Menopause

TOPLINE:

Women with hypothyroidism treated with levothyroxine show no significant cognitive decline across the menopausal transition compared with those without thyroid disease.

METHODOLOGY:

• Levothyroxine, the primary treatment for hypothyroidism, has been linked to perceived cognitive deficits, yet it is unclear whether this is due to the underlying condition being inadequately treated or other factors.
• Using data collected from the Study of Women’s Health Across the Nation, which encompasses five ethnic/racial groups from seven centers across the United States, researchers compared cognitive function over time between women with hypothyroidism treated with levothyroxine and those without thyroid disease.
• Participants underwent cognitive testing across three domains — processing speed, working memory, and episodic memory — which were assessed over a mean follow-up of 13 years.
• Further analyses assessed the impact of abnormal levels of thyroid-stimulating hormone on cognitive outcomes.

TAKEAWAY:

• Of 2033 women included, 227 (mean age, 49.8 years) had levothyroxine-treated hypothyroidism and 1806 (mean age, 50.0 years) did not have thyroid disease; the proportion of women with premenopausal or early perimenopausal status at baseline was higher in the hypothyroidism group (54.2% vs 49.8%; P = .010).
• At baseline, levothyroxine-treated women had higher scores for processing speed (mean score, 56.5 vs 54.4; P = .006) and working memory (mean score, 6.8 vs 6.4; P = .018) than those without thyroid disease; however, no difference in episodic memory was observed between the groups.
• Over the study period, there was no significant difference in cognitive decline between the groups.
• There was no significant effect of levothyroxine-treated hypothyroidism on working memory or episodic memory, although an annual decline in processing speed was observed (P < .001).
• Sensitivity analyses determined that abnormal levels of thyroid-stimulating hormone did not affect cognitive outcomes in women with hypothyroidism.

IN PRACTICE:

When cognitive decline is observed in these patients, the authors advised that “clinicians should resist anchoring on inadequate treatment of hypothyroidism as the cause of these symptoms and may investigate other disease processes (eg, iron deficiency, B12 deficiency, sleep apnea, celiac disease).”

SOURCE:

The study, led by Matthew D. Ettleson, Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, was published online in Thyroid.

LIMITATIONS:

The cognitive assessments in the study were not designed to provide a thorough evaluation of all aspects of cognitive function. The study may not have been adequately powered to detect small effects of levothyroxine-treated hypothyroidism on cognitive outcomes. The higher levels of education attained by the study population may have acted as a protective factor against cognitive decline, potentially biasing the results.

DISCLOSURES:

The Study of Women’s Health Across the Nation was supported by grants from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging, the National Institute of Nursing Research, and the NIH Office of Research on Women’s Health. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Women with hypothyroidism treated with levothyroxine show no significant cognitive decline across the menopausal transition compared with those without thyroid disease.

METHODOLOGY:

• Levothyroxine, the primary treatment for hypothyroidism, has been linked to perceived cognitive deficits, yet it is unclear whether this is due to the underlying condition being inadequately treated or other factors.
• Using data collected from the Study of Women’s Health Across the Nation, which encompasses five ethnic/racial groups from seven centers across the United States, researchers compared cognitive function over time between women with hypothyroidism treated with levothyroxine and those without thyroid disease.
• Participants underwent cognitive testing across three domains — processing speed, working memory, and episodic memory — which were assessed over a mean follow-up of 13 years.
• Further analyses assessed the impact of abnormal levels of thyroid-stimulating hormone on cognitive outcomes.

TAKEAWAY:

• Of 2033 women included, 227 (mean age, 49.8 years) had levothyroxine-treated hypothyroidism and 1806 (mean age, 50.0 years) did not have thyroid disease; the proportion of women with premenopausal or early perimenopausal status at baseline was higher in the hypothyroidism group (54.2% vs 49.8%; P = .010).
• At baseline, levothyroxine-treated women had higher scores for processing speed (mean score, 56.5 vs 54.4; P = .006) and working memory (mean score, 6.8 vs 6.4; P = .018) than those without thyroid disease; however, no difference in episodic memory was observed between the groups.
• Over the study period, there was no significant difference in cognitive decline between the groups.
• There was no significant effect of levothyroxine-treated hypothyroidism on working memory or episodic memory, although an annual decline in processing speed was observed (P < .001).
• Sensitivity analyses determined that abnormal levels of thyroid-stimulating hormone did not affect cognitive outcomes in women with hypothyroidism.

IN PRACTICE:

When cognitive decline is observed in these patients, the authors advised that “clinicians should resist anchoring on inadequate treatment of hypothyroidism as the cause of these symptoms and may investigate other disease processes (eg, iron deficiency, B12 deficiency, sleep apnea, celiac disease).”

SOURCE:

The study, led by Matthew D. Ettleson, Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, was published online in Thyroid.

LIMITATIONS:

The cognitive assessments in the study were not designed to provide a thorough evaluation of all aspects of cognitive function. The study may not have been adequately powered to detect small effects of levothyroxine-treated hypothyroidism on cognitive outcomes. The higher levels of education attained by the study population may have acted as a protective factor against cognitive decline, potentially biasing the results.

DISCLOSURES:

The Study of Women’s Health Across the Nation was supported by grants from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging, the National Institute of Nursing Research, and the NIH Office of Research on Women’s Health. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Women with hypothyroidism treated with levothyroxine show no significant cognitive decline across the menopausal transition compared with those without thyroid disease.

METHODOLOGY:

• Levothyroxine, the primary treatment for hypothyroidism, has been linked to perceived cognitive deficits, yet it is unclear whether this is due to the underlying condition being inadequately treated or other factors.
• Using data collected from the Study of Women’s Health Across the Nation, which encompasses five ethnic/racial groups from seven centers across the United States, researchers compared cognitive function over time between women with hypothyroidism treated with levothyroxine and those without thyroid disease.
• Participants underwent cognitive testing across three domains — processing speed, working memory, and episodic memory — which were assessed over a mean follow-up of 13 years.
• Further analyses assessed the impact of abnormal levels of thyroid-stimulating hormone on cognitive outcomes.

TAKEAWAY:

• Of 2033 women included, 227 (mean age, 49.8 years) had levothyroxine-treated hypothyroidism and 1806 (mean age, 50.0 years) did not have thyroid disease; the proportion of women with premenopausal or early perimenopausal status at baseline was higher in the hypothyroidism group (54.2% vs 49.8%; P = .010).
• At baseline, levothyroxine-treated women had higher scores for processing speed (mean score, 56.5 vs 54.4; P = .006) and working memory (mean score, 6.8 vs 6.4; P = .018) than those without thyroid disease; however, no difference in episodic memory was observed between the groups.
• Over the study period, there was no significant difference in cognitive decline between the groups.
• There was no significant effect of levothyroxine-treated hypothyroidism on working memory or episodic memory, although an annual decline in processing speed was observed (P < .001).
• Sensitivity analyses determined that abnormal levels of thyroid-stimulating hormone did not affect cognitive outcomes in women with hypothyroidism.

IN PRACTICE:

When cognitive decline is observed in these patients, the authors advised that “clinicians should resist anchoring on inadequate treatment of hypothyroidism as the cause of these symptoms and may investigate other disease processes (eg, iron deficiency, B12 deficiency, sleep apnea, celiac disease).”

SOURCE:

The study, led by Matthew D. Ettleson, Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, was published online in Thyroid.

LIMITATIONS:

The cognitive assessments in the study were not designed to provide a thorough evaluation of all aspects of cognitive function. The study may not have been adequately powered to detect small effects of levothyroxine-treated hypothyroidism on cognitive outcomes. The higher levels of education attained by the study population may have acted as a protective factor against cognitive decline, potentially biasing the results.

DISCLOSURES:

The Study of Women’s Health Across the Nation was supported by grants from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging, the National Institute of Nursing Research, and the NIH Office of Research on Women’s Health. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

There’s an unexpected treatment for hot flashes and other menopause symptoms that’s getting more popular: clinical hypnosis. 

Hypnosis is a state of highly focused attention that works through disassociating, or putting aside your conscious awareness of things that would ordinarily be in your consciousness, said David Spiegel, MD, a psychiatrist with Stanford Medical School in Califonrnia. 

“It increases your cognitive flexibility – a way to approach an old problem from a new point of view and just let go of your older ways of thinking about it,” he said. 

Usually around age 50, women have menopause, which is the end of their menstrual cycles. Estrogen levels drop, and hot flashes can happen 12-15 times per day, said Gary Elkins, PhD, a psychology and neuroscience professor at Baylor University in Waco, Texas.

Both clinical hypnosis and cognitive-behavioral therapy, a common form of talk therapy, have been shown to work as non-hormonal treatments for hot flashes, particularly for women who are unable to take hormones for health reasons, such as having a history with an estrogen-sensitive cancer (like breast cancer), according to research published by the Menopause Society in 2023. 

A new review presented at the 2024 annual meeting of the Menopause Society in Chicago analyzed 23 studies from 1996 to 2022 and compared how well clinical hypnosis and cognitive behavioral therapy worked as treatments for hot flashes and other menopause symptoms. Researchers found that clinical hypnosis is better at helping make hot flashes less frequent and less intense, even reducing symptoms by 60%. Findings on cognitive-behavioral therapy, on the other hand, showed only slight hot flash reduction, though it helped reduce daily stress linked with hot flashes. 

Hypnosis can address the “perfect storm” of mental and physical issues that come with menopause symptoms, explained Dr. Spiegel, who created a popular self-hypnosis app called Reveri. “You’re having a reduction in your levels of estrogen and progesterone, but it’s also a reminder that you’re going into a different stage of life where you’re no longer fertile, you’re getting older,” he said. “[With hypnosis], you can disassociate pain and your awareness of things that ordinarily would impede your consciousness and make you miserable.”

A hypnosis session can help you separate psychological discomfort from physical discomfort, Dr. Spiegel said. “Typically, people in hypnosis dealing with menopause will imagine they’re floating in a lake, feeling cool, tingling, numbness. They can literally change how hot they feel. They can change the hot flash and imagine themselves cool, comfortable. If they’re worried about something, picture it on an imaginary screen. Just picture it, but not feel it.”
 

Hypnosis for Sleep

Hot flashes that happen at night are called night sweats and can hinder your sleep. Hypnotherapy can help reduce both hot flashes and night sweats, to the point where sleep is not interrupted, Dr. Elkins said. “While sleep improves with the hypnotherapy intervention, it also involves general relaxation,” said Dr. Elkins, who is the director of the Mind-Body Medicine Research Laboratory at Baylor University. “As women practice self-hypnosis at night, they’re entering a more calm and relaxed state, which also may facilitate good sleep or improve sleep duration and sleep quality.”

Our subconscious mind influences our sleep patterns largely through experiences vs. words or thoughts, according to Emilie Leyes, a certified hypnotherapist based in Philadelphia. This explains why simply reciting the words “I’m relaxed,” when you’re stressed, is often less effective than a few deep breaths or a warm hug from a family member or friend, said Ms. Leyes, who hosts a brain-training podcast for mindset transformation called How to Like Your Life.

“In a similar way, hypnosis, which directly accesses the subconscious, allows us to offer our minds new, powerful experiences to reduce our stress, improve our mood, and increase our access to positive emotions,” she said. “Repeatedly exposing ourselves to these positive experiences in our minds can increase our capacity to feel good, and impact how we feel in our everyday lives.”
 

Your First Hypnosis Session

A hypnosis session always begins with deep relaxation, which can help your mind and body grow accustomed to what it’s like to feel calm, said Ms. Leyes. “By giving the brain and body experiences of safety, relaxation, and inner peace, we can more easily let go of our stressful thoughts of the day and drift off to sleep with ease at night.”

You will often start by sitting or lying in a comfortable position, and then the hypnotic induction begins with a focus of attention, according to Dr. Elkins. The person concentrates, with their eyelids closed, and then are given suggestions for deepening their relaxed state. “Usually that’s a safe, pleasant place, such as walking through the mountains or being near a beach,” he said. “And within that, suggestions are given that target the mechanism that underlies the symptoms [such as hot flashes].”

Dr. Spiegel usually starts off with a neutral test that can help measure how hypnotizable a person is on a 0-to-10 scale. For example, instructing the client to imagine that their hand is floating in the air. If they pull their hand down and it floats back up, the client finds they can “actually dissociate the psychological from the physiological aspects of their experience – their left hand feels different from their right hand,” Dr. Spiegel said. “I use that as an example for them to say, ‘look how you can change how your body feels. Now, let’s use it to help you with your anxiety with your menopausal symptoms.’ ”

A version of this article appeared on WebMD.com.

There’s an unexpected treatment for hot flashes and other menopause symptoms that’s getting more popular: clinical hypnosis. 

Hypnosis is a state of highly focused attention that works through disassociating, or putting aside your conscious awareness of things that would ordinarily be in your consciousness, said David Spiegel, MD, a psychiatrist with Stanford Medical School in Califonrnia. 

“It increases your cognitive flexibility – a way to approach an old problem from a new point of view and just let go of your older ways of thinking about it,” he said. 

Usually around age 50, women have menopause, which is the end of their menstrual cycles. Estrogen levels drop, and hot flashes can happen 12-15 times per day, said Gary Elkins, PhD, a psychology and neuroscience professor at Baylor University in Waco, Texas.

Both clinical hypnosis and cognitive-behavioral therapy, a common form of talk therapy, have been shown to work as non-hormonal treatments for hot flashes, particularly for women who are unable to take hormones for health reasons, such as having a history with an estrogen-sensitive cancer (like breast cancer), according to research published by the Menopause Society in 2023. 

A new review presented at the 2024 annual meeting of the Menopause Society in Chicago analyzed 23 studies from 1996 to 2022 and compared how well clinical hypnosis and cognitive behavioral therapy worked as treatments for hot flashes and other menopause symptoms. Researchers found that clinical hypnosis is better at helping make hot flashes less frequent and less intense, even reducing symptoms by 60%. Findings on cognitive-behavioral therapy, on the other hand, showed only slight hot flash reduction, though it helped reduce daily stress linked with hot flashes. 

Hypnosis can address the “perfect storm” of mental and physical issues that come with menopause symptoms, explained Dr. Spiegel, who created a popular self-hypnosis app called Reveri. “You’re having a reduction in your levels of estrogen and progesterone, but it’s also a reminder that you’re going into a different stage of life where you’re no longer fertile, you’re getting older,” he said. “[With hypnosis], you can disassociate pain and your awareness of things that ordinarily would impede your consciousness and make you miserable.”

A hypnosis session can help you separate psychological discomfort from physical discomfort, Dr. Spiegel said. “Typically, people in hypnosis dealing with menopause will imagine they’re floating in a lake, feeling cool, tingling, numbness. They can literally change how hot they feel. They can change the hot flash and imagine themselves cool, comfortable. If they’re worried about something, picture it on an imaginary screen. Just picture it, but not feel it.”
 

Hypnosis for Sleep

Hot flashes that happen at night are called night sweats and can hinder your sleep. Hypnotherapy can help reduce both hot flashes and night sweats, to the point where sleep is not interrupted, Dr. Elkins said. “While sleep improves with the hypnotherapy intervention, it also involves general relaxation,” said Dr. Elkins, who is the director of the Mind-Body Medicine Research Laboratory at Baylor University. “As women practice self-hypnosis at night, they’re entering a more calm and relaxed state, which also may facilitate good sleep or improve sleep duration and sleep quality.”

Our subconscious mind influences our sleep patterns largely through experiences vs. words or thoughts, according to Emilie Leyes, a certified hypnotherapist based in Philadelphia. This explains why simply reciting the words “I’m relaxed,” when you’re stressed, is often less effective than a few deep breaths or a warm hug from a family member or friend, said Ms. Leyes, who hosts a brain-training podcast for mindset transformation called How to Like Your Life.

“In a similar way, hypnosis, which directly accesses the subconscious, allows us to offer our minds new, powerful experiences to reduce our stress, improve our mood, and increase our access to positive emotions,” she said. “Repeatedly exposing ourselves to these positive experiences in our minds can increase our capacity to feel good, and impact how we feel in our everyday lives.”
 

Your First Hypnosis Session

A hypnosis session always begins with deep relaxation, which can help your mind and body grow accustomed to what it’s like to feel calm, said Ms. Leyes. “By giving the brain and body experiences of safety, relaxation, and inner peace, we can more easily let go of our stressful thoughts of the day and drift off to sleep with ease at night.”

You will often start by sitting or lying in a comfortable position, and then the hypnotic induction begins with a focus of attention, according to Dr. Elkins. The person concentrates, with their eyelids closed, and then are given suggestions for deepening their relaxed state. “Usually that’s a safe, pleasant place, such as walking through the mountains or being near a beach,” he said. “And within that, suggestions are given that target the mechanism that underlies the symptoms [such as hot flashes].”

Dr. Spiegel usually starts off with a neutral test that can help measure how hypnotizable a person is on a 0-to-10 scale. For example, instructing the client to imagine that their hand is floating in the air. If they pull their hand down and it floats back up, the client finds they can “actually dissociate the psychological from the physiological aspects of their experience – their left hand feels different from their right hand,” Dr. Spiegel said. “I use that as an example for them to say, ‘look how you can change how your body feels. Now, let’s use it to help you with your anxiety with your menopausal symptoms.’ ”

A version of this article appeared on WebMD.com.

There’s an unexpected treatment for hot flashes and other menopause symptoms that’s getting more popular: clinical hypnosis. 

Hypnosis is a state of highly focused attention that works through disassociating, or putting aside your conscious awareness of things that would ordinarily be in your consciousness, said David Spiegel, MD, a psychiatrist with Stanford Medical School in Califonrnia. 

“It increases your cognitive flexibility – a way to approach an old problem from a new point of view and just let go of your older ways of thinking about it,” he said. 

Usually around age 50, women have menopause, which is the end of their menstrual cycles. Estrogen levels drop, and hot flashes can happen 12-15 times per day, said Gary Elkins, PhD, a psychology and neuroscience professor at Baylor University in Waco, Texas.

Both clinical hypnosis and cognitive-behavioral therapy, a common form of talk therapy, have been shown to work as non-hormonal treatments for hot flashes, particularly for women who are unable to take hormones for health reasons, such as having a history with an estrogen-sensitive cancer (like breast cancer), according to research published by the Menopause Society in 2023. 

A new review presented at the 2024 annual meeting of the Menopause Society in Chicago analyzed 23 studies from 1996 to 2022 and compared how well clinical hypnosis and cognitive behavioral therapy worked as treatments for hot flashes and other menopause symptoms. Researchers found that clinical hypnosis is better at helping make hot flashes less frequent and less intense, even reducing symptoms by 60%. Findings on cognitive-behavioral therapy, on the other hand, showed only slight hot flash reduction, though it helped reduce daily stress linked with hot flashes. 

