efficacy can be achieved with alternative design and administration routes. A potential mechanism of action for the observed decreased effect could be due to adipose tissue acting as a heat insulator, promoting the effects of vasomotor symptoms.”

Dr. Pershad and her colleagues conducted a retrospective review of the medical records of 119 patients who presented to a menopause clinic at a Midsouth urban academic medical center between July 2018 and December 2022. Obesity was defined as having a body mass index (BMI) of 30 kg/m² or greater.

The patients with and without obesity were similar in terms of age, duration of menopause, use of hormone therapy, and therapy acceptance, but patients with obesity were more likely to identify themselves as Black (71% vs. 40%). Women with obesity were also significantly more likely than women without obesity to report vasomotor symptoms (74% vs. 45%, P = .002), genitourinary/vulvovaginal symptoms (60% vs. 21%, P < .001), mood disturbances (11% vs. 0%, P = .18), and decreased libido (29% vs. 11%, P = .017).

There were no significant differences in comorbidities between women with and without obesity, and among women who received systemic or localized HT, the same standard dosing was used for both groups.

Women with obesity were much less likely to see a satisfying reduction in their menopausal symptoms than women without obesity (odds ratio 0.07, 95% confidence interval, 0.01-0.64; P = .006), though the subgroups for each category of HT were small. Among the 20 women receiving systemic hormone therapy, only 1 of the 12 with obesity (8.3%) reported improvement in symptoms, compared with 7 of the 8 women without obesity (88%; P = .0004). Among 33 women using localized hormone therapy, 46% of the 24 women with obesity vs. 89% of the 9 women without obesity experienced symptom improvement (P = .026).

The proportions of women reporting relief from only lifestyle modifications or from nonhormonal medications, such as SSRIs/SNRIs, trazodone, and clonidine, were not statistically different. There were 33 women who relied only on lifestyle modifications, with 31% of the 16 women with obesity and 59% of the 17 women without obesity reporting improvement in their symptoms (P = .112). Similarly, among the 33 women using nonhormonal medications, 75% of the 20 women with obesity and 77% of the 13 women without obesity experienced relief (P = .9).
 

Women with obesity are undertreated

Dr. Pershad emphasized the need to improve care and counseling for diverse patients seeking treatment for menopausal symptoms.

“More research is needed to examine how women with medical comorbidities are uniquely impacted by menopause and respond to therapies,” Dr. Pershad said in an interview. “This can be achieved by actively including more diverse patient populations in women’s health studies, burdened by the social determinants of health and medical comorbidities such as obesity.”

Faubian_Stephanie_S_MN_web.jpg

Stephanie S. Faubion, MD, MBA, director for Mayo Clinic’s Center for Women’s Health, Rochester, Minn., and medical director for The Menopause Society, was not surprised by the findings, particularly given that women with obesity tend to have more hot flashes and night sweats as a result of their extra weight. However, dosage data was not adjusted for BMI in the study and data on hormone levels was unavailable, she said, so it’s difficult to determine from the data whether HT was less effective for women with obesity or whether they were underdosed.

“I think women with obesity are undertreated,” Dr. Faubion said in an interview. “My guess is people are afraid. Women with obesity also may have other comorbidities,” such as hypertension and diabetes, she said, and “the greater the number of cardiovascular risk factors, the higher risk hormone therapy is.” Providers may therefore be leery of prescribing HT or prescribing it at an appropriately high enough dose to treat menopausal symptoms.

Common practice is to start patients at the lowest dose and titrate up according to symptoms, but “if people are afraid of it, they’re going to start the lowest dose” and may not increase it, Dr. Faubion said. She noted that other nonhormonal options are available, though providers should be conscientious about selecting ones whose adverse events do not include weight gain.

Although the study focused on an understudied population within hormone therapy research, the study was limited by its small size, low overall use of hormone therapy, recall bias, and the researchers’ inability to control for other medications the participants may have been taking.

Dr. Pershad said she is continuing research to try to identify the mechanisms underlying the reduced efficacy in women with obesity.

The research did not use any external funding. Dr. Pershad had no industry disclosures, but her colleagues reported honoraria from or speaking for TherapeuticsMD, Astella Pharma, Scynexis, Pharmavite, and Pfizer. Dr. Faubion had no disclosures.

PHILADELPHIA – Women with obesity experience greater menopausal symptoms but substantially less relief from hormone therapy (HT) than women without obesity, according to a small, retrospective study presented at the annual meeting of the Menopause Society (formerly the North American Menopause Society).

More than 40% of women over age 40 in the United States have obesity, presenter Anita Pershad, MD, an ob.gyn. medical resident at Eastern Virginia Medical School, Norfolk, told attendees. Yet most of the large-scale studies investigating perimenopausal and postmenopausal hormone therapy included participants without major medical comorbidities, so little data exist on how effectively HT works in women with these comorbidities, she said

“The main takeaway of our study is that obesity may worsen a woman’s menopausal symptoms and limit the amount of relief she gets from hormone therapy,” Dr. Pershad said in an interview. “It remains unclear if hormone therapy is less effective in women with obesity overall, or if the expected efficacy can be achieved with alternative design and administration routes. A potential mechanism of action for the observed decreased effect could be due to adipose tissue acting as a heat insulator, promoting the effects of vasomotor symptoms.”

Dr. Pershad and her colleagues conducted a retrospective review of the medical records of 119 patients who presented to a menopause clinic at a Midsouth urban academic medical center between July 2018 and December 2022. Obesity was defined as having a body mass index (BMI) of 30 kg/m² or greater.

The patients with and without obesity were similar in terms of age, duration of menopause, use of hormone therapy, and therapy acceptance, but patients with obesity were more likely to identify themselves as Black (71% vs. 40%). Women with obesity were also significantly more likely than women without obesity to report vasomotor symptoms (74% vs. 45%, P = .002), genitourinary/vulvovaginal symptoms (60% vs. 21%, P < .001), mood disturbances (11% vs. 0%, P = .18), and decreased libido (29% vs. 11%, P = .017).

There were no significant differences in comorbidities between women with and without obesity, and among women who received systemic or localized HT, the same standard dosing was used for both groups.

Women with obesity were much less likely to see a satisfying reduction in their menopausal symptoms than women without obesity (odds ratio 0.07, 95% confidence interval, 0.01-0.64; P = .006), though the subgroups for each category of HT were small. Among the 20 women receiving systemic hormone therapy, only 1 of the 12 with obesity (8.3%) reported improvement in symptoms, compared with 7 of the 8 women without obesity (88%; P = .0004). Among 33 women using localized hormone therapy, 46% of the 24 women with obesity vs. 89% of the 9 women without obesity experienced symptom improvement (P = .026).

The proportions of women reporting relief from only lifestyle modifications or from nonhormonal medications, such as SSRIs/SNRIs, trazodone, and clonidine, were not statistically different. There were 33 women who relied only on lifestyle modifications, with 31% of the 16 women with obesity and 59% of the 17 women without obesity reporting improvement in their symptoms (P = .112). Similarly, among the 33 women using nonhormonal medications, 75% of the 20 women with obesity and 77% of the 13 women without obesity experienced relief (P = .9).
 

Women with obesity are undertreated

Dr. Pershad emphasized the need to improve care and counseling for diverse patients seeking treatment for menopausal symptoms.

“More research is needed to examine how women with medical comorbidities are uniquely impacted by menopause and respond to therapies,” Dr. Pershad said in an interview. “This can be achieved by actively including more diverse patient populations in women’s health studies, burdened by the social determinants of health and medical comorbidities such as obesity.”

Faubian_Stephanie_S_MN_web.jpg

Stephanie S. Faubion, MD, MBA, director for Mayo Clinic’s Center for Women’s Health, Rochester, Minn., and medical director for The Menopause Society, was not surprised by the findings, particularly given that women with obesity tend to have more hot flashes and night sweats as a result of their extra weight. However, dosage data was not adjusted for BMI in the study and data on hormone levels was unavailable, she said, so it’s difficult to determine from the data whether HT was less effective for women with obesity or whether they were underdosed.

“I think women with obesity are undertreated,” Dr. Faubion said in an interview. “My guess is people are afraid. Women with obesity also may have other comorbidities,” such as hypertension and diabetes, she said, and “the greater the number of cardiovascular risk factors, the higher risk hormone therapy is.” Providers may therefore be leery of prescribing HT or prescribing it at an appropriately high enough dose to treat menopausal symptoms.

Common practice is to start patients at the lowest dose and titrate up according to symptoms, but “if people are afraid of it, they’re going to start the lowest dose” and may not increase it, Dr. Faubion said. She noted that other nonhormonal options are available, though providers should be conscientious about selecting ones whose adverse events do not include weight gain.

Although the study focused on an understudied population within hormone therapy research, the study was limited by its small size, low overall use of hormone therapy, recall bias, and the researchers’ inability to control for other medications the participants may have been taking.

Dr. Pershad said she is continuing research to try to identify the mechanisms underlying the reduced efficacy in women with obesity.

The research did not use any external funding. Dr. Pershad had no industry disclosures, but her colleagues reported honoraria from or speaking for TherapeuticsMD, Astella Pharma, Scynexis, Pharmavite, and Pfizer. Dr. Faubion had no disclosures.

PHILADELPHIA – Cognitive behavioral therapy (CBT) was effective in addressing peri- and postmenopausal women’s sexual concerns, according to a small study presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society). Four CBT sessions specifically focused on sexual concerns resulted in decreased sexual distress and concern, reduced depressive and menopausal symptoms, and increased sexual desire and functioning, as well as improved body image and relationship satisfaction.

An estimated 68%-87% of perimenopausal and postmenopausal women report sexual concerns, Sheryl Green, PhD, CPsych, an associate professor of psychiatry and behavioral neurosciences at McMaster University and a psychologist at St. Joseph’s Healthcare’s Women’s Health Concerns Clinic, both in Hamilton, Ont., told attendees at the meeting.

“Sexual concerns over the menopausal transition are not just physical, but they’re also psychological and emotional,” Dr. Green said. “Three common challenges include decreased sexual desire, a reduction in physical arousal and ability to achieve an orgasm, and sexual pain and discomfort during intercourse.”

The reasons for these concerns are multifactorial, she said. Decreased sexual desire can stem from stress, medical problems, their relationship with their partner, or other causes. A woman’s difficulty with reduced physical arousal or ability to have an orgasm can result from changes in hormone levels and vaginal changes, such as vaginal atrophy, which can also contribute to the sexual pain or discomfort reported by 17%-45% of postmenopausal women.

Two pharmacologic treatments exist for sexual concerns: oral flibanserin (Addyi) and injectable bremelanotide (Vyleesi). But many women may be unable or unwilling to take medication for their concerns. Previous research from Lori Brotto has found cognitive behavioral therapy and mindfulness interventions to effectively improve sexual functioning in women treated for gynecologic cancer and in women without a history of cancer.

“Sexual function needs to be understood from a bio-psychosocial model, looking at the biologic factors, the psychological factors, the sociocultural factors, and the interpersonal factors,” Sheryl Kingsberg, PhD, a professor of psychiatry and reproductive biology at Case Western Reserve University and a psychologist at University Hospitals in Cleveland, said in an interview.

Kingsberg_Sheryl_A_OH_web.jpg

“They can all overlap, and the clinician can ask a few pointed questions that help identify what the source of the problem is,” said Dr. Kingsberg, who was not involved in this study. She noted that the International Society for the Study of Women’s Sexual Health has an algorithm that can help in determining the source of the problems.

“Sometimes it’s going to be a biologic condition for which pharmacologic options are nice, but even if it is primarily pharmacologic, psychotherapy is always useful,” Dr. Kingsberg said. “Once the problem is there, even if it’s biologically based, then you have all the things in terms of the cognitive distortion, anxiety,” and other issues that a cognitive behavioral approach can help address. “And access is now much wider because of telehealth,” she added.
 

‘Psychology of menopause’

The study led by Dr. Green focused on peri- and postmenopausal women, with an average age of 50, who were experiencing primary sexual concerns based on a score of at least 26 on the Female Sexual Function Index (FSFI). Among the 20 women recruited for the study, 6 had already been prescribed hormone therapy for sexual concerns.

All reported decreased sexual desire, 17 reported decreased sexual arousal, 14 had body image dissatisfaction related to sexual concerns, and 6 reported urogenital problems. Nine of the women were in full remission from major depressive disorder, one had post-traumatic stress syndrome, and one had subclinical generalized anxiety disorder.

After spending 4 weeks on a wait list as self-control group for the study, the 15 women who completed the trial underwent four individual CBT sessions focusing on sexual concerns. The first session focused on psychoeducation and thought monitoring, and the second focused on cognitive distortions, cognitive strategies, and unhelpful beliefs or expectations related to sexual concerns. The third session looked at the role of problematic behaviors and behavioral experiments, and the fourth focused on continuation of strategies, long-term goals, and maintaining gains.

The participants completed eight measures at baseline, after the 4 weeks on the wait list, and after the four CBT sessions to assess the following:

• Sexual satisfaction, distress, and desire, using the FSFI, the Female Sexual Distress Scale-Revised (FSDS-R), and the Female Sexual Desire Questionnaire (FSDQ).
• Menopause symptoms, using the Greene Climacteric Scale (GCS).
• Body image, using the Dresden Body Image Questionnaire (DBIQ).
• Relationship satisfaction, using the Couples Satisfaction Index (CSI).
• Depression, using the Beck Depression Inventory-II (BDI-II).
• Anxiety, using the Hamilton Anxiety Rating Scale (HAM-A).

The women did not experience any significant changes while on the wait list except a slight decrease on the FSDQ concern subscale. Following the CBT sessions, however, the women experienced a significant decrease in sexual distress and concern as well as an increase in sexual dyadic desire and sexual functioning (P = .003 for FSFI, P = .002 for FSDS-R, and P = .003 for FSDQ).

Participants also experienced a decrease in depression (P < .0001) and menopausal symptoms (P = .001) and an increase in body-image satisfaction (P = .018) and relationship satisfaction (P = .0011) after the CBT sessions. The researchers assessed participants’ satisfaction with the Client Satisfaction Questionnaire after the CBT sessions and reported some of the qualitative findings.

“The treatment program was able to assist me with recognizing that some of my sexual concerns were normal, emotional as well as physical and hormonal, and provided me the ability to delve more deeply into the psychology of menopause and how to work through symptoms and concerns in more manageable pieces,” one participant wrote. Another found helpful the “homework exercises of recognizing a thought/feeling/emotion surrounding how I feel about myself/body and working through. More positive thought pattern/restructuring a response the most helpful.”

The main complaint about the program was that it was too short, with women wanting more sessions to help continue their progress.
 

Not an ‘either-or’ approach

Dr. Kingsberg said ISSWSH has a variety of sexual medicine practitioners, including providers who can provide CBT for sexual concerns, and the American Association of Sexuality Educators, Counselors and Therapists has a referral directory.

“Keeping in mind the bio-psychosocial model, sometimes psychotherapy is going to be a really effective treatment for sexual concerns,” Dr. Kingsberg said. “Sometimes the pharmacologic option is going to be a really effective treatment for some concerns, and sometimes the combination is going to have a really nice treatment effect. So it’s not a one-size-fits-all, and it doesn’t have to be an either-or.”

The sexual concerns of women still do not get adequately addressed in medical schools and residencies, Dr. Kingsberg said, which is distinctly different from how male sexual concerns are addressed in health care.

“Erectile dysfunction is kind of in the norm, and women are still a little hesitant to bring up their sexual concerns,” Dr. Kingsberg said. “They don’t know if it’s appropriate and they’re hoping that their clinician will ask.”

One way clinicians can do that is with a global question for all their patients: “Most of my patients have sexual questions or concerns; what concerns do you have?”

“They don’t have to go through a checklist of 10 things,” Dr. Kingsberg said. If the patient does not bring anything up, providers can then ask a single follow up question: “Do you have any concerns with desire, arousal, orgasm, or pain?” That question, Dr. Kingsberg said, covers the four main areas of concern.

The study was funded by the Canadian Institute of Health Research. Dr. Green reported no disclosures. Dr. Kingsberg has consulted for or served on the advisory board for Alloy, Astellas, Bayer, Dare Bioscience, Freya, Reunion Neuroscience, Materna Medical, Madorra, Palatin, Pfizer, ReJoy, Sprout, Strategic Science Technologies, and MsMedicine.

PHILADELPHIA – Cognitive behavioral therapy (CBT) was effective in addressing peri- and postmenopausal women’s sexual concerns, according to a small study presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society). Four CBT sessions specifically focused on sexual concerns resulted in decreased sexual distress and concern, reduced depressive and menopausal symptoms, and increased sexual desire and functioning, as well as improved body image and relationship satisfaction.

An estimated 68%-87% of perimenopausal and postmenopausal women report sexual concerns, Sheryl Green, PhD, CPsych, an associate professor of psychiatry and behavioral neurosciences at McMaster University and a psychologist at St. Joseph’s Healthcare’s Women’s Health Concerns Clinic, both in Hamilton, Ont., told attendees at the meeting.

“Sexual concerns over the menopausal transition are not just physical, but they’re also psychological and emotional,” Dr. Green said. “Three common challenges include decreased sexual desire, a reduction in physical arousal and ability to achieve an orgasm, and sexual pain and discomfort during intercourse.”

The reasons for these concerns are multifactorial, she said. Decreased sexual desire can stem from stress, medical problems, their relationship with their partner, or other causes. A woman’s difficulty with reduced physical arousal or ability to have an orgasm can result from changes in hormone levels and vaginal changes, such as vaginal atrophy, which can also contribute to the sexual pain or discomfort reported by 17%-45% of postmenopausal women.

Two pharmacologic treatments exist for sexual concerns: oral flibanserin (Addyi) and injectable bremelanotide (Vyleesi). But many women may be unable or unwilling to take medication for their concerns. Previous research from Lori Brotto has found cognitive behavioral therapy and mindfulness interventions to effectively improve sexual functioning in women treated for gynecologic cancer and in women without a history of cancer.

“Sexual function needs to be understood from a bio-psychosocial model, looking at the biologic factors, the psychological factors, the sociocultural factors, and the interpersonal factors,” Sheryl Kingsberg, PhD, a professor of psychiatry and reproductive biology at Case Western Reserve University and a psychologist at University Hospitals in Cleveland, said in an interview.

Kingsberg_Sheryl_A_OH_web.jpg

“They can all overlap, and the clinician can ask a few pointed questions that help identify what the source of the problem is,” said Dr. Kingsberg, who was not involved in this study. She noted that the International Society for the Study of Women’s Sexual Health has an algorithm that can help in determining the source of the problems.

“Sometimes it’s going to be a biologic condition for which pharmacologic options are nice, but even if it is primarily pharmacologic, psychotherapy is always useful,” Dr. Kingsberg said. “Once the problem is there, even if it’s biologically based, then you have all the things in terms of the cognitive distortion, anxiety,” and other issues that a cognitive behavioral approach can help address. “And access is now much wider because of telehealth,” she added.
 

‘Psychology of menopause’

The study led by Dr. Green focused on peri- and postmenopausal women, with an average age of 50, who were experiencing primary sexual concerns based on a score of at least 26 on the Female Sexual Function Index (FSFI). Among the 20 women recruited for the study, 6 had already been prescribed hormone therapy for sexual concerns.

All reported decreased sexual desire, 17 reported decreased sexual arousal, 14 had body image dissatisfaction related to sexual concerns, and 6 reported urogenital problems. Nine of the women were in full remission from major depressive disorder, one had post-traumatic stress syndrome, and one had subclinical generalized anxiety disorder.

After spending 4 weeks on a wait list as self-control group for the study, the 15 women who completed the trial underwent four individual CBT sessions focusing on sexual concerns. The first session focused on psychoeducation and thought monitoring, and the second focused on cognitive distortions, cognitive strategies, and unhelpful beliefs or expectations related to sexual concerns. The third session looked at the role of problematic behaviors and behavioral experiments, and the fourth focused on continuation of strategies, long-term goals, and maintaining gains.

The participants completed eight measures at baseline, after the 4 weeks on the wait list, and after the four CBT sessions to assess the following:

• Sexual satisfaction, distress, and desire, using the FSFI, the Female Sexual Distress Scale-Revised (FSDS-R), and the Female Sexual Desire Questionnaire (FSDQ).
• Menopause symptoms, using the Greene Climacteric Scale (GCS).
• Body image, using the Dresden Body Image Questionnaire (DBIQ).
• Relationship satisfaction, using the Couples Satisfaction Index (CSI).
• Depression, using the Beck Depression Inventory-II (BDI-II).
• Anxiety, using the Hamilton Anxiety Rating Scale (HAM-A).

The women did not experience any significant changes while on the wait list except a slight decrease on the FSDQ concern subscale. Following the CBT sessions, however, the women experienced a significant decrease in sexual distress and concern as well as an increase in sexual dyadic desire and sexual functioning (P = .003 for FSFI, P = .002 for FSDS-R, and P = .003 for FSDQ).

Participants also experienced a decrease in depression (P < .0001) and menopausal symptoms (P = .001) and an increase in body-image satisfaction (P = .018) and relationship satisfaction (P = .0011) after the CBT sessions. The researchers assessed participants’ satisfaction with the Client Satisfaction Questionnaire after the CBT sessions and reported some of the qualitative findings.

“The treatment program was able to assist me with recognizing that some of my sexual concerns were normal, emotional as well as physical and hormonal, and provided me the ability to delve more deeply into the psychology of menopause and how to work through symptoms and concerns in more manageable pieces,” one participant wrote. Another found helpful the “homework exercises of recognizing a thought/feeling/emotion surrounding how I feel about myself/body and working through. More positive thought pattern/restructuring a response the most helpful.”

The main complaint about the program was that it was too short, with women wanting more sessions to help continue their progress.
 

Not an ‘either-or’ approach

Dr. Kingsberg said ISSWSH has a variety of sexual medicine practitioners, including providers who can provide CBT for sexual concerns, and the American Association of Sexuality Educators, Counselors and Therapists has a referral directory.

“Keeping in mind the bio-psychosocial model, sometimes psychotherapy is going to be a really effective treatment for sexual concerns,” Dr. Kingsberg said. “Sometimes the pharmacologic option is going to be a really effective treatment for some concerns, and sometimes the combination is going to have a really nice treatment effect. So it’s not a one-size-fits-all, and it doesn’t have to be an either-or.”

The sexual concerns of women still do not get adequately addressed in medical schools and residencies, Dr. Kingsberg said, which is distinctly different from how male sexual concerns are addressed in health care.

“Erectile dysfunction is kind of in the norm, and women are still a little hesitant to bring up their sexual concerns,” Dr. Kingsberg said. “They don’t know if it’s appropriate and they’re hoping that their clinician will ask.”

One way clinicians can do that is with a global question for all their patients: “Most of my patients have sexual questions or concerns; what concerns do you have?”

“They don’t have to go through a checklist of 10 things,” Dr. Kingsberg said. If the patient does not bring anything up, providers can then ask a single follow up question: “Do you have any concerns with desire, arousal, orgasm, or pain?” That question, Dr. Kingsberg said, covers the four main areas of concern.

The study was funded by the Canadian Institute of Health Research. Dr. Green reported no disclosures. Dr. Kingsberg has consulted for or served on the advisory board for Alloy, Astellas, Bayer, Dare Bioscience, Freya, Reunion Neuroscience, Materna Medical, Madorra, Palatin, Pfizer, ReJoy, Sprout, Strategic Science Technologies, and MsMedicine.

PHILADELPHIA – Cognitive behavioral therapy (CBT) was effective in addressing peri- and postmenopausal women’s sexual concerns, according to a small study presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society). Four CBT sessions specifically focused on sexual concerns resulted in decreased sexual distress and concern, reduced depressive and menopausal symptoms, and increased sexual desire and functioning, as well as improved body image and relationship satisfaction.

An estimated 68%-87% of perimenopausal and postmenopausal women report sexual concerns, Sheryl Green, PhD, CPsych, an associate professor of psychiatry and behavioral neurosciences at McMaster University and a psychologist at St. Joseph’s Healthcare’s Women’s Health Concerns Clinic, both in Hamilton, Ont., told attendees at the meeting.

“Sexual concerns over the menopausal transition are not just physical, but they’re also psychological and emotional,” Dr. Green said. “Three common challenges include decreased sexual desire, a reduction in physical arousal and ability to achieve an orgasm, and sexual pain and discomfort during intercourse.”

The reasons for these concerns are multifactorial, she said. Decreased sexual desire can stem from stress, medical problems, their relationship with their partner, or other causes. A woman’s difficulty with reduced physical arousal or ability to have an orgasm can result from changes in hormone levels and vaginal changes, such as vaginal atrophy, which can also contribute to the sexual pain or discomfort reported by 17%-45% of postmenopausal women.

Two pharmacologic treatments exist for sexual concerns: oral flibanserin (Addyi) and injectable bremelanotide (Vyleesi). But many women may be unable or unwilling to take medication for their concerns. Previous research from Lori Brotto has found cognitive behavioral therapy and mindfulness interventions to effectively improve sexual functioning in women treated for gynecologic cancer and in women without a history of cancer.

“Sexual function needs to be understood from a bio-psychosocial model, looking at the biologic factors, the psychological factors, the sociocultural factors, and the interpersonal factors,” Sheryl Kingsberg, PhD, a professor of psychiatry and reproductive biology at Case Western Reserve University and a psychologist at University Hospitals in Cleveland, said in an interview.

