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Catch-up HPV screenings help detect cancer in women over 65
The findings, published in PLOS Medicine, included women between ages 65 and 69 years in Denmark who had no record of cervical cancer screening or an HPV test in the previous 5 years.
“It may be valuable to get women above the current screening age to get this one-time catch-up HPV test if they haven’t had one before,” said Mette Tranberg, PhD, a cancer epidemiologist and researcher at Randers Regional Hospital in Denmark and lead author of the study. “That is valuable knowledge for health care providers and policy makers.”
Cervical cancer in the United States is most often diagnosed in women aged 35-44 years, according to the American Cancer Society, with the average age at diagnosis of 50 years. The cancer rarely occurs in women who have undergone regular screenings.
Though current guidelines recommend that clinicians stop screening women for cervical cancer at age 65 years if their previous screening results have been normal, Dr. Tranberg said that many women do not get screened as they get closer to age 65 years.
A study from researchers at the University of California, Davis, found several factors contribute to older women not receiving adequate screening. Some women may think that they no longer need Pap smears after going through menopause, or they might have received a hysterectomy and think that they no longer require screening. And although Pap tests have built-in HPV screenings, these tend to be less accurate in postmenopausal women.
But women older than 65 years account for about 20% of new cervical cancer cases.
According to the Centers for Disease Control and Prevention, until women reach age 80 years, they are as likely to get cervical cancer as are younger women. Jack Cuzick, PhD, professor of epidemiology at Queen Mary University of London, said that the new data should inform patient care and public health efforts.
“People often don’t realize HPV can last even if people haven’t been sexually active,” Dr. Cuzick said. “Even if somebody is nearing 70, it’s probably still worth getting an exit test.”
The intervention group
Study participants were assigned to two groups, one of which was invited to participate in a free HPV screening, either with their general practitioner or by ordering a vaginal self-sampling kit. The control group received standard care, which in Denmark, includes having the opportunity to undergo routine cervical cytology.
Dr. Tranberg and her colleagues found that among women in the intervention group, 62.2% were screened within 1 year. Among the control group, 2.2% had a Pap test. The rate of diagnosed cervical intraepithelial neoplasia grade 2 or worse was 3.9 cases per 1,000 eligible women in the intervention group and 0.3 cases per 1,000 eligible women in the control group (P < .001).
The study also found that women who had been insufficiently screened between ages 50 and 64 years had a higher prevalence of HPV, with more grade 2 cervical intraepithelial neoplasia lesions or worse, than did those who were sufficiently screened.
High-risk HPV tests are replacing the Pap smear as the primary cervical cancer screening test because of superior sensitivity, according to Dr. Tranberg. Though Pap smears detect abnormal cells on the cervix that can lead to cervical cancer, HPV tests specifically look for certain high-risk types of HPV on the cervix.
In the United States, patient histories of screenings, diagnosis, and treatment of HPV are often unavailable because electronic health records between health systems are often not linked, according to Cosette Wheeler, PhD, professor at the University of New Mexico Comprehensive Cancer Center in Albuquerque, and founding director of the New Mexico HPV Pap Registry. Clinicians may not know whether a patient needs a screening.
HPV tests usually have a high threshold of detection in an effort to produce fewer false positives, according to Dr. Wheeler, who was not involved in the latest study. But fewer false positives means that the test could produce more false negatives. Older women could benefit from more sensitive screening, such as the high-risk test that the Danish researchers used, according to Dr. Wheeler.
Dr. Tranberg said that she was surprised and pleased by the high percentage of women who accepted the screening tests in the intervention group, especially those who received at-home tests and followed up with a clinician.
“Female life expectancy is really increasing and therefore the number of cervical cancers in women over the age of 65 is expected to rise,” Dr. Tranberg said. “That’s a big reason to rethink whether or not we should do something for these older women.”
The HPV test kits in the intervention region were provided by Roche Diagnostics. According to the contract between Roche and Randers Regional Hospital, Roche had no influence on the scientific process and no editorial rights pertaining to this manuscript.