Hypnosis can address the “perfect storm” of mental and physical issues that come with menopause symptoms, explained Dr. Spiegel, who created a popular self-hypnosis app called Reveri. “You’re having a reduction in your levels of estrogen and progesterone, but it’s also a reminder that you’re going into a different stage of life where you’re no longer fertile, you’re getting older,” he said. “[With hypnosis], you can disassociate pain and your awareness of things that ordinarily would impede your consciousness and make you miserable.”

A hypnosis session can help you separate psychological discomfort from physical discomfort, Dr. Spiegel said. “Typically, people in hypnosis dealing with menopause will imagine they’re floating in a lake, feeling cool, tingling, numbness. They can literally change how hot they feel. They can change the hot flash and imagine themselves cool, comfortable. If they’re worried about something, picture it on an imaginary screen. Just picture it, but not feel it.”
 

Hypnosis for Sleep

Hot flashes that happen at night are called night sweats and can hinder your sleep. Hypnotherapy can help reduce both hot flashes and night sweats, to the point where sleep is not interrupted, Dr. Elkins said. “While sleep improves with the hypnotherapy intervention, it also involves general relaxation,” said Dr. Elkins, who is the director of the Mind-Body Medicine Research Laboratory at Baylor University. “As women practice self-hypnosis at night, they’re entering a more calm and relaxed state, which also may facilitate good sleep or improve sleep duration and sleep quality.”

Our subconscious mind influences our sleep patterns largely through experiences vs. words or thoughts, according to Emilie Leyes, a certified hypnotherapist based in Philadelphia. This explains why simply reciting the words “I’m relaxed,” when you’re stressed, is often less effective than a few deep breaths or a warm hug from a family member or friend, said Ms. Leyes, who hosts a brain-training podcast for mindset transformation called How to Like Your Life.

“In a similar way, hypnosis, which directly accesses the subconscious, allows us to offer our minds new, powerful experiences to reduce our stress, improve our mood, and increase our access to positive emotions,” she said. “Repeatedly exposing ourselves to these positive experiences in our minds can increase our capacity to feel good, and impact how we feel in our everyday lives.”
 

Your First Hypnosis Session

A hypnosis session always begins with deep relaxation, which can help your mind and body grow accustomed to what it’s like to feel calm, said Ms. Leyes. “By giving the brain and body experiences of safety, relaxation, and inner peace, we can more easily let go of our stressful thoughts of the day and drift off to sleep with ease at night.”

You will often start by sitting or lying in a comfortable position, and then the hypnotic induction begins with a focus of attention, according to Dr. Elkins. The person concentrates, with their eyelids closed, and then are given suggestions for deepening their relaxed state. “Usually that’s a safe, pleasant place, such as walking through the mountains or being near a beach,” he said. “And within that, suggestions are given that target the mechanism that underlies the symptoms [such as hot flashes].”

Dr. Spiegel usually starts off with a neutral test that can help measure how hypnotizable a person is on a 0-to-10 scale. For example, instructing the client to imagine that their hand is floating in the air. If they pull their hand down and it floats back up, the client finds they can “actually dissociate the psychological from the physiological aspects of their experience – their left hand feels different from their right hand,” Dr. Spiegel said. “I use that as an example for them to say, ‘look how you can change how your body feels. Now, let’s use it to help you with your anxiety with your menopausal symptoms.’ ”

A version of this article appeared on WebMD.com.

CHICAGO — The nonhormonal investigational drug elinzanetant led to significant improvement in hot flashes as well as sleep disturbance and quality of life, according to data from three randomized controlled trials presented at The Menopause Society 2024 Annual Meeting in Chicago. Two phase 3 trials, OASIS 1 and 2, were also published in JAMA, and the longer-term OASIS 3 trial was presented as a poster at the conference.

Elinzanetant is a selective neurokinin (NK) receptor antagonist, similar to fezolinetant, the first drug in this class approved by the US Food and Drug Administration (FDA) for vasomotor symptoms in May 2023. This class of medications targets the estrogen-sensitive kisspeptin/NK B/dynorphin (KNDy) neurons thought to play a role in thermoregulation and hot flashes during menopause. While fezolinetant targets only the NK-3 receptor, elinzanetant is a dual NK receptor antagonist that targets both NK-1 and NK-3. Bayer submitted a New Drug Application for elinzanetant to the FDA on August 1.

For those in whom hormone therapy is contraindicated, “it’s always been difficult for women with really severe symptoms to have a safe and effective therapy,” lead author JoAnn Pinkerton, MD, a professor of ob.gyn. at the University of Virginia in Charlottesville, Virginia, told this news organization. “The nonhormonal therapies we’ve used mostly off-label — the antidepressants, gabapentin, clonidine, oxybutynin — do help the hot flashes, but they don’t work nearly as effectively as these new NK receptor antagonists, and having one that looks like it might have a broader use for hot flashes, night sweats, mood, and sleep is just really exciting.”

Dr. Pinkerton said approximately 80% of the women in the OASIS 1 and 2 studies had at least a 50% reduction in hot flashes. “It was a very strong, dramatic positive finding, but the improvements in sleep and mood have really encouraged us to go further,” she said.

Declining estrogen levels during and after menopause can cause hypertrophy and hyperactivity of the KNDy neurons, which has been linked to thermoregulation disruptions that may trigger hot flashes, James Simon, MD, a clinical professor of ob.gyn. at The George Washington University School of Medicine & Health Sciences and medical director of IntimMedicine in Washington, DC, told attendees. He presented pooled data from OASIS 1 and 2. The NK-1 receptor, targeted by elinzanetant but not fezolinetant, is also thought to play a role in insomnia and possibly in mood.

“Oftentimes the focus on a lot of these drugs is hot flashes, hot flashes, hot flashes, but we know hot flashes do not occur in isolation,” Chrisandra Shufelt, MD, professor and chair of general internal medicine and associate director of the Women’s Health Research Center at Mayo Clinic in Jacksonville, Florida, told this news organization. Elinzanetant is “an interesting compound because it actually works on sleep, and that was critical because sleep disturbance precedes” many other menopausal symptoms, said Dr. Shufelt, who was not involved in the study.

“I think it is an outstanding option for women who don’t have the opportunity to get hormones,” Dr. Shufelt said, and she was particularly pleased to see there were no safety concerns for the liver in the trial data. The FDA issued a warning on September 12 about the risk for rare liver injury with fezolinetant, but the early signals that had been seen in fezolinetant data were not seen in these elinzanetant data.

The OASIS 1 and 2 trials enrolled postmenopausal women, aged 40-65 years, who had at least 50 moderate to severe vasomotor occurrences per week.

“A moderate hot flash is a hot flash that is also associated with sweating, and a severe hot flash is a moderate hot flash that stops a woman in her tracks,” Dr. Simon said. “Namely, it’s severe enough with sweating and central nervous system effects that she is interrupted in whatever it is that she’s doing at the time.”

Exclusion criteria for the trials included a history of arrhythmias, heart block, or QT prolongation; abnormal lab results; history of malignancy within the past 5 years; uncontrolled or treatment-resistant hypertension, hypothyroidism, or hyperthyroidism; unexplained postmenopausal bleeding; clinically relevant abnormal mammogram findings; or disordered proliferative endometrium, endometrial hyperplasia, polyp, or endometrial cancer.

The predominantly White (80%) women were an average 54 years old, with an average body mass index (BMI) of 27.8, and were an average 3.5 years from their last period. For the first 12 weeks of the trials, 399 women were assigned to receive 120 mg once daily of oral elinzanetant and 397 were assigned to once daily placebo. Then the women taking placebo switched to elinzanetant for the final 14 weeks of the study.

The endpoints included mean change in frequency and severity of vasomotor symptoms at weeks 1, 4, and 12 as well as change in sleep disturbance and quality of life at week 12. Sleep was assessed with the Patient-Reported Outcomes Measurement Information System Sleep Disturbance–Short Form score, which ranges from 28.9 to 76.5, with a higher number denoting greater sleep disturbance. The Menopause-Specific Quality-of-Life score ranges from 1 to 8, with a higher score indicating poorer quality of life.

Daily frequency of vasomotor symptoms was 14 per day at baseline in the elinzanetant group, decreasing by 4.8 per day at week 1, 8 per day at week 4, and 9.4 per day at week 12. In the placebo group, women had an average 15.2 occurrences per day at baseline, which decreased by 3.2 at week 1, 5.2 at week 4, and 6.4 at week 12. Comparing the groups at 12 weeks, those receiving elinzanetant had 3.2 fewer daily vasomotor symptoms than those receiving placebo (P < .0001).

The severity of vasomotor symptoms also improved more in the elinzanetant group than in the placebo group over 12 weeks, after which severity improved further in those who switched from placebo to elinzanetant (P < .0001).

Sleep disturbance scores, starting at a mean 61.5 in the elinzanetant group and 60.5 in the placebo group, fell 10.7 points in the elinzanetant group and 5.3 points in the placebo group at 12 weeks, for a difference of 4.9 points (P < .0001). Sleep then further improved in those who switched from placebo to elinzanetant. Quality-of-life scores improved 1.37 points (from 4.52 at baseline) in the elinzanetant group and 0.96 points (from 4.49 at baseline) in the placebo group, for a mean difference at 12 weeks of 0.36 (P < .0001).

Though no head-to-head data exist comparing elinzanetant and fezolinetant, Dr. Simon told this news organization the side effects with fezolinetant “tend to be gastrointestinal, whereas the side effects for elinzanetant tend to be central nervous system,” such as drowsiness and lethargy.

The women who are the best candidates for elinzanetant, Dr. Pinkerton told this news organization, include those who have had an estrogen-sensitive cancer, such as breast or endometrial cancer, or who have fear of it, a family history, or are otherwise high risk. Other ideal candidates include those with a history of venous thromboembolism, people who have migraine with aura (due to concerns about increased risk for stroke), and those who have endometriosis or large fibroids.

“Then the last group might be women who took hormone therapy in their 50s and want to continue, but they’re trying to go off, and they have a recurrence of their hot flashes or night sweats or sleep issues,” Dr. Pinkerton said. “This might be a great group to switch over.”

OASIS 3 assessed the drug for 1 year and “supported the results of OASIS 1 and 2, demonstrating efficacy over a longer study duration and in a population with a vasomotor symptom profile representative of that seen in clinical practice,” Nick Panay, BSc, MBBS, director of the Menopause & PMS Centre at Queen Charlotte’s Hospital & Imperial College London, London, England, and his colleague reported.

Among 628 postmenopausal women aged 40-65, the predominantly White (78.5%) women were an average 54 years old, with an average BMI of 27.6, and were an average 5 years past their last period. Half received 120 mg elinzanetant and half received a placebo for 52 weeks.

At 12 weeks, the women receiving elinzanetant reported an average 1.6 moderate to severe vasomotor symptoms per day, down from 6.7 at baseline. Daily average symptoms in the placebo group fell from 6.8 at baseline to 3.4 at 12 weeks, for a difference of 1.6 fewer occurrences per day in the elinzanetant group (P < .0001).

Sleep disturbances also improved, falling 9.4 points from a baseline 57.4 in the elinzanetant group and 5.7 points from a baseline 58 in the placebo group. Quality-of-life scores improved from 4.1 to 2.8 (−1.3 change) in the elinzanetant group and from 4.4 to 3.3 (−1.1 change) in the placebo group.

In addition to looking at treatment-emergent adverse events, the safety assessments also included endometrial biopsies; bone mineral density in the femoral neck, hip, and lumbar spine; weight; and labs. Adverse events related to the study drug occurred in 30.4% of those in the elinzanetant group and 14.6% of those in the placebo group. The most commonly reported adverse events were headache (9.6% elinzanetant vs 7% placebo), fatigue (7% vs 10.2%), and sleepiness (5.1% vs 1.3%). A higher proportion of women taking elinzanetant (12.5%) than those taking placebo (4.1%) discontinued the study.

No serious adverse events deemed to be treatment-related occurred in either group, and no endometrial hyperplasia or malignant neoplasm occurred in either group. Bone mineral density changes in both groups were within the expected range for the women’s age, and their weight remained stable over the 52 weeks.

Six women taking elinzanetant and four taking placebo met predefined criteria for close liver observation, but none showed hepatotoxicity or evidence of possible drug-induced liver injury.

The research was funded by Bayer. Dr. Pinkerton has run a trial funded by Bayer and is a consultant for Bayer and Pfizer. Dr. Shufelt had no disclosures. Dr. Simon had grant/research support, consulting/advisory board participation, and/or speaking disclosures with AbbVie, Bayer Healthcare, Besins Healthcare, California Institute of Integral Studies, Camargo Pharmaceutical Services, Covance, Daré Bioscience, DEKA M.E.L.A S.r.l., Femasys, Ipsen, KaNDy/NeRRe Therapeutics, Khyria, Madorra, Mayne Pharma, Mitsubishi Tanabe Pharma Development America, Mylan/Viatris Inc, Myovant Sciences, ObsEva SA, Pfizer, Pharmavite, QUE Oncology, Scynexis, Sebela Pharmaceuticals, Sprout Pharmaceuticals, TherapeuticsMD, Vella Bioscience, and Viveve Medical, and he is a stockholder in Sermonix Pharmaceuticals.

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

CHICAGO — The nonhormonal investigational drug elinzanetant led to significant improvement in hot flashes as well as sleep disturbance and quality of life, according to data from three randomized controlled trials presented at The Menopause Society 2024 Annual Meeting in Chicago. Two phase 3 trials, OASIS 1 and 2, were also published in JAMA, and the longer-term OASIS 3 trial was presented as a poster at the conference.

Elinzanetant is a selective neurokinin (NK) receptor antagonist, similar to fezolinetant, the first drug in this class approved by the US Food and Drug Administration (FDA) for vasomotor symptoms in May 2023. This class of medications targets the estrogen-sensitive kisspeptin/NK B/dynorphin (KNDy) neurons thought to play a role in thermoregulation and hot flashes during menopause. While fezolinetant targets only the NK-3 receptor, elinzanetant is a dual NK receptor antagonist that targets both NK-1 and NK-3. Bayer submitted a New Drug Application for elinzanetant to the FDA on August 1.

For those in whom hormone therapy is contraindicated, “it’s always been difficult for women with really severe symptoms to have a safe and effective therapy,” lead author JoAnn Pinkerton, MD, a professor of ob.gyn. at the University of Virginia in Charlottesville, Virginia, told this news organization. “The nonhormonal therapies we’ve used mostly off-label — the antidepressants, gabapentin, clonidine, oxybutynin — do help the hot flashes, but they don’t work nearly as effectively as these new NK receptor antagonists, and having one that looks like it might have a broader use for hot flashes, night sweats, mood, and sleep is just really exciting.”

Dr. Pinkerton said approximately 80% of the women in the OASIS 1 and 2 studies had at least a 50% reduction in hot flashes. “It was a very strong, dramatic positive finding, but the improvements in sleep and mood have really encouraged us to go further,” she said.

Declining estrogen levels during and after menopause can cause hypertrophy and hyperactivity of the KNDy neurons, which has been linked to thermoregulation disruptions that may trigger hot flashes, James Simon, MD, a clinical professor of ob.gyn. at The George Washington University School of Medicine & Health Sciences and medical director of IntimMedicine in Washington, DC, told attendees. He presented pooled data from OASIS 1 and 2. The NK-1 receptor, targeted by elinzanetant but not fezolinetant, is also thought to play a role in insomnia and possibly in mood.

“Oftentimes the focus on a lot of these drugs is hot flashes, hot flashes, hot flashes, but we know hot flashes do not occur in isolation,” Chrisandra Shufelt, MD, professor and chair of general internal medicine and associate director of the Women’s Health Research Center at Mayo Clinic in Jacksonville, Florida, told this news organization. Elinzanetant is “an interesting compound because it actually works on sleep, and that was critical because sleep disturbance precedes” many other menopausal symptoms, said Dr. Shufelt, who was not involved in the study.

“I think it is an outstanding option for women who don’t have the opportunity to get hormones,” Dr. Shufelt said, and she was particularly pleased to see there were no safety concerns for the liver in the trial data. The FDA issued a warning on September 12 about the risk for rare liver injury with fezolinetant, but the early signals that had been seen in fezolinetant data were not seen in these elinzanetant data.

The OASIS 1 and 2 trials enrolled postmenopausal women, aged 40-65 years, who had at least 50 moderate to severe vasomotor occurrences per week.

“A moderate hot flash is a hot flash that is also associated with sweating, and a severe hot flash is a moderate hot flash that stops a woman in her tracks,” Dr. Simon said. “Namely, it’s severe enough with sweating and central nervous system effects that she is interrupted in whatever it is that she’s doing at the time.”

Exclusion criteria for the trials included a history of arrhythmias, heart block, or QT prolongation; abnormal lab results; history of malignancy within the past 5 years; uncontrolled or treatment-resistant hypertension, hypothyroidism, or hyperthyroidism; unexplained postmenopausal bleeding; clinically relevant abnormal mammogram findings; or disordered proliferative endometrium, endometrial hyperplasia, polyp, or endometrial cancer.

The predominantly White (80%) women were an average 54 years old, with an average body mass index (BMI) of 27.8, and were an average 3.5 years from their last period. For the first 12 weeks of the trials, 399 women were assigned to receive 120 mg once daily of oral elinzanetant and 397 were assigned to once daily placebo. Then the women taking placebo switched to elinzanetant for the final 14 weeks of the study.

The endpoints included mean change in frequency and severity of vasomotor symptoms at weeks 1, 4, and 12 as well as change in sleep disturbance and quality of life at week 12. Sleep was assessed with the Patient-Reported Outcomes Measurement Information System Sleep Disturbance–Short Form score, which ranges from 28.9 to 76.5, with a higher number denoting greater sleep disturbance. The Menopause-Specific Quality-of-Life score ranges from 1 to 8, with a higher score indicating poorer quality of life.

Daily frequency of vasomotor symptoms was 14 per day at baseline in the elinzanetant group, decreasing by 4.8 per day at week 1, 8 per day at week 4, and 9.4 per day at week 12. In the placebo group, women had an average 15.2 occurrences per day at baseline, which decreased by 3.2 at week 1, 5.2 at week 4, and 6.4 at week 12. Comparing the groups at 12 weeks, those receiving elinzanetant had 3.2 fewer daily vasomotor symptoms than those receiving placebo (P < .0001).

The severity of vasomotor symptoms also improved more in the elinzanetant group than in the placebo group over 12 weeks, after which severity improved further in those who switched from placebo to elinzanetant (P < .0001).

Sleep disturbance scores, starting at a mean 61.5 in the elinzanetant group and 60.5 in the placebo group, fell 10.7 points in the elinzanetant group and 5.3 points in the placebo group at 12 weeks, for a difference of 4.9 points (P < .0001). Sleep then further improved in those who switched from placebo to elinzanetant. Quality-of-life scores improved 1.37 points (from 4.52 at baseline) in the elinzanetant group and 0.96 points (from 4.49 at baseline) in the placebo group, for a mean difference at 12 weeks of 0.36 (P < .0001).