Kingsberg_Sheryl_A_OH_web.jpg

“They can all overlap, and the clinician can ask a few pointed questions that help identify what the source of the problem is,” said Dr. Kingsberg, who was not involved in this study. She noted that the International Society for the Study of Women’s Sexual Health has an algorithm that can help in determining the source of the problems.

“Sometimes it’s going to be a biologic condition for which pharmacologic options are nice, but even if it is primarily pharmacologic, psychotherapy is always useful,” Dr. Kingsberg said. “Once the problem is there, even if it’s biologically based, then you have all the things in terms of the cognitive distortion, anxiety,” and other issues that a cognitive behavioral approach can help address. “And access is now much wider because of telehealth,” she added.
 

‘Psychology of menopause’

The study led by Dr. Green focused on peri- and postmenopausal women, with an average age of 50, who were experiencing primary sexual concerns based on a score of at least 26 on the Female Sexual Function Index (FSFI). Among the 20 women recruited for the study, 6 had already been prescribed hormone therapy for sexual concerns.

All reported decreased sexual desire, 17 reported decreased sexual arousal, 14 had body image dissatisfaction related to sexual concerns, and 6 reported urogenital problems. Nine of the women were in full remission from major depressive disorder, one had post-traumatic stress syndrome, and one had subclinical generalized anxiety disorder.

After spending 4 weeks on a wait list as self-control group for the study, the 15 women who completed the trial underwent four individual CBT sessions focusing on sexual concerns. The first session focused on psychoeducation and thought monitoring, and the second focused on cognitive distortions, cognitive strategies, and unhelpful beliefs or expectations related to sexual concerns. The third session looked at the role of problematic behaviors and behavioral experiments, and the fourth focused on continuation of strategies, long-term goals, and maintaining gains.

The participants completed eight measures at baseline, after the 4 weeks on the wait list, and after the four CBT sessions to assess the following:

• Sexual satisfaction, distress, and desire, using the FSFI, the Female Sexual Distress Scale-Revised (FSDS-R), and the Female Sexual Desire Questionnaire (FSDQ).
• Menopause symptoms, using the Greene Climacteric Scale (GCS).
• Body image, using the Dresden Body Image Questionnaire (DBIQ).
• Relationship satisfaction, using the Couples Satisfaction Index (CSI).
• Depression, using the Beck Depression Inventory-II (BDI-II).
• Anxiety, using the Hamilton Anxiety Rating Scale (HAM-A).

The women did not experience any significant changes while on the wait list except a slight decrease on the FSDQ concern subscale. Following the CBT sessions, however, the women experienced a significant decrease in sexual distress and concern as well as an increase in sexual dyadic desire and sexual functioning (P = .003 for FSFI, P = .002 for FSDS-R, and P = .003 for FSDQ).

Participants also experienced a decrease in depression (P < .0001) and menopausal symptoms (P = .001) and an increase in body-image satisfaction (P = .018) and relationship satisfaction (P = .0011) after the CBT sessions. The researchers assessed participants’ satisfaction with the Client Satisfaction Questionnaire after the CBT sessions and reported some of the qualitative findings.

“The treatment program was able to assist me with recognizing that some of my sexual concerns were normal, emotional as well as physical and hormonal, and provided me the ability to delve more deeply into the psychology of menopause and how to work through symptoms and concerns in more manageable pieces,” one participant wrote. Another found helpful the “homework exercises of recognizing a thought/feeling/emotion surrounding how I feel about myself/body and working through. More positive thought pattern/restructuring a response the most helpful.”

The main complaint about the program was that it was too short, with women wanting more sessions to help continue their progress.
 

Not an ‘either-or’ approach

Dr. Kingsberg said ISSWSH has a variety of sexual medicine practitioners, including providers who can provide CBT for sexual concerns, and the American Association of Sexuality Educators, Counselors and Therapists has a referral directory.

“Keeping in mind the bio-psychosocial model, sometimes psychotherapy is going to be a really effective treatment for sexual concerns,” Dr. Kingsberg said. “Sometimes the pharmacologic option is going to be a really effective treatment for some concerns, and sometimes the combination is going to have a really nice treatment effect. So it’s not a one-size-fits-all, and it doesn’t have to be an either-or.”

The sexual concerns of women still do not get adequately addressed in medical schools and residencies, Dr. Kingsberg said, which is distinctly different from how male sexual concerns are addressed in health care.

“Erectile dysfunction is kind of in the norm, and women are still a little hesitant to bring up their sexual concerns,” Dr. Kingsberg said. “They don’t know if it’s appropriate and they’re hoping that their clinician will ask.”

One way clinicians can do that is with a global question for all their patients: “Most of my patients have sexual questions or concerns; what concerns do you have?”

“They don’t have to go through a checklist of 10 things,” Dr. Kingsberg said. If the patient does not bring anything up, providers can then ask a single follow up question: “Do you have any concerns with desire, arousal, orgasm, or pain?” That question, Dr. Kingsberg said, covers the four main areas of concern.

The study was funded by the Canadian Institute of Health Research. Dr. Green reported no disclosures. Dr. Kingsberg has consulted for or served on the advisory board for Alloy, Astellas, Bayer, Dare Bioscience, Freya, Reunion Neuroscience, Materna Medical, Madorra, Palatin, Pfizer, ReJoy, Sprout, Strategic Science Technologies, and MsMedicine.

PHILADELPHIA – The prescribing, counseling, and use of hormone therapy (HT) to treat menopausal symptoms is substantially more common among white women than among Black women, according to a review of published studies presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

“Gaps in treatment can be used to inform health care providers about menopausal HT prescribing disparities, with the goal of improving equitable and advanced patient care among disadvantaged populations,” wrote Danette Conklin, PhD, an assistant professor of psychiatry and reproductive biology at Case Western Reserve University, Cleveland, and a psychologist at University Hospitals Cleveland Medical Center; Sally MacPhedran, MD, an associate professor of reproductive biology at Case Western Reserve University and an ob.gyn at MetroHealth Medical Center, also in Cleveland; and their colleagues.

The researchers combed through PubMed, CINAHL, Cochrane Library, Web of Science and PsychInfo databases to identify all studies conducted in the United States since 1940 that contained data on patient demographics and prescribing patterns for hormone therapy to treat menopausal symptoms. In addition to excluding men, children, teens, trans men, and women who had contraindications for HT, the investigators excluded randomized clinical trials so that prescribing patterns would not be based on protocols or RCT participatory criteria.

The researchers identified 20 studies, ranging from 1973 through 2015, including 9 national studies and the others across different U.S. regions. They then analyzed differences in HT prescribing according to age, race/ethnicity, education, income, insurance type, body mass index, and mental health, including alcohol or substance use.

Seven of the studies assessed HT use based on patient surveys, seven used medical or medication records showing an HT prescription, two studies used insurance claims to show an HT prescription, and one study surveyed patients about whether they received an HT prescription. Another four studies used surveys that asked patients whether they received HT counseling but did not indicate if the patients received a prescription.

Half of the studies showed racial disparities in HT prescribing. In all of them, Black women used or were prescribed or counseled on using HT less than white, Hispanic, or Asian women. White women had greater use, prescribing, or counseling than all other races/ethnicities except one study in which Hispanic women were prescribed vaginal estrogen more often than white women.

Six of the studies showed education disparities in which menopausal women with lower education levels used less HT or were prescribed or counseled on HT less than women with higher education.
 

Complex reasons

Monica Christmas, MD, an associate professor of obstetrics and gynecology at the University of Chicago and director of the Menopause Program and the Center for Women’s Integrated Health, said the study’s findings were not surprising, but the reasons for the racial disparities are likely complex.

Christmas_Monica_ILL_web.jpg

Implicit bias in providers is likely one contributing factor, with some providers not thinking of offering HT to certain patients or not expecting the patients to be interested in it. Providers may also hesitate to prescribe HT to patients with more comorbidities because of concerns about HT risks, so if Black patients have more comorbidities, that could play a role in how many are offered or counseled on HT, she said.

“Probably the biggest take home is that it is important to be asking all of our patients about their symptoms and being proactive about talking about it,” Dr. Christmas said in an interview.

At the same time, in her anecdotal experience at a previous institution, Dr. Christmas noticed that her Black patients were less receptive to using hormone therapy than her White patients even though her Black patients tended to exhibit or report greater or more severe symptoms. But there’s been a “paradigm shift” more recently, Dr. Christmas said. With awareness about menopause growing in the media and particularly on social media, and with greater awareness about racial disparities in menopausal symptoms and care – including that shown in Dr. Christmas’s work in the SWAN Study – Dr. Christmas has had more Black patients asking about HT and other treatments for their menopausal symptoms more recently.

“Just 10 years ago, I was trying to talk to people about hormones, and I’ve been giving them to people that need them for a long time, and I couldn’t,” Dr. Christmas said. “Now people are coming in, saying ‘no one’s ever talked to me about it’ or ‘I deserve this.’ It shows you the persuasion that social media and the Internet have on our thinking too, and I think that’s going to be interesting to look at, to see how that impacts people’s perception about wanting treatment.”

Dr. Conklin agreed that reasons for the disparities likely involve a combination of factors, including providers’ assumptions about different racial groups’ knowledge and receptiveness toward different treatments. One of the studies in their review also reported provider barriers to prescribing HT, which included lack of time, lack of adequate knowledge, and concern about risks to patients’ health.

“Medical providers tend to have less time with their patients compared to PhDs, and that time factor really makes a big difference in terms of what the focus is going to be in that [short] appointment,” Dr. Conklin said in an interview. “Perhaps from a provider point of view, they are prioritizing what they think is more important to their patient and not really listening deeply to what their patient is saying.”
 

Educating clinicians

Potentially supporting that possibility, Dr. Conklin and Dr. MacPhedran also had a poster at the conference that looked at prescribing of HT in both Black and White women with a diagnosis of depression, anxiety, or bipolar disorder.

“In a population with a high percentage of Black patients known to have more menopause symptoms, the data demonstrated a surprisingly low rate of documented menopause symptoms (11%) compared to prior reports of up to 80%,” the researchers reported. “This low rate may be related to patient reporting, physician inquiry, or physician documentation of menopause symptoms.” They further found that White women with menopause symptoms and one of those psychiatric diagnosis were 40% more likely to receive an HT prescription for menopausal symptoms than Black women with the same diagnoses and symptoms.

Dr. Conklin emphasized the importance of providers not overlooking women who have mental health disorders when it comes to treating menopausal symptoms, particularly since mental health conditions and menopausal symptoms can exacerbate each other.

“Their depression could worsen irritability, and anxiety can worsen during the transition, and it could be overlooked or thought of as another [psychiatric] episode,” Dr. Conklin said. Providers may need to “dig a little deeper,” especially if patients are reporting having hot flashes or brain fog.

A key way to help overcome the racial disparities – whether they result from systemic issues, implicit bias or assumptions, or patients’ own reticence – is education, Dr. Conklin said. She recommended that providers have educational material about menopause and treatments for menopausal symptoms in the waiting room and then ask patients about their symptoms and invite patients to ask questions.

Dr. MacPhedran added that education for clinicians is key as well.

“Now is a great time – menopause is hot, menopause is interesting, and it’s getting a little bit of a push in terms of research dollars,” Dr. MacPhedran said. “That will trickle down to more emphasis in medical education, whether that’s nurse practitioners, physicians, PAs, or midwives. Everybody needs more education on menopause so they can be more comfortable asking and answering these questions.”

Dr. Conklin said she would like to see expanded education on menopause for medical residents and in health psychology curricula as well.

Among the 13 studies that found disparities in prescribing patterns by age, seven studies showed that older women used or were prescribed or counseled on HT more often than younger women. Four studies found the opposite, with older women less likely to use or be prescribed or counseled about HT. One study had mixed results, and one study had expected prescribing patterns.

Five studies found income disparities and five studies found disparities by medical conditions in terms of HT use, prescribing, or counseling. Other disparities identified in smaller numbers of studies (four or fewer) included natural versus surgical menopause, insurance coverage, body mass index, geographic region, smoking and alcohol use.

The two biggest limitations of the research were its heterogeneity and the small number of studies included, which points to how scarce research on racial disparities in HT use really are, Dr. Conklin said.

The research did not use any external funding. The authors had no industry disclosures. Dr. Christmas has done an educational video for FertilityIQ.

PHILADELPHIA – The prescribing, counseling, and use of hormone therapy (HT) to treat menopausal symptoms is substantially more common among white women than among Black women, according to a review of published studies presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

“Gaps in treatment can be used to inform health care providers about menopausal HT prescribing disparities, with the goal of improving equitable and advanced patient care among disadvantaged populations,” wrote Danette Conklin, PhD, an assistant professor of psychiatry and reproductive biology at Case Western Reserve University, Cleveland, and a psychologist at University Hospitals Cleveland Medical Center; Sally MacPhedran, MD, an associate professor of reproductive biology at Case Western Reserve University and an ob.gyn at MetroHealth Medical Center, also in Cleveland; and their colleagues.

The researchers combed through PubMed, CINAHL, Cochrane Library, Web of Science and PsychInfo databases to identify all studies conducted in the United States since 1940 that contained data on patient demographics and prescribing patterns for hormone therapy to treat menopausal symptoms. In addition to excluding men, children, teens, trans men, and women who had contraindications for HT, the investigators excluded randomized clinical trials so that prescribing patterns would not be based on protocols or RCT participatory criteria.

The researchers identified 20 studies, ranging from 1973 through 2015, including 9 national studies and the others across different U.S. regions. They then analyzed differences in HT prescribing according to age, race/ethnicity, education, income, insurance type, body mass index, and mental health, including alcohol or substance use.

Seven of the studies assessed HT use based on patient surveys, seven used medical or medication records showing an HT prescription, two studies used insurance claims to show an HT prescription, and one study surveyed patients about whether they received an HT prescription. Another four studies used surveys that asked patients whether they received HT counseling but did not indicate if the patients received a prescription.

Half of the studies showed racial disparities in HT prescribing. In all of them, Black women used or were prescribed or counseled on using HT less than white, Hispanic, or Asian women. White women had greater use, prescribing, or counseling than all other races/ethnicities except one study in which Hispanic women were prescribed vaginal estrogen more often than white women.

Six of the studies showed education disparities in which menopausal women with lower education levels used less HT or were prescribed or counseled on HT less than women with higher education.
 

Complex reasons

Monica Christmas, MD, an associate professor of obstetrics and gynecology at the University of Chicago and director of the Menopause Program and the Center for Women’s Integrated Health, said the study’s findings were not surprising, but the reasons for the racial disparities are likely complex.

Christmas_Monica_ILL_web.jpg

Implicit bias in providers is likely one contributing factor, with some providers not thinking of offering HT to certain patients or not expecting the patients to be interested in it. Providers may also hesitate to prescribe HT to patients with more comorbidities because of concerns about HT risks, so if Black patients have more comorbidities, that could play a role in how many are offered or counseled on HT, she said.

“Probably the biggest take home is that it is important to be asking all of our patients about their symptoms and being proactive about talking about it,” Dr. Christmas said in an interview.

At the same time, in her anecdotal experience at a previous institution, Dr. Christmas noticed that her Black patients were less receptive to using hormone therapy than her White patients even though her Black patients tended to exhibit or report greater or more severe symptoms. But there’s been a “paradigm shift” more recently, Dr. Christmas said. With awareness about menopause growing in the media and particularly on social media, and with greater awareness about racial disparities in menopausal symptoms and care – including that shown in Dr. Christmas’s work in the SWAN Study – Dr. Christmas has had more Black patients asking about HT and other treatments for their menopausal symptoms more recently.

“Just 10 years ago, I was trying to talk to people about hormones, and I’ve been giving them to people that need them for a long time, and I couldn’t,” Dr. Christmas said. “Now people are coming in, saying ‘no one’s ever talked to me about it’ or ‘I deserve this.’ It shows you the persuasion that social media and the Internet have on our thinking too, and I think that’s going to be interesting to look at, to see how that impacts people’s perception about wanting treatment.”

Dr. Conklin agreed that reasons for the disparities likely involve a combination of factors, including providers’ assumptions about different racial groups’ knowledge and receptiveness toward different treatments. One of the studies in their review also reported provider barriers to prescribing HT, which included lack of time, lack of adequate knowledge, and concern about risks to patients’ health.

“Medical providers tend to have less time with their patients compared to PhDs, and that time factor really makes a big difference in terms of what the focus is going to be in that [short] appointment,” Dr. Conklin said in an interview. “Perhaps from a provider point of view, they are prioritizing what they think is more important to their patient and not really listening deeply to what their patient is saying.”
 

Educating clinicians

Potentially supporting that possibility, Dr. Conklin and Dr. MacPhedran also had a poster at the conference that looked at prescribing of HT in both Black and White women with a diagnosis of depression, anxiety, or bipolar disorder.

“In a population with a high percentage of Black patients known to have more menopause symptoms, the data demonstrated a surprisingly low rate of documented menopause symptoms (11%) compared to prior reports of up to 80%,” the researchers reported. “This low rate may be related to patient reporting, physician inquiry, or physician documentation of menopause symptoms.” They further found that White women with menopause symptoms and one of those psychiatric diagnosis were 40% more likely to receive an HT prescription for menopausal symptoms than Black women with the same diagnoses and symptoms.

Dr. Conklin emphasized the importance of providers not overlooking women who have mental health disorders when it comes to treating menopausal symptoms, particularly since mental health conditions and menopausal symptoms can exacerbate each other.

“Their depression could worsen irritability, and anxiety can worsen during the transition, and it could be overlooked or thought of as another [psychiatric] episode,” Dr. Conklin said. Providers may need to “dig a little deeper,” especially if patients are reporting having hot flashes or brain fog.

A key way to help overcome the racial disparities – whether they result from systemic issues, implicit bias or assumptions, or patients’ own reticence – is education, Dr. Conklin said. She recommended that providers have educational material about menopause and treatments for menopausal symptoms in the waiting room and then ask patients about their symptoms and invite patients to ask questions.

Dr. MacPhedran added that education for clinicians is key as well.

“Now is a great time – menopause is hot, menopause is interesting, and it’s getting a little bit of a push in terms of research dollars,” Dr. MacPhedran said. “That will trickle down to more emphasis in medical education, whether that’s nurse practitioners, physicians, PAs, or midwives. Everybody needs more education on menopause so they can be more comfortable asking and answering these questions.”

Dr. Conklin said she would like to see expanded education on menopause for medical residents and in health psychology curricula as well.

Among the 13 studies that found disparities in prescribing patterns by age, seven studies showed that older women used or were prescribed or counseled on HT more often than younger women. Four studies found the opposite, with older women less likely to use or be prescribed or counseled about HT. One study had mixed results, and one study had expected prescribing patterns.

Five studies found income disparities and five studies found disparities by medical conditions in terms of HT use, prescribing, or counseling. Other disparities identified in smaller numbers of studies (four or fewer) included natural versus surgical menopause, insurance coverage, body mass index, geographic region, smoking and alcohol use.

The two biggest limitations of the research were its heterogeneity and the small number of studies included, which points to how scarce research on racial disparities in HT use really are, Dr. Conklin said.

The research did not use any external funding. The authors had no industry disclosures. Dr. Christmas has done an educational video for FertilityIQ.

PHILADELPHIA – The prescribing, counseling, and use of hormone therapy (HT) to treat menopausal symptoms is substantially more common among white women than among Black women, according to a review of published studies presented at the annual meeting of the Menopause Society (formerly The North American Menopause Society).

“Gaps in treatment can be used to inform health care providers about menopausal HT prescribing disparities, with the goal of improving equitable and advanced patient care among disadvantaged populations,” wrote Danette Conklin, PhD, an assistant professor of psychiatry and reproductive biology at Case Western Reserve University, Cleveland, and a psychologist at University Hospitals Cleveland Medical Center; Sally MacPhedran, MD, an associate professor of reproductive biology at Case Western Reserve University and an ob.gyn at MetroHealth Medical Center, also in Cleveland; and their colleagues.

The researchers combed through PubMed, CINAHL, Cochrane Library, Web of Science and PsychInfo databases to identify all studies conducted in the United States since 1940 that contained data on patient demographics and prescribing patterns for hormone therapy to treat menopausal symptoms. In addition to excluding men, children, teens, trans men, and women who had contraindications for HT, the investigators excluded randomized clinical trials so that prescribing patterns would not be based on protocols or RCT participatory criteria.

The researchers identified 20 studies, ranging from 1973 through 2015, including 9 national studies and the others across different U.S. regions. They then analyzed differences in HT prescribing according to age, race/ethnicity, education, income, insurance type, body mass index, and mental health, including alcohol or substance use.

Seven of the studies assessed HT use based on patient surveys, seven used medical or medication records showing an HT prescription, two studies used insurance claims to show an HT prescription, and one study surveyed patients about whether they received an HT prescription. Another four studies used surveys that asked patients whether they received HT counseling but did not indicate if the patients received a prescription.

Half of the studies showed racial disparities in HT prescribing. In all of them, Black women used or were prescribed or counseled on using HT less than white, Hispanic, or Asian women. White women had greater use, prescribing, or counseling than all other races/ethnicities except one study in which Hispanic women were prescribed vaginal estrogen more often than white women.

Six of the studies showed education disparities in which menopausal women with lower education levels used less HT or were prescribed or counseled on HT less than women with higher education.
 

Complex reasons

Monica Christmas, MD, an associate professor of obstetrics and gynecology at the University of Chicago and director of the Menopause Program and the Center for Women’s Integrated Health, said the study’s findings were not surprising, but the reasons for the racial disparities are likely complex.

Christmas_Monica_ILL_web.jpg

Implicit bias in providers is likely one contributing factor, with some providers not thinking of offering HT to certain patients or not expecting the patients to be interested in it. Providers may also hesitate to prescribe HT to patients with more comorbidities because of concerns about HT risks, so if Black patients have more comorbidities, that could play a role in how many are offered or counseled on HT, she said.

“Probably the biggest take home is that it is important to be asking all of our patients about their symptoms and being proactive about talking about it,” Dr. Christmas said in an interview.

At the same time, in her anecdotal experience at a previous institution, Dr. Christmas noticed that her Black patients were less receptive to using hormone therapy than her White patients even though her Black patients tended to exhibit or report greater or more severe symptoms. But there’s been a “paradigm shift” more recently, Dr. Christmas said. With awareness about menopause growing in the media and particularly on social media, and with greater awareness about racial disparities in menopausal symptoms and care – including that shown in Dr. Christmas’s work in the SWAN Study – Dr. Christmas has had more Black patients asking about HT and other treatments for their menopausal symptoms more recently.

“Just 10 years ago, I was trying to talk to people about hormones, and I’ve been giving them to people that need them for a long time, and I couldn’t,” Dr. Christmas said. “Now people are coming in, saying ‘no one’s ever talked to me about it’ or ‘I deserve this.’ It shows you the persuasion that social media and the Internet have on our thinking too, and I think that’s going to be interesting to look at, to see how that impacts people’s perception about wanting treatment.”

Dr. Conklin agreed that reasons for the disparities likely involve a combination of factors, including providers’ assumptions about different racial groups’ knowledge and receptiveness toward different treatments. One of the studies in their review also reported provider barriers to prescribing HT, which included lack of time, lack of adequate knowledge, and concern about risks to patients’ health.

“Medical providers tend to have less time with their patients compared to PhDs, and that time factor really makes a big difference in terms of what the focus is going to be in that [short] appointment,” Dr. Conklin said in an interview. “Perhaps from a provider point of view, they are prioritizing what they think is more important to their patient and not really listening deeply to what their patient is saying.”
 

Educating clinicians

Potentially supporting that possibility, Dr. Conklin and Dr. MacPhedran also had a poster at the conference that looked at prescribing of HT in both Black and White women with a diagnosis of depression, anxiety, or bipolar disorder.

“In a population with a high percentage of Black patients known to have more menopause symptoms, the data demonstrated a surprisingly low rate of documented menopause symptoms (11%) compared to prior reports of up to 80%,” the researchers reported. “This low rate may be related to patient reporting, physician inquiry, or physician documentation of menopause symptoms.” They further found that White women with menopause symptoms and one of those psychiatric diagnosis were 40% more likely to receive an HT prescription for menopausal symptoms than Black women with the same diagnoses and symptoms.

Dr. Conklin emphasized the importance of providers not overlooking women who have mental health disorders when it comes to treating menopausal symptoms, particularly since mental health conditions and menopausal symptoms can exacerbate each other.

“Their depression could worsen irritability, and anxiety can worsen during the transition, and it could be overlooked or thought of as another [psychiatric] episode,” Dr. Conklin said. Providers may need to “dig a little deeper,” especially if patients are reporting having hot flashes or brain fog.

A key way to help overcome the racial disparities – whether they result from systemic issues, implicit bias or assumptions, or patients’ own reticence – is education, Dr. Conklin said. She recommended that providers have educational material about menopause and treatments for menopausal symptoms in the waiting room and then ask patients about their symptoms and invite patients to ask questions.

Dr. MacPhedran added that education for clinicians is key as well.

“Now is a great time – menopause is hot, menopause is interesting, and it’s getting a little bit of a push in terms of research dollars,” Dr. MacPhedran said. “That will trickle down to more emphasis in medical education, whether that’s nurse practitioners, physicians, PAs, or midwives. Everybody needs more education on menopause so they can be more comfortable asking and answering these questions.”