A version of this article first appeared on Medscape.com.
The findings, published in PLOS Medicine, included women between ages 65 and 69 years in Denmark who had no record of cervical cancer screening or an HPV test in the previous 5 years.
“It may be valuable to get women above the current screening age to get this one-time catch-up HPV test if they haven’t had one before,” said Mette Tranberg, PhD, a cancer epidemiologist and researcher at Randers Regional Hospital in Denmark and lead author of the study. “That is valuable knowledge for health care providers and policy makers.”
Cervical cancer in the United States is most often diagnosed in women aged 35-44 years, according to the American Cancer Society, with the average age at diagnosis of 50 years. The cancer rarely occurs in women who have undergone regular screenings.
Though current guidelines recommend that clinicians stop screening women for cervical cancer at age 65 years if their previous screening results have been normal, Dr. Tranberg said that many women do not get screened as they get closer to age 65 years.
A study from researchers at the University of California, Davis, found several factors contribute to older women not receiving adequate screening. Some women may think that they no longer need Pap smears after going through menopause, or they might have received a hysterectomy and think that they no longer require screening. And although Pap tests have built-in HPV screenings, these tend to be less accurate in postmenopausal women.
But women older than 65 years account for about 20% of new cervical cancer cases.
According to the Centers for Disease Control and Prevention, until women reach age 80 years, they are as likely to get cervical cancer as are younger women. Jack Cuzick, PhD, professor of epidemiology at Queen Mary University of London, said that the new data should inform patient care and public health efforts.
“People often don’t realize HPV can last even if people haven’t been sexually active,” Dr. Cuzick said. “Even if somebody is nearing 70, it’s probably still worth getting an exit test.”
The intervention group
Study participants were assigned to two groups, one of which was invited to participate in a free HPV screening, either with their general practitioner or by ordering a vaginal self-sampling kit. The control group received standard care, which in Denmark, includes having the opportunity to undergo routine cervical cytology.
Dr. Tranberg and her colleagues found that among women in the intervention group, 62.2% were screened within 1 year. Among the control group, 2.2% had a Pap test. The rate of diagnosed cervical intraepithelial neoplasia grade 2 or worse was 3.9 cases per 1,000 eligible women in the intervention group and 0.3 cases per 1,000 eligible women in the control group (P < .001).
The study also found that women who had been insufficiently screened between ages 50 and 64 years had a higher prevalence of HPV, with more grade 2 cervical intraepithelial neoplasia lesions or worse, than did those who were sufficiently screened.
High-risk HPV tests are replacing the Pap smear as the primary cervical cancer screening test because of superior sensitivity, according to Dr. Tranberg. Though Pap smears detect abnormal cells on the cervix that can lead to cervical cancer, HPV tests specifically look for certain high-risk types of HPV on the cervix.
In the United States, patient histories of screenings, diagnosis, and treatment of HPV are often unavailable because electronic health records between health systems are often not linked, according to Cosette Wheeler, PhD, professor at the University of New Mexico Comprehensive Cancer Center in Albuquerque, and founding director of the New Mexico HPV Pap Registry. Clinicians may not know whether a patient needs a screening.
HPV tests usually have a high threshold of detection in an effort to produce fewer false positives, according to Dr. Wheeler, who was not involved in the latest study. But fewer false positives means that the test could produce more false negatives. Older women could benefit from more sensitive screening, such as the high-risk test that the Danish researchers used, according to Dr. Wheeler.
Dr. Tranberg said that she was surprised and pleased by the high percentage of women who accepted the screening tests in the intervention group, especially those who received at-home tests and followed up with a clinician.
“Female life expectancy is really increasing and therefore the number of cervical cancers in women over the age of 65 is expected to rise,” Dr. Tranberg said. “That’s a big reason to rethink whether or not we should do something for these older women.”
The HPV test kits in the intervention region were provided by Roche Diagnostics. According to the contract between Roche and Randers Regional Hospital, Roche had no influence on the scientific process and no editorial rights pertaining to this manuscript.