Though no head-to-head data exist comparing elinzanetant and fezolinetant, Dr. Simon told this news organization the side effects with fezolinetant “tend to be gastrointestinal, whereas the side effects for elinzanetant tend to be central nervous system,” such as drowsiness and lethargy.

The women who are the best candidates for elinzanetant, Dr. Pinkerton told this news organization, include those who have had an estrogen-sensitive cancer, such as breast or endometrial cancer, or who have fear of it, a family history, or are otherwise high risk. Other ideal candidates include those with a history of venous thromboembolism, people who have migraine with aura (due to concerns about increased risk for stroke), and those who have endometriosis or large fibroids.

“Then the last group might be women who took hormone therapy in their 50s and want to continue, but they’re trying to go off, and they have a recurrence of their hot flashes or night sweats or sleep issues,” Dr. Pinkerton said. “This might be a great group to switch over.”

OASIS 3 assessed the drug for 1 year and “supported the results of OASIS 1 and 2, demonstrating efficacy over a longer study duration and in a population with a vasomotor symptom profile representative of that seen in clinical practice,” Nick Panay, BSc, MBBS, director of the Menopause & PMS Centre at Queen Charlotte’s Hospital & Imperial College London, London, England, and his colleague reported.

Among 628 postmenopausal women aged 40-65, the predominantly White (78.5%) women were an average 54 years old, with an average BMI of 27.6, and were an average 5 years past their last period. Half received 120 mg elinzanetant and half received a placebo for 52 weeks.

At 12 weeks, the women receiving elinzanetant reported an average 1.6 moderate to severe vasomotor symptoms per day, down from 6.7 at baseline. Daily average symptoms in the placebo group fell from 6.8 at baseline to 3.4 at 12 weeks, for a difference of 1.6 fewer occurrences per day in the elinzanetant group (P < .0001).

Sleep disturbances also improved, falling 9.4 points from a baseline 57.4 in the elinzanetant group and 5.7 points from a baseline 58 in the placebo group. Quality-of-life scores improved from 4.1 to 2.8 (−1.3 change) in the elinzanetant group and from 4.4 to 3.3 (−1.1 change) in the placebo group.

In addition to looking at treatment-emergent adverse events, the safety assessments also included endometrial biopsies; bone mineral density in the femoral neck, hip, and lumbar spine; weight; and labs. Adverse events related to the study drug occurred in 30.4% of those in the elinzanetant group and 14.6% of those in the placebo group. The most commonly reported adverse events were headache (9.6% elinzanetant vs 7% placebo), fatigue (7% vs 10.2%), and sleepiness (5.1% vs 1.3%). A higher proportion of women taking elinzanetant (12.5%) than those taking placebo (4.1%) discontinued the study.

No serious adverse events deemed to be treatment-related occurred in either group, and no endometrial hyperplasia or malignant neoplasm occurred in either group. Bone mineral density changes in both groups were within the expected range for the women’s age, and their weight remained stable over the 52 weeks.

Six women taking elinzanetant and four taking placebo met predefined criteria for close liver observation, but none showed hepatotoxicity or evidence of possible drug-induced liver injury.

The research was funded by Bayer. Dr. Pinkerton has run a trial funded by Bayer and is a consultant for Bayer and Pfizer. Dr. Shufelt had no disclosures. Dr. Simon had grant/research support, consulting/advisory board participation, and/or speaking disclosures with AbbVie, Bayer Healthcare, Besins Healthcare, California Institute of Integral Studies, Camargo Pharmaceutical Services, Covance, Daré Bioscience, DEKA M.E.L.A S.r.l., Femasys, Ipsen, KaNDy/NeRRe Therapeutics, Khyria, Madorra, Mayne Pharma, Mitsubishi Tanabe Pharma Development America, Mylan/Viatris Inc, Myovant Sciences, ObsEva SA, Pfizer, Pharmavite, QUE Oncology, Scynexis, Sebela Pharmaceuticals, Sprout Pharmaceuticals, TherapeuticsMD, Vella Bioscience, and Viveve Medical, and he is a stockholder in Sermonix Pharmaceuticals.

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

CHICAGO — The nonhormonal investigational drug elinzanetant led to significant improvement in hot flashes as well as sleep disturbance and quality of life, according to data from three randomized controlled trials presented at The Menopause Society 2024 Annual Meeting in Chicago. Two phase 3 trials, OASIS 1 and 2, were also published in JAMA, and the longer-term OASIS 3 trial was presented as a poster at the conference.

Elinzanetant is a selective neurokinin (NK) receptor antagonist, similar to fezolinetant, the first drug in this class approved by the US Food and Drug Administration (FDA) for vasomotor symptoms in May 2023. This class of medications targets the estrogen-sensitive kisspeptin/NK B/dynorphin (KNDy) neurons thought to play a role in thermoregulation and hot flashes during menopause. While fezolinetant targets only the NK-3 receptor, elinzanetant is a dual NK receptor antagonist that targets both NK-1 and NK-3. Bayer submitted a New Drug Application for elinzanetant to the FDA on August 1.

For those in whom hormone therapy is contraindicated, “it’s always been difficult for women with really severe symptoms to have a safe and effective therapy,” lead author JoAnn Pinkerton, MD, a professor of ob.gyn. at the University of Virginia in Charlottesville, Virginia, told this news organization. “The nonhormonal therapies we’ve used mostly off-label — the antidepressants, gabapentin, clonidine, oxybutynin — do help the hot flashes, but they don’t work nearly as effectively as these new NK receptor antagonists, and having one that looks like it might have a broader use for hot flashes, night sweats, mood, and sleep is just really exciting.”

Dr. Pinkerton said approximately 80% of the women in the OASIS 1 and 2 studies had at least a 50% reduction in hot flashes. “It was a very strong, dramatic positive finding, but the improvements in sleep and mood have really encouraged us to go further,” she said.

Declining estrogen levels during and after menopause can cause hypertrophy and hyperactivity of the KNDy neurons, which has been linked to thermoregulation disruptions that may trigger hot flashes, James Simon, MD, a clinical professor of ob.gyn. at The George Washington University School of Medicine & Health Sciences and medical director of IntimMedicine in Washington, DC, told attendees. He presented pooled data from OASIS 1 and 2. The NK-1 receptor, targeted by elinzanetant but not fezolinetant, is also thought to play a role in insomnia and possibly in mood.

“Oftentimes the focus on a lot of these drugs is hot flashes, hot flashes, hot flashes, but we know hot flashes do not occur in isolation,” Chrisandra Shufelt, MD, professor and chair of general internal medicine and associate director of the Women’s Health Research Center at Mayo Clinic in Jacksonville, Florida, told this news organization. Elinzanetant is “an interesting compound because it actually works on sleep, and that was critical because sleep disturbance precedes” many other menopausal symptoms, said Dr. Shufelt, who was not involved in the study.

“I think it is an outstanding option for women who don’t have the opportunity to get hormones,” Dr. Shufelt said, and she was particularly pleased to see there were no safety concerns for the liver in the trial data. The FDA issued a warning on September 12 about the risk for rare liver injury with fezolinetant, but the early signals that had been seen in fezolinetant data were not seen in these elinzanetant data.

The OASIS 1 and 2 trials enrolled postmenopausal women, aged 40-65 years, who had at least 50 moderate to severe vasomotor occurrences per week.

“A moderate hot flash is a hot flash that is also associated with sweating, and a severe hot flash is a moderate hot flash that stops a woman in her tracks,” Dr. Simon said. “Namely, it’s severe enough with sweating and central nervous system effects that she is interrupted in whatever it is that she’s doing at the time.”

Exclusion criteria for the trials included a history of arrhythmias, heart block, or QT prolongation; abnormal lab results; history of malignancy within the past 5 years; uncontrolled or treatment-resistant hypertension, hypothyroidism, or hyperthyroidism; unexplained postmenopausal bleeding; clinically relevant abnormal mammogram findings; or disordered proliferative endometrium, endometrial hyperplasia, polyp, or endometrial cancer.

The predominantly White (80%) women were an average 54 years old, with an average body mass index (BMI) of 27.8, and were an average 3.5 years from their last period. For the first 12 weeks of the trials, 399 women were assigned to receive 120 mg once daily of oral elinzanetant and 397 were assigned to once daily placebo. Then the women taking placebo switched to elinzanetant for the final 14 weeks of the study.

The endpoints included mean change in frequency and severity of vasomotor symptoms at weeks 1, 4, and 12 as well as change in sleep disturbance and quality of life at week 12. Sleep was assessed with the Patient-Reported Outcomes Measurement Information System Sleep Disturbance–Short Form score, which ranges from 28.9 to 76.5, with a higher number denoting greater sleep disturbance. The Menopause-Specific Quality-of-Life score ranges from 1 to 8, with a higher score indicating poorer quality of life.

Daily frequency of vasomotor symptoms was 14 per day at baseline in the elinzanetant group, decreasing by 4.8 per day at week 1, 8 per day at week 4, and 9.4 per day at week 12. In the placebo group, women had an average 15.2 occurrences per day at baseline, which decreased by 3.2 at week 1, 5.2 at week 4, and 6.4 at week 12. Comparing the groups at 12 weeks, those receiving elinzanetant had 3.2 fewer daily vasomotor symptoms than those receiving placebo (P < .0001).

The severity of vasomotor symptoms also improved more in the elinzanetant group than in the placebo group over 12 weeks, after which severity improved further in those who switched from placebo to elinzanetant (P < .0001).

Sleep disturbance scores, starting at a mean 61.5 in the elinzanetant group and 60.5 in the placebo group, fell 10.7 points in the elinzanetant group and 5.3 points in the placebo group at 12 weeks, for a difference of 4.9 points (P < .0001). Sleep then further improved in those who switched from placebo to elinzanetant. Quality-of-life scores improved 1.37 points (from 4.52 at baseline) in the elinzanetant group and 0.96 points (from 4.49 at baseline) in the placebo group, for a mean difference at 12 weeks of 0.36 (P < .0001).

Though no head-to-head data exist comparing elinzanetant and fezolinetant, Dr. Simon told this news organization the side effects with fezolinetant “tend to be gastrointestinal, whereas the side effects for elinzanetant tend to be central nervous system,” such as drowsiness and lethargy.

The women who are the best candidates for elinzanetant, Dr. Pinkerton told this news organization, include those who have had an estrogen-sensitive cancer, such as breast or endometrial cancer, or who have fear of it, a family history, or are otherwise high risk. Other ideal candidates include those with a history of venous thromboembolism, people who have migraine with aura (due to concerns about increased risk for stroke), and those who have endometriosis or large fibroids.

“Then the last group might be women who took hormone therapy in their 50s and want to continue, but they’re trying to go off, and they have a recurrence of their hot flashes or night sweats or sleep issues,” Dr. Pinkerton said. “This might be a great group to switch over.”

OASIS 3 assessed the drug for 1 year and “supported the results of OASIS 1 and 2, demonstrating efficacy over a longer study duration and in a population with a vasomotor symptom profile representative of that seen in clinical practice,” Nick Panay, BSc, MBBS, director of the Menopause & PMS Centre at Queen Charlotte’s Hospital & Imperial College London, London, England, and his colleague reported.

Among 628 postmenopausal women aged 40-65, the predominantly White (78.5%) women were an average 54 years old, with an average BMI of 27.6, and were an average 5 years past their last period. Half received 120 mg elinzanetant and half received a placebo for 52 weeks.

At 12 weeks, the women receiving elinzanetant reported an average 1.6 moderate to severe vasomotor symptoms per day, down from 6.7 at baseline. Daily average symptoms in the placebo group fell from 6.8 at baseline to 3.4 at 12 weeks, for a difference of 1.6 fewer occurrences per day in the elinzanetant group (P < .0001).

Sleep disturbances also improved, falling 9.4 points from a baseline 57.4 in the elinzanetant group and 5.7 points from a baseline 58 in the placebo group. Quality-of-life scores improved from 4.1 to 2.8 (−1.3 change) in the elinzanetant group and from 4.4 to 3.3 (−1.1 change) in the placebo group.

In addition to looking at treatment-emergent adverse events, the safety assessments also included endometrial biopsies; bone mineral density in the femoral neck, hip, and lumbar spine; weight; and labs. Adverse events related to the study drug occurred in 30.4% of those in the elinzanetant group and 14.6% of those in the placebo group. The most commonly reported adverse events were headache (9.6% elinzanetant vs 7% placebo), fatigue (7% vs 10.2%), and sleepiness (5.1% vs 1.3%). A higher proportion of women taking elinzanetant (12.5%) than those taking placebo (4.1%) discontinued the study.

No serious adverse events deemed to be treatment-related occurred in either group, and no endometrial hyperplasia or malignant neoplasm occurred in either group. Bone mineral density changes in both groups were within the expected range for the women’s age, and their weight remained stable over the 52 weeks.

Six women taking elinzanetant and four taking placebo met predefined criteria for close liver observation, but none showed hepatotoxicity or evidence of possible drug-induced liver injury.

The research was funded by Bayer. Dr. Pinkerton has run a trial funded by Bayer and is a consultant for Bayer and Pfizer. Dr. Shufelt had no disclosures. Dr. Simon had grant/research support, consulting/advisory board participation, and/or speaking disclosures with AbbVie, Bayer Healthcare, Besins Healthcare, California Institute of Integral Studies, Camargo Pharmaceutical Services, Covance, Daré Bioscience, DEKA M.E.L.A S.r.l., Femasys, Ipsen, KaNDy/NeRRe Therapeutics, Khyria, Madorra, Mayne Pharma, Mitsubishi Tanabe Pharma Development America, Mylan/Viatris Inc, Myovant Sciences, ObsEva SA, Pfizer, Pharmavite, QUE Oncology, Scynexis, Sebela Pharmaceuticals, Sprout Pharmaceuticals, TherapeuticsMD, Vella Bioscience, and Viveve Medical, and he is a stockholder in Sermonix Pharmaceuticals.

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

CHICAGO — The vast majority of women experiencing genitourinary syndrome of menopause (GSM) symptoms did not receive a prescription for hormonal vaginal therapies prior to seeking care at a specialized menopause clinic, according to research presented at the annual meeting of The Menopause Society.

“GSM symptoms are very common and affect women’s health and quality of life, often worsening without effective therapy,” Leticia Hernández Galán, PhD, of the Department of Obstetrics & Gynecology, McMaster University, Hamilton, Ontario, Canada, and colleagues reported. “We have demonstrated that most women seeking specialty care in an urban center with GSM symptoms have not been given a trial of local vaginal therapies by referring providers despite guidelines about safety and lack of contraindications. Given very long wait times for menopause providers in Canada, improved education for both women and their providers is needed to reduce needless suffering and improve care.”

Stephanie Faubion, MD, MBA, director of the Mayo Clinic Women’s Health in Jacksonville, Florida, and medical director of The Menopause Society, was not involved with the study but agreed with the authors’ assessment of the findings.

“This study highlights the treatment gap for women with genitourinary syndrome of menopause,” Dr. Faubion told this news organization. “Clearly, there is underutilization of low-dose vaginal hormonal therapies, which are known to be safe and effective. We still have work to do in terms of educating both women and providers on established treatment options for this common concern in menopausal women.” 

The findings match previous ones that found a majority of women with GSM do not receive treatment. A 2017 study, which was cited in the 2020 Menopause Society position statement on the condition, found that half of women with GSM had never used any treatment.

GSM is the current term that replaces previously used “vulvovaginal atrophy” and “atrophic vaginitis” because it encompasses all the menopause symptoms and signs associated with menopause that affect the vagina, vulva, and urinary tract. Anywhere from 50% to 84% of postmenopausal women experience GSM, the authors noted, with symptoms that include “burning, itching, or irritation of the vulva” and “lack of lubrication and discomfort or pain with sexual activity as well as dysuria, increased frequency or urgency of urination, and increased risk for urinary tract infections.”

First-line treatment of mild GSM often includes nonhormonal vaginal lubricants and moisturizers, but vaginal estrogen is considered the most effective treatment for more severe or bothersome cases. Other treatments include systematic hormone therapy and ospemifene or other selective estrogen receptor modulators.
 

Increased Risk for Urinary Tract Infections (UTIs)

Untreated GSM is not simply a quality of life issue; it increases the risk of developing serious UTIs, explained JoAnn Pinkerton, MD, a professor of obstetrics and gynecology at the University of Virginia, Charlottesville, who was not involved in the study.

“Estrogen depletion alters the vaginal epithelium, with distinct impairments in lubrication, elasticity, pH, and blood flow,” Dr. Pinkerton said. “The vaginal microbiome changes, with increasing pH following menopause and loss of lactobacillus predominance. These alterations allow a more hospitable environment for bacterial growth and increase the risk of UTI.”

Vaginal estrogen, meanwhile, reduces UTI risk because it “increases the presence of lactobacillus in the vagina due to improvements in vaginal pH, rebuilding superficial cells, elasticity, and connectivity,” she said.

The study assessed the incidence of GSM among patients at a single specialized Canadian institution, St. Joseph’s Healthcare Menopause Clinic in Hamilton, Ontario, between January 2021 and August 2024. Patients completed a Menopause Rating Scale that quantified two sets of GSM symptoms relating to “dryness of the vagina” and “bladder problems.” Patients also answered questions about the provider they had seen before coming to the specialized clinic and whether they had been prescribed local vaginal products before their visit.

Among 529 patients, the average age was 51, and the vast majority (88%) had some amount of tertiary education beyond high school. Only 21.5% were still menstruating, whereas the other respondents had stopped menstruating. The patient population was mostly White (85.6%), with Black, Hispanic, Asian, Middle Eastern, and Indigenous patients making up most of the other patient groups.

Among the 521 patients who answered the question on vaginal dryness, answers were similarly split between none (26%), mild (23%), moderate (21%), severe (15%), and very severe (15%). One third of the 526 women (34%) who answered the question on bladder problems said they had none, whereas the remainder reported their problems as mild (24%), moderate (24%), severe (11%), or very severe (7%).

Despite about half the participants reporting moderate to very severe vaginal dryness, 85% of them had not been prescribed local vaginal hormone therapies before their visit to the menopause clinic. Women were more likely to have been prescribed a localized therapy if they were older, were postmenopausal instead of perimenopausal, or had a female healthcare provider prior to this visit.

The survey also asked about the specialty and years in practice for the providers women had seen before visiting the clinic, but neither of these were predictors for receiving a hormone prescription. The patient’s education, partner status, and ethnicity were also not associated with the likelihood of a prescription.

Among 62 women who had been prescribed a vaginal hormone treatment, most were prescribed Vagifem (29%) or Premarin Vaginal cream (26%), followed by Intrarosa (19%), Estragyn cream (16%), Estring (3%), or something else (18%).
 

Serious Complications of GSM

Dr. Pinkerton described how GSM, particularly in older women, can run the risk of becoming life-threatening if untreated and unrecognized.