Dr. Conklin said she would like to see expanded education on menopause for medical residents and in health psychology curricula as well.

Among the 13 studies that found disparities in prescribing patterns by age, seven studies showed that older women used or were prescribed or counseled on HT more often than younger women. Four studies found the opposite, with older women less likely to use or be prescribed or counseled about HT. One study had mixed results, and one study had expected prescribing patterns.

Five studies found income disparities and five studies found disparities by medical conditions in terms of HT use, prescribing, or counseling. Other disparities identified in smaller numbers of studies (four or fewer) included natural versus surgical menopause, insurance coverage, body mass index, geographic region, smoking and alcohol use.

The two biggest limitations of the research were its heterogeneity and the small number of studies included, which points to how scarce research on racial disparities in HT use really are, Dr. Conklin said.

The research did not use any external funding. The authors had no industry disclosures. Dr. Christmas has done an educational video for FertilityIQ.

When they started the open biopsy, surgeons didn’t know what they were going to find, but they certainly didn’t expect this.

The stringlike worm was five-sixteenths of an inch long, was alive, and wiggled.

“It stunned everyone in that operating theater,” Sanjaya Senanayake, MBBS, an associate professor of infectious disease at Australian National University, Canberra, and senior author of the case report, said in an interview. “When you operate on a brain, you don’t expect to find anything alive.”

The parasitic worm was about half the width of a dime. Helminths like it can usually be seen with the naked eye but are often found in the intestines after being transmitted by soil and infecting the gastrointestinal tract. But this one made it into a woman’s brain in a first-of-its-kind case reported in the journal Emerging Infectious Diseases).

“We weren’t suspecting a worm at all,” Dr. Senanayake said. “There was something abnormal there. Was it going to be granulomatous lesion? Was it going to be cancer? Who knows, but it needed to be biopsied, and a worm was the last thing at the back of anyone’s mind,” he said.
 

A year of inexplicable symptoms

The 64-year-old woman was diagnosed with pneumonia and had a high white blood cell count, low hemoglobin, high platelets, and a very high C-reactive protein of 102 mg/L.

She hadn’t fully recovered from her illness when the abdominal pain and diarrhea started. And then she had a dry cough and night sweats.

After 3 weeks of discomfort, she was admitted to the hospital. She had a history of diabetes, hypothyroidism, and depression, and doctors began looking for answers to her acute illness.

They tested for autoimmune diseases and parasitic infections and prescribed prednisolone to help ease symptoms.

But 3 weeks later, her fever and cough persisted, and she was readmitted to the hospital. Doctors ordered more tests, and her eosinophils were still high, plus there were lesions on her liver, spleen, and lungs.

But tests were negative for bacterial, fungal, and mycobacterial cultures. Her stools showed no evidence of parasites.

She was prescribed mycophenolate and then ivermectin in case her tests for roundworm were a false negative. Doctors suspected Strongyloides, but lesions remained on her spleen even as the liver and lung lesions improved.

Reducing the prednisolone dose affected respiratory symptoms, so by January 2022, a year after initial symptoms began, the medical team added the monoclonal antibody mepolizumab. But her symptoms worsened, and she developed forgetfulness and more depression.

After a brain MRI revealed a right frontal lobe lesion, the team recommended an open biopsy and discovered the worm. The specimen was Ophidascaris robertsi, the intestinal roundworm typically of the carpet python. Never before seen in a human, the only other animals in its life cycle are small marsupials or mammals consumed by pythons.
 

A snake’s bug

Although this is the first case of an Ophidascaris infection in a human, other cases could occur, warn the doctors in their case report.

The best guess for how the patient contracted the infection was by inadvertently consuming larval eggs on wild vegetation that she collected near her home to eat. She lived near a lake known to be home to carpet pythons, so the eggs could have been on the plants she collected or on her hands or kitchen equipment.

“If you’re foraging or using native grasses or plants in recipes, it would be a good idea to cook those instead of having a salad,” Dr. Senanayake said. “That would make the chance of getting something really rare even less likely.”

It’s unclear how or why the worm, which usually stays in the gut, made its way into the patient’s brain, but her long course of immunosuppressing drugs may have played a role, the team points out. “If the normal immune barriers are reduced, then it’s easier for the parasite to move around between organ systems,” Dr. Senanayake said.

Doctors also wondered if she may have been getting re-infected when she went home between hospital admissions. After removing the worm, she received 4 weeks of treatment with albendazole to eliminate any other possible larvae in other organs, especially since Ophidascaris larvae have been known to survive for long periods – more than 4 years in laboratory rats. “The hope is that she’s been cured of this parasitic infection,” Dr. Senanayake said.

As people around the world contend with the global COVID pandemic, they might not realize that new infections are arising around the world every year, he explained.
 

Novel parasitic infections

“The reality is that 30 new infections appeared in the last 30 years, and three-quarters of them are zoonotic, animal infections spilling over into the human world,” Dr. Senanayake said.

Though some of that number is the result of improved surveillance and diagnostics, a real increase has been occurring as human settlements continue expanding.

“This is just a reflection of how burgeoning human populations are encroaching upon animal habitats, and we’re getting more interactions between humans and wild animals, domestic animals and wild animals, and humans and natural flora, which is increasing the risk of this type of infection being recognized,” he explained.

The Ophidascaris worm found in this instance is in other snake species in different continents around the world, too. “Awareness of this case will hopefully lead to the diagnosis and treatment of other cases,” Dr. Senanayake added.

Though it’s certainly surprising to find this particular parasite in a human, finding a zoonotic organism in a person isn’t that strange, according to Janet Foley, DVM, PhD, a professor of veterinary medicine at the University of California, Davis. This is especially true if the usual host is closely related to humans, like primates, or spends a lot of time around them, like rats.

“There are still a lot of parasites and diseases out there in wildlife that haven’t been discovered, and we don’t know the risk,” said Dr. Foley. “But still, the risk would have to be low, generally, or we would see more human cases.”

In the United States, the roundworm common in raccoon feces is Baylisascaris procyonis and can be dangerous for people. “There have been deaths in people exposed to these worms, which do seem to prefer to travel to a human brain,” Dr. Foley said.

A 2016 Centers for Disease Control and Prevention report described seven U.S. cases identified between May 2013 and December 2015, including six that caused central nervous system disease. Another case report in 2018 involved a toddler who had eaten dirt and animal feces in his backyard.

And this past June, an Emerging Infectious Diseases case report described a B. procyonis infection in a 7-year-old with autism spectrum disorder and a history of pica. He had put material in his mouth from the ground near a tree where epidemiologists later found raccoon feces.

Still, Dr. Senanayake cautions against people jumping to conclusions about parasitic infections when they experience symptoms that aren’t otherwise immediately explainable.

The typical person who develops forgetfulness, depression, and a fever probably doesn’t have a worm in their brain or need an immediate MRI, he pointed out. “There may be other cases out there, but common things happen commonly, and this is likely to be rare,” Dr. Senanayake said.

This case demonstrates the challenge in picking a course of treatment when the differential diagnoses for hypereosinophilic syndromes is so broad.
 

Tricky hypereosinophilic syndromes

One of those differentials for the syndromes is parasitic infections, for which treatment would be antiparasitic agents, but another differential is an autoimmune condition that would call for immunosuppression.

“Obviously, as with this case, you don’t want to give someone immunosuppressive treatment if they’ve got a parasite, so you want to look really hard for a parasite before you start them on immunosuppressive treatment for an immunological condition,” Dr. Senanayake said.

But all the blood tests for different antibodies came back negative for parasites, “and this parasite was simply difficult to find until they pulled it from her brain,” he said.

Infectious disease physicians are always looking for the unusual and exotic, Dr. Senanayake explained. But it’s important to exclude the common, easy things first, he added. It’s after exhausting all the likely culprits that “you have to start really thinking laterally and putting resources into unusual tests.”

A version of this article first appeared on Medscape.com.

When they started the open biopsy, surgeons didn’t know what they were going to find, but they certainly didn’t expect this.

The stringlike worm was five-sixteenths of an inch long, was alive, and wiggled.

“It stunned everyone in that operating theater,” Sanjaya Senanayake, MBBS, an associate professor of infectious disease at Australian National University, Canberra, and senior author of the case report, said in an interview. “When you operate on a brain, you don’t expect to find anything alive.”

The parasitic worm was about half the width of a dime. Helminths like it can usually be seen with the naked eye but are often found in the intestines after being transmitted by soil and infecting the gastrointestinal tract. But this one made it into a woman’s brain in a first-of-its-kind case reported in the journal Emerging Infectious Diseases).

“We weren’t suspecting a worm at all,” Dr. Senanayake said. “There was something abnormal there. Was it going to be granulomatous lesion? Was it going to be cancer? Who knows, but it needed to be biopsied, and a worm was the last thing at the back of anyone’s mind,” he said.
 

A year of inexplicable symptoms

The 64-year-old woman was diagnosed with pneumonia and had a high white blood cell count, low hemoglobin, high platelets, and a very high C-reactive protein of 102 mg/L.

She hadn’t fully recovered from her illness when the abdominal pain and diarrhea started. And then she had a dry cough and night sweats.

After 3 weeks of discomfort, she was admitted to the hospital. She had a history of diabetes, hypothyroidism, and depression, and doctors began looking for answers to her acute illness.

They tested for autoimmune diseases and parasitic infections and prescribed prednisolone to help ease symptoms.

But 3 weeks later, her fever and cough persisted, and she was readmitted to the hospital. Doctors ordered more tests, and her eosinophils were still high, plus there were lesions on her liver, spleen, and lungs.

But tests were negative for bacterial, fungal, and mycobacterial cultures. Her stools showed no evidence of parasites.

She was prescribed mycophenolate and then ivermectin in case her tests for roundworm were a false negative. Doctors suspected Strongyloides, but lesions remained on her spleen even as the liver and lung lesions improved.

Reducing the prednisolone dose affected respiratory symptoms, so by January 2022, a year after initial symptoms began, the medical team added the monoclonal antibody mepolizumab. But her symptoms worsened, and she developed forgetfulness and more depression.

After a brain MRI revealed a right frontal lobe lesion, the team recommended an open biopsy and discovered the worm. The specimen was Ophidascaris robertsi, the intestinal roundworm typically of the carpet python. Never before seen in a human, the only other animals in its life cycle are small marsupials or mammals consumed by pythons.
 

A snake’s bug

Although this is the first case of an Ophidascaris infection in a human, other cases could occur, warn the doctors in their case report.

The best guess for how the patient contracted the infection was by inadvertently consuming larval eggs on wild vegetation that she collected near her home to eat. She lived near a lake known to be home to carpet pythons, so the eggs could have been on the plants she collected or on her hands or kitchen equipment.

“If you’re foraging or using native grasses or plants in recipes, it would be a good idea to cook those instead of having a salad,” Dr. Senanayake said. “That would make the chance of getting something really rare even less likely.”

It’s unclear how or why the worm, which usually stays in the gut, made its way into the patient’s brain, but her long course of immunosuppressing drugs may have played a role, the team points out. “If the normal immune barriers are reduced, then it’s easier for the parasite to move around between organ systems,” Dr. Senanayake said.

Doctors also wondered if she may have been getting re-infected when she went home between hospital admissions. After removing the worm, she received 4 weeks of treatment with albendazole to eliminate any other possible larvae in other organs, especially since Ophidascaris larvae have been known to survive for long periods – more than 4 years in laboratory rats. “The hope is that she’s been cured of this parasitic infection,” Dr. Senanayake said.

As people around the world contend with the global COVID pandemic, they might not realize that new infections are arising around the world every year, he explained.
 

Novel parasitic infections

“The reality is that 30 new infections appeared in the last 30 years, and three-quarters of them are zoonotic, animal infections spilling over into the human world,” Dr. Senanayake said.

Though some of that number is the result of improved surveillance and diagnostics, a real increase has been occurring as human settlements continue expanding.

“This is just a reflection of how burgeoning human populations are encroaching upon animal habitats, and we’re getting more interactions between humans and wild animals, domestic animals and wild animals, and humans and natural flora, which is increasing the risk of this type of infection being recognized,” he explained.

The Ophidascaris worm found in this instance is in other snake species in different continents around the world, too. “Awareness of this case will hopefully lead to the diagnosis and treatment of other cases,” Dr. Senanayake added.

Though it’s certainly surprising to find this particular parasite in a human, finding a zoonotic organism in a person isn’t that strange, according to Janet Foley, DVM, PhD, a professor of veterinary medicine at the University of California, Davis. This is especially true if the usual host is closely related to humans, like primates, or spends a lot of time around them, like rats.

“There are still a lot of parasites and diseases out there in wildlife that haven’t been discovered, and we don’t know the risk,” said Dr. Foley. “But still, the risk would have to be low, generally, or we would see more human cases.”

In the United States, the roundworm common in raccoon feces is Baylisascaris procyonis and can be dangerous for people. “There have been deaths in people exposed to these worms, which do seem to prefer to travel to a human brain,” Dr. Foley said.

A 2016 Centers for Disease Control and Prevention report described seven U.S. cases identified between May 2013 and December 2015, including six that caused central nervous system disease. Another case report in 2018 involved a toddler who had eaten dirt and animal feces in his backyard.

And this past June, an Emerging Infectious Diseases case report described a B. procyonis infection in a 7-year-old with autism spectrum disorder and a history of pica. He had put material in his mouth from the ground near a tree where epidemiologists later found raccoon feces.

Still, Dr. Senanayake cautions against people jumping to conclusions about parasitic infections when they experience symptoms that aren’t otherwise immediately explainable.

The typical person who develops forgetfulness, depression, and a fever probably doesn’t have a worm in their brain or need an immediate MRI, he pointed out. “There may be other cases out there, but common things happen commonly, and this is likely to be rare,” Dr. Senanayake said.

This case demonstrates the challenge in picking a course of treatment when the differential diagnoses for hypereosinophilic syndromes is so broad.
 

Tricky hypereosinophilic syndromes

One of those differentials for the syndromes is parasitic infections, for which treatment would be antiparasitic agents, but another differential is an autoimmune condition that would call for immunosuppression.

“Obviously, as with this case, you don’t want to give someone immunosuppressive treatment if they’ve got a parasite, so you want to look really hard for a parasite before you start them on immunosuppressive treatment for an immunological condition,” Dr. Senanayake said.

But all the blood tests for different antibodies came back negative for parasites, “and this parasite was simply difficult to find until they pulled it from her brain,” he said.

Infectious disease physicians are always looking for the unusual and exotic, Dr. Senanayake explained. But it’s important to exclude the common, easy things first, he added. It’s after exhausting all the likely culprits that “you have to start really thinking laterally and putting resources into unusual tests.”

A version of this article first appeared on Medscape.com.

When they started the open biopsy, surgeons didn’t know what they were going to find, but they certainly didn’t expect this.

The stringlike worm was five-sixteenths of an inch long, was alive, and wiggled.

“It stunned everyone in that operating theater,” Sanjaya Senanayake, MBBS, an associate professor of infectious disease at Australian National University, Canberra, and senior author of the case report, said in an interview. “When you operate on a brain, you don’t expect to find anything alive.”

The parasitic worm was about half the width of a dime. Helminths like it can usually be seen with the naked eye but are often found in the intestines after being transmitted by soil and infecting the gastrointestinal tract. But this one made it into a woman’s brain in a first-of-its-kind case reported in the journal Emerging Infectious Diseases).

“We weren’t suspecting a worm at all,” Dr. Senanayake said. “There was something abnormal there. Was it going to be granulomatous lesion? Was it going to be cancer? Who knows, but it needed to be biopsied, and a worm was the last thing at the back of anyone’s mind,” he said.
 

A year of inexplicable symptoms

The 64-year-old woman was diagnosed with pneumonia and had a high white blood cell count, low hemoglobin, high platelets, and a very high C-reactive protein of 102 mg/L.

She hadn’t fully recovered from her illness when the abdominal pain and diarrhea started. And then she had a dry cough and night sweats.

After 3 weeks of discomfort, she was admitted to the hospital. She had a history of diabetes, hypothyroidism, and depression, and doctors began looking for answers to her acute illness.

They tested for autoimmune diseases and parasitic infections and prescribed prednisolone to help ease symptoms.

But 3 weeks later, her fever and cough persisted, and she was readmitted to the hospital. Doctors ordered more tests, and her eosinophils were still high, plus there were lesions on her liver, spleen, and lungs.

But tests were negative for bacterial, fungal, and mycobacterial cultures. Her stools showed no evidence of parasites.

She was prescribed mycophenolate and then ivermectin in case her tests for roundworm were a false negative. Doctors suspected Strongyloides, but lesions remained on her spleen even as the liver and lung lesions improved.

Reducing the prednisolone dose affected respiratory symptoms, so by January 2022, a year after initial symptoms began, the medical team added the monoclonal antibody mepolizumab. But her symptoms worsened, and she developed forgetfulness and more depression.

After a brain MRI revealed a right frontal lobe lesion, the team recommended an open biopsy and discovered the worm. The specimen was Ophidascaris robertsi, the intestinal roundworm typically of the carpet python. Never before seen in a human, the only other animals in its life cycle are small marsupials or mammals consumed by pythons.
 

A snake’s bug

Although this is the first case of an Ophidascaris infection in a human, other cases could occur, warn the doctors in their case report.

The best guess for how the patient contracted the infection was by inadvertently consuming larval eggs on wild vegetation that she collected near her home to eat. She lived near a lake known to be home to carpet pythons, so the eggs could have been on the plants she collected or on her hands or kitchen equipment.

“If you’re foraging or using native grasses or plants in recipes, it would be a good idea to cook those instead of having a salad,” Dr. Senanayake said. “That would make the chance of getting something really rare even less likely.”

It’s unclear how or why the worm, which usually stays in the gut, made its way into the patient’s brain, but her long course of immunosuppressing drugs may have played a role, the team points out. “If the normal immune barriers are reduced, then it’s easier for the parasite to move around between organ systems,” Dr. Senanayake said.

Doctors also wondered if she may have been getting re-infected when she went home between hospital admissions. After removing the worm, she received 4 weeks of treatment with albendazole to eliminate any other possible larvae in other organs, especially since Ophidascaris larvae have been known to survive for long periods – more than 4 years in laboratory rats. “The hope is that she’s been cured of this parasitic infection,” Dr. Senanayake said.

As people around the world contend with the global COVID pandemic, they might not realize that new infections are arising around the world every year, he explained.
 

Novel parasitic infections

“The reality is that 30 new infections appeared in the last 30 years, and three-quarters of them are zoonotic, animal infections spilling over into the human world,” Dr. Senanayake said.

Though some of that number is the result of improved surveillance and diagnostics, a real increase has been occurring as human settlements continue expanding.

“This is just a reflection of how burgeoning human populations are encroaching upon animal habitats, and we’re getting more interactions between humans and wild animals, domestic animals and wild animals, and humans and natural flora, which is increasing the risk of this type of infection being recognized,” he explained.

The Ophidascaris worm found in this instance is in other snake species in different continents around the world, too. “Awareness of this case will hopefully lead to the diagnosis and treatment of other cases,” Dr. Senanayake added.

Though it’s certainly surprising to find this particular parasite in a human, finding a zoonotic organism in a person isn’t that strange, according to Janet Foley, DVM, PhD, a professor of veterinary medicine at the University of California, Davis. This is especially true if the usual host is closely related to humans, like primates, or spends a lot of time around them, like rats.

“There are still a lot of parasites and diseases out there in wildlife that haven’t been discovered, and we don’t know the risk,” said Dr. Foley. “But still, the risk would have to be low, generally, or we would see more human cases.”

In the United States, the roundworm common in raccoon feces is Baylisascaris procyonis and can be dangerous for people. “There have been deaths in people exposed to these worms, which do seem to prefer to travel to a human brain,” Dr. Foley said.

A 2016 Centers for Disease Control and Prevention report described seven U.S. cases identified between May 2013 and December 2015, including six that caused central nervous system disease. Another case report in 2018 involved a toddler who had eaten dirt and animal feces in his backyard.

And this past June, an Emerging Infectious Diseases case report described a B. procyonis infection in a 7-year-old with autism spectrum disorder and a history of pica. He had put material in his mouth from the ground near a tree where epidemiologists later found raccoon feces.

Still, Dr. Senanayake cautions against people jumping to conclusions about parasitic infections when they experience symptoms that aren’t otherwise immediately explainable.

The typical person who develops forgetfulness, depression, and a fever probably doesn’t have a worm in their brain or need an immediate MRI, he pointed out. “There may be other cases out there, but common things happen commonly, and this is likely to be rare,” Dr. Senanayake said.

This case demonstrates the challenge in picking a course of treatment when the differential diagnoses for hypereosinophilic syndromes is so broad.
 

Tricky hypereosinophilic syndromes

One of those differentials for the syndromes is parasitic infections, for which treatment would be antiparasitic agents, but another differential is an autoimmune condition that would call for immunosuppression.

“Obviously, as with this case, you don’t want to give someone immunosuppressive treatment if they’ve got a parasite, so you want to look really hard for a parasite before you start them on immunosuppressive treatment for an immunological condition,” Dr. Senanayake said.

But all the blood tests for different antibodies came back negative for parasites, “and this parasite was simply difficult to find until they pulled it from her brain,” he said.

Infectious disease physicians are always looking for the unusual and exotic, Dr. Senanayake explained. But it’s important to exclude the common, easy things first, he added. It’s after exhausting all the likely culprits that “you have to start really thinking laterally and putting resources into unusual tests.”

A version of this article first appeared on Medscape.com.

AURORA, COLO. – Several drugs for multiple sclerosis (MS) that are contraindicated during pregnancy nevertheless have not shown concerning safety signals in a series of small studies presented as posters at the annual meeting of the Consortium of Multiple Sclerosis Centers. The industry-sponsored research included an assessment of pregnancy and infant outcomes for cladribine, ocrelizumab, ofatumumab, and ozanimod, all of which are not recommended during pregnancy based primarily on minimal data that suggests, but does not confirm, possible teratogenicity.

“When these new medications hit the market, maternal-fetal medicine physicians and obstetricians are left with very scant data on how to counsel patients, and it’s often based on theory, case reports, or animal studies,” said Teodora Kolarova, MD, a maternal-fetal medicine physician at the University of Washington, Seattle, who was not involved in any of the research. “Although these sample sizes seem small, the population they are sampling from – patients with MS who take immunomodulators who then experience a pregnancy – is much smaller than all pregnant patients.”

Taken together, the findings suggest no increased risk of miscarriage or congenital malformation, compared with baseline risk, Dr. Kolarova said.

“As a whole, these studies are overall reassuring with, of course, some caveats, including timing of medication exposure, limited sample size, and limited outcome data,” Dr. Kolarova said. She noted that embryonic organ formation is complete by 10 weeks gestation, by which time an unplanned pregnancy may not have been recognized yet. “In the subset of patients in the studies that were exposed during the first trimester, there was no increase in congenital malformations from a baseline risk of about 2%-3% in the general population, which is helpful for patient counseling.”
 

Counseling during the childbearing years

That kind of counseling is important yet absent for many people capable of pregnancy, suggests separate research also presented at the conference by Suma Shah, MD, an associate professor of neurology at Duke University, Durham, N.C. Dr. Shah gave 13-question surveys to female MS patients of all ages at her institution and presented an analysis of data from 38 completed surveys. Among those taking disease-modifying therapies, their medications included ocrelizumab, rituximab, teriflunomide, fingolimod, fumarates, interferons, natalizumab, and cladribine.

“MS disproportionately impacts women among 20 to 40 years, and that’s a really big part of their childbearing years when there are big decisions being made about whether they’re going to choose to grow family or not,” said Dr. Shah. The average age of those who completed the survey was 44. Dr. Shah noted that a lot of research has looked at the safety of older disease-modifying agents in pregnancy, but that information doesn’t appear to be filtering down to patients. “What I really wanted to look at is what do our parent patients understand about whether or not they can even think about pregnancy – and there’s a lot of work to be done.”

Just under a third of survey respondents said they did not have as many children as they would like, and a quarter said they were told they couldn’t have children if they had a diagnosis of MS.

“That was a little heartbreaking to hear because that’s not the truth,” Dr. Shah said. She said it’s necessary to have a more detailed conversation looking at tailored decisions for patients. “Both of those things – patients not being able to grow their family to the number that they desire, and not feeling like they can grow a family – I would think in 2023 we would have come farther than that, and there’s still a lot of room there to improve.”

She advised clinicians not to assume that MS patients know what their options are regarding family planning. “There’s still a lot of room for conversations,” she said. She also explicitly recommends discussing family planning and pregnancy planning with every patient, no matter their gender, early and often.
 

Cladribine shows no miscarriage, malformations

Dr. Kolarova noted that one of the studies, on cladribine, had a fairly robust sample size with its 180 pregnancy exposures. In that study, led by Kerstin Hellwig, MD, of Ruhr University in Bochum, Germany, data came from the global surveillance program MAPLE-MS, established to assess cladribine effects on pregnancy and infant outcomes. The researchers analyzed data from 76 mothers and 9 fathers who, at any time from 2017 to 2022, were taking cladribine during pregnancy or up to 6 months before pregnancy. Outcomes included live birth, miscarriage, stillbirth, elective abortion, ectopic pregnancy, and major congenital anomalies.