A version of this article first appeared on Medscape.com.
The findings, published in PLOS Medicine, included women between ages 65 and 69 years in Denmark who had no record of cervical cancer screening or an HPV test in the previous 5 years.
“It may be valuable to get women above the current screening age to get this one-time catch-up HPV test if they haven’t had one before,” said Mette Tranberg, PhD, a cancer epidemiologist and researcher at Randers Regional Hospital in Denmark and lead author of the study. “That is valuable knowledge for health care providers and policy makers.”
Cervical cancer in the United States is most often diagnosed in women aged 35-44 years, according to the American Cancer Society, with the average age at diagnosis of 50 years. The cancer rarely occurs in women who have undergone regular screenings.
Though current guidelines recommend that clinicians stop screening women for cervical cancer at age 65 years if their previous screening results have been normal, Dr. Tranberg said that many women do not get screened as they get closer to age 65 years.
A study from researchers at the University of California, Davis, found several factors contribute to older women not receiving adequate screening. Some women may think that they no longer need Pap smears after going through menopause, or they might have received a hysterectomy and think that they no longer require screening. And although Pap tests have built-in HPV screenings, these tend to be less accurate in postmenopausal women.
But women older than 65 years account for about 20% of new cervical cancer cases.
According to the Centers for Disease Control and Prevention, until women reach age 80 years, they are as likely to get cervical cancer as are younger women. Jack Cuzick, PhD, professor of epidemiology at Queen Mary University of London, said that the new data should inform patient care and public health efforts.
“People often don’t realize HPV can last even if people haven’t been sexually active,” Dr. Cuzick said. “Even if somebody is nearing 70, it’s probably still worth getting an exit test.”
The intervention group
Study participants were assigned to two groups, one of which was invited to participate in a free HPV screening, either with their general practitioner or by ordering a vaginal self-sampling kit. The control group received standard care, which in Denmark, includes having the opportunity to undergo routine cervical cytology.
Dr. Tranberg and her colleagues found that among women in the intervention group, 62.2% were screened within 1 year. Among the control group, 2.2% had a Pap test. The rate of diagnosed cervical intraepithelial neoplasia grade 2 or worse was 3.9 cases per 1,000 eligible women in the intervention group and 0.3 cases per 1,000 eligible women in the control group (P < .001).
The study also found that women who had been insufficiently screened between ages 50 and 64 years had a higher prevalence of HPV, with more grade 2 cervical intraepithelial neoplasia lesions or worse, than did those who were sufficiently screened.
High-risk HPV tests are replacing the Pap smear as the primary cervical cancer screening test because of superior sensitivity, according to Dr. Tranberg. Though Pap smears detect abnormal cells on the cervix that can lead to cervical cancer, HPV tests specifically look for certain high-risk types of HPV on the cervix.
In the United States, patient histories of screenings, diagnosis, and treatment of HPV are often unavailable because electronic health records between health systems are often not linked, according to Cosette Wheeler, PhD, professor at the University of New Mexico Comprehensive Cancer Center in Albuquerque, and founding director of the New Mexico HPV Pap Registry. Clinicians may not know whether a patient needs a screening.
HPV tests usually have a high threshold of detection in an effort to produce fewer false positives, according to Dr. Wheeler, who was not involved in the latest study. But fewer false positives means that the test could produce more false negatives. Older women could benefit from more sensitive screening, such as the high-risk test that the Danish researchers used, according to Dr. Wheeler.
Dr. Tranberg said that she was surprised and pleased by the high percentage of women who accepted the screening tests in the intervention group, especially those who received at-home tests and followed up with a clinician.
“Female life expectancy is really increasing and therefore the number of cervical cancers in women over the age of 65 is expected to rise,” Dr. Tranberg said. “That’s a big reason to rethink whether or not we should do something for these older women.”
The HPV test kits in the intervention region were provided by Roche Diagnostics. According to the contract between Roche and Randers Regional Hospital, Roche had no influence on the scientific process and no editorial rights pertaining to this manuscript.