“For some women, UTIs can lead to urosepsis, as both the vaginal tissues and bladder tissues are thin with blood vessels close to the surface,” Dr. Pinkerton said. “What may have started as a UTI, can ascend to the kidneys or get into the bloodstream, which, in some, can develop into urosepsis, which can be life-threatening. The bacterial pathogen initiates the disease process, but host immune responses drive whether sepsis develops and its severity.”

The research by Dr. Hernández Galán was funded by the Canadian Institutes of Health Research, the Canadian Menopause Society, and Pfizer. Dr. Faubion had no disclosures, and Dr. Pinkerton has run a trial funded by Bayer and is a consultant for Bayer and Pfizer.

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

CHICAGO — The vast majority of women experiencing genitourinary syndrome of menopause (GSM) symptoms did not receive a prescription for hormonal vaginal therapies prior to seeking care at a specialized menopause clinic, according to research presented at the annual meeting of The Menopause Society.

“GSM symptoms are very common and affect women’s health and quality of life, often worsening without effective therapy,” Leticia Hernández Galán, PhD, of the Department of Obstetrics & Gynecology, McMaster University, Hamilton, Ontario, Canada, and colleagues reported. “We have demonstrated that most women seeking specialty care in an urban center with GSM symptoms have not been given a trial of local vaginal therapies by referring providers despite guidelines about safety and lack of contraindications. Given very long wait times for menopause providers in Canada, improved education for both women and their providers is needed to reduce needless suffering and improve care.”

Stephanie Faubion, MD, MBA, director of the Mayo Clinic Women’s Health in Jacksonville, Florida, and medical director of The Menopause Society, was not involved with the study but agreed with the authors’ assessment of the findings.

“This study highlights the treatment gap for women with genitourinary syndrome of menopause,” Dr. Faubion told this news organization. “Clearly, there is underutilization of low-dose vaginal hormonal therapies, which are known to be safe and effective. We still have work to do in terms of educating both women and providers on established treatment options for this common concern in menopausal women.” 

The findings match previous ones that found a majority of women with GSM do not receive treatment. A 2017 study, which was cited in the 2020 Menopause Society position statement on the condition, found that half of women with GSM had never used any treatment.

GSM is the current term that replaces previously used “vulvovaginal atrophy” and “atrophic vaginitis” because it encompasses all the menopause symptoms and signs associated with menopause that affect the vagina, vulva, and urinary tract. Anywhere from 50% to 84% of postmenopausal women experience GSM, the authors noted, with symptoms that include “burning, itching, or irritation of the vulva” and “lack of lubrication and discomfort or pain with sexual activity as well as dysuria, increased frequency or urgency of urination, and increased risk for urinary tract infections.”

First-line treatment of mild GSM often includes nonhormonal vaginal lubricants and moisturizers, but vaginal estrogen is considered the most effective treatment for more severe or bothersome cases. Other treatments include systematic hormone therapy and ospemifene or other selective estrogen receptor modulators.
 

Increased Risk for Urinary Tract Infections (UTIs)

Untreated GSM is not simply a quality of life issue; it increases the risk of developing serious UTIs, explained JoAnn Pinkerton, MD, a professor of obstetrics and gynecology at the University of Virginia, Charlottesville, who was not involved in the study.

“Estrogen depletion alters the vaginal epithelium, with distinct impairments in lubrication, elasticity, pH, and blood flow,” Dr. Pinkerton said. “The vaginal microbiome changes, with increasing pH following menopause and loss of lactobacillus predominance. These alterations allow a more hospitable environment for bacterial growth and increase the risk of UTI.”

Vaginal estrogen, meanwhile, reduces UTI risk because it “increases the presence of lactobacillus in the vagina due to improvements in vaginal pH, rebuilding superficial cells, elasticity, and connectivity,” she said.

The study assessed the incidence of GSM among patients at a single specialized Canadian institution, St. Joseph’s Healthcare Menopause Clinic in Hamilton, Ontario, between January 2021 and August 2024. Patients completed a Menopause Rating Scale that quantified two sets of GSM symptoms relating to “dryness of the vagina” and “bladder problems.” Patients also answered questions about the provider they had seen before coming to the specialized clinic and whether they had been prescribed local vaginal products before their visit.

Among 529 patients, the average age was 51, and the vast majority (88%) had some amount of tertiary education beyond high school. Only 21.5% were still menstruating, whereas the other respondents had stopped menstruating. The patient population was mostly White (85.6%), with Black, Hispanic, Asian, Middle Eastern, and Indigenous patients making up most of the other patient groups.

Among the 521 patients who answered the question on vaginal dryness, answers were similarly split between none (26%), mild (23%), moderate (21%), severe (15%), and very severe (15%). One third of the 526 women (34%) who answered the question on bladder problems said they had none, whereas the remainder reported their problems as mild (24%), moderate (24%), severe (11%), or very severe (7%).

Despite about half the participants reporting moderate to very severe vaginal dryness, 85% of them had not been prescribed local vaginal hormone therapies before their visit to the menopause clinic. Women were more likely to have been prescribed a localized therapy if they were older, were postmenopausal instead of perimenopausal, or had a female healthcare provider prior to this visit.

The survey also asked about the specialty and years in practice for the providers women had seen before visiting the clinic, but neither of these were predictors for receiving a hormone prescription. The patient’s education, partner status, and ethnicity were also not associated with the likelihood of a prescription.

Among 62 women who had been prescribed a vaginal hormone treatment, most were prescribed Vagifem (29%) or Premarin Vaginal cream (26%), followed by Intrarosa (19%), Estragyn cream (16%), Estring (3%), or something else (18%).
 

Serious Complications of GSM

Dr. Pinkerton described how GSM, particularly in older women, can run the risk of becoming life-threatening if untreated and unrecognized.

“For some women, UTIs can lead to urosepsis, as both the vaginal tissues and bladder tissues are thin with blood vessels close to the surface,” Dr. Pinkerton said. “What may have started as a UTI, can ascend to the kidneys or get into the bloodstream, which, in some, can develop into urosepsis, which can be life-threatening. The bacterial pathogen initiates the disease process, but host immune responses drive whether sepsis develops and its severity.”

The research by Dr. Hernández Galán was funded by the Canadian Institutes of Health Research, the Canadian Menopause Society, and Pfizer. Dr. Faubion had no disclosures, and Dr. Pinkerton has run a trial funded by Bayer and is a consultant for Bayer and Pfizer.

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

CHICAGO — The vast majority of women experiencing genitourinary syndrome of menopause (GSM) symptoms did not receive a prescription for hormonal vaginal therapies prior to seeking care at a specialized menopause clinic, according to research presented at the annual meeting of The Menopause Society.

“GSM symptoms are very common and affect women’s health and quality of life, often worsening without effective therapy,” Leticia Hernández Galán, PhD, of the Department of Obstetrics & Gynecology, McMaster University, Hamilton, Ontario, Canada, and colleagues reported. “We have demonstrated that most women seeking specialty care in an urban center with GSM symptoms have not been given a trial of local vaginal therapies by referring providers despite guidelines about safety and lack of contraindications. Given very long wait times for menopause providers in Canada, improved education for both women and their providers is needed to reduce needless suffering and improve care.”

Stephanie Faubion, MD, MBA, director of the Mayo Clinic Women’s Health in Jacksonville, Florida, and medical director of The Menopause Society, was not involved with the study but agreed with the authors’ assessment of the findings.

“This study highlights the treatment gap for women with genitourinary syndrome of menopause,” Dr. Faubion told this news organization. “Clearly, there is underutilization of low-dose vaginal hormonal therapies, which are known to be safe and effective. We still have work to do in terms of educating both women and providers on established treatment options for this common concern in menopausal women.” 

The findings match previous ones that found a majority of women with GSM do not receive treatment. A 2017 study, which was cited in the 2020 Menopause Society position statement on the condition, found that half of women with GSM had never used any treatment.

GSM is the current term that replaces previously used “vulvovaginal atrophy” and “atrophic vaginitis” because it encompasses all the menopause symptoms and signs associated with menopause that affect the vagina, vulva, and urinary tract. Anywhere from 50% to 84% of postmenopausal women experience GSM, the authors noted, with symptoms that include “burning, itching, or irritation of the vulva” and “lack of lubrication and discomfort or pain with sexual activity as well as dysuria, increased frequency or urgency of urination, and increased risk for urinary tract infections.”

First-line treatment of mild GSM often includes nonhormonal vaginal lubricants and moisturizers, but vaginal estrogen is considered the most effective treatment for more severe or bothersome cases. Other treatments include systematic hormone therapy and ospemifene or other selective estrogen receptor modulators.
 

Increased Risk for Urinary Tract Infections (UTIs)

Untreated GSM is not simply a quality of life issue; it increases the risk of developing serious UTIs, explained JoAnn Pinkerton, MD, a professor of obstetrics and gynecology at the University of Virginia, Charlottesville, who was not involved in the study.

“Estrogen depletion alters the vaginal epithelium, with distinct impairments in lubrication, elasticity, pH, and blood flow,” Dr. Pinkerton said. “The vaginal microbiome changes, with increasing pH following menopause and loss of lactobacillus predominance. These alterations allow a more hospitable environment for bacterial growth and increase the risk of UTI.”

Vaginal estrogen, meanwhile, reduces UTI risk because it “increases the presence of lactobacillus in the vagina due to improvements in vaginal pH, rebuilding superficial cells, elasticity, and connectivity,” she said.

The study assessed the incidence of GSM among patients at a single specialized Canadian institution, St. Joseph’s Healthcare Menopause Clinic in Hamilton, Ontario, between January 2021 and August 2024. Patients completed a Menopause Rating Scale that quantified two sets of GSM symptoms relating to “dryness of the vagina” and “bladder problems.” Patients also answered questions about the provider they had seen before coming to the specialized clinic and whether they had been prescribed local vaginal products before their visit.

Among 529 patients, the average age was 51, and the vast majority (88%) had some amount of tertiary education beyond high school. Only 21.5% were still menstruating, whereas the other respondents had stopped menstruating. The patient population was mostly White (85.6%), with Black, Hispanic, Asian, Middle Eastern, and Indigenous patients making up most of the other patient groups.

Among the 521 patients who answered the question on vaginal dryness, answers were similarly split between none (26%), mild (23%), moderate (21%), severe (15%), and very severe (15%). One third of the 526 women (34%) who answered the question on bladder problems said they had none, whereas the remainder reported their problems as mild (24%), moderate (24%), severe (11%), or very severe (7%).

Despite about half the participants reporting moderate to very severe vaginal dryness, 85% of them had not been prescribed local vaginal hormone therapies before their visit to the menopause clinic. Women were more likely to have been prescribed a localized therapy if they were older, were postmenopausal instead of perimenopausal, or had a female healthcare provider prior to this visit.

The survey also asked about the specialty and years in practice for the providers women had seen before visiting the clinic, but neither of these were predictors for receiving a hormone prescription. The patient’s education, partner status, and ethnicity were also not associated with the likelihood of a prescription.

Among 62 women who had been prescribed a vaginal hormone treatment, most were prescribed Vagifem (29%) or Premarin Vaginal cream (26%), followed by Intrarosa (19%), Estragyn cream (16%), Estring (3%), or something else (18%).
 

Serious Complications of GSM

Dr. Pinkerton described how GSM, particularly in older women, can run the risk of becoming life-threatening if untreated and unrecognized.

“For some women, UTIs can lead to urosepsis, as both the vaginal tissues and bladder tissues are thin with blood vessels close to the surface,” Dr. Pinkerton said. “What may have started as a UTI, can ascend to the kidneys or get into the bloodstream, which, in some, can develop into urosepsis, which can be life-threatening. The bacterial pathogen initiates the disease process, but host immune responses drive whether sepsis develops and its severity.”

The research by Dr. Hernández Galán was funded by the Canadian Institutes of Health Research, the Canadian Menopause Society, and Pfizer. Dr. Faubion had no disclosures, and Dr. Pinkerton has run a trial funded by Bayer and is a consultant for Bayer and Pfizer.

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

CHICAGO — Less than 4% of American women aged 50-59 years use hormone therapy (HT) to treat menopausal symptoms today, approximately 10 times lower than the peak use of HT before the publication of the 2002 Women’s Health Initiative (WHI) study that misguidedly cast doubt on the safety of HT. Though subsequent research has addressed the flaws of the WHI study and supports the use of HT in most menopausal women younger than 60 years, use of this therapy has never recovered, according to research presented at the annual meeting of The Menopause Society (formerly The North American Menopause Society).

“Despite evidence supporting the efficacy and safety of HT, usage rates of US Food and Drug Administration–approved HT remain low,” Stephanie Faubion, MD, MBA, director of the Mayo Clinic Women’s Health in Jacksonville, Florida, and medical director of The Menopause Society, told attendees. “Improved education of clinicians and patients is critically needed.”

Today, “there is more clarity on the risk/benefit ratio of HT use with the benefits typically outweighing the risks in women who initiate therapy under the age of 60 years and within 10 years of menopause onset.”

Using medical and pharmacy claims data from OptumLabs, Dr. Faubion and her colleagues examined utilization rates from 2007 to 2023 of transdermal vs oral estrogen and of conjugated estrogen vs estradiol in women aged 40 years or older. The data included more than 200 million people throughout the United States covered by commercial insurance or Medicare Advantage. The researchers defined annual rate of HT use as the proportion of women who had at least 180 days of a filled prescription for a systemic HT preparation with estrogen.

The study population increased from an estimated 2 million women in 2007 to 4.5 million women in 2023, and the average age of enrollees increased from 53 in 2007 to 66 in 2023. Starting at 4.6% in 2007, HT use steadily declined to a low of 1.8% in 2023 for the whole cohort of women aged 40 years or older.

Though rates remained highest in women aged 50-64 years, it still declined within each age group: From 6% in 2007 to 3.6% in 2023 among women aged 50-54 years, from 7.3% to 3.8% among women aged 55-59 years, and from 7.5% to 2.9% among women aged 60-64 years. It also declined in younger women, from 3.2% in 2007 to 1.5% in 2023 in those aged 45-50 years. Estradiol was the most common formulation used, and oral administration was the most common route.

The researchers also saw a gradual decline during the study period in the use of high-dose oral HT and an increase in the use of low-dose oral HT, whereas standard dosages remained fairly consistent as the most common dose prescribed. Similarly, the use of high transdermal doses declined, whereas low transdermal doses increased and surpassed the use of standard doses. Conjugated estrogen use plummeted during the study period across all age groups, from 2%-5% in most age groups to < 1% in all age groups by 2023.

One limitation of the study was that it could not examine rates of compounded HT use because those would not be reflected in insurance claims, pointed out JoAnn Pinkerton, MD, a professor of ob.gyn. at the University of Virginia in Charlottesville, Virginia, who was not involved in the study. Dr. Pinkerton found it surprising that the numbers were so low, despite the fact that research estimates suggest less than 15% of menopausal women are receiving adequate treatment, she told this news organization. “You can see there’s a large unmet need to get treatment,” she said. “All major medical societies say the same thing: For healthy, symptomatic menopausal women, you can use hormone therapy safely and effectively.” 

The lack of education among providers is likely the biggest reason for the decline, Dr. Pinkerton says. “I think it’s because there’s a whole group of providers that did not receive any training, and that’s OB/GYNs, internal medicine, family practice, endocrinologists,” she said. “Now that people are starting to feel more confident that we can use it safely, we’re trying to get that training out to people about vasomotor symptoms, about hormone therapy, and now about new nonhormone therapies.”

Dr. Pinkerton noted that The Menopause Society has begun a new teaching program, Menopause Step-by-Step, aimed at providing short articles on the basics of menopause, HT, non-HT, and vaginal issues.

A separate poster presented at the conference provides insight into another potential factor contributing to low HT rates. A survey of 1050 American and Canadian women found that 90% discussed their symptoms with their healthcare providers, yet only 25% said their doctor identified the symptoms as likely due to perimenopause or menopause on their first visit — and only 10% of respondents said their doctor was the one to bring up perimenopause/menopause.

The respondents comprised a convenience sample of those who saw the survey on social media, in an email, or on the website of Morphus, a Toronto-based company aimed at providing support, information, and products related to menopause. Though the survey is ongoing, the analyzed responses are from March to May 2024.

Though 40% of the women said their provider attributed their symptoms to perimenopause or menopause on the second or third visit, 18% saw a provider four to five times, and 17% saw a provider more than five times before the provider considered menopause as a cause. About a third of the women (35%) brought it up to their doctor themselves and found their provider receptive, but 40% said the response was dismissive when they brought it up, and 15% said the topic was never broached at all.

Andrea Donsky, RHN, founder of Morphus who conducted the study, found these numbers surprising because she would have hoped that more doctors would have brought up perimenopause/menopause sooner. “We still have a lot of work to do to help educate women and healthcare providers,” Ms. Donsky told this news organization. “A lot of women spend years not knowing they’re in this phase of life, so they visit their doctors/HCPs [healthcare providers] many times because the connection isn’t made on the first visit.”

Danielle Meitiv, MS, a study co-author and health coach based in Silver Spring, Maryland, added, “Everyone wonders why we end up with Dr. Google; that’s the only doctor who’s talking to us about menopause.”

Dr. Pinkerton was less surprised by these survey findings. “As a menopause specialist, my most common new patient is a perimenopausal woman who feels like she hasn’t been listened to,” whether it’s her primary care doctor, her ob.gyn., or another clinician. “If the provider doesn’t ask or if the women doesn’t tell, then you don’t have the conversation,” Dr. Pinkerton said. “So many women in perimenopause are busy with work, families, partnerships, aging parents — all of the issues that they’re dealing with — that when they start to have sleep issues or mood issues or easy crying, they relate it to their life stressors, instead of recognizing that it’s fluctuating hormones.”

When Ms. Donsky examined the 1223 responses they had received through August 2024, the most common treatments advised for symptoms were antidepressants and HT, both recommended by 38% of providers. Other common recommendations were to “lose weight,” “eat less and exercise more,” supplements, or birth control pills.

Dr. Faubion had no disclosures, and her study used no external funding. Dr. Pinkerton has run a trial funded by Bayer and is a consultant for Bayer and Pfizer. Ms. Donsky is the owner of Morphus. Ms. Meitiv had no disclosures. The poster on women’s experiences with providers was funded by Morphus Inc.

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

CHICAGO — Less than 4% of American women aged 50-59 years use hormone therapy (HT) to treat menopausal symptoms today, approximately 10 times lower than the peak use of HT before the publication of the 2002 Women’s Health Initiative (WHI) study that misguidedly cast doubt on the safety of HT. Though subsequent research has addressed the flaws of the WHI study and supports the use of HT in most menopausal women younger than 60 years, use of this therapy has never recovered, according to research presented at the annual meeting of The Menopause Society (formerly The North American Menopause Society).