Just over half the mothers (53.9%) were exposed before pregnancy, and about a quarter (26.3%) were exposed during the first trimester. The timing was unknown for most of the other mothers (18.4%). Among the fathers, two-thirds (66.7%) were exposed before pregnancy, and one-third had unknown timing.

Among the 180 pregnancies in the maternal cohort, 42.2% had known outcomes. Nearly half the women (48.7%) taking cladribine had live births, 28.9% had elective abortions, and 21.1% had miscarriages. Only 9 of the 22 pregnancies in the paternal cohort had known outcomes, which included 88.9% live births and 11.1% miscarriages. None of the pregnancies resulted in stillbirth or in a live birth with major congenital anomalies.

”Robust conclusions cannot be made about the risks of adverse pregnancy outcomes with cladribine tablets, but no increase has been signaled thus far,” the researchers reported. ”It is necessary to counsel patients to prevent pregnancy and to use effective contraception during cladribine tablets intake and for at least 6 months after the last cladribine tablet intake in each treatment year.”

Emily Evans, MD, MBE, medical director at U.S. Neurology and Immunology in Rockland, Mass., speaking on behalf of the findings, said they were fairly encouraging.

“Of course, we don’t encourage patients to get pregnant within 6 months of their last dose of cladribine tablets,” Dr. Evans said, but “within those individuals who have gotten pregnant within 6 months of their last dose of cladribine, or who have fathered a child within 6 months of their last dose of cladribine tablets, we’re seeing overall encouraging outcomes. We’re specifically not seeing any differences in the rates of spontaneous abortions, and we’re not seeing any differences in the rates of congenital malformations.”
 

Ocrelizumab and ofatumumab: No infections so far

Current recommendations for ocrelizumab are to avoid pregnancy for 6 months after the last infusion and stop any breastfeeding during therapy. Yet these recommendations are only because of insufficient data rather than evidence of risk, according to Lana Zhovtis Ryerson, MD, of the NYU Multiple Sclerosis Comprehensive Care Center in New York. She and her colleagues identified all women of childbearing age who had received ocrelizumab within 1 year of pregnancy at their NYU institution. A retrospective chart review found 18 women, with an average age of 35, an average 11 years of an MS diagnosis, and an average 11 months taking ocrelizumab.

Among the 18 pregnancies, four women had a first trimester miscarriage, one had a second trimester miscarriage, and one had an abortion. The miscarriage rate could have been partly influenced by the older maternal population, the authors noted. Of the remaining 12 live births, one infant was premature at 34 weeks, and three infants stayed in NICU but were discharged within 2 weeks.

One patient experienced an MS relapse postpartum, despite receiving ocrelizumab within 45 days of delivery. Of the 16 women who agreed to participate in a Pregnancy Assessment Monitoring System (PRAMS) developed by the CDC, two women chose to breastfeed, and seven said their neurologist recommended against breastfeeding. None of the children’s pediatricians advised delaying vaccinations.

“This small sample observational study has not identified a potential additional risk with ocrelizumab for an adverse pregnancy outcome,” the authors concluded, but they added that ongoing studies, MINORE and SOPRANINO, can help guide future recommendations.

Though still limited, slightly more data exists on ofatumumab during pregnancy, including transient B-cell depletion and lymphopenia in infants whose mothers received anti-CD20 antibodies during pregnancy. However, research has found minimal IgG transfer in the first trimester, though it begins rising in the second trimester, and in utero ofatumumab exposure did not lead to any maternal toxicity or adverse prenatal or postnatal developmental effects in cynomolgus monkeys.

Riley Love, MD, of the University of California, San Francisco, Weill Institute for Neuroscience, and her colleagues both prospectively and retrospectively examined pregnancy and infant outcomes for up to 1 year post partum in women with MS who took ofatumumab during pregnancy or in the 6 months leading up to pregnancy. Their population included 104 prospective cases, most of which (84%) included first trimester exposure, and 14 retrospective cases. One in five of the prospective cases occurred during a clinical trial, while the remaining 80% occurred in postmarketing surveillance.

The prospectively followed women were an average 32 years old and were an average 7 weeks pregnant at the time of reporting. Among the 106 fetuses (including two twin pregnancies), only 30 outcomes had data at the cutoff time, including 16 live births, 9 abortions, and 5 miscarriages. None of the live births had congenital anomalies or serious infections. Another 30 pregnancies were lost to follow-up, and 46 were ongoing.

In the 14 retrospective cases, 57% of women were exposed in the first trimester, and 43% were exposed leading up to pregnancy. Half the cases occurred during clinical trials, and half in postmarketing surveillance. The women were an average 32 years old and were an average 10 weeks pregnant at reporting. Among the 14 pregnancies, nine were miscarriages, one was aborted, and four were born live with no congenital anomalies.

The authors did not draw any conclusions from the findings; they cited too little data and an ongoing study by Novartis to investigate ofatumumab in pregnancy.

“Therapies such as ofatumumab and ocrelizumab can lead to increased risk of infection due to transient B-cell depletion in neonates, but the two studies looking at this did not demonstrate increased infectious morbidity for these infants,” Dr. Kolarova said. “As with all poster presentations, I look forward to reading the full papers once they are published as they will often include a lot more detail about when during pregnancy medication exposure occurred and more detailed outcome data that was assessed.”
 

Ozanimod outcomes within general population’s ‘expected ranges’

The final study looked at outcomes of pregnancies in people taking ozanimod and in the partners of people taking ozanimod in a clinical trial setting. The findings show low rates of miscarriage, preterm birth, and congenital anomalies that the authors concluded were within the typical range expected for the general population.

“While pregnancy should be avoided when taking and for 3 months after stopping ozanimod to allow for drug elimination, there is no evidence to date of increased occurrence of adverse pregnancy outcomes with ozanimod exposure during early pregnancy,” wrote Anthony Krakovich, of Bristol Myers Squibb in Princeton, N.J., and his associates.

Ozanimod is an oral sphingosine 1-phosphate (S1P) receptor 1 and 5 modulator whose therapeutic mechanism is not fully understood “but may involve the reduction of lymphocyte migration into the central nervous system and intestine,” the authors wrote. S1P receptors are involved in vascular formation during embryogenesis, and animal studies in rats and rabbits have shown toxicity to the embryo and fetus from S1P receptor modulators, including death and malformations. S1P receptor modulator labels therefore note potential fetal risk and the need for effective contraception while taking the drug.

The study prospectively tracked clinical trial participants taking ozanimod as healthy volunteers or for relapsing MS, ulcerative colitis, or Crohn’s disease. Most of the participants who became pregnant (73%) had relapsing MS, while 18% had ulcerative colitis and 8% had Crohn’s disease.

In female patients receiving ozanimod, 78 pregnancies resulted in 12 miscarriages (including one twin), 15 abortions, and 42 live births, with 6 pregnancies ongoing at the time of reporting and no data available for the remaining 4 pregnancies. Among the 42 live births, 4 were premature but otherwise healthy, 1 had a duplex kidney, and the other 37 infants were typical with no apparent health concerns. These rates of miscarriage, preterm birth, and congenital anomalies were within the expected ranges for the general population, the researchers wrote.

The researchers also assessed pregnancy outcomes for partners of male participants taking ozanimod. The 29 partner pregnancies resulted in 21 live births and one miscarriage, with one pregnancy ongoing and no information available for the other seven. The live births included 5 premature infants (including twins), 13 typical and healthy infants, 1 with Hirschsprung’s disease, 1 with a congenital hydrocele, and 1 with a partial atrioventricular septal defect. Again, the researchers concluded that these rates were within the typical range for the general population and that “no teratogenicity was observed.”

“We often encourage patients with MS, regardless of disease activity and therapies, to seek preconception evaluations with Maternal-Fetal Medicine and their neurologists in order to make plans for pregnancy and postpartum care,” Dr. Kolarova said. “That being said, access to subspecialized health care is not available to all, and pregnancy prior to such consultation does occur. These studies provide novel information that we have not had access to in the past and can improve patient counseling regarding their risks and options.”

The study on cladribine was funded by Merck KGaA, at which two authors are employed. Dr. Hellwig reported consulting, speaker, and/or research support from Bayer, Biogen, Teva, Novartis, Roche, Sanofi, Schering Healthcare, Serono, and Merck, and one author is a former employee of EMD Serono. The study on ocrelizumab was funded by Genentech. Dr. Zhovtis Ryerson reported personal fees from Biogen, Genentech, and Novartis, and research grants from Biogen, Genentech, and CMSC. The other authors had no disclosures. The study on ofatumumab was funded by Novartis. Dr. Bove has received research funds from Biogen, Novartis, and Roche Genentech, and consulting fees from EMD Serono, Horizon, Janssen, and TG Therapeutics; she has an ownership interest in Global Consult MD. Five authors are Novartis employees. Her coauthors, including Dr. Hellwig, reported advisory, consulting, research, speaking, or traveling fees from Alexion, Bayer, Biogen, Celgene BMS, EMD Serono, Horizon, Janssen, Lundbeck, Merck, Pfizer, Roche Genentech, Sanofi Genzyme, Schering Healthcare, Teva, TG Therapeutics, and Novartis. The study on ozanimod was funded by Bristol Myers Squibb. Dr. Krakovich and another author are employees and/or shareholders of Bristol Myers Squibb. The other authors reported consulting, speaking, advisory board, and/or research fees from AbbVie, Almirall, Arena, Biogen, Boehringer Ingelhei, Celgene, Celltrion, EXCEMED, Falk Benelux, Ferring, Forward Pharma, Genentech, Genzyme, Gilead, Janssen, Lilly, Merck, Novartis, Ono Pharma, Pfizer, Prometheus Labs, Protagonist, Roche, Sanofi, Synthon, Takeda, and Teva. Dr. Kolarova had no disclosures. Dr. Shah has received research support from Biogen and VeraSci.
 

AURORA, COLO. – Several drugs for multiple sclerosis (MS) that are contraindicated during pregnancy nevertheless have not shown concerning safety signals in a series of small studies presented as posters at the annual meeting of the Consortium of Multiple Sclerosis Centers. The industry-sponsored research included an assessment of pregnancy and infant outcomes for cladribine, ocrelizumab, ofatumumab, and ozanimod, all of which are not recommended during pregnancy based primarily on minimal data that suggests, but does not confirm, possible teratogenicity.

“When these new medications hit the market, maternal-fetal medicine physicians and obstetricians are left with very scant data on how to counsel patients, and it’s often based on theory, case reports, or animal studies,” said Teodora Kolarova, MD, a maternal-fetal medicine physician at the University of Washington, Seattle, who was not involved in any of the research. “Although these sample sizes seem small, the population they are sampling from – patients with MS who take immunomodulators who then experience a pregnancy – is much smaller than all pregnant patients.”

Taken together, the findings suggest no increased risk of miscarriage or congenital malformation, compared with baseline risk, Dr. Kolarova said.

“As a whole, these studies are overall reassuring with, of course, some caveats, including timing of medication exposure, limited sample size, and limited outcome data,” Dr. Kolarova said. She noted that embryonic organ formation is complete by 10 weeks gestation, by which time an unplanned pregnancy may not have been recognized yet. “In the subset of patients in the studies that were exposed during the first trimester, there was no increase in congenital malformations from a baseline risk of about 2%-3% in the general population, which is helpful for patient counseling.”
 

Counseling during the childbearing years

That kind of counseling is important yet absent for many people capable of pregnancy, suggests separate research also presented at the conference by Suma Shah, MD, an associate professor of neurology at Duke University, Durham, N.C. Dr. Shah gave 13-question surveys to female MS patients of all ages at her institution and presented an analysis of data from 38 completed surveys. Among those taking disease-modifying therapies, their medications included ocrelizumab, rituximab, teriflunomide, fingolimod, fumarates, interferons, natalizumab, and cladribine.

“MS disproportionately impacts women among 20 to 40 years, and that’s a really big part of their childbearing years when there are big decisions being made about whether they’re going to choose to grow family or not,” said Dr. Shah. The average age of those who completed the survey was 44. Dr. Shah noted that a lot of research has looked at the safety of older disease-modifying agents in pregnancy, but that information doesn’t appear to be filtering down to patients. “What I really wanted to look at is what do our parent patients understand about whether or not they can even think about pregnancy – and there’s a lot of work to be done.”

Just under a third of survey respondents said they did not have as many children as they would like, and a quarter said they were told they couldn’t have children if they had a diagnosis of MS.

“That was a little heartbreaking to hear because that’s not the truth,” Dr. Shah said. She said it’s necessary to have a more detailed conversation looking at tailored decisions for patients. “Both of those things – patients not being able to grow their family to the number that they desire, and not feeling like they can grow a family – I would think in 2023 we would have come farther than that, and there’s still a lot of room there to improve.”

She advised clinicians not to assume that MS patients know what their options are regarding family planning. “There’s still a lot of room for conversations,” she said. She also explicitly recommends discussing family planning and pregnancy planning with every patient, no matter their gender, early and often.
 

Cladribine shows no miscarriage, malformations

Dr. Kolarova noted that one of the studies, on cladribine, had a fairly robust sample size with its 180 pregnancy exposures. In that study, led by Kerstin Hellwig, MD, of Ruhr University in Bochum, Germany, data came from the global surveillance program MAPLE-MS, established to assess cladribine effects on pregnancy and infant outcomes. The researchers analyzed data from 76 mothers and 9 fathers who, at any time from 2017 to 2022, were taking cladribine during pregnancy or up to 6 months before pregnancy. Outcomes included live birth, miscarriage, stillbirth, elective abortion, ectopic pregnancy, and major congenital anomalies.

Just over half the mothers (53.9%) were exposed before pregnancy, and about a quarter (26.3%) were exposed during the first trimester. The timing was unknown for most of the other mothers (18.4%). Among the fathers, two-thirds (66.7%) were exposed before pregnancy, and one-third had unknown timing.

Among the 180 pregnancies in the maternal cohort, 42.2% had known outcomes. Nearly half the women (48.7%) taking cladribine had live births, 28.9% had elective abortions, and 21.1% had miscarriages. Only 9 of the 22 pregnancies in the paternal cohort had known outcomes, which included 88.9% live births and 11.1% miscarriages. None of the pregnancies resulted in stillbirth or in a live birth with major congenital anomalies.

”Robust conclusions cannot be made about the risks of adverse pregnancy outcomes with cladribine tablets, but no increase has been signaled thus far,” the researchers reported. ”It is necessary to counsel patients to prevent pregnancy and to use effective contraception during cladribine tablets intake and for at least 6 months after the last cladribine tablet intake in each treatment year.”

Emily Evans, MD, MBE, medical director at U.S. Neurology and Immunology in Rockland, Mass., speaking on behalf of the findings, said they were fairly encouraging.

“Of course, we don’t encourage patients to get pregnant within 6 months of their last dose of cladribine tablets,” Dr. Evans said, but “within those individuals who have gotten pregnant within 6 months of their last dose of cladribine, or who have fathered a child within 6 months of their last dose of cladribine tablets, we’re seeing overall encouraging outcomes. We’re specifically not seeing any differences in the rates of spontaneous abortions, and we’re not seeing any differences in the rates of congenital malformations.”
 

Ocrelizumab and ofatumumab: No infections so far

Current recommendations for ocrelizumab are to avoid pregnancy for 6 months after the last infusion and stop any breastfeeding during therapy. Yet these recommendations are only because of insufficient data rather than evidence of risk, according to Lana Zhovtis Ryerson, MD, of the NYU Multiple Sclerosis Comprehensive Care Center in New York. She and her colleagues identified all women of childbearing age who had received ocrelizumab within 1 year of pregnancy at their NYU institution. A retrospective chart review found 18 women, with an average age of 35, an average 11 years of an MS diagnosis, and an average 11 months taking ocrelizumab.

Among the 18 pregnancies, four women had a first trimester miscarriage, one had a second trimester miscarriage, and one had an abortion. The miscarriage rate could have been partly influenced by the older maternal population, the authors noted. Of the remaining 12 live births, one infant was premature at 34 weeks, and three infants stayed in NICU but were discharged within 2 weeks.

One patient experienced an MS relapse postpartum, despite receiving ocrelizumab within 45 days of delivery. Of the 16 women who agreed to participate in a Pregnancy Assessment Monitoring System (PRAMS) developed by the CDC, two women chose to breastfeed, and seven said their neurologist recommended against breastfeeding. None of the children’s pediatricians advised delaying vaccinations.

“This small sample observational study has not identified a potential additional risk with ocrelizumab for an adverse pregnancy outcome,” the authors concluded, but they added that ongoing studies, MINORE and SOPRANINO, can help guide future recommendations.

Though still limited, slightly more data exists on ofatumumab during pregnancy, including transient B-cell depletion and lymphopenia in infants whose mothers received anti-CD20 antibodies during pregnancy. However, research has found minimal IgG transfer in the first trimester, though it begins rising in the second trimester, and in utero ofatumumab exposure did not lead to any maternal toxicity or adverse prenatal or postnatal developmental effects in cynomolgus monkeys.

Riley Love, MD, of the University of California, San Francisco, Weill Institute for Neuroscience, and her colleagues both prospectively and retrospectively examined pregnancy and infant outcomes for up to 1 year post partum in women with MS who took ofatumumab during pregnancy or in the 6 months leading up to pregnancy. Their population included 104 prospective cases, most of which (84%) included first trimester exposure, and 14 retrospective cases. One in five of the prospective cases occurred during a clinical trial, while the remaining 80% occurred in postmarketing surveillance.

The prospectively followed women were an average 32 years old and were an average 7 weeks pregnant at the time of reporting. Among the 106 fetuses (including two twin pregnancies), only 30 outcomes had data at the cutoff time, including 16 live births, 9 abortions, and 5 miscarriages. None of the live births had congenital anomalies or serious infections. Another 30 pregnancies were lost to follow-up, and 46 were ongoing.

In the 14 retrospective cases, 57% of women were exposed in the first trimester, and 43% were exposed leading up to pregnancy. Half the cases occurred during clinical trials, and half in postmarketing surveillance. The women were an average 32 years old and were an average 10 weeks pregnant at reporting. Among the 14 pregnancies, nine were miscarriages, one was aborted, and four were born live with no congenital anomalies.

The authors did not draw any conclusions from the findings; they cited too little data and an ongoing study by Novartis to investigate ofatumumab in pregnancy.

“Therapies such as ofatumumab and ocrelizumab can lead to increased risk of infection due to transient B-cell depletion in neonates, but the two studies looking at this did not demonstrate increased infectious morbidity for these infants,” Dr. Kolarova said. “As with all poster presentations, I look forward to reading the full papers once they are published as they will often include a lot more detail about when during pregnancy medication exposure occurred and more detailed outcome data that was assessed.”
 

Ozanimod outcomes within general population’s ‘expected ranges’

The final study looked at outcomes of pregnancies in people taking ozanimod and in the partners of people taking ozanimod in a clinical trial setting. The findings show low rates of miscarriage, preterm birth, and congenital anomalies that the authors concluded were within the typical range expected for the general population.

“While pregnancy should be avoided when taking and for 3 months after stopping ozanimod to allow for drug elimination, there is no evidence to date of increased occurrence of adverse pregnancy outcomes with ozanimod exposure during early pregnancy,” wrote Anthony Krakovich, of Bristol Myers Squibb in Princeton, N.J., and his associates.

Ozanimod is an oral sphingosine 1-phosphate (S1P) receptor 1 and 5 modulator whose therapeutic mechanism is not fully understood “but may involve the reduction of lymphocyte migration into the central nervous system and intestine,” the authors wrote. S1P receptors are involved in vascular formation during embryogenesis, and animal studies in rats and rabbits have shown toxicity to the embryo and fetus from S1P receptor modulators, including death and malformations. S1P receptor modulator labels therefore note potential fetal risk and the need for effective contraception while taking the drug.

The study prospectively tracked clinical trial participants taking ozanimod as healthy volunteers or for relapsing MS, ulcerative colitis, or Crohn’s disease. Most of the participants who became pregnant (73%) had relapsing MS, while 18% had ulcerative colitis and 8% had Crohn’s disease.

In female patients receiving ozanimod, 78 pregnancies resulted in 12 miscarriages (including one twin), 15 abortions, and 42 live births, with 6 pregnancies ongoing at the time of reporting and no data available for the remaining 4 pregnancies. Among the 42 live births, 4 were premature but otherwise healthy, 1 had a duplex kidney, and the other 37 infants were typical with no apparent health concerns. These rates of miscarriage, preterm birth, and congenital anomalies were within the expected ranges for the general population, the researchers wrote.

The researchers also assessed pregnancy outcomes for partners of male participants taking ozanimod. The 29 partner pregnancies resulted in 21 live births and one miscarriage, with one pregnancy ongoing and no information available for the other seven. The live births included 5 premature infants (including twins), 13 typical and healthy infants, 1 with Hirschsprung’s disease, 1 with a congenital hydrocele, and 1 with a partial atrioventricular septal defect. Again, the researchers concluded that these rates were within the typical range for the general population and that “no teratogenicity was observed.”

“We often encourage patients with MS, regardless of disease activity and therapies, to seek preconception evaluations with Maternal-Fetal Medicine and their neurologists in order to make plans for pregnancy and postpartum care,” Dr. Kolarova said. “That being said, access to subspecialized health care is not available to all, and pregnancy prior to such consultation does occur. These studies provide novel information that we have not had access to in the past and can improve patient counseling regarding their risks and options.”

The study on cladribine was funded by Merck KGaA, at which two authors are employed. Dr. Hellwig reported consulting, speaker, and/or research support from Bayer, Biogen, Teva, Novartis, Roche, Sanofi, Schering Healthcare, Serono, and Merck, and one author is a former employee of EMD Serono. The study on ocrelizumab was funded by Genentech. Dr. Zhovtis Ryerson reported personal fees from Biogen, Genentech, and Novartis, and research grants from Biogen, Genentech, and CMSC. The other authors had no disclosures. The study on ofatumumab was funded by Novartis. Dr. Bove has received research funds from Biogen, Novartis, and Roche Genentech, and consulting fees from EMD Serono, Horizon, Janssen, and TG Therapeutics; she has an ownership interest in Global Consult MD. Five authors are Novartis employees. Her coauthors, including Dr. Hellwig, reported advisory, consulting, research, speaking, or traveling fees from Alexion, Bayer, Biogen, Celgene BMS, EMD Serono, Horizon, Janssen, Lundbeck, Merck, Pfizer, Roche Genentech, Sanofi Genzyme, Schering Healthcare, Teva, TG Therapeutics, and Novartis. The study on ozanimod was funded by Bristol Myers Squibb. Dr. Krakovich and another author are employees and/or shareholders of Bristol Myers Squibb. The other authors reported consulting, speaking, advisory board, and/or research fees from AbbVie, Almirall, Arena, Biogen, Boehringer Ingelhei, Celgene, Celltrion, EXCEMED, Falk Benelux, Ferring, Forward Pharma, Genentech, Genzyme, Gilead, Janssen, Lilly, Merck, Novartis, Ono Pharma, Pfizer, Prometheus Labs, Protagonist, Roche, Sanofi, Synthon, Takeda, and Teva. Dr. Kolarova had no disclosures. Dr. Shah has received research support from Biogen and VeraSci.
 

AURORA, COLO. – Several drugs for multiple sclerosis (MS) that are contraindicated during pregnancy nevertheless have not shown concerning safety signals in a series of small studies presented as posters at the annual meeting of the Consortium of Multiple Sclerosis Centers. The industry-sponsored research included an assessment of pregnancy and infant outcomes for cladribine, ocrelizumab, ofatumumab, and ozanimod, all of which are not recommended during pregnancy based primarily on minimal data that suggests, but does not confirm, possible teratogenicity.

“When these new medications hit the market, maternal-fetal medicine physicians and obstetricians are left with very scant data on how to counsel patients, and it’s often based on theory, case reports, or animal studies,” said Teodora Kolarova, MD, a maternal-fetal medicine physician at the University of Washington, Seattle, who was not involved in any of the research. “Although these sample sizes seem small, the population they are sampling from – patients with MS who take immunomodulators who then experience a pregnancy – is much smaller than all pregnant patients.”

Taken together, the findings suggest no increased risk of miscarriage or congenital malformation, compared with baseline risk, Dr. Kolarova said.

“As a whole, these studies are overall reassuring with, of course, some caveats, including timing of medication exposure, limited sample size, and limited outcome data,” Dr. Kolarova said. She noted that embryonic organ formation is complete by 10 weeks gestation, by which time an unplanned pregnancy may not have been recognized yet. “In the subset of patients in the studies that were exposed during the first trimester, there was no increase in congenital malformations from a baseline risk of about 2%-3% in the general population, which is helpful for patient counseling.”
 

Counseling during the childbearing years

That kind of counseling is important yet absent for many people capable of pregnancy, suggests separate research also presented at the conference by Suma Shah, MD, an associate professor of neurology at Duke University, Durham, N.C. Dr. Shah gave 13-question surveys to female MS patients of all ages at her institution and presented an analysis of data from 38 completed surveys. Among those taking disease-modifying therapies, their medications included ocrelizumab, rituximab, teriflunomide, fingolimod, fumarates, interferons, natalizumab, and cladribine.