A version of this article first appeared on Medscape.com.
FROM PLOS MEDICINE
New clues to an old mystery: Recent gains in endometriosis
In 1927, American gynecologist John Sampson published his theory of the etiology of endometriosis, postulating that retrograde flow of endometrial debris flows backward through the fallopian tubes during menses into the peritoneal cavity. Dr. Sampson’s notion remains the main paradigm today, mentioned still in recent articles on the topic, but it has a flaw: Although the theory may account for how endometrial tissue escapes the uterus, a 1984 study revealed that this phenomenon occurs in 90% of women. Why, then, do only 10% of women suffer from endometriosis?
Endometriosis describes a condition in which endometrial tissue lining the uterus is found outside the uterus. The disease can be painful, even crippling. As many as 30% of women in their reproductive years who have endometriosis are infertile as a consequence. The hallmarks of the condition are superficial peritoneal lesions of varying color, cysts in the ovaries, deeper nodules accompanied by scarring and adhesion, primarily in the pelvis but sometimes appearing outside the pelvis. The syndrome can be challenging to identify, requiring laparoscopy for definitive diagnosis.
John Sampson aside, scientists have struggled for the past century to identify the cause, or causes, of endometriosis. Hormones clearly play a role in its development, and women with endometriosis have an elevated risk of clear-cell and endometrioid ovarian cancer and autoimmune diseases. Immunodeficiency also could be to blame, if a faulty immune system fails to find and remove endometrial tissue outside of the uterus. A class of chemicals known as endocrine disruptors have been linked to endometriosis, but not definitively. Twin studies have demonstrated that as many as 50% of cases have a genetic basis, while mice with surgically induced endometriosis have been found to have a higher ratio of harmful to beneficial bacteria in their gut.
Several studies published this year point to new insights into the old mystery – with possible implications for ways to treat the disorder.
Perhaps the most surprising came out earlier this year in Science Translational Medicine, as a team of researchers in Japan reported that invasive infection by bacteria of the genus Fusobacterium may cause at least some cases of endometriosis.
Is Fusobacterium the new Helicobacter pylori?
The researchers, from Nagoya University, are the first to suggest that not only might a single bacterial genus cause endometriosis, but that antibiotic treatment could prevent progression of the disease. Using endometrial tissue obtained from 79 women undergoing hysterectomy for endometriosis and 76 women undergoing hysterectomy for other reasons (such as cervical cancer), the team started with gene expression profiling to explore differences between the two sets of samples.
They uncovered an interesting chain of cellular events: macrophages found in endometriotic lesions were secreting transforming growth factor-beta (TGF-beta). TGF-beta in turn stimulated high levels of expression of a gene called TAGLN in fibroblast cells from women with endometriosis but not in fibroblasts from women without endometriosis.
Turning on TAGLN transformed these previously inactive cells into active myofibroblasts, leading to increased proliferation, mobility, and attachment to mesothelial cells, the layer of cells that line body cavities and internal organs. In short, they identified some key players in an environment that seemed very favorable to the development of endometriosis.
“So, the question is: Why are macrophages activated?” said Yutaka Kondo, MD, PhD, the senior author of the study and a professor in the division of cancer biology at the Nagoya (Japan) University Graduate School of Medicine. “We think that there are always bacteria in the endometrium.”
After reviewing data from a previously published study, they used quantitative polymerase chain reaction to rule out one candidate, Erysipelothrix, but scored on their next attempt, identifying Fusobacterium species in endometrial tissue from 64% of the women with endometriosis, compared with fewer than 10% of the controls.
To confirm that the bacteria could cause disease and were not simply bystanders, Dr. Kondo’s team turned to a mouse model for endometriosis, in which endometrial cells are surgically removed from the uteri of mice and injected into the peritoneum of recipient mice, leading to the formation of endometriotic lesions. When mice received further injections of uterine tissue from mice that were infected with F. nucleatum, their lesions were more numerous when compared with mice that received injections of uninfected uterine tissue. Furthermore, antibiotic treatment with metronidazole or chloramphenicol immediately after surgery largely prevented progression to endometriosis, Dr. Kondo and his colleagues reported.