“Despite evidence supporting the efficacy and safety of HT, usage rates of US Food and Drug Administration–approved HT remain low,” Stephanie Faubion, MD, MBA, director of the Mayo Clinic Women’s Health in Jacksonville, Florida, and medical director of The Menopause Society, told attendees. “Improved education of clinicians and patients is critically needed.”

Today, “there is more clarity on the risk/benefit ratio of HT use with the benefits typically outweighing the risks in women who initiate therapy under the age of 60 years and within 10 years of menopause onset.”

Using medical and pharmacy claims data from OptumLabs, Dr. Faubion and her colleagues examined utilization rates from 2007 to 2023 of transdermal vs oral estrogen and of conjugated estrogen vs estradiol in women aged 40 years or older. The data included more than 200 million people throughout the United States covered by commercial insurance or Medicare Advantage. The researchers defined annual rate of HT use as the proportion of women who had at least 180 days of a filled prescription for a systemic HT preparation with estrogen.

The study population increased from an estimated 2 million women in 2007 to 4.5 million women in 2023, and the average age of enrollees increased from 53 in 2007 to 66 in 2023. Starting at 4.6% in 2007, HT use steadily declined to a low of 1.8% in 2023 for the whole cohort of women aged 40 years or older.

Though rates remained highest in women aged 50-64 years, it still declined within each age group: From 6% in 2007 to 3.6% in 2023 among women aged 50-54 years, from 7.3% to 3.8% among women aged 55-59 years, and from 7.5% to 2.9% among women aged 60-64 years. It also declined in younger women, from 3.2% in 2007 to 1.5% in 2023 in those aged 45-50 years. Estradiol was the most common formulation used, and oral administration was the most common route.

The researchers also saw a gradual decline during the study period in the use of high-dose oral HT and an increase in the use of low-dose oral HT, whereas standard dosages remained fairly consistent as the most common dose prescribed. Similarly, the use of high transdermal doses declined, whereas low transdermal doses increased and surpassed the use of standard doses. Conjugated estrogen use plummeted during the study period across all age groups, from 2%-5% in most age groups to < 1% in all age groups by 2023.

One limitation of the study was that it could not examine rates of compounded HT use because those would not be reflected in insurance claims, pointed out JoAnn Pinkerton, MD, a professor of ob.gyn. at the University of Virginia in Charlottesville, Virginia, who was not involved in the study. Dr. Pinkerton found it surprising that the numbers were so low, despite the fact that research estimates suggest less than 15% of menopausal women are receiving adequate treatment, she told this news organization. “You can see there’s a large unmet need to get treatment,” she said. “All major medical societies say the same thing: For healthy, symptomatic menopausal women, you can use hormone therapy safely and effectively.” 

The lack of education among providers is likely the biggest reason for the decline, Dr. Pinkerton says. “I think it’s because there’s a whole group of providers that did not receive any training, and that’s OB/GYNs, internal medicine, family practice, endocrinologists,” she said. “Now that people are starting to feel more confident that we can use it safely, we’re trying to get that training out to people about vasomotor symptoms, about hormone therapy, and now about new nonhormone therapies.”

Dr. Pinkerton noted that The Menopause Society has begun a new teaching program, Menopause Step-by-Step, aimed at providing short articles on the basics of menopause, HT, non-HT, and vaginal issues.

A separate poster presented at the conference provides insight into another potential factor contributing to low HT rates. A survey of 1050 American and Canadian women found that 90% discussed their symptoms with their healthcare providers, yet only 25% said their doctor identified the symptoms as likely due to perimenopause or menopause on their first visit — and only 10% of respondents said their doctor was the one to bring up perimenopause/menopause.

The respondents comprised a convenience sample of those who saw the survey on social media, in an email, or on the website of Morphus, a Toronto-based company aimed at providing support, information, and products related to menopause. Though the survey is ongoing, the analyzed responses are from March to May 2024.

Though 40% of the women said their provider attributed their symptoms to perimenopause or menopause on the second or third visit, 18% saw a provider four to five times, and 17% saw a provider more than five times before the provider considered menopause as a cause. About a third of the women (35%) brought it up to their doctor themselves and found their provider receptive, but 40% said the response was dismissive when they brought it up, and 15% said the topic was never broached at all.

Andrea Donsky, RHN, founder of Morphus who conducted the study, found these numbers surprising because she would have hoped that more doctors would have brought up perimenopause/menopause sooner. “We still have a lot of work to do to help educate women and healthcare providers,” Ms. Donsky told this news organization. “A lot of women spend years not knowing they’re in this phase of life, so they visit their doctors/HCPs [healthcare providers] many times because the connection isn’t made on the first visit.”

Danielle Meitiv, MS, a study co-author and health coach based in Silver Spring, Maryland, added, “Everyone wonders why we end up with Dr. Google; that’s the only doctor who’s talking to us about menopause.”

Dr. Pinkerton was less surprised by these survey findings. “As a menopause specialist, my most common new patient is a perimenopausal woman who feels like she hasn’t been listened to,” whether it’s her primary care doctor, her ob.gyn., or another clinician. “If the provider doesn’t ask or if the women doesn’t tell, then you don’t have the conversation,” Dr. Pinkerton said. “So many women in perimenopause are busy with work, families, partnerships, aging parents — all of the issues that they’re dealing with — that when they start to have sleep issues or mood issues or easy crying, they relate it to their life stressors, instead of recognizing that it’s fluctuating hormones.”

When Ms. Donsky examined the 1223 responses they had received through August 2024, the most common treatments advised for symptoms were antidepressants and HT, both recommended by 38% of providers. Other common recommendations were to “lose weight,” “eat less and exercise more,” supplements, or birth control pills.

Dr. Faubion had no disclosures, and her study used no external funding. Dr. Pinkerton has run a trial funded by Bayer and is a consultant for Bayer and Pfizer. Ms. Donsky is the owner of Morphus. Ms. Meitiv had no disclosures. The poster on women’s experiences with providers was funded by Morphus Inc.

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

CHICAGO — Less than 4% of American women aged 50-59 years use hormone therapy (HT) to treat menopausal symptoms today, approximately 10 times lower than the peak use of HT before the publication of the 2002 Women’s Health Initiative (WHI) study that misguidedly cast doubt on the safety of HT. Though subsequent research has addressed the flaws of the WHI study and supports the use of HT in most menopausal women younger than 60 years, use of this therapy has never recovered, according to research presented at the annual meeting of The Menopause Society (formerly The North American Menopause Society).

“Despite evidence supporting the efficacy and safety of HT, usage rates of US Food and Drug Administration–approved HT remain low,” Stephanie Faubion, MD, MBA, director of the Mayo Clinic Women’s Health in Jacksonville, Florida, and medical director of The Menopause Society, told attendees. “Improved education of clinicians and patients is critically needed.”

Today, “there is more clarity on the risk/benefit ratio of HT use with the benefits typically outweighing the risks in women who initiate therapy under the age of 60 years and within 10 years of menopause onset.”

Using medical and pharmacy claims data from OptumLabs, Dr. Faubion and her colleagues examined utilization rates from 2007 to 2023 of transdermal vs oral estrogen and of conjugated estrogen vs estradiol in women aged 40 years or older. The data included more than 200 million people throughout the United States covered by commercial insurance or Medicare Advantage. The researchers defined annual rate of HT use as the proportion of women who had at least 180 days of a filled prescription for a systemic HT preparation with estrogen.

The study population increased from an estimated 2 million women in 2007 to 4.5 million women in 2023, and the average age of enrollees increased from 53 in 2007 to 66 in 2023. Starting at 4.6% in 2007, HT use steadily declined to a low of 1.8% in 2023 for the whole cohort of women aged 40 years or older.

Though rates remained highest in women aged 50-64 years, it still declined within each age group: From 6% in 2007 to 3.6% in 2023 among women aged 50-54 years, from 7.3% to 3.8% among women aged 55-59 years, and from 7.5% to 2.9% among women aged 60-64 years. It also declined in younger women, from 3.2% in 2007 to 1.5% in 2023 in those aged 45-50 years. Estradiol was the most common formulation used, and oral administration was the most common route.

The researchers also saw a gradual decline during the study period in the use of high-dose oral HT and an increase in the use of low-dose oral HT, whereas standard dosages remained fairly consistent as the most common dose prescribed. Similarly, the use of high transdermal doses declined, whereas low transdermal doses increased and surpassed the use of standard doses. Conjugated estrogen use plummeted during the study period across all age groups, from 2%-5% in most age groups to < 1% in all age groups by 2023.

One limitation of the study was that it could not examine rates of compounded HT use because those would not be reflected in insurance claims, pointed out JoAnn Pinkerton, MD, a professor of ob.gyn. at the University of Virginia in Charlottesville, Virginia, who was not involved in the study. Dr. Pinkerton found it surprising that the numbers were so low, despite the fact that research estimates suggest less than 15% of menopausal women are receiving adequate treatment, she told this news organization. “You can see there’s a large unmet need to get treatment,” she said. “All major medical societies say the same thing: For healthy, symptomatic menopausal women, you can use hormone therapy safely and effectively.” 

The lack of education among providers is likely the biggest reason for the decline, Dr. Pinkerton says. “I think it’s because there’s a whole group of providers that did not receive any training, and that’s OB/GYNs, internal medicine, family practice, endocrinologists,” she said. “Now that people are starting to feel more confident that we can use it safely, we’re trying to get that training out to people about vasomotor symptoms, about hormone therapy, and now about new nonhormone therapies.”

Dr. Pinkerton noted that The Menopause Society has begun a new teaching program, Menopause Step-by-Step, aimed at providing short articles on the basics of menopause, HT, non-HT, and vaginal issues.

A separate poster presented at the conference provides insight into another potential factor contributing to low HT rates. A survey of 1050 American and Canadian women found that 90% discussed their symptoms with their healthcare providers, yet only 25% said their doctor identified the symptoms as likely due to perimenopause or menopause on their first visit — and only 10% of respondents said their doctor was the one to bring up perimenopause/menopause.

The respondents comprised a convenience sample of those who saw the survey on social media, in an email, or on the website of Morphus, a Toronto-based company aimed at providing support, information, and products related to menopause. Though the survey is ongoing, the analyzed responses are from March to May 2024.

Though 40% of the women said their provider attributed their symptoms to perimenopause or menopause on the second or third visit, 18% saw a provider four to five times, and 17% saw a provider more than five times before the provider considered menopause as a cause. About a third of the women (35%) brought it up to their doctor themselves and found their provider receptive, but 40% said the response was dismissive when they brought it up, and 15% said the topic was never broached at all.

Andrea Donsky, RHN, founder of Morphus who conducted the study, found these numbers surprising because she would have hoped that more doctors would have brought up perimenopause/menopause sooner. “We still have a lot of work to do to help educate women and healthcare providers,” Ms. Donsky told this news organization. “A lot of women spend years not knowing they’re in this phase of life, so they visit their doctors/HCPs [healthcare providers] many times because the connection isn’t made on the first visit.”

Danielle Meitiv, MS, a study co-author and health coach based in Silver Spring, Maryland, added, “Everyone wonders why we end up with Dr. Google; that’s the only doctor who’s talking to us about menopause.”

Dr. Pinkerton was less surprised by these survey findings. “As a menopause specialist, my most common new patient is a perimenopausal woman who feels like she hasn’t been listened to,” whether it’s her primary care doctor, her ob.gyn., or another clinician. “If the provider doesn’t ask or if the women doesn’t tell, then you don’t have the conversation,” Dr. Pinkerton said. “So many women in perimenopause are busy with work, families, partnerships, aging parents — all of the issues that they’re dealing with — that when they start to have sleep issues or mood issues or easy crying, they relate it to their life stressors, instead of recognizing that it’s fluctuating hormones.”

When Ms. Donsky examined the 1223 responses they had received through August 2024, the most common treatments advised for symptoms were antidepressants and HT, both recommended by 38% of providers. Other common recommendations were to “lose weight,” “eat less and exercise more,” supplements, or birth control pills.

Dr. Faubion had no disclosures, and her study used no external funding. Dr. Pinkerton has run a trial funded by Bayer and is a consultant for Bayer and Pfizer. Ms. Donsky is the owner of Morphus. Ms. Meitiv had no disclosures. The poster on women’s experiences with providers was funded by Morphus Inc.

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

CHICAGO — Use of CO₂ lasers and similar “energy-based” treatments result in little to no benefit for genitourinary syndrome of menopause (GSM) symptoms, according to research presented at the The Menopause Society 2024 Annual Meeting in Chicago on September 12.

“There was a concern that menopausal women are being targeted for treatments that may not have a lot of benefit and might have significant harms,” Elisheva Danan, MD, MPH, a physician at the Minneapolis VA Health Care System and an assistant professor of medicine at the University of Minnesota Medical School in Minneapolis, told this news organization. While she was not surprised to find little evidence of benefit, “we were a little bit surprised that we also didn’t find significant evidence of harms.”

The study was unable to evaluate the potential for financial harms, but Dr. Danan noted that these therapies are often expensive and not typically covered by insurance. The treatments appear to be used primarily in private practice, she said, while “most academic clinicians were not familiar with these and do not use these lasers.”

The American Urological Association had requested the review, Dr. Danan said, “to inform clinical guidelines that they could put out for practitioners about treating genital urinary syndrome from menopause.” Yet the evidence available remains slim. “There’s a lot of outcomes that were not looked at by most of these [trials], or they were looked at in a way that we couldn’t separate out,” she said.

Kamalini Das, MD, a professor of ob.gyn. at the University of Minnesota who was not involved in the research, was surprised by the findings because studies to date have been variable, “but since this looks at multiple studies and they find no benefits, I would take these results as more significant than any of the small studies,” she told this news organization.

Dr. Das said she has patients who ask about using these therapies and have had them done. “So far, I’ve told them the jury is out on whether it will help or not, that there are some studies that say they’re beneficial and some studies that they’re not,” Dr. Das said.

But this new review changes what she will tell patients going forward, she said. “This is a good study because it consolidates lots of little studies, so I think I would use this to say, looking at all the studies together, this treatment is not beneficial.”

GSM occurs due to the body’s reduced production of estrogen and affects anywhere from 27% to 84% of postmenopausal women. It can involve a constellation of symptoms ranging from vaginal discomfort and irritation to painful urination or intercourse. Typical recommended treatments for GSM include systemic hormone therapy, localized hormonal treatments such as vaginal estrogen or dehydroepiandrosterone, nonhormonal creams and moisturizers, and the prescription drug ospemifene.

Most of these have been found effective, according to a recent systematic review  Dr. Danan published in the Annals of Internal Medicine that this news organization covered. But recent years have also seen a rapid increase in interest and the availability of energy-based treatments for GSM, such as CO₂ laser and radiofrequency interventions, particularly for those who cannot or do not want to use hormonal treatments. The idea behind these newer therapies is that they “heat tissue to cause a denaturation of collagen fibers and induce a wound-healing response,” with the aim of “enhancement of vaginal elasticity, restoration of premenopausal epithelial function, and symptom improvement,” the authors wrote.

Evidence has been scant and uneven for the safety and effectiveness of these treatments, and they have not been evaluated by the US Food and Drug Administration. The agency issued a warning in 2018 with remarks from then Commissioner Scott Gottlieb that the “products have serious risks and don’t have adequate evidence to support their use for these purposes.”

Much of the evidence has focused on CO₂ lasers instead of other energy-based treatments, however, and a raft of new studies have been published on these interventions in the past 2 years. Dr. Danan and colleagues, therefore, assessed the most current state of the research with a systematic review of randomized controlled trials (RCTs) and prospective observational studies with control groups published through December 11, 2023.

Included studies needed to evaluate an energy-based treatment for at least 8 weeks in a minimum of 40 postmenopausal women (20 in each group) who had one or more GSM symptoms. The authors also included nonrandomized and uncontrolled studies with a follow-up of a year or more to assess possible adverse events. The studies also needed to assess at least one of eight core outcomes: Dyspareunia; vulvovaginal dryness; vulvovaginal discomfort/irritation; dysuria; change in most bothersome symptom; treatment satisfaction; adverse events; and distress, bother, or interference associated with genitourinary symptoms.

The authors identified 32 studies, including 16 RCTs, one quasi-RCT, and 15 nonrandomized studies. The researchers extracted and analyzed data from the 10 RCTs and one quasi-RCT that were rated as having low to moderate risk for bias.

Most of these studies assessed CO₂ lasers alone, while three assessed erbium:yttrium-aluminum-garnet (Er:YAG) laser, and one looked at CO₂ lasers vs radiofrequency treatments.

The average age of participants ranged from 56 to 64 years, and most trials were in the United States. Results showed that CO₂ lasers led to little or no difference in dysuria, dyspareunia, or quality of life when compared with sham lasers. The CO₂ laser therapy also showed little to no difference compared with vaginal estrogen creams for dyspareunia, dryness, discomfort/irritation, dysuria, or quality of life.

Most CO₂ laser studies reported on most outcomes, but the Er:YAG studies tended to report only on quality of life and/or one or two other outcomes. The radiofrequency study only assessed dyspareunia and quality of life.

“Treatment effects on other outcomes and effects of Er:YAG laser or radiofrequency on any outcomes are very uncertain,” the authors reported. Few adverse events and no serious adverse events were reported based on 15 studies, including the additional non-RCTs that had follow-up for at least a year.

“There are case reports and other types of studies that have shown some bad outcomes using laser therapies, and we really wanted to be expansive and include anything, especially because this is such a new treatment and all these trials were in the last couple of years,” Dr. Danan said. 

The review was limited by inconsistent or nonvalidated outcome reporting in the studies as well as small populations and short follow-up, typically less than 3 months.

The research was funded by the Agency for Healthcare Research and Quality and Patient-Centered Outcomes Research Institute. Dr. Danan and Dr. Das had no disclosures.
 

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

CHICAGO — Use of CO₂ lasers and similar “energy-based” treatments result in little to no benefit for genitourinary syndrome of menopause (GSM) symptoms, according to research presented at the The Menopause Society 2024 Annual Meeting in Chicago on September 12.

“There was a concern that menopausal women are being targeted for treatments that may not have a lot of benefit and might have significant harms,” Elisheva Danan, MD, MPH, a physician at the Minneapolis VA Health Care System and an assistant professor of medicine at the University of Minnesota Medical School in Minneapolis, told this news organization. While she was not surprised to find little evidence of benefit, “we were a little bit surprised that we also didn’t find significant evidence of harms.”

The study was unable to evaluate the potential for financial harms, but Dr. Danan noted that these therapies are often expensive and not typically covered by insurance. The treatments appear to be used primarily in private practice, she said, while “most academic clinicians were not familiar with these and do not use these lasers.”

The American Urological Association had requested the review, Dr. Danan said, “to inform clinical guidelines that they could put out for practitioners about treating genital urinary syndrome from menopause.” Yet the evidence available remains slim. “There’s a lot of outcomes that were not looked at by most of these [trials], or they were looked at in a way that we couldn’t separate out,” she said.