“MS disproportionately impacts women among 20 to 40 years, and that’s a really big part of their childbearing years when there are big decisions being made about whether they’re going to choose to grow family or not,” said Dr. Shah. The average age of those who completed the survey was 44. Dr. Shah noted that a lot of research has looked at the safety of older disease-modifying agents in pregnancy, but that information doesn’t appear to be filtering down to patients. “What I really wanted to look at is what do our parent patients understand about whether or not they can even think about pregnancy – and there’s a lot of work to be done.”

Just under a third of survey respondents said they did not have as many children as they would like, and a quarter said they were told they couldn’t have children if they had a diagnosis of MS.

“That was a little heartbreaking to hear because that’s not the truth,” Dr. Shah said. She said it’s necessary to have a more detailed conversation looking at tailored decisions for patients. “Both of those things – patients not being able to grow their family to the number that they desire, and not feeling like they can grow a family – I would think in 2023 we would have come farther than that, and there’s still a lot of room there to improve.”

She advised clinicians not to assume that MS patients know what their options are regarding family planning. “There’s still a lot of room for conversations,” she said. She also explicitly recommends discussing family planning and pregnancy planning with every patient, no matter their gender, early and often.
 

Cladribine shows no miscarriage, malformations

Dr. Kolarova noted that one of the studies, on cladribine, had a fairly robust sample size with its 180 pregnancy exposures. In that study, led by Kerstin Hellwig, MD, of Ruhr University in Bochum, Germany, data came from the global surveillance program MAPLE-MS, established to assess cladribine effects on pregnancy and infant outcomes. The researchers analyzed data from 76 mothers and 9 fathers who, at any time from 2017 to 2022, were taking cladribine during pregnancy or up to 6 months before pregnancy. Outcomes included live birth, miscarriage, stillbirth, elective abortion, ectopic pregnancy, and major congenital anomalies.

Just over half the mothers (53.9%) were exposed before pregnancy, and about a quarter (26.3%) were exposed during the first trimester. The timing was unknown for most of the other mothers (18.4%). Among the fathers, two-thirds (66.7%) were exposed before pregnancy, and one-third had unknown timing.

Among the 180 pregnancies in the maternal cohort, 42.2% had known outcomes. Nearly half the women (48.7%) taking cladribine had live births, 28.9% had elective abortions, and 21.1% had miscarriages. Only 9 of the 22 pregnancies in the paternal cohort had known outcomes, which included 88.9% live births and 11.1% miscarriages. None of the pregnancies resulted in stillbirth or in a live birth with major congenital anomalies.

”Robust conclusions cannot be made about the risks of adverse pregnancy outcomes with cladribine tablets, but no increase has been signaled thus far,” the researchers reported. ”It is necessary to counsel patients to prevent pregnancy and to use effective contraception during cladribine tablets intake and for at least 6 months after the last cladribine tablet intake in each treatment year.”

Emily Evans, MD, MBE, medical director at U.S. Neurology and Immunology in Rockland, Mass., speaking on behalf of the findings, said they were fairly encouraging.

“Of course, we don’t encourage patients to get pregnant within 6 months of their last dose of cladribine tablets,” Dr. Evans said, but “within those individuals who have gotten pregnant within 6 months of their last dose of cladribine, or who have fathered a child within 6 months of their last dose of cladribine tablets, we’re seeing overall encouraging outcomes. We’re specifically not seeing any differences in the rates of spontaneous abortions, and we’re not seeing any differences in the rates of congenital malformations.”
 

Ocrelizumab and ofatumumab: No infections so far

Current recommendations for ocrelizumab are to avoid pregnancy for 6 months after the last infusion and stop any breastfeeding during therapy. Yet these recommendations are only because of insufficient data rather than evidence of risk, according to Lana Zhovtis Ryerson, MD, of the NYU Multiple Sclerosis Comprehensive Care Center in New York. She and her colleagues identified all women of childbearing age who had received ocrelizumab within 1 year of pregnancy at their NYU institution. A retrospective chart review found 18 women, with an average age of 35, an average 11 years of an MS diagnosis, and an average 11 months taking ocrelizumab.

Among the 18 pregnancies, four women had a first trimester miscarriage, one had a second trimester miscarriage, and one had an abortion. The miscarriage rate could have been partly influenced by the older maternal population, the authors noted. Of the remaining 12 live births, one infant was premature at 34 weeks, and three infants stayed in NICU but were discharged within 2 weeks.

One patient experienced an MS relapse postpartum, despite receiving ocrelizumab within 45 days of delivery. Of the 16 women who agreed to participate in a Pregnancy Assessment Monitoring System (PRAMS) developed by the CDC, two women chose to breastfeed, and seven said their neurologist recommended against breastfeeding. None of the children’s pediatricians advised delaying vaccinations.

“This small sample observational study has not identified a potential additional risk with ocrelizumab for an adverse pregnancy outcome,” the authors concluded, but they added that ongoing studies, MINORE and SOPRANINO, can help guide future recommendations.

Though still limited, slightly more data exists on ofatumumab during pregnancy, including transient B-cell depletion and lymphopenia in infants whose mothers received anti-CD20 antibodies during pregnancy. However, research has found minimal IgG transfer in the first trimester, though it begins rising in the second trimester, and in utero ofatumumab exposure did not lead to any maternal toxicity or adverse prenatal or postnatal developmental effects in cynomolgus monkeys.

Riley Love, MD, of the University of California, San Francisco, Weill Institute for Neuroscience, and her colleagues both prospectively and retrospectively examined pregnancy and infant outcomes for up to 1 year post partum in women with MS who took ofatumumab during pregnancy or in the 6 months leading up to pregnancy. Their population included 104 prospective cases, most of which (84%) included first trimester exposure, and 14 retrospective cases. One in five of the prospective cases occurred during a clinical trial, while the remaining 80% occurred in postmarketing surveillance.

The prospectively followed women were an average 32 years old and were an average 7 weeks pregnant at the time of reporting. Among the 106 fetuses (including two twin pregnancies), only 30 outcomes had data at the cutoff time, including 16 live births, 9 abortions, and 5 miscarriages. None of the live births had congenital anomalies or serious infections. Another 30 pregnancies were lost to follow-up, and 46 were ongoing.

In the 14 retrospective cases, 57% of women were exposed in the first trimester, and 43% were exposed leading up to pregnancy. Half the cases occurred during clinical trials, and half in postmarketing surveillance. The women were an average 32 years old and were an average 10 weeks pregnant at reporting. Among the 14 pregnancies, nine were miscarriages, one was aborted, and four were born live with no congenital anomalies.

The authors did not draw any conclusions from the findings; they cited too little data and an ongoing study by Novartis to investigate ofatumumab in pregnancy.

“Therapies such as ofatumumab and ocrelizumab can lead to increased risk of infection due to transient B-cell depletion in neonates, but the two studies looking at this did not demonstrate increased infectious morbidity for these infants,” Dr. Kolarova said. “As with all poster presentations, I look forward to reading the full papers once they are published as they will often include a lot more detail about when during pregnancy medication exposure occurred and more detailed outcome data that was assessed.”
 

Ozanimod outcomes within general population’s ‘expected ranges’

The final study looked at outcomes of pregnancies in people taking ozanimod and in the partners of people taking ozanimod in a clinical trial setting. The findings show low rates of miscarriage, preterm birth, and congenital anomalies that the authors concluded were within the typical range expected for the general population.

“While pregnancy should be avoided when taking and for 3 months after stopping ozanimod to allow for drug elimination, there is no evidence to date of increased occurrence of adverse pregnancy outcomes with ozanimod exposure during early pregnancy,” wrote Anthony Krakovich, of Bristol Myers Squibb in Princeton, N.J., and his associates.

Ozanimod is an oral sphingosine 1-phosphate (S1P) receptor 1 and 5 modulator whose therapeutic mechanism is not fully understood “but may involve the reduction of lymphocyte migration into the central nervous system and intestine,” the authors wrote. S1P receptors are involved in vascular formation during embryogenesis, and animal studies in rats and rabbits have shown toxicity to the embryo and fetus from S1P receptor modulators, including death and malformations. S1P receptor modulator labels therefore note potential fetal risk and the need for effective contraception while taking the drug.

The study prospectively tracked clinical trial participants taking ozanimod as healthy volunteers or for relapsing MS, ulcerative colitis, or Crohn’s disease. Most of the participants who became pregnant (73%) had relapsing MS, while 18% had ulcerative colitis and 8% had Crohn’s disease.

In female patients receiving ozanimod, 78 pregnancies resulted in 12 miscarriages (including one twin), 15 abortions, and 42 live births, with 6 pregnancies ongoing at the time of reporting and no data available for the remaining 4 pregnancies. Among the 42 live births, 4 were premature but otherwise healthy, 1 had a duplex kidney, and the other 37 infants were typical with no apparent health concerns. These rates of miscarriage, preterm birth, and congenital anomalies were within the expected ranges for the general population, the researchers wrote.

The researchers also assessed pregnancy outcomes for partners of male participants taking ozanimod. The 29 partner pregnancies resulted in 21 live births and one miscarriage, with one pregnancy ongoing and no information available for the other seven. The live births included 5 premature infants (including twins), 13 typical and healthy infants, 1 with Hirschsprung’s disease, 1 with a congenital hydrocele, and 1 with a partial atrioventricular septal defect. Again, the researchers concluded that these rates were within the typical range for the general population and that “no teratogenicity was observed.”

“We often encourage patients with MS, regardless of disease activity and therapies, to seek preconception evaluations with Maternal-Fetal Medicine and their neurologists in order to make plans for pregnancy and postpartum care,” Dr. Kolarova said. “That being said, access to subspecialized health care is not available to all, and pregnancy prior to such consultation does occur. These studies provide novel information that we have not had access to in the past and can improve patient counseling regarding their risks and options.”

The study on cladribine was funded by Merck KGaA, at which two authors are employed. Dr. Hellwig reported consulting, speaker, and/or research support from Bayer, Biogen, Teva, Novartis, Roche, Sanofi, Schering Healthcare, Serono, and Merck, and one author is a former employee of EMD Serono. The study on ocrelizumab was funded by Genentech. Dr. Zhovtis Ryerson reported personal fees from Biogen, Genentech, and Novartis, and research grants from Biogen, Genentech, and CMSC. The other authors had no disclosures. The study on ofatumumab was funded by Novartis. Dr. Bove has received research funds from Biogen, Novartis, and Roche Genentech, and consulting fees from EMD Serono, Horizon, Janssen, and TG Therapeutics; she has an ownership interest in Global Consult MD. Five authors are Novartis employees. Her coauthors, including Dr. Hellwig, reported advisory, consulting, research, speaking, or traveling fees from Alexion, Bayer, Biogen, Celgene BMS, EMD Serono, Horizon, Janssen, Lundbeck, Merck, Pfizer, Roche Genentech, Sanofi Genzyme, Schering Healthcare, Teva, TG Therapeutics, and Novartis. The study on ozanimod was funded by Bristol Myers Squibb. Dr. Krakovich and another author are employees and/or shareholders of Bristol Myers Squibb. The other authors reported consulting, speaking, advisory board, and/or research fees from AbbVie, Almirall, Arena, Biogen, Boehringer Ingelhei, Celgene, Celltrion, EXCEMED, Falk Benelux, Ferring, Forward Pharma, Genentech, Genzyme, Gilead, Janssen, Lilly, Merck, Novartis, Ono Pharma, Pfizer, Prometheus Labs, Protagonist, Roche, Sanofi, Synthon, Takeda, and Teva. Dr. Kolarova had no disclosures. Dr. Shah has received research support from Biogen and VeraSci.
 

BALTIMORE – Receiving the first dose of the human papillomavirus (HPV) vaccine at age 9, rather than bundling it with the Tdap and meningitis vaccines, appears to increase the likelihood that children will complete the HPV vaccine series, according to a retrospective cohort study of commercially insured youth presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. The research was published ahead of print in Human Vaccines and Immunotherapeutics.

Changing attitudes

“These findings are novel because they emphasize starting at age 9, and that is different than prior studies that emphasize bundling of these vaccines,” Kevin Ault, MD, professor and chair of the department of obstetrics and gynecology at Western Michigan University Homer Stryker MD School of Medicine and a former member of the CDC’s Advisory Committee on Immunization Practices, said in an interview.

Dr. Ault was not involved in the study but noted that these findings support the AAP’s recommendation to start the HPV vaccine series at age 9. The Centers for Disease Control and Prevention currently recommends giving the first dose of the HPV vaccine at ages 11-12, at the same time as the Tdap and meningitis vaccines. This recommendation to “bundle” the HPV vaccine with the Tdap and meningitis vaccines aims to facilitate provider-family discussion about the HPV vaccine, ideally reducing parent hesitancy and concerns about the vaccines. Multiple studies have shown improved HPV vaccine uptake when providers offer the HPV vaccine at the same time as the Tdap and meningococcal vaccines.

However, shifts in parents’ attitudes have occurred toward the HPV vaccine since those studies on bundling: Concerns about sexual activity have receded while concerns about safety remain high. The American Academy of Pediatrics and the American Cancer Society both advise starting the HPV vaccine series at age 9, based on evidence showing that more children complete the series when they get the first shot before age 11 compared to getting it at 11 or 12.

“The bundling was really to vaccinate people by the age of 13, thinking that onset of sexual activity was after that,” study author Sidika Kajtezovic, MD, a resident at Boston Medical Center and Boston University Obstetrics and Gynecology, said in an interview. But Dr. Kajtezovic said she delivers babies for 13-year-old patients. “Kids are having sex sooner or sooner.” It’s also clear that using the bundling strategy is not making up the entire gap right now: Ninety percent of children are getting the meningococcal vaccine while only 49% are getting the HPV vaccine, Dr. Kajtezovic pointed out. “There’s a disconnect happening there, even with the bundling,” she said.
 

Debundling vaccines

Dr. Kajtezovic and her colleagues used a national database of employee-sponsored health insurance to analyze the records of 100,857 children who were continuously enrolled in a plan from age 9 in 2015 to age 13 in 2019. They calculated the odds of children completing the HPV vaccine series based on whether they started the series before, at the same time as, or after the Tdap vaccination.

Youth who received the HPV vaccine before their Tdap vaccine had 38% greater odds of completing the series – getting both doses – than did those who received the HPV vaccine at the same time as the Tdap vaccine. Meanwhile, in line with prior evidence, those who got the first HPV dose after their Tdap were less likely – 68% lower odds – to complete the two- or three-dose (if starting above age 14) series.

The researchers identified several other factors that were linked to completing the HPV vaccine series. Females had greater odds than did males of completing the series, as did those living in urban, rather than rural, areas. Other factors associated with completing the series included living in the Northeast United States and receiving primary care from a pediatrician rather than a family medicine physician.
 

Timing is important

“I am encouraged by the findings of this study,” Dr. Ault said in an interview. “However, I would have liked the authors to expand the age range a bit higher. There are data that continuing to discuss the HPV vaccine with parents and teens will increase uptake into the later teen years.”

One challenge is that research shows attendance at primary care visits declines in older adolescence. Since there is no second Tdap or meningitis shot, families need to return for the second HPV vaccine dose after those shots, though they could get the second dose at the same time as other two vaccines if they receive the first dose before age 11. There’s also evidence suggesting that providers find conversations about the HPV vaccine easier when sexual activity is not the focus.

“I often feel that, before a child reaches adolescence, they’re almost, in a way, not sexualized yet, so talking about cancer prevention for an 8- or 9-year-old sometimes sounds a little different to patients versus protecting your 12-year-old, who’s starting to go through adolescence and developing breasts” and other signs of puberty, Dr. Kajtezovic said. Keeping the focus of HPV vaccine discussions on cancer prevention also allows providers to point out the protection against anal cancer, vulvar cancer, vaginal cancer, and head and neck cancer. “They are horrible, and even if they’re treatable, they’re often very hard to treat at an advanced stage,” Dr. Kajtezovic said. “The surgery required is so life disabling and disfiguring.”

The HPV Roundtable advises continuing bundling at practices having success with it but encourages practices to consider earlier vaccination if their uptake is lagging. Quality improvement initiatives, such as earlier electronic medical record prompts and multi-level interventions in pediatric practices, have shown substantial increases in HPV vaccine uptake at 9 and 10 years old. One survey in 2021 found that one in five primary care providers already routinely recommend the HPV vaccine at ages 9-10, and nearly half of others would consider doing so.

“My hope is in the next few years, when [the CDC] refreshes their vaccine recommendations, that they will either unbundle it or move the bar a few years earlier so that you can initiate it to encourage earlier initiation,” Dr. Kajtezovic said.

Dr. Ault had no other disclosures besides prior service on ACIP. Dr. Kajtezovic had no disclosures.

BALTIMORE – Receiving the first dose of the human papillomavirus (HPV) vaccine at age 9, rather than bundling it with the Tdap and meningitis vaccines, appears to increase the likelihood that children will complete the HPV vaccine series, according to a retrospective cohort study of commercially insured youth presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. The research was published ahead of print in Human Vaccines and Immunotherapeutics.

Changing attitudes

“These findings are novel because they emphasize starting at age 9, and that is different than prior studies that emphasize bundling of these vaccines,” Kevin Ault, MD, professor and chair of the department of obstetrics and gynecology at Western Michigan University Homer Stryker MD School of Medicine and a former member of the CDC’s Advisory Committee on Immunization Practices, said in an interview.

Dr. Ault was not involved in the study but noted that these findings support the AAP’s recommendation to start the HPV vaccine series at age 9. The Centers for Disease Control and Prevention currently recommends giving the first dose of the HPV vaccine at ages 11-12, at the same time as the Tdap and meningitis vaccines. This recommendation to “bundle” the HPV vaccine with the Tdap and meningitis vaccines aims to facilitate provider-family discussion about the HPV vaccine, ideally reducing parent hesitancy and concerns about the vaccines. Multiple studies have shown improved HPV vaccine uptake when providers offer the HPV vaccine at the same time as the Tdap and meningococcal vaccines.

However, shifts in parents’ attitudes have occurred toward the HPV vaccine since those studies on bundling: Concerns about sexual activity have receded while concerns about safety remain high. The American Academy of Pediatrics and the American Cancer Society both advise starting the HPV vaccine series at age 9, based on evidence showing that more children complete the series when they get the first shot before age 11 compared to getting it at 11 or 12.

“The bundling was really to vaccinate people by the age of 13, thinking that onset of sexual activity was after that,” study author Sidika Kajtezovic, MD, a resident at Boston Medical Center and Boston University Obstetrics and Gynecology, said in an interview. But Dr. Kajtezovic said she delivers babies for 13-year-old patients. “Kids are having sex sooner or sooner.” It’s also clear that using the bundling strategy is not making up the entire gap right now: Ninety percent of children are getting the meningococcal vaccine while only 49% are getting the HPV vaccine, Dr. Kajtezovic pointed out. “There’s a disconnect happening there, even with the bundling,” she said.
 

Debundling vaccines

Dr. Kajtezovic and her colleagues used a national database of employee-sponsored health insurance to analyze the records of 100,857 children who were continuously enrolled in a plan from age 9 in 2015 to age 13 in 2019. They calculated the odds of children completing the HPV vaccine series based on whether they started the series before, at the same time as, or after the Tdap vaccination.

Youth who received the HPV vaccine before their Tdap vaccine had 38% greater odds of completing the series – getting both doses – than did those who received the HPV vaccine at the same time as the Tdap vaccine. Meanwhile, in line with prior evidence, those who got the first HPV dose after their Tdap were less likely – 68% lower odds – to complete the two- or three-dose (if starting above age 14) series.

The researchers identified several other factors that were linked to completing the HPV vaccine series. Females had greater odds than did males of completing the series, as did those living in urban, rather than rural, areas. Other factors associated with completing the series included living in the Northeast United States and receiving primary care from a pediatrician rather than a family medicine physician.
 

Timing is important

“I am encouraged by the findings of this study,” Dr. Ault said in an interview. “However, I would have liked the authors to expand the age range a bit higher. There are data that continuing to discuss the HPV vaccine with parents and teens will increase uptake into the later teen years.”

One challenge is that research shows attendance at primary care visits declines in older adolescence. Since there is no second Tdap or meningitis shot, families need to return for the second HPV vaccine dose after those shots, though they could get the second dose at the same time as other two vaccines if they receive the first dose before age 11. There’s also evidence suggesting that providers find conversations about the HPV vaccine easier when sexual activity is not the focus.

“I often feel that, before a child reaches adolescence, they’re almost, in a way, not sexualized yet, so talking about cancer prevention for an 8- or 9-year-old sometimes sounds a little different to patients versus protecting your 12-year-old, who’s starting to go through adolescence and developing breasts” and other signs of puberty, Dr. Kajtezovic said. Keeping the focus of HPV vaccine discussions on cancer prevention also allows providers to point out the protection against anal cancer, vulvar cancer, vaginal cancer, and head and neck cancer. “They are horrible, and even if they’re treatable, they’re often very hard to treat at an advanced stage,” Dr. Kajtezovic said. “The surgery required is so life disabling and disfiguring.”

The HPV Roundtable advises continuing bundling at practices having success with it but encourages practices to consider earlier vaccination if their uptake is lagging. Quality improvement initiatives, such as earlier electronic medical record prompts and multi-level interventions in pediatric practices, have shown substantial increases in HPV vaccine uptake at 9 and 10 years old. One survey in 2021 found that one in five primary care providers already routinely recommend the HPV vaccine at ages 9-10, and nearly half of others would consider doing so.

“My hope is in the next few years, when [the CDC] refreshes their vaccine recommendations, that they will either unbundle it or move the bar a few years earlier so that you can initiate it to encourage earlier initiation,” Dr. Kajtezovic said.

Dr. Ault had no other disclosures besides prior service on ACIP. Dr. Kajtezovic had no disclosures.

BALTIMORE – Receiving the first dose of the human papillomavirus (HPV) vaccine at age 9, rather than bundling it with the Tdap and meningitis vaccines, appears to increase the likelihood that children will complete the HPV vaccine series, according to a retrospective cohort study of commercially insured youth presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. The research was published ahead of print in Human Vaccines and Immunotherapeutics.

Changing attitudes

“These findings are novel because they emphasize starting at age 9, and that is different than prior studies that emphasize bundling of these vaccines,” Kevin Ault, MD, professor and chair of the department of obstetrics and gynecology at Western Michigan University Homer Stryker MD School of Medicine and a former member of the CDC’s Advisory Committee on Immunization Practices, said in an interview.

Dr. Ault was not involved in the study but noted that these findings support the AAP’s recommendation to start the HPV vaccine series at age 9. The Centers for Disease Control and Prevention currently recommends giving the first dose of the HPV vaccine at ages 11-12, at the same time as the Tdap and meningitis vaccines. This recommendation to “bundle” the HPV vaccine with the Tdap and meningitis vaccines aims to facilitate provider-family discussion about the HPV vaccine, ideally reducing parent hesitancy and concerns about the vaccines. Multiple studies have shown improved HPV vaccine uptake when providers offer the HPV vaccine at the same time as the Tdap and meningococcal vaccines.

However, shifts in parents’ attitudes have occurred toward the HPV vaccine since those studies on bundling: Concerns about sexual activity have receded while concerns about safety remain high. The American Academy of Pediatrics and the American Cancer Society both advise starting the HPV vaccine series at age 9, based on evidence showing that more children complete the series when they get the first shot before age 11 compared to getting it at 11 or 12.

“The bundling was really to vaccinate people by the age of 13, thinking that onset of sexual activity was after that,” study author Sidika Kajtezovic, MD, a resident at Boston Medical Center and Boston University Obstetrics and Gynecology, said in an interview. But Dr. Kajtezovic said she delivers babies for 13-year-old patients. “Kids are having sex sooner or sooner.” It’s also clear that using the bundling strategy is not making up the entire gap right now: Ninety percent of children are getting the meningococcal vaccine while only 49% are getting the HPV vaccine, Dr. Kajtezovic pointed out. “There’s a disconnect happening there, even with the bundling,” she said.
 

Debundling vaccines

Dr. Kajtezovic and her colleagues used a national database of employee-sponsored health insurance to analyze the records of 100,857 children who were continuously enrolled in a plan from age 9 in 2015 to age 13 in 2019. They calculated the odds of children completing the HPV vaccine series based on whether they started the series before, at the same time as, or after the Tdap vaccination.

Youth who received the HPV vaccine before their Tdap vaccine had 38% greater odds of completing the series – getting both doses – than did those who received the HPV vaccine at the same time as the Tdap vaccine. Meanwhile, in line with prior evidence, those who got the first HPV dose after their Tdap were less likely – 68% lower odds – to complete the two- or three-dose (if starting above age 14) series.

The researchers identified several other factors that were linked to completing the HPV vaccine series. Females had greater odds than did males of completing the series, as did those living in urban, rather than rural, areas. Other factors associated with completing the series included living in the Northeast United States and receiving primary care from a pediatrician rather than a family medicine physician.
 

Timing is important

“I am encouraged by the findings of this study,” Dr. Ault said in an interview. “However, I would have liked the authors to expand the age range a bit higher. There are data that continuing to discuss the HPV vaccine with parents and teens will increase uptake into the later teen years.”

One challenge is that research shows attendance at primary care visits declines in older adolescence. Since there is no second Tdap or meningitis shot, families need to return for the second HPV vaccine dose after those shots, though they could get the second dose at the same time as other two vaccines if they receive the first dose before age 11. There’s also evidence suggesting that providers find conversations about the HPV vaccine easier when sexual activity is not the focus.