Dr. Kondo likened this relationship between Fusobacterium and endometriosis to that of the link between Helicobacter pylori and peptic ulcers but acknowledged that he doesn’t have all the answers.
“We need more clinical trials, and also we have to know what kind of treatment might be the most effective for the treatment of endometriosis,” Dr. Kondo said, pointing out that other therapies should still be pursued in addition to antibiotics, as not all the samples from women with endometriosis harbored Fusobacterium. “It might be possible that other mechanisms are also involved.”
Don’t write off gut microbiota
Ramakrishna Kommagani, PhD, associate professor of pathology and immunology at Baylor College of Medicine in Houston, agreed. “Endometriosis is a complex disease, which appears to be impacted by many factors, including genetic, epigenetic, and environmental factors,” Dr. Kommagani said.
A key difference between his work and Dr. Kondo’s is his focus on gut microbiota, whereas the Japanese team looked at bacteria in the vagina and endometrium. But Dr. Kommagani said he thinks both could play a role. “Maybe the vaginal microbiome might have a direct impact on disease similar to what we showed on the gut,” he said.
But he said at least part of the answer to why some women develop endometriosis may have to do more with the balance of beneficial and harmful bacteria in the gut rather than because of a single family of microbes like Fusobacterium.
Most recently, by dovetailing a mouse model for inducing endometriosis in mice treated with antibiotics to deplete their gut microbiome, Dr. Kommagani’s lab expanded on its previous work: They showed that the animals developed fewer of the typical lesions seen in endometriosis than those that did not receive antibiotics before all of the mice underwent the surgical procedure used by researchers to induce endometriosis – possibly because they had no bacteria in their gut triggering the inflammatory response required for the development of endometriosis.
But after oral feedings with fecal matter from mice without endometriosis, the microbiota-depleted rodents began developing lesions typical of endometriosis, suggesting that altered gut flora from mice with endometriosis appeared to promote the disorder. Meanwhile, their microbiota-depleted counterparts who were fed fecal matter from mice without endometriosis did not develop the typical lesions.
Dr. Kommagani’s team then compared metabolites from bacteria in stool from mice with and without endometriosis and investigated the in vitro effect of these metabolites on cells from human endometriotic lesions. One of them, quinic acid, increased the proliferation of human endometriotic epithelial cells.
“Some metabolites such as fiber-derived short-chain fatty acids have beneficial effects; they inhibit the disease,” Dr. Kommagani said. “But maybe an amino acid derivative such as quinic acid, [may] promote disease, and these are generated because there is a gut dysbiosis.”
This statement hints at some of the possible therapeutic approaches for endometriosis, such as a high-fiber diet to promote healthy gut flora, or perhaps antibiotics to eradicate unhealthy bacteria. But as with other conditions that have been linked to dysbiosis, like inflammatory bowel disease, use of antibiotics is a bit like balancing on a tightrope; although antibiotics may remove harmful bacteria, their use may negatively affect the beneficial bacteria.
Clues in genetic variants
Krina Zondervan, DPhil, professor and head of the department of reproductive and genomic epidemiology at the University of Oxford (England), focuses on genomic, molecular, and epidemiologic approaches to understanding endometriosis.
“It’s one thing identifying risk variants and the next question is, okay, well, what do those variants actually do in terms of biology?” Dr. Zondervan said. The Oxford team next explored how the identified genetic variants affect gene expression and the proteins generated, drawing on previously collected data on gene expression from samples of human blood and endometrial and uterine tissue.
They found many of the genes implicated in the risk for endometriosis code for proteins that affect sex hormones, uterine development, transformation of healthy cells into cancerous tissue, inflammatory adhesion molecules, and factors promoting development of new blood vessels. All of that, she said, explains how a few endometrial cells making their way into the pelvis can attach to ovaries, ligaments, and peritoneal surfaces; proliferate; and acquire a blood supply to ensure their survival.