Kamalini Das, MD, a professor of ob.gyn. at the University of Minnesota who was not involved in the research, was surprised by the findings because studies to date have been variable, “but since this looks at multiple studies and they find no benefits, I would take these results as more significant than any of the small studies,” she told this news organization.

Dr. Das said she has patients who ask about using these therapies and have had them done. “So far, I’ve told them the jury is out on whether it will help or not, that there are some studies that say they’re beneficial and some studies that they’re not,” Dr. Das said.

But this new review changes what she will tell patients going forward, she said. “This is a good study because it consolidates lots of little studies, so I think I would use this to say, looking at all the studies together, this treatment is not beneficial.”

GSM occurs due to the body’s reduced production of estrogen and affects anywhere from 27% to 84% of postmenopausal women. It can involve a constellation of symptoms ranging from vaginal discomfort and irritation to painful urination or intercourse. Typical recommended treatments for GSM include systemic hormone therapy, localized hormonal treatments such as vaginal estrogen or dehydroepiandrosterone, nonhormonal creams and moisturizers, and the prescription drug ospemifene.

Most of these have been found effective, according to a recent systematic review  Dr. Danan published in the Annals of Internal Medicine that this news organization covered. But recent years have also seen a rapid increase in interest and the availability of energy-based treatments for GSM, such as CO₂ laser and radiofrequency interventions, particularly for those who cannot or do not want to use hormonal treatments. The idea behind these newer therapies is that they “heat tissue to cause a denaturation of collagen fibers and induce a wound-healing response,” with the aim of “enhancement of vaginal elasticity, restoration of premenopausal epithelial function, and symptom improvement,” the authors wrote.

Evidence has been scant and uneven for the safety and effectiveness of these treatments, and they have not been evaluated by the US Food and Drug Administration. The agency issued a warning in 2018 with remarks from then Commissioner Scott Gottlieb that the “products have serious risks and don’t have adequate evidence to support their use for these purposes.”

Much of the evidence has focused on CO₂ lasers instead of other energy-based treatments, however, and a raft of new studies have been published on these interventions in the past 2 years. Dr. Danan and colleagues, therefore, assessed the most current state of the research with a systematic review of randomized controlled trials (RCTs) and prospective observational studies with control groups published through December 11, 2023.

Included studies needed to evaluate an energy-based treatment for at least 8 weeks in a minimum of 40 postmenopausal women (20 in each group) who had one or more GSM symptoms. The authors also included nonrandomized and uncontrolled studies with a follow-up of a year or more to assess possible adverse events. The studies also needed to assess at least one of eight core outcomes: Dyspareunia; vulvovaginal dryness; vulvovaginal discomfort/irritation; dysuria; change in most bothersome symptom; treatment satisfaction; adverse events; and distress, bother, or interference associated with genitourinary symptoms.

The authors identified 32 studies, including 16 RCTs, one quasi-RCT, and 15 nonrandomized studies. The researchers extracted and analyzed data from the 10 RCTs and one quasi-RCT that were rated as having low to moderate risk for bias.

Most of these studies assessed CO₂ lasers alone, while three assessed erbium:yttrium-aluminum-garnet (Er:YAG) laser, and one looked at CO₂ lasers vs radiofrequency treatments.

The average age of participants ranged from 56 to 64 years, and most trials were in the United States. Results showed that CO₂ lasers led to little or no difference in dysuria, dyspareunia, or quality of life when compared with sham lasers. The CO₂ laser therapy also showed little to no difference compared with vaginal estrogen creams for dyspareunia, dryness, discomfort/irritation, dysuria, or quality of life.

Most CO₂ laser studies reported on most outcomes, but the Er:YAG studies tended to report only on quality of life and/or one or two other outcomes. The radiofrequency study only assessed dyspareunia and quality of life.

“Treatment effects on other outcomes and effects of Er:YAG laser or radiofrequency on any outcomes are very uncertain,” the authors reported. Few adverse events and no serious adverse events were reported based on 15 studies, including the additional non-RCTs that had follow-up for at least a year.

“There are case reports and other types of studies that have shown some bad outcomes using laser therapies, and we really wanted to be expansive and include anything, especially because this is such a new treatment and all these trials were in the last couple of years,” Dr. Danan said. 

The review was limited by inconsistent or nonvalidated outcome reporting in the studies as well as small populations and short follow-up, typically less than 3 months.

The research was funded by the Agency for Healthcare Research and Quality and Patient-Centered Outcomes Research Institute. Dr. Danan and Dr. Das had no disclosures.
 

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

CHICAGO — Use of CO₂ lasers and similar “energy-based” treatments result in little to no benefit for genitourinary syndrome of menopause (GSM) symptoms, according to research presented at the The Menopause Society 2024 Annual Meeting in Chicago on September 12.

“There was a concern that menopausal women are being targeted for treatments that may not have a lot of benefit and might have significant harms,” Elisheva Danan, MD, MPH, a physician at the Minneapolis VA Health Care System and an assistant professor of medicine at the University of Minnesota Medical School in Minneapolis, told this news organization. While she was not surprised to find little evidence of benefit, “we were a little bit surprised that we also didn’t find significant evidence of harms.”

The study was unable to evaluate the potential for financial harms, but Dr. Danan noted that these therapies are often expensive and not typically covered by insurance. The treatments appear to be used primarily in private practice, she said, while “most academic clinicians were not familiar with these and do not use these lasers.”

The American Urological Association had requested the review, Dr. Danan said, “to inform clinical guidelines that they could put out for practitioners about treating genital urinary syndrome from menopause.” Yet the evidence available remains slim. “There’s a lot of outcomes that were not looked at by most of these [trials], or they were looked at in a way that we couldn’t separate out,” she said.

Kamalini Das, MD, a professor of ob.gyn. at the University of Minnesota who was not involved in the research, was surprised by the findings because studies to date have been variable, “but since this looks at multiple studies and they find no benefits, I would take these results as more significant than any of the small studies,” she told this news organization.

Dr. Das said she has patients who ask about using these therapies and have had them done. “So far, I’ve told them the jury is out on whether it will help or not, that there are some studies that say they’re beneficial and some studies that they’re not,” Dr. Das said.

But this new review changes what she will tell patients going forward, she said. “This is a good study because it consolidates lots of little studies, so I think I would use this to say, looking at all the studies together, this treatment is not beneficial.”

GSM occurs due to the body’s reduced production of estrogen and affects anywhere from 27% to 84% of postmenopausal women. It can involve a constellation of symptoms ranging from vaginal discomfort and irritation to painful urination or intercourse. Typical recommended treatments for GSM include systemic hormone therapy, localized hormonal treatments such as vaginal estrogen or dehydroepiandrosterone, nonhormonal creams and moisturizers, and the prescription drug ospemifene.

Most of these have been found effective, according to a recent systematic review  Dr. Danan published in the Annals of Internal Medicine that this news organization covered. But recent years have also seen a rapid increase in interest and the availability of energy-based treatments for GSM, such as CO₂ laser and radiofrequency interventions, particularly for those who cannot or do not want to use hormonal treatments. The idea behind these newer therapies is that they “heat tissue to cause a denaturation of collagen fibers and induce a wound-healing response,” with the aim of “enhancement of vaginal elasticity, restoration of premenopausal epithelial function, and symptom improvement,” the authors wrote.

Evidence has been scant and uneven for the safety and effectiveness of these treatments, and they have not been evaluated by the US Food and Drug Administration. The agency issued a warning in 2018 with remarks from then Commissioner Scott Gottlieb that the “products have serious risks and don’t have adequate evidence to support their use for these purposes.”

Much of the evidence has focused on CO₂ lasers instead of other energy-based treatments, however, and a raft of new studies have been published on these interventions in the past 2 years. Dr. Danan and colleagues, therefore, assessed the most current state of the research with a systematic review of randomized controlled trials (RCTs) and prospective observational studies with control groups published through December 11, 2023.

Included studies needed to evaluate an energy-based treatment for at least 8 weeks in a minimum of 40 postmenopausal women (20 in each group) who had one or more GSM symptoms. The authors also included nonrandomized and uncontrolled studies with a follow-up of a year or more to assess possible adverse events. The studies also needed to assess at least one of eight core outcomes: Dyspareunia; vulvovaginal dryness; vulvovaginal discomfort/irritation; dysuria; change in most bothersome symptom; treatment satisfaction; adverse events; and distress, bother, or interference associated with genitourinary symptoms.

The authors identified 32 studies, including 16 RCTs, one quasi-RCT, and 15 nonrandomized studies. The researchers extracted and analyzed data from the 10 RCTs and one quasi-RCT that were rated as having low to moderate risk for bias.

Most of these studies assessed CO₂ lasers alone, while three assessed erbium:yttrium-aluminum-garnet (Er:YAG) laser, and one looked at CO₂ lasers vs radiofrequency treatments.

The average age of participants ranged from 56 to 64 years, and most trials were in the United States. Results showed that CO₂ lasers led to little or no difference in dysuria, dyspareunia, or quality of life when compared with sham lasers. The CO₂ laser therapy also showed little to no difference compared with vaginal estrogen creams for dyspareunia, dryness, discomfort/irritation, dysuria, or quality of life.

Most CO₂ laser studies reported on most outcomes, but the Er:YAG studies tended to report only on quality of life and/or one or two other outcomes. The radiofrequency study only assessed dyspareunia and quality of life.

“Treatment effects on other outcomes and effects of Er:YAG laser or radiofrequency on any outcomes are very uncertain,” the authors reported. Few adverse events and no serious adverse events were reported based on 15 studies, including the additional non-RCTs that had follow-up for at least a year.

“There are case reports and other types of studies that have shown some bad outcomes using laser therapies, and we really wanted to be expansive and include anything, especially because this is such a new treatment and all these trials were in the last couple of years,” Dr. Danan said. 

The review was limited by inconsistent or nonvalidated outcome reporting in the studies as well as small populations and short follow-up, typically less than 3 months.

The research was funded by the Agency for Healthcare Research and Quality and Patient-Centered Outcomes Research Institute. Dr. Danan and Dr. Das had no disclosures.
 

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

This transcript has been edited for clarity.

I’d like to talk about a recent report in the journal Menopause linking menopausal symptoms to increased risk for cognitive impairment. I’d also like to discuss some of the recent studies that have addressed whether hot flashes are linked to increased risk for heart disease and other forms of cardiovascular disease (CVD). 

Given that 75%-80% of perimenopausal and postmenopausal women have hot flashes and vasomotor symptoms, it’s undoubtedly a more complex relationship between hot flashes and these outcomes than a simple one-size-fits-all, yes-or-no question.

Increasing evidence shows that several additional factors are important, including the age at which the symptoms are occurring, the time since menopause, the severity of the symptoms, whether they co-occur with night sweats and sleep disruption, and the cardiovascular status of the woman.

Several studies suggest that women who have more severe hot flashes and vasomotor symptoms are more likely to have prevalent cardiovascular risk factors — hypertension, dyslipidemia, high body mass index, endothelial dysfunction — as measured by flow-mediated vasodilation and other measures.

It is quite plausible that hot flashes could be a marker for increased risk for cognitive impairment. But the question remains, are hot flashes associated with cognitive impairment independent of these other risk factors? It appears that the associations between hot flashes, vasomotor symptoms, and CVD, and other adverse outcomes, may be more likely when hot flashes persist after age 60 or are newly occurring in later menopause. In the Women’s Health Initiative observational study, the presence of hot flashes and vasomotor symptoms in early menopause was not linked to any increased risk for heart attack, stroke, total CVD, or all-cause mortality.

However, the onset of these symptoms, especially new onset of these symptoms after age 60 or in later menopause, was in fact linked to increased risk for CVD and all-cause mortality. With respect to cognitive impairment, if a woman is having hot flashes and night sweats with regular sleep disruption, performance on cognitive testing would not be as favorable as it would be in the absence of these symptoms.

This brings us to the new study in Menopause that included approximately 1300 Latino women in nine Latin American countries, with an average age of 55 years. Looking at the association between severe menopausal symptoms and cognitive impairment, researchers found that women with severe symptoms were more likely to have cognitive impairment.

Conversely, they found that the women who had a favorable CVD risk factor status (physically active, lower BMI, healthier) and were ever users of estrogen were less likely to have cognitive impairment.

Clearly, for estrogen therapy, we need randomized clinical trials of the presence or absence of vasomotor symptoms and cognitive and CVD outcomes. Such analyses are ongoing, and new randomized trials focused specifically on women in early menopause would be very beneficial.

At the present time, it’s important that we not alarm women about the associations seen in some of these studies because often they are not independent associations; they aren’t independent of other risk factors that are commonly linked to hot flashes and night sweats. There are many other complexities in the relationship between hot flashes and cognitive impairment.

We need to appreciate that women who have moderate to severe hot flashes (especially when associated with disrupted sleep) do have impaired quality of life. It’s important to treat these symptoms, especially in early menopause, and very effective hormonal and nonhormonal treatments are available.

For women with symptoms that persist into later menopause or who have new onset of symptoms in later menopause, it’s important to prioritize cardiovascular health. For example, be more vigilant about behavioral lifestyle counseling to lower risk, and be even more aggressive in treating dyslipidemia and diabetes.

JoAnn E. Manson, Professor of Medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School; Chief, Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, Massachusetts; and Past President, North American Menopause Society, 2011-2012, has disclosed the following relevant financial relationships: Received study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

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

This transcript has been edited for clarity.

I’d like to talk about a recent report in the journal Menopause linking menopausal symptoms to increased risk for cognitive impairment. I’d also like to discuss some of the recent studies that have addressed whether hot flashes are linked to increased risk for heart disease and other forms of cardiovascular disease (CVD). 

Given that 75%-80% of perimenopausal and postmenopausal women have hot flashes and vasomotor symptoms, it’s undoubtedly a more complex relationship between hot flashes and these outcomes than a simple one-size-fits-all, yes-or-no question.

Increasing evidence shows that several additional factors are important, including the age at which the symptoms are occurring, the time since menopause, the severity of the symptoms, whether they co-occur with night sweats and sleep disruption, and the cardiovascular status of the woman.

Several studies suggest that women who have more severe hot flashes and vasomotor symptoms are more likely to have prevalent cardiovascular risk factors — hypertension, dyslipidemia, high body mass index, endothelial dysfunction — as measured by flow-mediated vasodilation and other measures.

It is quite plausible that hot flashes could be a marker for increased risk for cognitive impairment. But the question remains, are hot flashes associated with cognitive impairment independent of these other risk factors? It appears that the associations between hot flashes, vasomotor symptoms, and CVD, and other adverse outcomes, may be more likely when hot flashes persist after age 60 or are newly occurring in later menopause. In the Women’s Health Initiative observational study, the presence of hot flashes and vasomotor symptoms in early menopause was not linked to any increased risk for heart attack, stroke, total CVD, or all-cause mortality.

However, the onset of these symptoms, especially new onset of these symptoms after age 60 or in later menopause, was in fact linked to increased risk for CVD and all-cause mortality. With respect to cognitive impairment, if a woman is having hot flashes and night sweats with regular sleep disruption, performance on cognitive testing would not be as favorable as it would be in the absence of these symptoms.

This brings us to the new study in Menopause that included approximately 1300 Latino women in nine Latin American countries, with an average age of 55 years. Looking at the association between severe menopausal symptoms and cognitive impairment, researchers found that women with severe symptoms were more likely to have cognitive impairment.

Conversely, they found that the women who had a favorable CVD risk factor status (physically active, lower BMI, healthier) and were ever users of estrogen were less likely to have cognitive impairment.

Clearly, for estrogen therapy, we need randomized clinical trials of the presence or absence of vasomotor symptoms and cognitive and CVD outcomes. Such analyses are ongoing, and new randomized trials focused specifically on women in early menopause would be very beneficial.

At the present time, it’s important that we not alarm women about the associations seen in some of these studies because often they are not independent associations; they aren’t independent of other risk factors that are commonly linked to hot flashes and night sweats. There are many other complexities in the relationship between hot flashes and cognitive impairment.

We need to appreciate that women who have moderate to severe hot flashes (especially when associated with disrupted sleep) do have impaired quality of life. It’s important to treat these symptoms, especially in early menopause, and very effective hormonal and nonhormonal treatments are available.

For women with symptoms that persist into later menopause or who have new onset of symptoms in later menopause, it’s important to prioritize cardiovascular health. For example, be more vigilant about behavioral lifestyle counseling to lower risk, and be even more aggressive in treating dyslipidemia and diabetes.

JoAnn E. Manson, Professor of Medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School; Chief, Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, Massachusetts; and Past President, North American Menopause Society, 2011-2012, has disclosed the following relevant financial relationships: Received study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

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

This transcript has been edited for clarity.

I’d like to talk about a recent report in the journal Menopause linking menopausal symptoms to increased risk for cognitive impairment. I’d also like to discuss some of the recent studies that have addressed whether hot flashes are linked to increased risk for heart disease and other forms of cardiovascular disease (CVD). 

Given that 75%-80% of perimenopausal and postmenopausal women have hot flashes and vasomotor symptoms, it’s undoubtedly a more complex relationship between hot flashes and these outcomes than a simple one-size-fits-all, yes-or-no question.

Increasing evidence shows that several additional factors are important, including the age at which the symptoms are occurring, the time since menopause, the severity of the symptoms, whether they co-occur with night sweats and sleep disruption, and the cardiovascular status of the woman.

Several studies suggest that women who have more severe hot flashes and vasomotor symptoms are more likely to have prevalent cardiovascular risk factors — hypertension, dyslipidemia, high body mass index, endothelial dysfunction — as measured by flow-mediated vasodilation and other measures.

It is quite plausible that hot flashes could be a marker for increased risk for cognitive impairment. But the question remains, are hot flashes associated with cognitive impairment independent of these other risk factors? It appears that the associations between hot flashes, vasomotor symptoms, and CVD, and other adverse outcomes, may be more likely when hot flashes persist after age 60 or are newly occurring in later menopause. In the Women’s Health Initiative observational study, the presence of hot flashes and vasomotor symptoms in early menopause was not linked to any increased risk for heart attack, stroke, total CVD, or all-cause mortality.

However, the onset of these symptoms, especially new onset of these symptoms after age 60 or in later menopause, was in fact linked to increased risk for CVD and all-cause mortality. With respect to cognitive impairment, if a woman is having hot flashes and night sweats with regular sleep disruption, performance on cognitive testing would not be as favorable as it would be in the absence of these symptoms.

This brings us to the new study in Menopause that included approximately 1300 Latino women in nine Latin American countries, with an average age of 55 years. Looking at the association between severe menopausal symptoms and cognitive impairment, researchers found that women with severe symptoms were more likely to have cognitive impairment.

Conversely, they found that the women who had a favorable CVD risk factor status (physically active, lower BMI, healthier) and were ever users of estrogen were less likely to have cognitive impairment.