“I often feel that, before a child reaches adolescence, they’re almost, in a way, not sexualized yet, so talking about cancer prevention for an 8- or 9-year-old sometimes sounds a little different to patients versus protecting your 12-year-old, who’s starting to go through adolescence and developing breasts” and other signs of puberty, Dr. Kajtezovic said. Keeping the focus of HPV vaccine discussions on cancer prevention also allows providers to point out the protection against anal cancer, vulvar cancer, vaginal cancer, and head and neck cancer. “They are horrible, and even if they’re treatable, they’re often very hard to treat at an advanced stage,” Dr. Kajtezovic said. “The surgery required is so life disabling and disfiguring.”

The HPV Roundtable advises continuing bundling at practices having success with it but encourages practices to consider earlier vaccination if their uptake is lagging. Quality improvement initiatives, such as earlier electronic medical record prompts and multi-level interventions in pediatric practices, have shown substantial increases in HPV vaccine uptake at 9 and 10 years old. One survey in 2021 found that one in five primary care providers already routinely recommend the HPV vaccine at ages 9-10, and nearly half of others would consider doing so.

“My hope is in the next few years, when [the CDC] refreshes their vaccine recommendations, that they will either unbundle it or move the bar a few years earlier so that you can initiate it to encourage earlier initiation,” Dr. Kajtezovic said.

Dr. Ault had no other disclosures besides prior service on ACIP. Dr. Kajtezovic had no disclosures.

Like hundreds of other medical experts, Leana Wen, MD, an emergency physician and former Baltimore health commissioner, was an early and avid supporter of COVID vaccines and their ability to prevent severe disease, hospitalization, and death from SARS-CoV-2 infections.

When 51-year-old Scott Eli Harris, of Aubrey, Tex., heard of Dr. Wen’s stance in July 2021, the self-described “fifth-generation U.S. Army veteran and a sniper” sent Dr. Wen an electronic invective laden with racist language and very specific threats to shoot her.

Mr. Harris pled guilty to transmitting threats via interstate commerce last February and began serving 6 months in federal prison in the fall of 2022, but his threats wouldn’t be the last for Dr. Wen. Just 2 days after Mr. Harris was sentenced, charges were unsealed against another man in Massachusetts, who threatened that Dr. Wen would “end up in pieces” if she continued “pushing” her thoughts publicly.’

Dr. Wen has plenty of company. In an August 2022 survey of emergency doctors conducted by the American College of Emergency Physicians, 85% of respondents said violence against them is increasing. One in four doctors said they’re being assaulted by patients and their family and friends multiple times a week, compared with just 8% of doctors who said as much in 2018. About 64% of emergency physicians reported receiving verbal assaults and threats of violence; 40% reported being hit or slapped, and 26% were kicked.

This uptick of violence and threats against physicians didn’t come out of nowhere; violence against health care workers has been gradually increasing over the past decade. Health care providers can attest to the hostility that particular topics have sparked for years: vaccines in pediatrics, abortion in ob.gyn., and gender-affirming care in endocrinology.

But the pandemic fueled the fire. While there have always been hot-button issues in medicine, the ire they arouse today is more intense than ever before. The proliferation of misinformation (often via social media) and the politicization of public health and medicine are at the center of the problem.
 

‘The people attacking are themselves victims’

The misinformation problem first came to a head in one area of public health: vaccines. The pandemic accelerated antagonism in medicine – thanks, in part, to decades of antivaccine activism.

The antivaccine movement, which has ebbed and flowed in the United States and across the globe since the first vaccine, experienced a new wave in the early 2000s with the combination of concerns about thimerosal in vaccines and a now disproven link between autism and the MMR vaccine. But that movement grew. It picked up steam when activists gained political clout after a 2014 measles outbreak at Disneyland led California schools to tighten up policies regarding vaccinations for kids who enrolled. These stronger public school vaccination laws ran up against religious freedom arguments from antivaccine advocates.

Use of social media continues to grow, and with it, the spread of misinformation. A recent study found that Facebook “users’ social media habits doubled, and in some cases, tripled the amount of fake news they shared.”

In the face of growing confusion, health care providers and public health experts have often struggled to treat their patients – and communicate to the public – without appearing political.

Hotez_Peter_TEXAS_web.jpg

“The people that are doing the attacking are in some ways themselves victims,” said Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor College of Medicine, Houston. “They’re victims of the antiscience, antihealth ecosystem coming out of Fox News, the House Freedom Caucus, the CPAC conference, coming out of contrarian intellectuals.”

Many of Dr. Hotez’s colleagues don’t want to talk about the political right as an enabler of scientific disinformation, he said, but that doesn’t change what the evidence shows. The vast majority of state and national bills opposing vaccination, gender-affirming care, comprehensive reproductive care, and other evidence-based medical care often come from Republican legislators.
 

When politics and health care collide

“We’re in an incredible status quo,” said William Schaffner, MD, the previous director of the Infectious Diseases Society of America and a professor of infectious diseases and preventive medicine at Vanderbilt University, Nashville, Tenn. “You can’t get away from the politics, because you have [political] candidates espousing certain concepts that are antithetical to good public health.”

Schaffner_William_TENN_web.jpg

In March 2023, Florida Gov. Ron DeSantis’s surgeon general, Joseph Ladapo, MD, PhD, warned that COVID vaccines are harmful to young men, prompting rebukes from federal health authorities. It later came out that Dr. Ladapo had changed some of the results of the study before issuing his warning. But long before 2023, there emerged an increasing gap in COVID deaths between red states and blue states, mirroring the vaccination rates in those states. The redder the state, the higher the death toll.

It’s not just Republican Party culture warriors; medical misinformation is also finding increasing purchase on the far left. Robert F. Kennedy Jr. and Marianne Williamson, both of whom have launched long-shot challenges to President Biden for the 2024 Democratic nomination, had promoted antivaccine ideas long before the COVID pandemic. Mr. Kennedy continues to spread misinformation.

In June 2023, Joe Rogan hosted Mr. Kennedy, on his podcast. During the episode, Mr. Rogan listened uncritically as Mr. Kennedy told his millions of listeners that vaccines cause autism and that 5G causes cancer, among other fringe, often-debunked theories.

Dr. Hotez, a prominent misinformation debunker who was also part of a team that designed a low-cost COVID-19 vaccine, wrote on Twitter that the episode was “just awful.”

The backlash began almost immediately. Mr. Rogan, who has over 11 million followers on Twitter, responded with a public challenge for Dr. Hotez to debate Mr. Kennedy on Mr. Rogan’s show, with a reward of $100,000 to the charity of Dr. Hotez’s choice. More offers streamed in, including from Elon Musk, who tweeted that Dr. Hotez was “afraid of a public debate, because he knows he’s wrong.” More supporters of Mr. Kennedy and Mr. Rogan piled on.

Vaccine skeptics even showed up at Dr. Hotez’s house, filming him as he was returning from buying a Father’s Day cake and taunting him to debate Mr. Kennedy.
 

A turn in the pandemic

For a precious few weeks at the start of the pandemic, it felt as though the country was all in this together. There were arguments against closing schools and shutting down businesses, but for the most part, the nation had about 4 solid weeks of solidarity.

As masking mandates changed and the public health establishment lost the confidence of Americans, the veneer of solidarity began to chip away.

“Things were changing so rapidly during the pandemic that it was very hard for staff and patients to understand the changing guidelines, whether it was visitor constraints or masking,” said Carrie Nelson, the chief medical officer at the telehealth company AmWell, who worked as a supervisor at a large health care system in the Midwest until 2021.

In the midst of the public health crisis, former President Trump was downplaying the severity of the disease and was silencing officials from the Centers for Disease Control and Prevention, such as Nancy Messonier, who warned from the very beginning of the pandemic’s potential.

When the vaccines came out, the latent antivaccine movement flared up once again. And this time – unlike in decades past – the debate over vaccines had become partisan.

“Before the pandemic,” said Christopher Thomas, an emergency physician on the West Coast who requested that a pseudonym be used because of personal threats he has received, “patients wouldn’t really challenge me or throw out weird questions.” It’s not that he never encountered pushback, but the stakes felt lower, and people largely deferred to his medical expertise. “If we got a parent who had not vaccinated their child, I would totally engage back then,” Dr. Thomas said.

But the pandemic – and America’s response to it – changed the conversation. “The rhetoric ... switched from downplaying the virus to demonizing the vaccines,” Dr. Thomas said.
 

The toll on health care professionals

By the time vaccines were available, the public had begun to conflate doctors with public health experts, since both were “pushing” the vaccine.

“Most people probably don’t really know the difference between clinical medicine and public health,” said Richard Pan, MD, MPH, a pediatrician and California legislator who sponsored two bills – now laws – that strengthened state childhood vaccination requirements.

At first, it was clearly public health officials, such as Anthony Fauci, MD, who were the face of measures to mitigate the virus. But as doctors became the enforcers of those measures, the line between physicians and public health officials blurred.

A lot of the anger then shifted toward doctors, nurses, and other health care professionals, Dr. Pan said, “because we were, of course, the ones who would be administering the vaccines. They don’t really think of their doctor as a government person until your doctor is carrying a [government] message.”

Given the pressures and struggles of the past few years, it’s no surprise that burnout among health care professionals is high. According to an April 2023 study by the National Council of State Boards of Nursing and the National Forum of State Nursing Workforce Centers, an estimated 800,000 nurses expect to leave the profession by 2027, driven first and foremost by “stress and burnout.”

All of these departures in medicine’s “great resignation” have left hospitals and health care organizations even more short staffed, thereby increasing even more the pressure and burnout on those left.

The pandemic had already badly exacerbated the already widespread problem of burnout in the medical field, which Ms. Nelson said has contributed to the tension.

“The burnout problem that we have in health care is not a good basis for the development of a good therapeutic relationship,” Ms. Nelson said. “Burnout is fraught with apathy and desensitization to human emotions. It takes away the empathy that we once had for people that we see.”
 

What comes next?

Almost exactly 3 years after the world learned about SARS-CoV-2, Biden declared an end to the coronavirus public health emergency in April 2023. Yet, Americans continue to die from COVID, and the anger that bloomed and spread has not abated.

“I think we’re in a new steady state of violence in health care settings,” Ms. Nelson said. “It’s not gone down, because people are still very distressed.” That’s evident from the high prevalence of mental health conditions, the financial strain of first the pandemic and then inflation, and the overall traumatic impact the pandemic had on people, whether they recognize it or not.

The first step to solving any problem is, as the saying goes, to admit that there is a problem.

“I think people need to start stepping out of their comfort bubbles and start to look at things that make them uncomfortable,” Dr. Thomas said, but he doesn’t see that happening any time soon. “I’ve been very let down by physicians and embarrassed by the American physician organizations.”

The medical board in his state, he said, has stood by as some doctors continue misrepresenting medical evidence. “That’s been really, really hard on me. I didn’t think that the medical boards would go so far as to look the other way for something that was this tremendously bad.”

There are others who can take the lead – if they’re willing.

“There are some things the medical societies and academic health centers can do,” Dr. Hotez said, “starting with building up a culture of physicians and health care providers feeling comfortable in the public domain.” He said the messaging when he was getting his degrees was not to engage the public and not to talk to journalists because that was “self-promotion” or “grandstanding.” But the world is different now. Health care professionals need training in public engagement and communication, he said, and the culture needs to change so that health care providers feel comfortable speaking out without feeling “the sword of Damocles over their heads” every time they talk to a reporter, Dr. Hotez said.

There may be no silver bullet to solve the big-picture trust problem in medicine and public health. No TV appearance or quote in an article can solve it. But on an individual level — through careful relationship building with patients – doctors can strengthen that trust.

Telehealth may help with that, but there’s a fine balance there, Ms. Nelson cautioned. On the one hand, with the doctor and the patient each in their own private spaces, where they feel safe and comfortable, the overall experience can be more therapeutic and less stressful. At the same time, telehealth can pile on change-management tasks that can exacerbate burnout, “so it’s a delicate thing we have to approach.”

One very thin silver lining that could emerge from the way in which patients have begun to try to take charge of their care.

“They should fully understand the reasoning behind the recommendations that physicians are making,” Ms. Nelson said. “I’d like to see us get to a happy medium where it’s a partnership. We can’t go back to the old school where the doctor knows best and you don’t ever question him.

“What we need is the partnership, and I would love to see that as the silver lining, but the anger has got to settle down in order for that kind of productive thing to happen.”

As for the big picture? There’s a limit to what even society’s “miracle workers” can do. “The biggest priority right now for the health system is to protect their staff whatever way they can and do some training in deescalation,” Ms. Nelson said. “But I don’t think health care can solve the societal issues that seem to be creating this.”

A version of this article first appeared on Medscape.com.

Like hundreds of other medical experts, Leana Wen, MD, an emergency physician and former Baltimore health commissioner, was an early and avid supporter of COVID vaccines and their ability to prevent severe disease, hospitalization, and death from SARS-CoV-2 infections.

When 51-year-old Scott Eli Harris, of Aubrey, Tex., heard of Dr. Wen’s stance in July 2021, the self-described “fifth-generation U.S. Army veteran and a sniper” sent Dr. Wen an electronic invective laden with racist language and very specific threats to shoot her.

Mr. Harris pled guilty to transmitting threats via interstate commerce last February and began serving 6 months in federal prison in the fall of 2022, but his threats wouldn’t be the last for Dr. Wen. Just 2 days after Mr. Harris was sentenced, charges were unsealed against another man in Massachusetts, who threatened that Dr. Wen would “end up in pieces” if she continued “pushing” her thoughts publicly.’

Dr. Wen has plenty of company. In an August 2022 survey of emergency doctors conducted by the American College of Emergency Physicians, 85% of respondents said violence against them is increasing. One in four doctors said they’re being assaulted by patients and their family and friends multiple times a week, compared with just 8% of doctors who said as much in 2018. About 64% of emergency physicians reported receiving verbal assaults and threats of violence; 40% reported being hit or slapped, and 26% were kicked.

This uptick of violence and threats against physicians didn’t come out of nowhere; violence against health care workers has been gradually increasing over the past decade. Health care providers can attest to the hostility that particular topics have sparked for years: vaccines in pediatrics, abortion in ob.gyn., and gender-affirming care in endocrinology.

But the pandemic fueled the fire. While there have always been hot-button issues in medicine, the ire they arouse today is more intense than ever before. The proliferation of misinformation (often via social media) and the politicization of public health and medicine are at the center of the problem.
 

‘The people attacking are themselves victims’

The misinformation problem first came to a head in one area of public health: vaccines. The pandemic accelerated antagonism in medicine – thanks, in part, to decades of antivaccine activism.

The antivaccine movement, which has ebbed and flowed in the United States and across the globe since the first vaccine, experienced a new wave in the early 2000s with the combination of concerns about thimerosal in vaccines and a now disproven link between autism and the MMR vaccine. But that movement grew. It picked up steam when activists gained political clout after a 2014 measles outbreak at Disneyland led California schools to tighten up policies regarding vaccinations for kids who enrolled. These stronger public school vaccination laws ran up against religious freedom arguments from antivaccine advocates.

Use of social media continues to grow, and with it, the spread of misinformation. A recent study found that Facebook “users’ social media habits doubled, and in some cases, tripled the amount of fake news they shared.”

In the face of growing confusion, health care providers and public health experts have often struggled to treat their patients – and communicate to the public – without appearing political.

Hotez_Peter_TEXAS_web.jpg

“The people that are doing the attacking are in some ways themselves victims,” said Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor College of Medicine, Houston. “They’re victims of the antiscience, antihealth ecosystem coming out of Fox News, the House Freedom Caucus, the CPAC conference, coming out of contrarian intellectuals.”

Many of Dr. Hotez’s colleagues don’t want to talk about the political right as an enabler of scientific disinformation, he said, but that doesn’t change what the evidence shows. The vast majority of state and national bills opposing vaccination, gender-affirming care, comprehensive reproductive care, and other evidence-based medical care often come from Republican legislators.
 

When politics and health care collide

“We’re in an incredible status quo,” said William Schaffner, MD, the previous director of the Infectious Diseases Society of America and a professor of infectious diseases and preventive medicine at Vanderbilt University, Nashville, Tenn. “You can’t get away from the politics, because you have [political] candidates espousing certain concepts that are antithetical to good public health.”

Schaffner_William_TENN_web.jpg

In March 2023, Florida Gov. Ron DeSantis’s surgeon general, Joseph Ladapo, MD, PhD, warned that COVID vaccines are harmful to young men, prompting rebukes from federal health authorities. It later came out that Dr. Ladapo had changed some of the results of the study before issuing his warning. But long before 2023, there emerged an increasing gap in COVID deaths between red states and blue states, mirroring the vaccination rates in those states. The redder the state, the higher the death toll.

It’s not just Republican Party culture warriors; medical misinformation is also finding increasing purchase on the far left. Robert F. Kennedy Jr. and Marianne Williamson, both of whom have launched long-shot challenges to President Biden for the 2024 Democratic nomination, had promoted antivaccine ideas long before the COVID pandemic. Mr. Kennedy continues to spread misinformation.

In June 2023, Joe Rogan hosted Mr. Kennedy, on his podcast. During the episode, Mr. Rogan listened uncritically as Mr. Kennedy told his millions of listeners that vaccines cause autism and that 5G causes cancer, among other fringe, often-debunked theories.

Dr. Hotez, a prominent misinformation debunker who was also part of a team that designed a low-cost COVID-19 vaccine, wrote on Twitter that the episode was “just awful.”

The backlash began almost immediately. Mr. Rogan, who has over 11 million followers on Twitter, responded with a public challenge for Dr. Hotez to debate Mr. Kennedy on Mr. Rogan’s show, with a reward of $100,000 to the charity of Dr. Hotez’s choice. More offers streamed in, including from Elon Musk, who tweeted that Dr. Hotez was “afraid of a public debate, because he knows he’s wrong.” More supporters of Mr. Kennedy and Mr. Rogan piled on.

Vaccine skeptics even showed up at Dr. Hotez’s house, filming him as he was returning from buying a Father’s Day cake and taunting him to debate Mr. Kennedy.
 

A turn in the pandemic

For a precious few weeks at the start of the pandemic, it felt as though the country was all in this together. There were arguments against closing schools and shutting down businesses, but for the most part, the nation had about 4 solid weeks of solidarity.

As masking mandates changed and the public health establishment lost the confidence of Americans, the veneer of solidarity began to chip away.

“Things were changing so rapidly during the pandemic that it was very hard for staff and patients to understand the changing guidelines, whether it was visitor constraints or masking,” said Carrie Nelson, the chief medical officer at the telehealth company AmWell, who worked as a supervisor at a large health care system in the Midwest until 2021.

In the midst of the public health crisis, former President Trump was downplaying the severity of the disease and was silencing officials from the Centers for Disease Control and Prevention, such as Nancy Messonier, who warned from the very beginning of the pandemic’s potential.

When the vaccines came out, the latent antivaccine movement flared up once again. And this time – unlike in decades past – the debate over vaccines had become partisan.

“Before the pandemic,” said Christopher Thomas, an emergency physician on the West Coast who requested that a pseudonym be used because of personal threats he has received, “patients wouldn’t really challenge me or throw out weird questions.” It’s not that he never encountered pushback, but the stakes felt lower, and people largely deferred to his medical expertise. “If we got a parent who had not vaccinated their child, I would totally engage back then,” Dr. Thomas said.

But the pandemic – and America’s response to it – changed the conversation. “The rhetoric ... switched from downplaying the virus to demonizing the vaccines,” Dr. Thomas said.
 

The toll on health care professionals

By the time vaccines were available, the public had begun to conflate doctors with public health experts, since both were “pushing” the vaccine.

“Most people probably don’t really know the difference between clinical medicine and public health,” said Richard Pan, MD, MPH, a pediatrician and California legislator who sponsored two bills – now laws – that strengthened state childhood vaccination requirements.

At first, it was clearly public health officials, such as Anthony Fauci, MD, who were the face of measures to mitigate the virus. But as doctors became the enforcers of those measures, the line between physicians and public health officials blurred.

A lot of the anger then shifted toward doctors, nurses, and other health care professionals, Dr. Pan said, “because we were, of course, the ones who would be administering the vaccines. They don’t really think of their doctor as a government person until your doctor is carrying a [government] message.”

Given the pressures and struggles of the past few years, it’s no surprise that burnout among health care professionals is high. According to an April 2023 study by the National Council of State Boards of Nursing and the National Forum of State Nursing Workforce Centers, an estimated 800,000 nurses expect to leave the profession by 2027, driven first and foremost by “stress and burnout.”

All of these departures in medicine’s “great resignation” have left hospitals and health care organizations even more short staffed, thereby increasing even more the pressure and burnout on those left.

The pandemic had already badly exacerbated the already widespread problem of burnout in the medical field, which Ms. Nelson said has contributed to the tension.

“The burnout problem that we have in health care is not a good basis for the development of a good therapeutic relationship,” Ms. Nelson said. “Burnout is fraught with apathy and desensitization to human emotions. It takes away the empathy that we once had for people that we see.”
 

What comes next?

Almost exactly 3 years after the world learned about SARS-CoV-2, Biden declared an end to the coronavirus public health emergency in April 2023. Yet, Americans continue to die from COVID, and the anger that bloomed and spread has not abated.

“I think we’re in a new steady state of violence in health care settings,” Ms. Nelson said. “It’s not gone down, because people are still very distressed.” That’s evident from the high prevalence of mental health conditions, the financial strain of first the pandemic and then inflation, and the overall traumatic impact the pandemic had on people, whether they recognize it or not.

The first step to solving any problem is, as the saying goes, to admit that there is a problem.

“I think people need to start stepping out of their comfort bubbles and start to look at things that make them uncomfortable,” Dr. Thomas said, but he doesn’t see that happening any time soon. “I’ve been very let down by physicians and embarrassed by the American physician organizations.”

The medical board in his state, he said, has stood by as some doctors continue misrepresenting medical evidence. “That’s been really, really hard on me. I didn’t think that the medical boards would go so far as to look the other way for something that was this tremendously bad.”

There are others who can take the lead – if they’re willing.

“There are some things the medical societies and academic health centers can do,” Dr. Hotez said, “starting with building up a culture of physicians and health care providers feeling comfortable in the public domain.” He said the messaging when he was getting his degrees was not to engage the public and not to talk to journalists because that was “self-promotion” or “grandstanding.” But the world is different now. Health care professionals need training in public engagement and communication, he said, and the culture needs to change so that health care providers feel comfortable speaking out without feeling “the sword of Damocles over their heads” every time they talk to a reporter, Dr. Hotez said.

There may be no silver bullet to solve the big-picture trust problem in medicine and public health. No TV appearance or quote in an article can solve it. But on an individual level — through careful relationship building with patients – doctors can strengthen that trust.

Telehealth may help with that, but there’s a fine balance there, Ms. Nelson cautioned. On the one hand, with the doctor and the patient each in their own private spaces, where they feel safe and comfortable, the overall experience can be more therapeutic and less stressful. At the same time, telehealth can pile on change-management tasks that can exacerbate burnout, “so it’s a delicate thing we have to approach.”

One very thin silver lining that could emerge from the way in which patients have begun to try to take charge of their care.

“They should fully understand the reasoning behind the recommendations that physicians are making,” Ms. Nelson said. “I’d like to see us get to a happy medium where it’s a partnership. We can’t go back to the old school where the doctor knows best and you don’t ever question him.

“What we need is the partnership, and I would love to see that as the silver lining, but the anger has got to settle down in order for that kind of productive thing to happen.”

As for the big picture? There’s a limit to what even society’s “miracle workers” can do. “The biggest priority right now for the health system is to protect their staff whatever way they can and do some training in deescalation,” Ms. Nelson said. “But I don’t think health care can solve the societal issues that seem to be creating this.”

A version of this article first appeared on Medscape.com.

Like hundreds of other medical experts, Leana Wen, MD, an emergency physician and former Baltimore health commissioner, was an early and avid supporter of COVID vaccines and their ability to prevent severe disease, hospitalization, and death from SARS-CoV-2 infections.

When 51-year-old Scott Eli Harris, of Aubrey, Tex., heard of Dr. Wen’s stance in July 2021, the self-described “fifth-generation U.S. Army veteran and a sniper” sent Dr. Wen an electronic invective laden with racist language and very specific threats to shoot her.

Mr. Harris pled guilty to transmitting threats via interstate commerce last February and began serving 6 months in federal prison in the fall of 2022, but his threats wouldn’t be the last for Dr. Wen. Just 2 days after Mr. Harris was sentenced, charges were unsealed against another man in Massachusetts, who threatened that Dr. Wen would “end up in pieces” if she continued “pushing” her thoughts publicly.’

Dr. Wen has plenty of company. In an August 2022 survey of emergency doctors conducted by the American College of Emergency Physicians, 85% of respondents said violence against them is increasing. One in four doctors said they’re being assaulted by patients and their family and friends multiple times a week, compared with just 8% of doctors who said as much in 2018. About 64% of emergency physicians reported receiving verbal assaults and threats of violence; 40% reported being hit or slapped, and 26% were kicked.

This uptick of violence and threats against physicians didn’t come out of nowhere; violence against health care workers has been gradually increasing over the past decade. Health care providers can attest to the hostility that particular topics have sparked for years: vaccines in pediatrics, abortion in ob.gyn., and gender-affirming care in endocrinology.