“We were able to identify a whole host of things that were likely causal to the disease,” Dr. Zondervan said. And that finding led to her next question: “Are there particular genes or areas around them that can be targeted with certain medications?”
The surprising answer was that several of the genes linked to endometriosis share pathways with clinical syndromes that often occur in women with endometriosis. Many of these are chronic pain conditions – such as migraines, headaches, and back pain – but also include inflammatory illnesses such as asthma and osteoarthritis.
As Dr. Zondervan explained, “A lot of the variance that we see for endometriosis is also experienced for low back pain and migraine, and that clearly has something to do with pain perception and pain mechanisms.”
A connection between the development of neural pathways and endometriosis has been proposed before, as researchers have found that endometriotic lesions can develop their own nerve supply, creating a direct interaction between the lesions and the central nervous system. And some clinicians have been employing treatment strategies that employ multimodal therapies – employing physical therapists, mental health practitioners, nutritionists, and pain specialists prior to and following surgical removal of lesions – to improve overall success rates of treatment.
But Dr. Zondervan’s team is the first to uncover an important clue about how this happens.
The study findings also provide solid clues to researchers about which genes and proteins to focus on for drug target discovery. In particular, the gene pathways shared by endometriosis and various pain conditions could allow for repurposing of drugs developed for other conditions for treating endometriosis, reported Dr. Zondervan.
Dr. Zondervan’s other important conclusion, echoed by Dr. Kondo and Dr. Kommagani, is that endometriosis is not one disease. Rather, it appears to be akin to cancer in terms of the heterogeneity of how it presents and the different subtypes of diseases. The Oxford study corroborated this belief, identifying certain genes that were closely associated with cystic lesions in ovaries, but failing to turn up a genetic link to other types of lesions in the pelvis long considered to be part of the spectrum of endometriosis disease.
Dr. Zondervan agreed that the potential link with Fusobacterium is a fascinating area given the critical role of inflammation in the pathogenesis of endometriosis, although she’d like to see the work replicated with larger sample sizes. “From a personal point of view, I’d be really fascinated to see how genetics interplays with this,” she added.
What’s next?
The chief limitation of human studies looking at mechanisms of endometriosis is that they are correlational: Tissue samples are collected from women with and without endometriosis, often through an invasive procedure such as laparoscopy or biopsy, at one point in time. Currently, the best tools for proving causation are animal models of endometriosis, such as the those used by Dr. Kondo’s and Dr. Kommagani’s teams.
Better diagnostic tools would solve that problem. The ultimate goal is a noninvasive test for endometriosis that would allow clinicians to follow women over time and permit the monitoring of disease progression, or regression, without the need for painful procedures. Such a diagnostic tool would facilitate rigorous longitudinal studies evaluating mechanisms of disease, as well as monitoring outcomes of clinical trials of new treatments.
Could stool samples be the answer?
The Japanese team found that women harboring Fusobacterium in endometrial tissue also had Fusobacterium in vaginal samples taken at the time of their hysterectomy – and stool samples can pick up changes in the gut microbiome.
“Vaginal swab or stool tests are probably the best and easiest for noninvasive early detection,” Dr. Kommagani said.
Spit tests for DNA would be even easier to obtain. Polygenic risk scores could be developed to estimate an individual’s risk of disease based on the number of variants, but Dr. Zondervan cautioned that not all the genes that account for endometriosis are known.
“The things that we found altogether explain about 5% of disease variability, basically – which is still not an awful lot,” she said.
Dr. Kondo’s work was supported by the Grant-in-Aid for Scientific Research, the Japan Society for the Promotion of Science, and the Research Grant of the Princess Takamatsu Cancer Research Fund. A patent method for detecting bacteria of genus Fusobacterium in order to diagnose endometriosis (WO2023/ 042714), was submitted (international publication date, March 23, 2023).