Clearly, for estrogen therapy, we need randomized clinical trials of the presence or absence of vasomotor symptoms and cognitive and CVD outcomes. Such analyses are ongoing, and new randomized trials focused specifically on women in early menopause would be very beneficial.

At the present time, it’s important that we not alarm women about the associations seen in some of these studies because often they are not independent associations; they aren’t independent of other risk factors that are commonly linked to hot flashes and night sweats. There are many other complexities in the relationship between hot flashes and cognitive impairment.

We need to appreciate that women who have moderate to severe hot flashes (especially when associated with disrupted sleep) do have impaired quality of life. It’s important to treat these symptoms, especially in early menopause, and very effective hormonal and nonhormonal treatments are available.

For women with symptoms that persist into later menopause or who have new onset of symptoms in later menopause, it’s important to prioritize cardiovascular health. For example, be more vigilant about behavioral lifestyle counseling to lower risk, and be even more aggressive in treating dyslipidemia and diabetes.

JoAnn E. Manson, Professor of Medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School; Chief, Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, Massachusetts; and Past President, North American Menopause Society, 2011-2012, has disclosed the following relevant financial relationships: Received study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

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

A more definitive picture of how some hormones and moisturizers can offer relief to women experiencing vaginal dryness or painful intercourse during menopause was published in a recent systematic review in Annals of Internal Medicine. However, researchers noted scant long-term data on the safety of these products.

Vaginal dryness and challenges with intercourse and urination are among the symptoms of genitourinary syndrome of menopause (GSM). Hormones such as vaginal estrogen, vaginal dehydroepiandrosterone (DHEA), or oral ospemifene are common treatments, along with moisturizers.

“The main finding is that commonly used therapies are likely to be effective for the common symptoms people have for GSM,” particularly vaginal dryness and painful intercourse, said Elisheva Danan, MD, MPH, a primary care physician and health services researcher at the Minneapolis VA Health Care System and assistant professor of medicine at the University of Minnesota Medical School in Minneapolis, who was the lead study author.

Many women might recognize hot flashes as connected to menopause, Dr. Danan said, as these tend to occur with the cessation of the menstrual cycle. However, genitourinary effects may not manifest until a few years later and worsen over time, when the connection to menopause is less clear.

“Women might not bring it up or think there’s a treatment that can work,” Dr. Danan said.

The systematic review may provide clinicians with more evidence of specific treatments to recommend. However, most of the trials included in the analysis studied treatment periods of 12 weeks or less, so the safety of long-term use is unclear.

“One question that hasn’t been answered yet in clinical trials is whether there could be a risk of uterine cancer with extended use of any of these treatments,” Dr. Danan said, because vaginal estrogen or ospemifene could stimulate growth of the uterine lining.

The studies Dr. Danan and colleagues found showed no increased risk for uterine cancer, but Dr, Danan noted that the maximum follow-up was 1 year, and study participants had a low risk for cancer to begin with. She advised that clinicians closely monitor women with risk factors if they use hormones to treat GSM indefinitely.
 

Forty-Six Randomized Controlled Trials, Many Open Questions

Dr. Danan and her colleagues conducted a systematic review of 46 randomized controlled trials, meant to inform an upcoming clinical practice guideline from the American Urological Association on treatment of GSM. Dr. Danan’s work was funded by the Patient-Centered Outcomes Research Institute.

Studies evaluated vaginal estrogen (22), other hormones such as vaginal oxytocin or vaginal testosterone (16), vaginal moisturizers (4), and multiple interventions (4).

Included trials lasted at least 8 weeks and included at least 20 postmenopausal women; most treatments lasted 12 weeks or less. Studies used varying definitions of GSM, and no head-to-head trials of different treatments were found.

Researchers used the Core Outcomes in Menopause (COMMA) framework, developed in 2021 to standardize outcomes research in menopause care and to understand treatment effectiveness. They applied this framework retroactively, as almost all the studies in the review were written before the COMMA framework existed.

Hormonal treatments were associated with reduced pain during intercourse and decreased vaginal dryness; moisturizers were linked to reduced dryness.

Vaginal estrogen did not reduce pain during intercourse as consistently as DHEA or oral ospemifene, per the review. Dr. Danan and her coauthors said this could be because the DHEA and ospemifene trials were larger and more uniformly conducted than those for vaginal estrogen. Even so, vaginal estrogen outperformed placebo at reducing painful intercourse.

But given the short timeframe of most studies and the differing definitions of GSM symptoms, Dr. Danan cautioned that all their conclusions have low certainty.

Few studies examined whether these treatments reduced vaginal itchiness or difficulties with urination. And the authors found no evidence for the benefit of oral DHEA, raloxifene, bazedoxifene, vaginal oxytocin, or vaginal testosterone for GSM treatment.

In an accompanying report, the researchers found no evidence for the benefits of treatments such as vaginal testosterone or vaginal laser therapy.

Stephanie Faubion, MD, MBA, medical director for the North American Menopause Society and director of the Mayo Clinic Center for Women’s Health, Rochester, Minnesota, wrote an accompanying editorial noting that the patients represented in the GSM treatment clinical trials were not diverse and that the exclusion criteria generally meant that women with cardiovascular challenges or cancer were not included.

“That’s one of the biggest questions — what is the safety in women with cardiovascular risk factors or history of a blood clot or history of a cancer? The data is just completely absent there,” Dr. Faubion said.
 

The Connection Between GSM and Urinary Tract Infections (UTIs)

“Genitourinary syndrome of menopause is not just a little bit of vaginal dryness that can be cured with moisturizers and lubricants, but the syndrome can lead to recurrent urinary tract infections, which are extremely harmful and dangerous to our patients and cost the healthcare system a lot of money,” said Rachel Rubin, MD, a urologist and sexual medicine specialist in Bethesda, Maryland.

Lubricants and moisturizers can all help with the symptoms of GSM, at least in the short term, Dr. Rubin noted. But only hormones can get to the root of the problem and reduce the risk for a recurrent UTI (rUTI), Dr. Rubin added, noting that the American Urological Association recommends the use of vaginal estrogen to reduce the risk for rUTIs and is developing the clinical practice guidelines for GSM.

Dr. Danan’s review did not address the association between UTIs and GSM, but Dr. Rubin said she sees the link in clinical practice.

“Recurrent urinary tract infections occur because of GSM, because of the lack of hormones to the tissue,” sometimes when a woman is in her 60s or 70s and thinks menopause is long over, Dr. Rubin said.

The reality is that women may need to take hormones for decades to reduce the risk for UTIs, another reason longer-term safety data are needed, Dr. Rubin said.

Dr. Danan, Dr. Faubion, and Dr. Rubin reported no relevant financial relationships.

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

A more definitive picture of how some hormones and moisturizers can offer relief to women experiencing vaginal dryness or painful intercourse during menopause was published in a recent systematic review in Annals of Internal Medicine. However, researchers noted scant long-term data on the safety of these products.

Vaginal dryness and challenges with intercourse and urination are among the symptoms of genitourinary syndrome of menopause (GSM). Hormones such as vaginal estrogen, vaginal dehydroepiandrosterone (DHEA), or oral ospemifene are common treatments, along with moisturizers.

“The main finding is that commonly used therapies are likely to be effective for the common symptoms people have for GSM,” particularly vaginal dryness and painful intercourse, said Elisheva Danan, MD, MPH, a primary care physician and health services researcher at the Minneapolis VA Health Care System and assistant professor of medicine at the University of Minnesota Medical School in Minneapolis, who was the lead study author.

Many women might recognize hot flashes as connected to menopause, Dr. Danan said, as these tend to occur with the cessation of the menstrual cycle. However, genitourinary effects may not manifest until a few years later and worsen over time, when the connection to menopause is less clear.

“Women might not bring it up or think there’s a treatment that can work,” Dr. Danan said.

The systematic review may provide clinicians with more evidence of specific treatments to recommend. However, most of the trials included in the analysis studied treatment periods of 12 weeks or less, so the safety of long-term use is unclear.

“One question that hasn’t been answered yet in clinical trials is whether there could be a risk of uterine cancer with extended use of any of these treatments,” Dr. Danan said, because vaginal estrogen or ospemifene could stimulate growth of the uterine lining.

The studies Dr. Danan and colleagues found showed no increased risk for uterine cancer, but Dr, Danan noted that the maximum follow-up was 1 year, and study participants had a low risk for cancer to begin with. She advised that clinicians closely monitor women with risk factors if they use hormones to treat GSM indefinitely.
 

Forty-Six Randomized Controlled Trials, Many Open Questions

Dr. Danan and her colleagues conducted a systematic review of 46 randomized controlled trials, meant to inform an upcoming clinical practice guideline from the American Urological Association on treatment of GSM. Dr. Danan’s work was funded by the Patient-Centered Outcomes Research Institute.

Studies evaluated vaginal estrogen (22), other hormones such as vaginal oxytocin or vaginal testosterone (16), vaginal moisturizers (4), and multiple interventions (4).

Included trials lasted at least 8 weeks and included at least 20 postmenopausal women; most treatments lasted 12 weeks or less. Studies used varying definitions of GSM, and no head-to-head trials of different treatments were found.

Researchers used the Core Outcomes in Menopause (COMMA) framework, developed in 2021 to standardize outcomes research in menopause care and to understand treatment effectiveness. They applied this framework retroactively, as almost all the studies in the review were written before the COMMA framework existed.

Hormonal treatments were associated with reduced pain during intercourse and decreased vaginal dryness; moisturizers were linked to reduced dryness.

Vaginal estrogen did not reduce pain during intercourse as consistently as DHEA or oral ospemifene, per the review. Dr. Danan and her coauthors said this could be because the DHEA and ospemifene trials were larger and more uniformly conducted than those for vaginal estrogen. Even so, vaginal estrogen outperformed placebo at reducing painful intercourse.

But given the short timeframe of most studies and the differing definitions of GSM symptoms, Dr. Danan cautioned that all their conclusions have low certainty.

Few studies examined whether these treatments reduced vaginal itchiness or difficulties with urination. And the authors found no evidence for the benefit of oral DHEA, raloxifene, bazedoxifene, vaginal oxytocin, or vaginal testosterone for GSM treatment.

In an accompanying report, the researchers found no evidence for the benefits of treatments such as vaginal testosterone or vaginal laser therapy.

Stephanie Faubion, MD, MBA, medical director for the North American Menopause Society and director of the Mayo Clinic Center for Women’s Health, Rochester, Minnesota, wrote an accompanying editorial noting that the patients represented in the GSM treatment clinical trials were not diverse and that the exclusion criteria generally meant that women with cardiovascular challenges or cancer were not included.

“That’s one of the biggest questions — what is the safety in women with cardiovascular risk factors or history of a blood clot or history of a cancer? The data is just completely absent there,” Dr. Faubion said.
 

The Connection Between GSM and Urinary Tract Infections (UTIs)

“Genitourinary syndrome of menopause is not just a little bit of vaginal dryness that can be cured with moisturizers and lubricants, but the syndrome can lead to recurrent urinary tract infections, which are extremely harmful and dangerous to our patients and cost the healthcare system a lot of money,” said Rachel Rubin, MD, a urologist and sexual medicine specialist in Bethesda, Maryland.

Lubricants and moisturizers can all help with the symptoms of GSM, at least in the short term, Dr. Rubin noted. But only hormones can get to the root of the problem and reduce the risk for a recurrent UTI (rUTI), Dr. Rubin added, noting that the American Urological Association recommends the use of vaginal estrogen to reduce the risk for rUTIs and is developing the clinical practice guidelines for GSM.

Dr. Danan’s review did not address the association between UTIs and GSM, but Dr. Rubin said she sees the link in clinical practice.

“Recurrent urinary tract infections occur because of GSM, because of the lack of hormones to the tissue,” sometimes when a woman is in her 60s or 70s and thinks menopause is long over, Dr. Rubin said.

The reality is that women may need to take hormones for decades to reduce the risk for UTIs, another reason longer-term safety data are needed, Dr. Rubin said.

Dr. Danan, Dr. Faubion, and Dr. Rubin reported no relevant financial relationships.

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

A more definitive picture of how some hormones and moisturizers can offer relief to women experiencing vaginal dryness or painful intercourse during menopause was published in a recent systematic review in Annals of Internal Medicine. However, researchers noted scant long-term data on the safety of these products.

Vaginal dryness and challenges with intercourse and urination are among the symptoms of genitourinary syndrome of menopause (GSM). Hormones such as vaginal estrogen, vaginal dehydroepiandrosterone (DHEA), or oral ospemifene are common treatments, along with moisturizers.

“The main finding is that commonly used therapies are likely to be effective for the common symptoms people have for GSM,” particularly vaginal dryness and painful intercourse, said Elisheva Danan, MD, MPH, a primary care physician and health services researcher at the Minneapolis VA Health Care System and assistant professor of medicine at the University of Minnesota Medical School in Minneapolis, who was the lead study author.

Many women might recognize hot flashes as connected to menopause, Dr. Danan said, as these tend to occur with the cessation of the menstrual cycle. However, genitourinary effects may not manifest until a few years later and worsen over time, when the connection to menopause is less clear.

“Women might not bring it up or think there’s a treatment that can work,” Dr. Danan said.

The systematic review may provide clinicians with more evidence of specific treatments to recommend. However, most of the trials included in the analysis studied treatment periods of 12 weeks or less, so the safety of long-term use is unclear.

“One question that hasn’t been answered yet in clinical trials is whether there could be a risk of uterine cancer with extended use of any of these treatments,” Dr. Danan said, because vaginal estrogen or ospemifene could stimulate growth of the uterine lining.

The studies Dr. Danan and colleagues found showed no increased risk for uterine cancer, but Dr, Danan noted that the maximum follow-up was 1 year, and study participants had a low risk for cancer to begin with. She advised that clinicians closely monitor women with risk factors if they use hormones to treat GSM indefinitely.
 

Forty-Six Randomized Controlled Trials, Many Open Questions

Dr. Danan and her colleagues conducted a systematic review of 46 randomized controlled trials, meant to inform an upcoming clinical practice guideline from the American Urological Association on treatment of GSM. Dr. Danan’s work was funded by the Patient-Centered Outcomes Research Institute.

Studies evaluated vaginal estrogen (22), other hormones such as vaginal oxytocin or vaginal testosterone (16), vaginal moisturizers (4), and multiple interventions (4).

Included trials lasted at least 8 weeks and included at least 20 postmenopausal women; most treatments lasted 12 weeks or less. Studies used varying definitions of GSM, and no head-to-head trials of different treatments were found.

Researchers used the Core Outcomes in Menopause (COMMA) framework, developed in 2021 to standardize outcomes research in menopause care and to understand treatment effectiveness. They applied this framework retroactively, as almost all the studies in the review were written before the COMMA framework existed.

Hormonal treatments were associated with reduced pain during intercourse and decreased vaginal dryness; moisturizers were linked to reduced dryness.

Vaginal estrogen did not reduce pain during intercourse as consistently as DHEA or oral ospemifene, per the review. Dr. Danan and her coauthors said this could be because the DHEA and ospemifene trials were larger and more uniformly conducted than those for vaginal estrogen. Even so, vaginal estrogen outperformed placebo at reducing painful intercourse.

But given the short timeframe of most studies and the differing definitions of GSM symptoms, Dr. Danan cautioned that all their conclusions have low certainty.

Few studies examined whether these treatments reduced vaginal itchiness or difficulties with urination. And the authors found no evidence for the benefit of oral DHEA, raloxifene, bazedoxifene, vaginal oxytocin, or vaginal testosterone for GSM treatment.

In an accompanying report, the researchers found no evidence for the benefits of treatments such as vaginal testosterone or vaginal laser therapy.

Stephanie Faubion, MD, MBA, medical director for the North American Menopause Society and director of the Mayo Clinic Center for Women’s Health, Rochester, Minnesota, wrote an accompanying editorial noting that the patients represented in the GSM treatment clinical trials were not diverse and that the exclusion criteria generally meant that women with cardiovascular challenges or cancer were not included.

“That’s one of the biggest questions — what is the safety in women with cardiovascular risk factors or history of a blood clot or history of a cancer? The data is just completely absent there,” Dr. Faubion said.
 

The Connection Between GSM and Urinary Tract Infections (UTIs)

“Genitourinary syndrome of menopause is not just a little bit of vaginal dryness that can be cured with moisturizers and lubricants, but the syndrome can lead to recurrent urinary tract infections, which are extremely harmful and dangerous to our patients and cost the healthcare system a lot of money,” said Rachel Rubin, MD, a urologist and sexual medicine specialist in Bethesda, Maryland.

Lubricants and moisturizers can all help with the symptoms of GSM, at least in the short term, Dr. Rubin noted. But only hormones can get to the root of the problem and reduce the risk for a recurrent UTI (rUTI), Dr. Rubin added, noting that the American Urological Association recommends the use of vaginal estrogen to reduce the risk for rUTIs and is developing the clinical practice guidelines for GSM.

Dr. Danan’s review did not address the association between UTIs and GSM, but Dr. Rubin said she sees the link in clinical practice.

“Recurrent urinary tract infections occur because of GSM, because of the lack of hormones to the tissue,” sometimes when a woman is in her 60s or 70s and thinks menopause is long over, Dr. Rubin said.

The reality is that women may need to take hormones for decades to reduce the risk for UTIs, another reason longer-term safety data are needed, Dr. Rubin said.

Dr. Danan, Dr. Faubion, and Dr. Rubin reported no relevant financial relationships.

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

Elinzanetant, the selective antagonist of neurokinin 1 and 3 receptors, led to rapid improvement in the frequency of vasomotor symptoms and significant improvements in the severity of symptoms, sleep disturbances, and menopause-related quality of life in two phase 3 studies. Researchers led by JoAnn V. Pinkerton, MD, from the University of Virginia Health in Charlottesville, reported their findings, which resulted from the randomized OASIS 1 and 2 studies, in JAMA.

“Women experience a variety of symptoms during their menopausal transition, including vasomotor symptoms ... and sleep disturbances, reported by up to 80% and 60%, respectively,” wrote the researchers. “Menopausal symptoms can negatively impact quality of life, reducing the capacity for daily activities and work productivity, and may be associated with long-term negative health outcomes such as cardiovascular events, depressive symptoms, cognitive decline, and other adverse brain outcomes.” The researchers also noted that some therapeutic options are available, including hormone replacement therapy and, in some countries, paroxetine, a selective serotonin reuptake inhibitor.

The Italian Ministry of Health’s menopause website points out that the transition generally occurs between ages 45 and 55 years. This huge hormonal change has consequences for women’s health. Ministry experts explain that diet and hormone replacement therapy (which should be taken under medical supervision) can prevent or counteract these consequences.