But the pandemic fueled the fire. While there have always been hot-button issues in medicine, the ire they arouse today is more intense than ever before. The proliferation of misinformation (often via social media) and the politicization of public health and medicine are at the center of the problem.
 

‘The people attacking are themselves victims’

The misinformation problem first came to a head in one area of public health: vaccines. The pandemic accelerated antagonism in medicine – thanks, in part, to decades of antivaccine activism.

The antivaccine movement, which has ebbed and flowed in the United States and across the globe since the first vaccine, experienced a new wave in the early 2000s with the combination of concerns about thimerosal in vaccines and a now disproven link between autism and the MMR vaccine. But that movement grew. It picked up steam when activists gained political clout after a 2014 measles outbreak at Disneyland led California schools to tighten up policies regarding vaccinations for kids who enrolled. These stronger public school vaccination laws ran up against religious freedom arguments from antivaccine advocates.

Use of social media continues to grow, and with it, the spread of misinformation. A recent study found that Facebook “users’ social media habits doubled, and in some cases, tripled the amount of fake news they shared.”

In the face of growing confusion, health care providers and public health experts have often struggled to treat their patients – and communicate to the public – without appearing political.

Hotez_Peter_TEXAS_web.jpg

“The people that are doing the attacking are in some ways themselves victims,” said Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor College of Medicine, Houston. “They’re victims of the antiscience, antihealth ecosystem coming out of Fox News, the House Freedom Caucus, the CPAC conference, coming out of contrarian intellectuals.”

Many of Dr. Hotez’s colleagues don’t want to talk about the political right as an enabler of scientific disinformation, he said, but that doesn’t change what the evidence shows. The vast majority of state and national bills opposing vaccination, gender-affirming care, comprehensive reproductive care, and other evidence-based medical care often come from Republican legislators.
 

When politics and health care collide

“We’re in an incredible status quo,” said William Schaffner, MD, the previous director of the Infectious Diseases Society of America and a professor of infectious diseases and preventive medicine at Vanderbilt University, Nashville, Tenn. “You can’t get away from the politics, because you have [political] candidates espousing certain concepts that are antithetical to good public health.”

Schaffner_William_TENN_web.jpg

In March 2023, Florida Gov. Ron DeSantis’s surgeon general, Joseph Ladapo, MD, PhD, warned that COVID vaccines are harmful to young men, prompting rebukes from federal health authorities. It later came out that Dr. Ladapo had changed some of the results of the study before issuing his warning. But long before 2023, there emerged an increasing gap in COVID deaths between red states and blue states, mirroring the vaccination rates in those states. The redder the state, the higher the death toll.

It’s not just Republican Party culture warriors; medical misinformation is also finding increasing purchase on the far left. Robert F. Kennedy Jr. and Marianne Williamson, both of whom have launched long-shot challenges to President Biden for the 2024 Democratic nomination, had promoted antivaccine ideas long before the COVID pandemic. Mr. Kennedy continues to spread misinformation.

In June 2023, Joe Rogan hosted Mr. Kennedy, on his podcast. During the episode, Mr. Rogan listened uncritically as Mr. Kennedy told his millions of listeners that vaccines cause autism and that 5G causes cancer, among other fringe, often-debunked theories.

Dr. Hotez, a prominent misinformation debunker who was also part of a team that designed a low-cost COVID-19 vaccine, wrote on Twitter that the episode was “just awful.”

The backlash began almost immediately. Mr. Rogan, who has over 11 million followers on Twitter, responded with a public challenge for Dr. Hotez to debate Mr. Kennedy on Mr. Rogan’s show, with a reward of $100,000 to the charity of Dr. Hotez’s choice. More offers streamed in, including from Elon Musk, who tweeted that Dr. Hotez was “afraid of a public debate, because he knows he’s wrong.” More supporters of Mr. Kennedy and Mr. Rogan piled on.

Vaccine skeptics even showed up at Dr. Hotez’s house, filming him as he was returning from buying a Father’s Day cake and taunting him to debate Mr. Kennedy.
 

A turn in the pandemic

For a precious few weeks at the start of the pandemic, it felt as though the country was all in this together. There were arguments against closing schools and shutting down businesses, but for the most part, the nation had about 4 solid weeks of solidarity.

As masking mandates changed and the public health establishment lost the confidence of Americans, the veneer of solidarity began to chip away.

“Things were changing so rapidly during the pandemic that it was very hard for staff and patients to understand the changing guidelines, whether it was visitor constraints or masking,” said Carrie Nelson, the chief medical officer at the telehealth company AmWell, who worked as a supervisor at a large health care system in the Midwest until 2021.

In the midst of the public health crisis, former President Trump was downplaying the severity of the disease and was silencing officials from the Centers for Disease Control and Prevention, such as Nancy Messonier, who warned from the very beginning of the pandemic’s potential.

When the vaccines came out, the latent antivaccine movement flared up once again. And this time – unlike in decades past – the debate over vaccines had become partisan.

“Before the pandemic,” said Christopher Thomas, an emergency physician on the West Coast who requested that a pseudonym be used because of personal threats he has received, “patients wouldn’t really challenge me or throw out weird questions.” It’s not that he never encountered pushback, but the stakes felt lower, and people largely deferred to his medical expertise. “If we got a parent who had not vaccinated their child, I would totally engage back then,” Dr. Thomas said.

But the pandemic – and America’s response to it – changed the conversation. “The rhetoric ... switched from downplaying the virus to demonizing the vaccines,” Dr. Thomas said.
 

The toll on health care professionals

By the time vaccines were available, the public had begun to conflate doctors with public health experts, since both were “pushing” the vaccine.

“Most people probably don’t really know the difference between clinical medicine and public health,” said Richard Pan, MD, MPH, a pediatrician and California legislator who sponsored two bills – now laws – that strengthened state childhood vaccination requirements.

At first, it was clearly public health officials, such as Anthony Fauci, MD, who were the face of measures to mitigate the virus. But as doctors became the enforcers of those measures, the line between physicians and public health officials blurred.

A lot of the anger then shifted toward doctors, nurses, and other health care professionals, Dr. Pan said, “because we were, of course, the ones who would be administering the vaccines. They don’t really think of their doctor as a government person until your doctor is carrying a [government] message.”

Given the pressures and struggles of the past few years, it’s no surprise that burnout among health care professionals is high. According to an April 2023 study by the National Council of State Boards of Nursing and the National Forum of State Nursing Workforce Centers, an estimated 800,000 nurses expect to leave the profession by 2027, driven first and foremost by “stress and burnout.”

All of these departures in medicine’s “great resignation” have left hospitals and health care organizations even more short staffed, thereby increasing even more the pressure and burnout on those left.

The pandemic had already badly exacerbated the already widespread problem of burnout in the medical field, which Ms. Nelson said has contributed to the tension.

“The burnout problem that we have in health care is not a good basis for the development of a good therapeutic relationship,” Ms. Nelson said. “Burnout is fraught with apathy and desensitization to human emotions. It takes away the empathy that we once had for people that we see.”
 

What comes next?

Almost exactly 3 years after the world learned about SARS-CoV-2, Biden declared an end to the coronavirus public health emergency in April 2023. Yet, Americans continue to die from COVID, and the anger that bloomed and spread has not abated.

“I think we’re in a new steady state of violence in health care settings,” Ms. Nelson said. “It’s not gone down, because people are still very distressed.” That’s evident from the high prevalence of mental health conditions, the financial strain of first the pandemic and then inflation, and the overall traumatic impact the pandemic had on people, whether they recognize it or not.

The first step to solving any problem is, as the saying goes, to admit that there is a problem.

“I think people need to start stepping out of their comfort bubbles and start to look at things that make them uncomfortable,” Dr. Thomas said, but he doesn’t see that happening any time soon. “I’ve been very let down by physicians and embarrassed by the American physician organizations.”

The medical board in his state, he said, has stood by as some doctors continue misrepresenting medical evidence. “That’s been really, really hard on me. I didn’t think that the medical boards would go so far as to look the other way for something that was this tremendously bad.”

There are others who can take the lead – if they’re willing.

“There are some things the medical societies and academic health centers can do,” Dr. Hotez said, “starting with building up a culture of physicians and health care providers feeling comfortable in the public domain.” He said the messaging when he was getting his degrees was not to engage the public and not to talk to journalists because that was “self-promotion” or “grandstanding.” But the world is different now. Health care professionals need training in public engagement and communication, he said, and the culture needs to change so that health care providers feel comfortable speaking out without feeling “the sword of Damocles over their heads” every time they talk to a reporter, Dr. Hotez said.

There may be no silver bullet to solve the big-picture trust problem in medicine and public health. No TV appearance or quote in an article can solve it. But on an individual level — through careful relationship building with patients – doctors can strengthen that trust.

Telehealth may help with that, but there’s a fine balance there, Ms. Nelson cautioned. On the one hand, with the doctor and the patient each in their own private spaces, where they feel safe and comfortable, the overall experience can be more therapeutic and less stressful. At the same time, telehealth can pile on change-management tasks that can exacerbate burnout, “so it’s a delicate thing we have to approach.”

One very thin silver lining that could emerge from the way in which patients have begun to try to take charge of their care.

“They should fully understand the reasoning behind the recommendations that physicians are making,” Ms. Nelson said. “I’d like to see us get to a happy medium where it’s a partnership. We can’t go back to the old school where the doctor knows best and you don’t ever question him.

“What we need is the partnership, and I would love to see that as the silver lining, but the anger has got to settle down in order for that kind of productive thing to happen.”

As for the big picture? There’s a limit to what even society’s “miracle workers” can do. “The biggest priority right now for the health system is to protect their staff whatever way they can and do some training in deescalation,” Ms. Nelson said. “But I don’t think health care can solve the societal issues that seem to be creating this.”

A version of this article first appeared on Medscape.com.

Growing up in south India, Deepu Madduri, MD, chose her career path to emulate an ear-nose-throat doctor who kept helping her recover. Today she belongs to a pioneering team of women hematologic oncologists who research innovative multiple myeloma treatments while mentoring the next generation of women in their field.

Inspired in childhood to study medicine, Dr. Madduri chose to specialize in oncology after losing a grandparent to cancer. After moving to the United States as a fifth grader, she went back to India every summer. While visiting as a college student, Dr. Madduri found her grandmother pale, with symptoms such as blood in the stool. Diagnosed with stage IV colon cancer, the grandmother died 6 months later.

Madduri_Deepu_NJ_web.jpg

“I realized I really wanted to be an oncologist because I wanted to see what I could have done to help my grandma,” Dr. Madduri said in an interview.

Today, as a senior medical director at Janssen Oncology, Dr. Madduri joins her colleague Lisa Kallenbach, MD, and others on a team of hematologist oncologists who are working to advance the treatment of multiple myeloma with chimeric antigen receptor (CAR) T-cell therapy. She and Dr. Kallenbach also mentor other blood cancer specialists through a company-sponsored Women in Hematology program.

Dr. Kallenbach, group medical director at the firm, had also long wanted to become a doctor. Unlike Dr. Madduri, however, Dr. Kallenbach took a “long and winding road” and didn’t start med school until age 30.

Put off by college premed requirements, Dr. Kallenbach majored in anthropology and suppressed her desire to study medicine while she got a master’s degree in public administration, worked in public health, and volunteered with the Peace Corps. Ultimately, she decided to do a postbaccalaureate program, entered Brown University in Providence, R.I., and loved it.

“No one in my family was a doctor, so it was all very mystical to me,” she said. “It wasn’t until I worked for a doctor where it was demystified, and I thought, ‘Ah, they’re not any smarter. They just work really hard, and I can work hard. I always do.’”
 

Time for a change

Hard work brought both Dr. Kallenbach and Dr. Madduri to Janssen at roughly the same time, for similar reasons.

Dr. Madduri had been a junior faculty member at Mount Sinai, where she followed her mentor’s advice and fought hard to become principal investigator of the CARTITUDE-1 trial, which she presented at the annual meetings of the American Society of Hematology in 2019 and 2020. This research led to the Food and Drug Administration’s approval of the CAR T therapy Carvykti for multiple myeloma. Dr. Madduri also launched the CAR T program at Mount Sinai and quickly gained prominence in her field, despite being the hospital’s youngest faculty member for myeloma. But when the pandemic hit, she decided to try something different.

“I was helping one person at a time as a physician, but [Janssen] gave me the opportunity to help people in a much broader sense,” said Dr. Madduri, who joined the firm in April 2021. “I’m now the one designing the trials and looking at what the needs are in myeloma.”

“Janssen’s CAR T product [Carvykti] revolutionized the space because after a one-time treatment, patients are in a deep and durable remission and living much longer,” she said. Furthermore, Janssen offered Dr. Madduri the chance to design the trials toward that long-held goal.

“I want to be part of the team where they’re really dedicated to curing myeloma,” Dr. Madduri said. And she continues to see patients as an adjunct assistant professor at Stanford (Calif.) University, where she did a blood & marrow transplantation fellowship.

Kallenbach_Lisa_NJ_web.jpg

Dr. Kallenbach was also drawn to Janssen because of her pandemic experiences – and the promise of broader opportunities, including a better work-life balance. One patient at a time, she was treating a variety of hematologic disorders and malignancies. Although she enjoyed it, she just needed a change.

“It had been 9 months of COVID, and it was just a really busy time and stressful,” Dr. Kallenbach said. When a friend shared the Janssen job posting, she took it as a sign. “I thought, I could really make an impact here. Now I’ve gone from treating one patient at a time to treating tons of patients and helping to get this drug [Carvykti] to patients who can really use it.”
 

A cancer field with potential

While it was Dr. Madduri’s grandmother’s illness that drew her to study oncology, she chose not to work on the colon cancer that killed her grandmother. It felt too personal, and she didn’t foresee being able to help patients in the ways she wanted. Instead of sending them to hospice when treatment options ran out, Dr. Madduri saw the myeloma landscape advancing rapidly, with more drugs becoming available.

“What really interests me is that this field is going somewhere, and we can potentially find something to cure these patients,” Dr. Madduri said. “There’s great need, but there’s rapid advancement happening as well. I wanted to go into something where I could really make a difference and help these patients that I couldn’t help before.”

She’s currently managing CARTITUDE-6, a head-to-head frontline trial testing CAR T-cell therapy (Carvykti) in patients eligible for transplant. “Right now the standard of care is transplant, so there’s a lot of excitement” with the idea of replacing transplant with CAR T in newly diagnosed patients, something that’s never been done. Dr. Madduri hopes this will move patients into deeper remission and eventually help pave the path to a cure. “We have to change the landscape. We have to push the boundaries, right?”

Similarly, Dr. Kallenbach was drawn to myeloma because of the rush of new therapies.

“From the time I was training to the time I was practicing, the treatments completely changed,” she said. “That’s always exciting when you’re making that much progress on a disease, to see these enormous changes. Now you’re actually seeing people who’ve had tons of prior therapies have responses that I’ve just never seen before.”

Dr. Kallenbach also found fulfillment through patient care. “People really connect with their oncologist, and that relationship is really special,” she said. “The other thing is that you really learn from cancer patients how to live your life, like what’s important. People’s priorities become very clear.”
 

Importance of mentorship

Both women credit part of their success to finding excellent mentors early on, and both are paying it forward by mentoring other women in their field.

Dr. Madduri met her mentor, Sundar Jagannath, MBBS, when he interviewed her at Icahn School of Medicine’s Tisch Cancer Institute in New York, where he’s director of the multiple myeloma program and the Myeloma Center of Excellence. Noting her enthusiasm and excellent training, Dr. Jagannath recruited Dr. Madduri and quickly discovered her organizational skills. When she expressed interest in running the CAR T program, he let her run with it, while advising her on how to ensure that she got respect and credit for her work.

“You have to do your part, but if you don’t have the right mentor telling you, it’d be really hard for someone who’s just starting out to know what to do,” Dr. Madduri said.

Dr. Jagannath’s guidance paid off. “When she made the ASH presentation, everybody was impressed,” he said. “She captured the attention of my peers who have been in the field for a long time, so she immediately made a national splash.”

Just a few years out of her own fellowship, Dr. Madduri had already begun mentoring other fellows. Through Women in Hematology, she helps gather data about the roles women play in her field and how to further their advancement. “The myeloma field is slowly starting to shift” toward more gender balance, she said – progress she feels happy to support.

Dr. Kallenbach’s mentoring is less formal, yet it makes a deep impact on those she takes under her wing. Her mentees are mostly the students she’s met on the Bryn Mawr College campus where she walks her two Labradors. That’s how she met Louise Breen, who, after a postbaccalaureate there, just graduated from University of Pennsylvania, Philadelphia, and is headed for residency at Mass General Hospital, Boston.

Dr. Breen said her mentor’s greatest gift has been “showing many of us that it’s possible to do it and what life could look like.” While fostering students’ self-confidence as they wrangle with imposter syndrome, Dr. Kallenbach has also demonstrated what a work-life balance in medicine can look like. She learned that from her own mentor, Hedy Smith, MD, PhD, now clinical director of inpatient hematology/oncology at MedStar Washington Hospital Center, and previously an associate professor at Tufts Medical Center.

Dr. Kallenbach quickly made an impression on Dr. Smith by coming to her door in tears one day.

“She was so devastated at the additions I made in her notes,” recalled Dr. Smith. “She felt that she had presented me with this less-than-adequate document. ... I told her, ‘this really says the world about who you are, who you’re going to become in oncology.’ I was struck by her character, a dedication to her work, and her desire to perfect it.”

Three years later, Dr. Smith remembers Dr. Kallenbach coming to her office with a big smile and saying: “Look at this. You didn’t make any changes.” Then Dr. Smith knew that her mentee was ready for the next chapter of her career.

They have kept in touch, with Dr. Kallenbach periodically calling to discuss a difficult case or to plan to meet up at conferences. “It always puts a smile on my face because this person who was once my student has now undergone this metamorphosis, and here we are, now truly equals and colleagues attending the meetings together,” Dr. Smith remarked.

Dr. Kallenbach feels grateful about finding a strong female mentor early in her medical career, especially given some of the everyday sexism she has encountered. A male colleague at a conference once expressed shock that she was practicing medicine full time while also being a mother. Dr. Kallenbach hasn’t encountered such attitudes while working in the pharmaceutical industry.

“I feel more valued as a doctor now than I ever did in practice,” she said. While before, she felt respected, “here, I feel like your expertise is valued, and you can actually help shape programs and inform how doctors practice.”

Dr. Madduri, too, feels like she’s where she’s supposed to be. “I went into the field because I really wanted to help people and make a difference,” she said. “I’m doing everything that I wanted to do.”

Growing up in south India, Deepu Madduri, MD, chose her career path to emulate an ear-nose-throat doctor who kept helping her recover. Today she belongs to a pioneering team of women hematologic oncologists who research innovative multiple myeloma treatments while mentoring the next generation of women in their field.

Inspired in childhood to study medicine, Dr. Madduri chose to specialize in oncology after losing a grandparent to cancer. After moving to the United States as a fifth grader, she went back to India every summer. While visiting as a college student, Dr. Madduri found her grandmother pale, with symptoms such as blood in the stool. Diagnosed with stage IV colon cancer, the grandmother died 6 months later.

Madduri_Deepu_NJ_web.jpg

“I realized I really wanted to be an oncologist because I wanted to see what I could have done to help my grandma,” Dr. Madduri said in an interview.

Today, as a senior medical director at Janssen Oncology, Dr. Madduri joins her colleague Lisa Kallenbach, MD, and others on a team of hematologist oncologists who are working to advance the treatment of multiple myeloma with chimeric antigen receptor (CAR) T-cell therapy. She and Dr. Kallenbach also mentor other blood cancer specialists through a company-sponsored Women in Hematology program.

Dr. Kallenbach, group medical director at the firm, had also long wanted to become a doctor. Unlike Dr. Madduri, however, Dr. Kallenbach took a “long and winding road” and didn’t start med school until age 30.

Put off by college premed requirements, Dr. Kallenbach majored in anthropology and suppressed her desire to study medicine while she got a master’s degree in public administration, worked in public health, and volunteered with the Peace Corps. Ultimately, she decided to do a postbaccalaureate program, entered Brown University in Providence, R.I., and loved it.

“No one in my family was a doctor, so it was all very mystical to me,” she said. “It wasn’t until I worked for a doctor where it was demystified, and I thought, ‘Ah, they’re not any smarter. They just work really hard, and I can work hard. I always do.’”
 

Time for a change

Hard work brought both Dr. Kallenbach and Dr. Madduri to Janssen at roughly the same time, for similar reasons.

Dr. Madduri had been a junior faculty member at Mount Sinai, where she followed her mentor’s advice and fought hard to become principal investigator of the CARTITUDE-1 trial, which she presented at the annual meetings of the American Society of Hematology in 2019 and 2020. This research led to the Food and Drug Administration’s approval of the CAR T therapy Carvykti for multiple myeloma. Dr. Madduri also launched the CAR T program at Mount Sinai and quickly gained prominence in her field, despite being the hospital’s youngest faculty member for myeloma. But when the pandemic hit, she decided to try something different.

“I was helping one person at a time as a physician, but [Janssen] gave me the opportunity to help people in a much broader sense,” said Dr. Madduri, who joined the firm in April 2021. “I’m now the one designing the trials and looking at what the needs are in myeloma.”

“Janssen’s CAR T product [Carvykti] revolutionized the space because after a one-time treatment, patients are in a deep and durable remission and living much longer,” she said. Furthermore, Janssen offered Dr. Madduri the chance to design the trials toward that long-held goal.

“I want to be part of the team where they’re really dedicated to curing myeloma,” Dr. Madduri said. And she continues to see patients as an adjunct assistant professor at Stanford (Calif.) University, where she did a blood & marrow transplantation fellowship.

Kallenbach_Lisa_NJ_web.jpg

Dr. Kallenbach was also drawn to Janssen because of her pandemic experiences – and the promise of broader opportunities, including a better work-life balance. One patient at a time, she was treating a variety of hematologic disorders and malignancies. Although she enjoyed it, she just needed a change.

“It had been 9 months of COVID, and it was just a really busy time and stressful,” Dr. Kallenbach said. When a friend shared the Janssen job posting, she took it as a sign. “I thought, I could really make an impact here. Now I’ve gone from treating one patient at a time to treating tons of patients and helping to get this drug [Carvykti] to patients who can really use it.”
 

A cancer field with potential

While it was Dr. Madduri’s grandmother’s illness that drew her to study oncology, she chose not to work on the colon cancer that killed her grandmother. It felt too personal, and she didn’t foresee being able to help patients in the ways she wanted. Instead of sending them to hospice when treatment options ran out, Dr. Madduri saw the myeloma landscape advancing rapidly, with more drugs becoming available.

“What really interests me is that this field is going somewhere, and we can potentially find something to cure these patients,” Dr. Madduri said. “There’s great need, but there’s rapid advancement happening as well. I wanted to go into something where I could really make a difference and help these patients that I couldn’t help before.”

She’s currently managing CARTITUDE-6, a head-to-head frontline trial testing CAR T-cell therapy (Carvykti) in patients eligible for transplant. “Right now the standard of care is transplant, so there’s a lot of excitement” with the idea of replacing transplant with CAR T in newly diagnosed patients, something that’s never been done. Dr. Madduri hopes this will move patients into deeper remission and eventually help pave the path to a cure. “We have to change the landscape. We have to push the boundaries, right?”

Similarly, Dr. Kallenbach was drawn to myeloma because of the rush of new therapies.

“From the time I was training to the time I was practicing, the treatments completely changed,” she said. “That’s always exciting when you’re making that much progress on a disease, to see these enormous changes. Now you’re actually seeing people who’ve had tons of prior therapies have responses that I’ve just never seen before.”

Dr. Kallenbach also found fulfillment through patient care. “People really connect with their oncologist, and that relationship is really special,” she said. “The other thing is that you really learn from cancer patients how to live your life, like what’s important. People’s priorities become very clear.”
 

Importance of mentorship

Both women credit part of their success to finding excellent mentors early on, and both are paying it forward by mentoring other women in their field.

Dr. Madduri met her mentor, Sundar Jagannath, MBBS, when he interviewed her at Icahn School of Medicine’s Tisch Cancer Institute in New York, where he’s director of the multiple myeloma program and the Myeloma Center of Excellence. Noting her enthusiasm and excellent training, Dr. Jagannath recruited Dr. Madduri and quickly discovered her organizational skills. When she expressed interest in running the CAR T program, he let her run with it, while advising her on how to ensure that she got respect and credit for her work.

“You have to do your part, but if you don’t have the right mentor telling you, it’d be really hard for someone who’s just starting out to know what to do,” Dr. Madduri said.

Dr. Jagannath’s guidance paid off. “When she made the ASH presentation, everybody was impressed,” he said. “She captured the attention of my peers who have been in the field for a long time, so she immediately made a national splash.”

Just a few years out of her own fellowship, Dr. Madduri had already begun mentoring other fellows. Through Women in Hematology, she helps gather data about the roles women play in her field and how to further their advancement. “The myeloma field is slowly starting to shift” toward more gender balance, she said – progress she feels happy to support.