Dr. Kommagani’s work was funded, in part, by National Institutes of Health/National Institute of Child Health and Human Development grants R01HD102680, R01HD065435, and R00HD080742. He has no other conflicts of interest. Dr. Zondervan received funding from the Wellcome Trust (216767; 104036; 084766; 212904; 076113 and 085475) and also reported grants from Bayer AG, AbbVie, Volition Rx, MDNA Life Sciences, and Roche Diagnostics outside the submitted work.
Dr. Thomas is a pediatrician and epidemiologist living in Portland, Ore.
A version of this article originally appeared on Medscape.com.
In 1927, American gynecologist John Sampson published his theory of the etiology of endometriosis, postulating that retrograde flow of endometrial debris flows backward through the fallopian tubes during menses into the peritoneal cavity. Dr. Sampson’s notion remains the main paradigm today, mentioned still in recent articles on the topic, but it has a flaw: Although the theory may account for how endometrial tissue escapes the uterus, a 1984 study revealed that this phenomenon occurs in 90% of women. Why, then, do only 10% of women suffer from endometriosis?
Endometriosis describes a condition in which endometrial tissue lining the uterus is found outside the uterus. The disease can be painful, even crippling. As many as 30% of women in their reproductive years who have endometriosis are infertile as a consequence. The hallmarks of the condition are superficial peritoneal lesions of varying color, cysts in the ovaries, deeper nodules accompanied by scarring and adhesion, primarily in the pelvis but sometimes appearing outside the pelvis. The syndrome can be challenging to identify, requiring laparoscopy for definitive diagnosis.
John Sampson aside, scientists have struggled for the past century to identify the cause, or causes, of endometriosis. Hormones clearly play a role in its development, and women with endometriosis have an elevated risk of clear-cell and endometrioid ovarian cancer and autoimmune diseases. Immunodeficiency also could be to blame, if a faulty immune system fails to find and remove endometrial tissue outside of the uterus. A class of chemicals known as endocrine disruptors have been linked to endometriosis, but not definitively. Twin studies have demonstrated that as many as 50% of cases have a genetic basis, while mice with surgically induced endometriosis have been found to have a higher ratio of harmful to beneficial bacteria in their gut.
Several studies published this year point to new insights into the old mystery – with possible implications for ways to treat the disorder.
Perhaps the most surprising came out earlier this year in Science Translational Medicine, as a team of researchers in Japan reported that invasive infection by bacteria of the genus Fusobacterium may cause at least some cases of endometriosis.
Is Fusobacterium the new Helicobacter pylori?
The researchers, from Nagoya University, are the first to suggest that not only might a single bacterial genus cause endometriosis, but that antibiotic treatment could prevent progression of the disease. Using endometrial tissue obtained from 79 women undergoing hysterectomy for endometriosis and 76 women undergoing hysterectomy for other reasons (such as cervical cancer), the team started with gene expression profiling to explore differences between the two sets of samples.
They uncovered an interesting chain of cellular events: macrophages found in endometriotic lesions were secreting transforming growth factor-beta (TGF-beta). TGF-beta in turn stimulated high levels of expression of a gene called TAGLN in fibroblast cells from women with endometriosis but not in fibroblasts from women without endometriosis.
Turning on TAGLN transformed these previously inactive cells into active myofibroblasts, leading to increased proliferation, mobility, and attachment to mesothelial cells, the layer of cells that line body cavities and internal organs. In short, they identified some key players in an environment that seemed very favorable to the development of endometriosis.
“So, the question is: Why are macrophages activated?” said Yutaka Kondo, MD, PhD, the senior author of the study and a professor in the division of cancer biology at the Nagoya (Japan) University Graduate School of Medicine. “We think that there are always bacteria in the endometrium.”
After reviewing data from a previously published study, they used quantitative polymerase chain reaction to rule out one candidate, Erysipelothrix, but scored on their next attempt, identifying Fusobacterium species in endometrial tissue from 64% of the women with endometriosis, compared with fewer than 10% of the controls.