“Many women have contraindications, have tolerability issues leading to discontinuation, or prefer not to take these treatments,” wrote Dr. Pinkerton and colleagues, who evaluated the efficacy and tolerability of elinzanetant, a nonhormonal alternative treatment in development. The two double-blind, randomized, phase 3 studies (OASIS 1 and 2) included postmenopausal participants between ages 40 and 65 years with moderate to severe vasomotor symptoms who were treated with elinzanetant (OASIS 1, n = 199; OASIS 2, n = 200) or placebo (OASIS 1, n = 197; OASIS 2, n = 200).

After 4 weeks of treatment, 62.8% of participants in the OASIS 1 study and 62.2% in the OASIS 2 study reported at least a 50% reduction in the frequency of vasomotor symptoms (29.2% and 32.3% in the respective placebo groups). Improvements increased by week 12, with 71.4% and 74.7% of women in the elinzanetant group achieving this reduction (42.0% and 48.3% in the respective placebo groups). Women who took the medication also reported a reduction in the severity of vasomotor symptoms and improvements in sleep and menopause-related quality of life, with no significant tolerability and safety issues. “Elinzanetant has the potential to provide a well-tolerated and efficacious nonhormonal treatment option to address the unmet health needs of many menopausal individuals with moderate to severe vasomotor symptoms,” the authors concluded.

“With the discovery of nonhormonal treatment options targeting the neurons responsible for vasomotor symptoms, menopause care should advance on this solid scientific footing to benefit affected individuals,” wrote Stephanie S. Faubion, MD, and Chrisandra L. Shufelt, MD, who are affiliated with the Mayo Clinic in Rochester, Minnesota, and Jacksonville, Florida, in an accompanying editorial.

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Elinzanetant, the selective antagonist of neurokinin 1 and 3 receptors, led to rapid improvement in the frequency of vasomotor symptoms and significant improvements in the severity of symptoms, sleep disturbances, and menopause-related quality of life in two phase 3 studies. Researchers led by JoAnn V. Pinkerton, MD, from the University of Virginia Health in Charlottesville, reported their findings, which resulted from the randomized OASIS 1 and 2 studies, in JAMA.

“Women experience a variety of symptoms during their menopausal transition, including vasomotor symptoms ... and sleep disturbances, reported by up to 80% and 60%, respectively,” wrote the researchers. “Menopausal symptoms can negatively impact quality of life, reducing the capacity for daily activities and work productivity, and may be associated with long-term negative health outcomes such as cardiovascular events, depressive symptoms, cognitive decline, and other adverse brain outcomes.” The researchers also noted that some therapeutic options are available, including hormone replacement therapy and, in some countries, paroxetine, a selective serotonin reuptake inhibitor.

The Italian Ministry of Health’s menopause website points out that the transition generally occurs between ages 45 and 55 years. This huge hormonal change has consequences for women’s health. Ministry experts explain that diet and hormone replacement therapy (which should be taken under medical supervision) can prevent or counteract these consequences.

“Many women have contraindications, have tolerability issues leading to discontinuation, or prefer not to take these treatments,” wrote Dr. Pinkerton and colleagues, who evaluated the efficacy and tolerability of elinzanetant, a nonhormonal alternative treatment in development. The two double-blind, randomized, phase 3 studies (OASIS 1 and 2) included postmenopausal participants between ages 40 and 65 years with moderate to severe vasomotor symptoms who were treated with elinzanetant (OASIS 1, n = 199; OASIS 2, n = 200) or placebo (OASIS 1, n = 197; OASIS 2, n = 200).

After 4 weeks of treatment, 62.8% of participants in the OASIS 1 study and 62.2% in the OASIS 2 study reported at least a 50% reduction in the frequency of vasomotor symptoms (29.2% and 32.3% in the respective placebo groups). Improvements increased by week 12, with 71.4% and 74.7% of women in the elinzanetant group achieving this reduction (42.0% and 48.3% in the respective placebo groups). Women who took the medication also reported a reduction in the severity of vasomotor symptoms and improvements in sleep and menopause-related quality of life, with no significant tolerability and safety issues. “Elinzanetant has the potential to provide a well-tolerated and efficacious nonhormonal treatment option to address the unmet health needs of many menopausal individuals with moderate to severe vasomotor symptoms,” the authors concluded.

“With the discovery of nonhormonal treatment options targeting the neurons responsible for vasomotor symptoms, menopause care should advance on this solid scientific footing to benefit affected individuals,” wrote Stephanie S. Faubion, MD, and Chrisandra L. Shufelt, MD, who are affiliated with the Mayo Clinic in Rochester, Minnesota, and Jacksonville, Florida, in an accompanying editorial.

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Elinzanetant, the selective antagonist of neurokinin 1 and 3 receptors, led to rapid improvement in the frequency of vasomotor symptoms and significant improvements in the severity of symptoms, sleep disturbances, and menopause-related quality of life in two phase 3 studies. Researchers led by JoAnn V. Pinkerton, MD, from the University of Virginia Health in Charlottesville, reported their findings, which resulted from the randomized OASIS 1 and 2 studies, in JAMA.

“Women experience a variety of symptoms during their menopausal transition, including vasomotor symptoms ... and sleep disturbances, reported by up to 80% and 60%, respectively,” wrote the researchers. “Menopausal symptoms can negatively impact quality of life, reducing the capacity for daily activities and work productivity, and may be associated with long-term negative health outcomes such as cardiovascular events, depressive symptoms, cognitive decline, and other adverse brain outcomes.” The researchers also noted that some therapeutic options are available, including hormone replacement therapy and, in some countries, paroxetine, a selective serotonin reuptake inhibitor.

The Italian Ministry of Health’s menopause website points out that the transition generally occurs between ages 45 and 55 years. This huge hormonal change has consequences for women’s health. Ministry experts explain that diet and hormone replacement therapy (which should be taken under medical supervision) can prevent or counteract these consequences.

“Many women have contraindications, have tolerability issues leading to discontinuation, or prefer not to take these treatments,” wrote Dr. Pinkerton and colleagues, who evaluated the efficacy and tolerability of elinzanetant, a nonhormonal alternative treatment in development. The two double-blind, randomized, phase 3 studies (OASIS 1 and 2) included postmenopausal participants between ages 40 and 65 years with moderate to severe vasomotor symptoms who were treated with elinzanetant (OASIS 1, n = 199; OASIS 2, n = 200) or placebo (OASIS 1, n = 197; OASIS 2, n = 200).

After 4 weeks of treatment, 62.8% of participants in the OASIS 1 study and 62.2% in the OASIS 2 study reported at least a 50% reduction in the frequency of vasomotor symptoms (29.2% and 32.3% in the respective placebo groups). Improvements increased by week 12, with 71.4% and 74.7% of women in the elinzanetant group achieving this reduction (42.0% and 48.3% in the respective placebo groups). Women who took the medication also reported a reduction in the severity of vasomotor symptoms and improvements in sleep and menopause-related quality of life, with no significant tolerability and safety issues. “Elinzanetant has the potential to provide a well-tolerated and efficacious nonhormonal treatment option to address the unmet health needs of many menopausal individuals with moderate to severe vasomotor symptoms,” the authors concluded.

“With the discovery of nonhormonal treatment options targeting the neurons responsible for vasomotor symptoms, menopause care should advance on this solid scientific footing to benefit affected individuals,” wrote Stephanie S. Faubion, MD, and Chrisandra L. Shufelt, MD, who are affiliated with the Mayo Clinic in Rochester, Minnesota, and Jacksonville, Florida, in an accompanying editorial.

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Hormone therapy (HT) can help women manage menopause symptoms into their 80s and the reasons are varied, according to a retrospective analysis being presented at the annual meeting of The Menopause Society.

“It’s important to know that this is a preselected group of women who had no contraindications to continuing their hormone therapy,” senior author Wendy Wolfman, MD, director of the Menopause Clinic and The Premature Ovarian Insufficiency Clinic at Mount Sinai Hospital in Toronto, Ontario, Canada, said in an interview. “They had the initiation of hormone therapy closer to menopause and carried on their hormones. We followed them for a long time and basically saw no real concerns about taking the hormones and the patients did very well. It’s important to emphasize this was not the new initiation of hormone therapy in elderly women.”

She said that, in her large tertiary referral center, “I still see patients who are referred who are told that they have to stop their hormones after 5 years based on a false assumption. Everybody ages at different rates and everybody has different risk factors.”

About 70%-80% of women experience menopause symptoms that restrict quality of life and productivity, the authors noted. HT has consistently been the most effective means for managing many of the side effects, especially hot flashes.

Hot flashes last on average 7-11 years. But they continue in up to 40% of women in their 60s and 10%-15% in their 70s, the authors wrote. 

The analysis included more than 100 women in Canada older than 65 who continue to use HT and explored the motivations of the women to use them.

The average age of the women was 71 and nearly 8% were age 80 or older. The mean age for starting HT was 52 years and the women continued HT for an average 18 years, though 42% used it regularly for more than 20 years. Most of the women (nearly 88%) used a transdermal form of estrogen; only 12% used oral estrogen pills. Fewer than 5% of participants used synthetic progestins.

Controlling hot flashes was the No. 1 reason the women continued HT beyond age 65 (55%), followed by a desire for a better quality of life (29%), and to reduce chronic pain and arthritis symptoms (7%).

Some adverse effects were reported – postmenopausal bleeding was the most common – but no strokes, myocardial infarctions, or uterine cancers were documented.

More than one fourth (26.4%) of the women tried stopping HT once, but 87% reported that the return of hot flashes was the main reason to restart HT.

In addition, “many women choose to continue hormone therapy long term for relief of nonvasomotor symptoms, preservation of bone density, and a desire to benefit from potential long-term cardiovascular protection,” said Lauren F. Streicher, MD, Professor of Obstetrics and Gynecology at Feinberg School of Medicine at Northwestern University in Chicago, who was not part of the research.

In 2022, The Menopause Society position statement on hormone therapy acknowledged that, on an individual basis, it is appropriate for women to continue hormone therapy long term with counseling on benefits and risks.

“However, few studies have evaluated the outcomes of using hormone therapy for more than 10 years, and individual motivation for doing so,” Dr. Streicher said. She pointed to a study that analyzed the insurance records of more than 10 million women who continued their HT past the age of 65 and reassuringly found that there were significant risk reductions in all-cause mortality, breast cancer, lung cancer, colorectal cancer, heart failure, venous thromboembolism, atrial fibrillation, acute myocardial infarction, and dementia. In that study, however, the reasons women chose to continue hormone therapy were not specified. 

“In this retrospective Canadian study,” she noted, “the outcomes were again reassuring, with no increase in strokes, myocardial infarctions, or uterine cancers. The reasons cited for continuing hormone therapy were not just to treat ongoing vasomotor symptoms, but also other menopause symptoms such as musculoskeletal aches and pains, and overall quality of life.

Dr. Streicher said that, while long-term longitudinal studies are needed to make definitive recommendations, “It is reassuring that women who choose to extend hormone therapy can safely do so. It is irresponsible, cruel, and nonsensical to continue to make blanket statements that hormone therapy should be discontinued based on age or years of use and commit women to enduring symptoms and depriving them of possible long-term benefits.”

Dr. Streicher gives lectures for Midi Health and owns Sermonix stock. Dr. Wolfman has been on the advisory boards for many pharmaceutical companies. She is the past president of the Canadian Menopause Society and is on the board of the International Menopause Society.

Hormone therapy (HT) can help women manage menopause symptoms into their 80s and the reasons are varied, according to a retrospective analysis being presented at the annual meeting of The Menopause Society.

“It’s important to know that this is a preselected group of women who had no contraindications to continuing their hormone therapy,” senior author Wendy Wolfman, MD, director of the Menopause Clinic and The Premature Ovarian Insufficiency Clinic at Mount Sinai Hospital in Toronto, Ontario, Canada, said in an interview. “They had the initiation of hormone therapy closer to menopause and carried on their hormones. We followed them for a long time and basically saw no real concerns about taking the hormones and the patients did very well. It’s important to emphasize this was not the new initiation of hormone therapy in elderly women.”

She said that, in her large tertiary referral center, “I still see patients who are referred who are told that they have to stop their hormones after 5 years based on a false assumption. Everybody ages at different rates and everybody has different risk factors.”

About 70%-80% of women experience menopause symptoms that restrict quality of life and productivity, the authors noted. HT has consistently been the most effective means for managing many of the side effects, especially hot flashes.

Hot flashes last on average 7-11 years. But they continue in up to 40% of women in their 60s and 10%-15% in their 70s, the authors wrote. 

The analysis included more than 100 women in Canada older than 65 who continue to use HT and explored the motivations of the women to use them.

The average age of the women was 71 and nearly 8% were age 80 or older. The mean age for starting HT was 52 years and the women continued HT for an average 18 years, though 42% used it regularly for more than 20 years. Most of the women (nearly 88%) used a transdermal form of estrogen; only 12% used oral estrogen pills. Fewer than 5% of participants used synthetic progestins.

Controlling hot flashes was the No. 1 reason the women continued HT beyond age 65 (55%), followed by a desire for a better quality of life (29%), and to reduce chronic pain and arthritis symptoms (7%).

Some adverse effects were reported – postmenopausal bleeding was the most common – but no strokes, myocardial infarctions, or uterine cancers were documented.

More than one fourth (26.4%) of the women tried stopping HT once, but 87% reported that the return of hot flashes was the main reason to restart HT.

In addition, “many women choose to continue hormone therapy long term for relief of nonvasomotor symptoms, preservation of bone density, and a desire to benefit from potential long-term cardiovascular protection,” said Lauren F. Streicher, MD, Professor of Obstetrics and Gynecology at Feinberg School of Medicine at Northwestern University in Chicago, who was not part of the research.

In 2022, The Menopause Society position statement on hormone therapy acknowledged that, on an individual basis, it is appropriate for women to continue hormone therapy long term with counseling on benefits and risks.

“However, few studies have evaluated the outcomes of using hormone therapy for more than 10 years, and individual motivation for doing so,” Dr. Streicher said. She pointed to a study that analyzed the insurance records of more than 10 million women who continued their HT past the age of 65 and reassuringly found that there were significant risk reductions in all-cause mortality, breast cancer, lung cancer, colorectal cancer, heart failure, venous thromboembolism, atrial fibrillation, acute myocardial infarction, and dementia. In that study, however, the reasons women chose to continue hormone therapy were not specified. 

“In this retrospective Canadian study,” she noted, “the outcomes were again reassuring, with no increase in strokes, myocardial infarctions, or uterine cancers. The reasons cited for continuing hormone therapy were not just to treat ongoing vasomotor symptoms, but also other menopause symptoms such as musculoskeletal aches and pains, and overall quality of life.

Dr. Streicher said that, while long-term longitudinal studies are needed to make definitive recommendations, “It is reassuring that women who choose to extend hormone therapy can safely do so. It is irresponsible, cruel, and nonsensical to continue to make blanket statements that hormone therapy should be discontinued based on age or years of use and commit women to enduring symptoms and depriving them of possible long-term benefits.”

Dr. Streicher gives lectures for Midi Health and owns Sermonix stock. Dr. Wolfman has been on the advisory boards for many pharmaceutical companies. She is the past president of the Canadian Menopause Society and is on the board of the International Menopause Society.

Hormone therapy (HT) can help women manage menopause symptoms into their 80s and the reasons are varied, according to a retrospective analysis being presented at the annual meeting of The Menopause Society.

“It’s important to know that this is a preselected group of women who had no contraindications to continuing their hormone therapy,” senior author Wendy Wolfman, MD, director of the Menopause Clinic and The Premature Ovarian Insufficiency Clinic at Mount Sinai Hospital in Toronto, Ontario, Canada, said in an interview. “They had the initiation of hormone therapy closer to menopause and carried on their hormones. We followed them for a long time and basically saw no real concerns about taking the hormones and the patients did very well. It’s important to emphasize this was not the new initiation of hormone therapy in elderly women.”

She said that, in her large tertiary referral center, “I still see patients who are referred who are told that they have to stop their hormones after 5 years based on a false assumption. Everybody ages at different rates and everybody has different risk factors.”

About 70%-80% of women experience menopause symptoms that restrict quality of life and productivity, the authors noted. HT has consistently been the most effective means for managing many of the side effects, especially hot flashes.

Hot flashes last on average 7-11 years. But they continue in up to 40% of women in their 60s and 10%-15% in their 70s, the authors wrote. 

The analysis included more than 100 women in Canada older than 65 who continue to use HT and explored the motivations of the women to use them.

The average age of the women was 71 and nearly 8% were age 80 or older. The mean age for starting HT was 52 years and the women continued HT for an average 18 years, though 42% used it regularly for more than 20 years. Most of the women (nearly 88%) used a transdermal form of estrogen; only 12% used oral estrogen pills. Fewer than 5% of participants used synthetic progestins.

Controlling hot flashes was the No. 1 reason the women continued HT beyond age 65 (55%), followed by a desire for a better quality of life (29%), and to reduce chronic pain and arthritis symptoms (7%).

Some adverse effects were reported – postmenopausal bleeding was the most common – but no strokes, myocardial infarctions, or uterine cancers were documented.

More than one fourth (26.4%) of the women tried stopping HT once, but 87% reported that the return of hot flashes was the main reason to restart HT.

In addition, “many women choose to continue hormone therapy long term for relief of nonvasomotor symptoms, preservation of bone density, and a desire to benefit from potential long-term cardiovascular protection,” said Lauren F. Streicher, MD, Professor of Obstetrics and Gynecology at Feinberg School of Medicine at Northwestern University in Chicago, who was not part of the research.

In 2022, The Menopause Society position statement on hormone therapy acknowledged that, on an individual basis, it is appropriate for women to continue hormone therapy long term with counseling on benefits and risks.

“However, few studies have evaluated the outcomes of using hormone therapy for more than 10 years, and individual motivation for doing so,” Dr. Streicher said. She pointed to a study that analyzed the insurance records of more than 10 million women who continued their HT past the age of 65 and reassuringly found that there were significant risk reductions in all-cause mortality, breast cancer, lung cancer, colorectal cancer, heart failure, venous thromboembolism, atrial fibrillation, acute myocardial infarction, and dementia. In that study, however, the reasons women chose to continue hormone therapy were not specified. 

“In this retrospective Canadian study,” she noted, “the outcomes were again reassuring, with no increase in strokes, myocardial infarctions, or uterine cancers. The reasons cited for continuing hormone therapy were not just to treat ongoing vasomotor symptoms, but also other menopause symptoms such as musculoskeletal aches and pains, and overall quality of life.

Dr. Streicher said that, while long-term longitudinal studies are needed to make definitive recommendations, “It is reassuring that women who choose to extend hormone therapy can safely do so. It is irresponsible, cruel, and nonsensical to continue to make blanket statements that hormone therapy should be discontinued based on age or years of use and commit women to enduring symptoms and depriving them of possible long-term benefits.”

Dr. Streicher gives lectures for Midi Health and owns Sermonix stock. Dr. Wolfman has been on the advisory boards for many pharmaceutical companies. She is the past president of the Canadian Menopause Society and is on the board of the International Menopause Society.