Dr. Kallenbach’s mentoring is less formal, yet it makes a deep impact on those she takes under her wing. Her mentees are mostly the students she’s met on the Bryn Mawr College campus where she walks her two Labradors. That’s how she met Louise Breen, who, after a postbaccalaureate there, just graduated from University of Pennsylvania, Philadelphia, and is headed for residency at Mass General Hospital, Boston.

Dr. Breen said her mentor’s greatest gift has been “showing many of us that it’s possible to do it and what life could look like.” While fostering students’ self-confidence as they wrangle with imposter syndrome, Dr. Kallenbach has also demonstrated what a work-life balance in medicine can look like. She learned that from her own mentor, Hedy Smith, MD, PhD, now clinical director of inpatient hematology/oncology at MedStar Washington Hospital Center, and previously an associate professor at Tufts Medical Center.

Dr. Kallenbach quickly made an impression on Dr. Smith by coming to her door in tears one day.

“She was so devastated at the additions I made in her notes,” recalled Dr. Smith. “She felt that she had presented me with this less-than-adequate document. ... I told her, ‘this really says the world about who you are, who you’re going to become in oncology.’ I was struck by her character, a dedication to her work, and her desire to perfect it.”

Three years later, Dr. Smith remembers Dr. Kallenbach coming to her office with a big smile and saying: “Look at this. You didn’t make any changes.” Then Dr. Smith knew that her mentee was ready for the next chapter of her career.

They have kept in touch, with Dr. Kallenbach periodically calling to discuss a difficult case or to plan to meet up at conferences. “It always puts a smile on my face because this person who was once my student has now undergone this metamorphosis, and here we are, now truly equals and colleagues attending the meetings together,” Dr. Smith remarked.

Dr. Kallenbach feels grateful about finding a strong female mentor early in her medical career, especially given some of the everyday sexism she has encountered. A male colleague at a conference once expressed shock that she was practicing medicine full time while also being a mother. Dr. Kallenbach hasn’t encountered such attitudes while working in the pharmaceutical industry.

“I feel more valued as a doctor now than I ever did in practice,” she said. While before, she felt respected, “here, I feel like your expertise is valued, and you can actually help shape programs and inform how doctors practice.”

Dr. Madduri, too, feels like she’s where she’s supposed to be. “I went into the field because I really wanted to help people and make a difference,” she said. “I’m doing everything that I wanted to do.”

Growing up in south India, Deepu Madduri, MD, chose her career path to emulate an ear-nose-throat doctor who kept helping her recover. Today she belongs to a pioneering team of women hematologic oncologists who research innovative multiple myeloma treatments while mentoring the next generation of women in their field.

Inspired in childhood to study medicine, Dr. Madduri chose to specialize in oncology after losing a grandparent to cancer. After moving to the United States as a fifth grader, she went back to India every summer. While visiting as a college student, Dr. Madduri found her grandmother pale, with symptoms such as blood in the stool. Diagnosed with stage IV colon cancer, the grandmother died 6 months later.

Madduri_Deepu_NJ_web.jpg

“I realized I really wanted to be an oncologist because I wanted to see what I could have done to help my grandma,” Dr. Madduri said in an interview.

Today, as a senior medical director at Janssen Oncology, Dr. Madduri joins her colleague Lisa Kallenbach, MD, and others on a team of hematologist oncologists who are working to advance the treatment of multiple myeloma with chimeric antigen receptor (CAR) T-cell therapy. She and Dr. Kallenbach also mentor other blood cancer specialists through a company-sponsored Women in Hematology program.

Dr. Kallenbach, group medical director at the firm, had also long wanted to become a doctor. Unlike Dr. Madduri, however, Dr. Kallenbach took a “long and winding road” and didn’t start med school until age 30.

Put off by college premed requirements, Dr. Kallenbach majored in anthropology and suppressed her desire to study medicine while she got a master’s degree in public administration, worked in public health, and volunteered with the Peace Corps. Ultimately, she decided to do a postbaccalaureate program, entered Brown University in Providence, R.I., and loved it.

“No one in my family was a doctor, so it was all very mystical to me,” she said. “It wasn’t until I worked for a doctor where it was demystified, and I thought, ‘Ah, they’re not any smarter. They just work really hard, and I can work hard. I always do.’”
 

Time for a change

Hard work brought both Dr. Kallenbach and Dr. Madduri to Janssen at roughly the same time, for similar reasons.

Dr. Madduri had been a junior faculty member at Mount Sinai, where she followed her mentor’s advice and fought hard to become principal investigator of the CARTITUDE-1 trial, which she presented at the annual meetings of the American Society of Hematology in 2019 and 2020. This research led to the Food and Drug Administration’s approval of the CAR T therapy Carvykti for multiple myeloma. Dr. Madduri also launched the CAR T program at Mount Sinai and quickly gained prominence in her field, despite being the hospital’s youngest faculty member for myeloma. But when the pandemic hit, she decided to try something different.

“I was helping one person at a time as a physician, but [Janssen] gave me the opportunity to help people in a much broader sense,” said Dr. Madduri, who joined the firm in April 2021. “I’m now the one designing the trials and looking at what the needs are in myeloma.”

“Janssen’s CAR T product [Carvykti] revolutionized the space because after a one-time treatment, patients are in a deep and durable remission and living much longer,” she said. Furthermore, Janssen offered Dr. Madduri the chance to design the trials toward that long-held goal.

“I want to be part of the team where they’re really dedicated to curing myeloma,” Dr. Madduri said. And she continues to see patients as an adjunct assistant professor at Stanford (Calif.) University, where she did a blood & marrow transplantation fellowship.

Kallenbach_Lisa_NJ_web.jpg

Dr. Kallenbach was also drawn to Janssen because of her pandemic experiences – and the promise of broader opportunities, including a better work-life balance. One patient at a time, she was treating a variety of hematologic disorders and malignancies. Although she enjoyed it, she just needed a change.

“It had been 9 months of COVID, and it was just a really busy time and stressful,” Dr. Kallenbach said. When a friend shared the Janssen job posting, she took it as a sign. “I thought, I could really make an impact here. Now I’ve gone from treating one patient at a time to treating tons of patients and helping to get this drug [Carvykti] to patients who can really use it.”
 

A cancer field with potential

While it was Dr. Madduri’s grandmother’s illness that drew her to study oncology, she chose not to work on the colon cancer that killed her grandmother. It felt too personal, and she didn’t foresee being able to help patients in the ways she wanted. Instead of sending them to hospice when treatment options ran out, Dr. Madduri saw the myeloma landscape advancing rapidly, with more drugs becoming available.

“What really interests me is that this field is going somewhere, and we can potentially find something to cure these patients,” Dr. Madduri said. “There’s great need, but there’s rapid advancement happening as well. I wanted to go into something where I could really make a difference and help these patients that I couldn’t help before.”

She’s currently managing CARTITUDE-6, a head-to-head frontline trial testing CAR T-cell therapy (Carvykti) in patients eligible for transplant. “Right now the standard of care is transplant, so there’s a lot of excitement” with the idea of replacing transplant with CAR T in newly diagnosed patients, something that’s never been done. Dr. Madduri hopes this will move patients into deeper remission and eventually help pave the path to a cure. “We have to change the landscape. We have to push the boundaries, right?”

Similarly, Dr. Kallenbach was drawn to myeloma because of the rush of new therapies.

“From the time I was training to the time I was practicing, the treatments completely changed,” she said. “That’s always exciting when you’re making that much progress on a disease, to see these enormous changes. Now you’re actually seeing people who’ve had tons of prior therapies have responses that I’ve just never seen before.”

Dr. Kallenbach also found fulfillment through patient care. “People really connect with their oncologist, and that relationship is really special,” she said. “The other thing is that you really learn from cancer patients how to live your life, like what’s important. People’s priorities become very clear.”
 

Importance of mentorship

Both women credit part of their success to finding excellent mentors early on, and both are paying it forward by mentoring other women in their field.

Dr. Madduri met her mentor, Sundar Jagannath, MBBS, when he interviewed her at Icahn School of Medicine’s Tisch Cancer Institute in New York, where he’s director of the multiple myeloma program and the Myeloma Center of Excellence. Noting her enthusiasm and excellent training, Dr. Jagannath recruited Dr. Madduri and quickly discovered her organizational skills. When she expressed interest in running the CAR T program, he let her run with it, while advising her on how to ensure that she got respect and credit for her work.

“You have to do your part, but if you don’t have the right mentor telling you, it’d be really hard for someone who’s just starting out to know what to do,” Dr. Madduri said.

Dr. Jagannath’s guidance paid off. “When she made the ASH presentation, everybody was impressed,” he said. “She captured the attention of my peers who have been in the field for a long time, so she immediately made a national splash.”

Just a few years out of her own fellowship, Dr. Madduri had already begun mentoring other fellows. Through Women in Hematology, she helps gather data about the roles women play in her field and how to further their advancement. “The myeloma field is slowly starting to shift” toward more gender balance, she said – progress she feels happy to support.

Dr. Kallenbach’s mentoring is less formal, yet it makes a deep impact on those she takes under her wing. Her mentees are mostly the students she’s met on the Bryn Mawr College campus where she walks her two Labradors. That’s how she met Louise Breen, who, after a postbaccalaureate there, just graduated from University of Pennsylvania, Philadelphia, and is headed for residency at Mass General Hospital, Boston.

Dr. Breen said her mentor’s greatest gift has been “showing many of us that it’s possible to do it and what life could look like.” While fostering students’ self-confidence as they wrangle with imposter syndrome, Dr. Kallenbach has also demonstrated what a work-life balance in medicine can look like. She learned that from her own mentor, Hedy Smith, MD, PhD, now clinical director of inpatient hematology/oncology at MedStar Washington Hospital Center, and previously an associate professor at Tufts Medical Center.

Dr. Kallenbach quickly made an impression on Dr. Smith by coming to her door in tears one day.

“She was so devastated at the additions I made in her notes,” recalled Dr. Smith. “She felt that she had presented me with this less-than-adequate document. ... I told her, ‘this really says the world about who you are, who you’re going to become in oncology.’ I was struck by her character, a dedication to her work, and her desire to perfect it.”

Three years later, Dr. Smith remembers Dr. Kallenbach coming to her office with a big smile and saying: “Look at this. You didn’t make any changes.” Then Dr. Smith knew that her mentee was ready for the next chapter of her career.

They have kept in touch, with Dr. Kallenbach periodically calling to discuss a difficult case or to plan to meet up at conferences. “It always puts a smile on my face because this person who was once my student has now undergone this metamorphosis, and here we are, now truly equals and colleagues attending the meetings together,” Dr. Smith remarked.

Dr. Kallenbach feels grateful about finding a strong female mentor early in her medical career, especially given some of the everyday sexism she has encountered. A male colleague at a conference once expressed shock that she was practicing medicine full time while also being a mother. Dr. Kallenbach hasn’t encountered such attitudes while working in the pharmaceutical industry.

“I feel more valued as a doctor now than I ever did in practice,” she said. While before, she felt respected, “here, I feel like your expertise is valued, and you can actually help shape programs and inform how doctors practice.”

Dr. Madduri, too, feels like she’s where she’s supposed to be. “I went into the field because I really wanted to help people and make a difference,” she said. “I’m doing everything that I wanted to do.”

DENVER – Taking ozanimod for relapsing multiple sclerosis (MS) at the same time as taking antidepressants that increase serotonin levels does not appear to increase the risk for hypertension or any other adverse events related to serotonin toxicity, according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

“Depression and anxiety are prevalent comorbidities occurring in up to 54% of patients with multiple sclerosis, and selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) are first-line treatments for depression and anxiety disorders,” Robert T. Naismith, MD, of Washington University in St. Louis, and his colleagues reported.

“Coadministration of ozanimod with drugs that increase serotonin could hypothetically lead to serotonin accumulation,” which can increase the likelihood of hypertension. U.S. prescribing information recommends that patients taking both ozanimod and medications that increase norepinephrine or serotonin be monitored for hypertension, an adverse reaction reported in 3.9% of patients receiving ozanimod in the phase 3 trials for relapsing MS.
 

Clarifying the risk

“It’s important to be aware of potential drug interactions and risks from MS disease modifying therapies,” Lauren Gluck, MD, an assistant professor and director of the division of multiple sclerosis at Montefiore Medical Center/Albert Einstein College of Medicine, New York, said in an interview. Dr. Gluck was not involved in this study but described some of the history that revealed the value of this type of research. For example, the first sphingosine-1-phosphate receptor (S1PR) modulator approved for MS, fingolimod (Gilenya), has a risk of cardiac conduction dysfunction with QTc prolongation, so people taking fingolimod with other medications that prolong QTc, such as SSRIs, need additional monitoring.

“Ozanimod is a newer, more selective S1PR modulator that initially raised concerns about interaction with serotonin-increasing drugs based on in vitro studies,” Dr. Gluck said. “This could mean that people on ozanimod and other serotonin-increasing medicine could be at risk for dangerous events like serotonin syndrome. However, in vitro studies do not always translate to how something affects the human body, so it is not clear how much risk truly exists.”
 

Examining open-label extension trial data

The researchers therefore evaluated the safety of taking ozanimod and SSRIs or SNRIs in a subset of patients with relapsing MS who participated in the DAYBREAK open-label extension trial. The phase 3 parent trials compared 30 mcg once weekly of intramuscular interferon beta-1a with 0.92 mg of once-daily oral ozanimod and 0.46 mg of once-daily oral ozanimod. In the DAYBREAK open-label extension, 2,256 participants underwent a dose escalation over one week until all reached 0.92 mg of ozanimod, where they remained for an average of just under 5 years of follow-up. Nearly all the participants (99.4%) were White, and two-thirds (66.5%) were female.

The researchers searched the study data for terms related to serotonin toxicity and compared the rates of adverse events related with those terms and the rates of hypertension in the 274 participants who were and the 2,032 participant who were not taking antidepressants at the same time as ozanimod.

They found that 13.9% of patients taking SSRIs or SNRIs experienced at least one treatment-emergent adverse event related to their search criteria, compared with 17.7% of patients not taking SSRIs or SNRIs. Similarly, 9.2% of trial participants not taking SSRIs or SNRIs had hypertension, compared with 4.7% of participants who were taking antidepressants. The authors further noted that “similar trends were observed when 6 weeks after the end date of concomitant SSRIs/SNRI use were included in the ‘on SSRI/SNRI’ analysis period.”

When the researchers searched specifically for three terms directly related to serotonin toxicity – “serotonin syndrome,” “neuroleptic malignant syndrome,” and “hyperthermia malignant” – they did not find any patients who had treatment-emergent adverse events related to those terms.

“SSRIs/SNRIs were freely allowed as concomitant medications in the DAYBREAK open-label extension, and among the patients from SUNBEAM or RADIANCE who were followed for up to 6 years, there have been no reported safety concerns during the concurrent administration of serotonergic antidepressants and ozanimod in patients with relapsing MS as of the data cutoff,” concluded the authors, though they also noted that the overall rate of SSRI and SNRI use was low in the extension trial.
 

A reassuring finding for clinicians and patients alike

“It is reassuring, if not unexpected, that there were no clinically significant rates of symptoms associated with excess serotonin in patients on ozanimod and SSRI/SNRIs,” Dr. Gluck commented. “These findings are important for both clinicians and patients – they can help [both] feel comfortable considering ozanimod if SSRI/SNRIs are already being used. There is also freedom to use SSRI/SNRIs for symptom management in patients already on ozanimod.”

The research was funded by Bristol Myers Squibb. Dr. Naismith reported consulting for Abata Therapeutics, Banner Life Sciences, BeiGene, Biogen, Bristol Myers Squibb, Celltrion, Genentech, Genzyme, GW Therapeutics, Janssen, Horizon Therapeutics, Lundbeck, NervGen, and TG Therapeutics. Six other authors reported disclosures for various pharmaceutical companies, and six other authors are employees and/or shareholders of Bristol Myers Squibb. Dr. Gluck has served on advisory boards with Genentech and EMD Serono.
 

DENVER – Taking ozanimod for relapsing multiple sclerosis (MS) at the same time as taking antidepressants that increase serotonin levels does not appear to increase the risk for hypertension or any other adverse events related to serotonin toxicity, according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

“Depression and anxiety are prevalent comorbidities occurring in up to 54% of patients with multiple sclerosis, and selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) are first-line treatments for depression and anxiety disorders,” Robert T. Naismith, MD, of Washington University in St. Louis, and his colleagues reported.

“Coadministration of ozanimod with drugs that increase serotonin could hypothetically lead to serotonin accumulation,” which can increase the likelihood of hypertension. U.S. prescribing information recommends that patients taking both ozanimod and medications that increase norepinephrine or serotonin be monitored for hypertension, an adverse reaction reported in 3.9% of patients receiving ozanimod in the phase 3 trials for relapsing MS.
 

Clarifying the risk

“It’s important to be aware of potential drug interactions and risks from MS disease modifying therapies,” Lauren Gluck, MD, an assistant professor and director of the division of multiple sclerosis at Montefiore Medical Center/Albert Einstein College of Medicine, New York, said in an interview. Dr. Gluck was not involved in this study but described some of the history that revealed the value of this type of research. For example, the first sphingosine-1-phosphate receptor (S1PR) modulator approved for MS, fingolimod (Gilenya), has a risk of cardiac conduction dysfunction with QTc prolongation, so people taking fingolimod with other medications that prolong QTc, such as SSRIs, need additional monitoring.

“Ozanimod is a newer, more selective S1PR modulator that initially raised concerns about interaction with serotonin-increasing drugs based on in vitro studies,” Dr. Gluck said. “This could mean that people on ozanimod and other serotonin-increasing medicine could be at risk for dangerous events like serotonin syndrome. However, in vitro studies do not always translate to how something affects the human body, so it is not clear how much risk truly exists.”
 

Examining open-label extension trial data

The researchers therefore evaluated the safety of taking ozanimod and SSRIs or SNRIs in a subset of patients with relapsing MS who participated in the DAYBREAK open-label extension trial. The phase 3 parent trials compared 30 mcg once weekly of intramuscular interferon beta-1a with 0.92 mg of once-daily oral ozanimod and 0.46 mg of once-daily oral ozanimod. In the DAYBREAK open-label extension, 2,256 participants underwent a dose escalation over one week until all reached 0.92 mg of ozanimod, where they remained for an average of just under 5 years of follow-up. Nearly all the participants (99.4%) were White, and two-thirds (66.5%) were female.

The researchers searched the study data for terms related to serotonin toxicity and compared the rates of adverse events related with those terms and the rates of hypertension in the 274 participants who were and the 2,032 participant who were not taking antidepressants at the same time as ozanimod.

They found that 13.9% of patients taking SSRIs or SNRIs experienced at least one treatment-emergent adverse event related to their search criteria, compared with 17.7% of patients not taking SSRIs or SNRIs. Similarly, 9.2% of trial participants not taking SSRIs or SNRIs had hypertension, compared with 4.7% of participants who were taking antidepressants. The authors further noted that “similar trends were observed when 6 weeks after the end date of concomitant SSRIs/SNRI use were included in the ‘on SSRI/SNRI’ analysis period.”

When the researchers searched specifically for three terms directly related to serotonin toxicity – “serotonin syndrome,” “neuroleptic malignant syndrome,” and “hyperthermia malignant” – they did not find any patients who had treatment-emergent adverse events related to those terms.

“SSRIs/SNRIs were freely allowed as concomitant medications in the DAYBREAK open-label extension, and among the patients from SUNBEAM or RADIANCE who were followed for up to 6 years, there have been no reported safety concerns during the concurrent administration of serotonergic antidepressants and ozanimod in patients with relapsing MS as of the data cutoff,” concluded the authors, though they also noted that the overall rate of SSRI and SNRI use was low in the extension trial.
 

A reassuring finding for clinicians and patients alike

“It is reassuring, if not unexpected, that there were no clinically significant rates of symptoms associated with excess serotonin in patients on ozanimod and SSRI/SNRIs,” Dr. Gluck commented. “These findings are important for both clinicians and patients – they can help [both] feel comfortable considering ozanimod if SSRI/SNRIs are already being used. There is also freedom to use SSRI/SNRIs for symptom management in patients already on ozanimod.”

The research was funded by Bristol Myers Squibb. Dr. Naismith reported consulting for Abata Therapeutics, Banner Life Sciences, BeiGene, Biogen, Bristol Myers Squibb, Celltrion, Genentech, Genzyme, GW Therapeutics, Janssen, Horizon Therapeutics, Lundbeck, NervGen, and TG Therapeutics. Six other authors reported disclosures for various pharmaceutical companies, and six other authors are employees and/or shareholders of Bristol Myers Squibb. Dr. Gluck has served on advisory boards with Genentech and EMD Serono.
 

DENVER – Taking ozanimod for relapsing multiple sclerosis (MS) at the same time as taking antidepressants that increase serotonin levels does not appear to increase the risk for hypertension or any other adverse events related to serotonin toxicity, according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

“Depression and anxiety are prevalent comorbidities occurring in up to 54% of patients with multiple sclerosis, and selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) are first-line treatments for depression and anxiety disorders,” Robert T. Naismith, MD, of Washington University in St. Louis, and his colleagues reported.

“Coadministration of ozanimod with drugs that increase serotonin could hypothetically lead to serotonin accumulation,” which can increase the likelihood of hypertension. U.S. prescribing information recommends that patients taking both ozanimod and medications that increase norepinephrine or serotonin be monitored for hypertension, an adverse reaction reported in 3.9% of patients receiving ozanimod in the phase 3 trials for relapsing MS.
 

Clarifying the risk

“It’s important to be aware of potential drug interactions and risks from MS disease modifying therapies,” Lauren Gluck, MD, an assistant professor and director of the division of multiple sclerosis at Montefiore Medical Center/Albert Einstein College of Medicine, New York, said in an interview. Dr. Gluck was not involved in this study but described some of the history that revealed the value of this type of research. For example, the first sphingosine-1-phosphate receptor (S1PR) modulator approved for MS, fingolimod (Gilenya), has a risk of cardiac conduction dysfunction with QTc prolongation, so people taking fingolimod with other medications that prolong QTc, such as SSRIs, need additional monitoring.

“Ozanimod is a newer, more selective S1PR modulator that initially raised concerns about interaction with serotonin-increasing drugs based on in vitro studies,” Dr. Gluck said. “This could mean that people on ozanimod and other serotonin-increasing medicine could be at risk for dangerous events like serotonin syndrome. However, in vitro studies do not always translate to how something affects the human body, so it is not clear how much risk truly exists.”
 

Examining open-label extension trial data

The researchers therefore evaluated the safety of taking ozanimod and SSRIs or SNRIs in a subset of patients with relapsing MS who participated in the DAYBREAK open-label extension trial. The phase 3 parent trials compared 30 mcg once weekly of intramuscular interferon beta-1a with 0.92 mg of once-daily oral ozanimod and 0.46 mg of once-daily oral ozanimod. In the DAYBREAK open-label extension, 2,256 participants underwent a dose escalation over one week until all reached 0.92 mg of ozanimod, where they remained for an average of just under 5 years of follow-up. Nearly all the participants (99.4%) were White, and two-thirds (66.5%) were female.

The researchers searched the study data for terms related to serotonin toxicity and compared the rates of adverse events related with those terms and the rates of hypertension in the 274 participants who were and the 2,032 participant who were not taking antidepressants at the same time as ozanimod.

They found that 13.9% of patients taking SSRIs or SNRIs experienced at least one treatment-emergent adverse event related to their search criteria, compared with 17.7% of patients not taking SSRIs or SNRIs. Similarly, 9.2% of trial participants not taking SSRIs or SNRIs had hypertension, compared with 4.7% of participants who were taking antidepressants. The authors further noted that “similar trends were observed when 6 weeks after the end date of concomitant SSRIs/SNRI use were included in the ‘on SSRI/SNRI’ analysis period.”

When the researchers searched specifically for three terms directly related to serotonin toxicity – “serotonin syndrome,” “neuroleptic malignant syndrome,” and “hyperthermia malignant” – they did not find any patients who had treatment-emergent adverse events related to those terms.

“SSRIs/SNRIs were freely allowed as concomitant medications in the DAYBREAK open-label extension, and among the patients from SUNBEAM or RADIANCE who were followed for up to 6 years, there have been no reported safety concerns during the concurrent administration of serotonergic antidepressants and ozanimod in patients with relapsing MS as of the data cutoff,” concluded the authors, though they also noted that the overall rate of SSRI and SNRI use was low in the extension trial.
 

A reassuring finding for clinicians and patients alike

“It is reassuring, if not unexpected, that there were no clinically significant rates of symptoms associated with excess serotonin in patients on ozanimod and SSRI/SNRIs,” Dr. Gluck commented. “These findings are important for both clinicians and patients – they can help [both] feel comfortable considering ozanimod if SSRI/SNRIs are already being used. There is also freedom to use SSRI/SNRIs for symptom management in patients already on ozanimod.”

The research was funded by Bristol Myers Squibb. Dr. Naismith reported consulting for Abata Therapeutics, Banner Life Sciences, BeiGene, Biogen, Bristol Myers Squibb, Celltrion, Genentech, Genzyme, GW Therapeutics, Janssen, Horizon Therapeutics, Lundbeck, NervGen, and TG Therapeutics. Six other authors reported disclosures for various pharmaceutical companies, and six other authors are employees and/or shareholders of Bristol Myers Squibb. Dr. Gluck has served on advisory boards with Genentech and EMD Serono.