To confirm that the bacteria could cause disease and were not simply bystanders, Dr. Kondo’s team turned to a mouse model for endometriosis, in which endometrial cells are surgically removed from the uteri of mice and injected into the peritoneum of recipient mice, leading to the formation of endometriotic lesions. When mice received further injections of uterine tissue from mice that were infected with F. nucleatum, their lesions were more numerous when compared with mice that received injections of uninfected uterine tissue. Furthermore, antibiotic treatment with metronidazole or chloramphenicol immediately after surgery largely prevented progression to endometriosis, Dr. Kondo and his colleagues reported.
Dr. Kondo likened this relationship between Fusobacterium and endometriosis to that of the link between Helicobacter pylori and peptic ulcers but acknowledged that he doesn’t have all the answers.
“We need more clinical trials, and also we have to know what kind of treatment might be the most effective for the treatment of endometriosis,” Dr. Kondo said, pointing out that other therapies should still be pursued in addition to antibiotics, as not all the samples from women with endometriosis harbored Fusobacterium. “It might be possible that other mechanisms are also involved.”
Don’t write off gut microbiota
Ramakrishna Kommagani, PhD, associate professor of pathology and immunology at Baylor College of Medicine in Houston, agreed. “Endometriosis is a complex disease, which appears to be impacted by many factors, including genetic, epigenetic, and environmental factors,” Dr. Kommagani said.
A key difference between his work and Dr. Kondo’s is his focus on gut microbiota, whereas the Japanese team looked at bacteria in the vagina and endometrium. But Dr. Kommagani said he thinks both could play a role. “Maybe the vaginal microbiome might have a direct impact on disease similar to what we showed on the gut,” he said.
But he said at least part of the answer to why some women develop endometriosis may have to do more with the balance of beneficial and harmful bacteria in the gut rather than because of a single family of microbes like Fusobacterium.
Most recently, by dovetailing a mouse model for inducing endometriosis in mice treated with antibiotics to deplete their gut microbiome, Dr. Kommagani’s lab expanded on its previous work: They showed that the animals developed fewer of the typical lesions seen in endometriosis than those that did not receive antibiotics before all of the mice underwent the surgical procedure used by researchers to induce endometriosis – possibly because they had no bacteria in their gut triggering the inflammatory response required for the development of endometriosis.
But after oral feedings with fecal matter from mice without endometriosis, the microbiota-depleted rodents began developing lesions typical of endometriosis, suggesting that altered gut flora from mice with endometriosis appeared to promote the disorder. Meanwhile, their microbiota-depleted counterparts who were fed fecal matter from mice without endometriosis did not develop the typical lesions.
Dr. Kommagani’s team then compared metabolites from bacteria in stool from mice with and without endometriosis and investigated the in vitro effect of these metabolites on cells from human endometriotic lesions. One of them, quinic acid, increased the proliferation of human endometriotic epithelial cells.
“Some metabolites such as fiber-derived short-chain fatty acids have beneficial effects; they inhibit the disease,” Dr. Kommagani said. “But maybe an amino acid derivative such as quinic acid, [may] promote disease, and these are generated because there is a gut dysbiosis.”
This statement hints at some of the possible therapeutic approaches for endometriosis, such as a high-fiber diet to promote healthy gut flora, or perhaps antibiotics to eradicate unhealthy bacteria. But as with other conditions that have been linked to dysbiosis, like inflammatory bowel disease, use of antibiotics is a bit like balancing on a tightrope; although antibiotics may remove harmful bacteria, their use may negatively affect the beneficial bacteria.
Clues in genetic variants
Krina Zondervan, DPhil, professor and head of the department of reproductive and genomic epidemiology at the University of Oxford (England), focuses on genomic, molecular, and epidemiologic approaches to understanding endometriosis.
“It’s one thing identifying risk variants and the next question is, okay, well, what do those variants actually do in terms of biology?” Dr. Zondervan said. The Oxford team next explored how the identified genetic variants affect gene expression and the proteins generated, drawing on previously collected data on gene expression from samples of human blood and endometrial and uterine tissue.
They found many of the genes implicated in the risk for endometriosis code for proteins that affect sex hormones, uterine development, transformation of healthy cells into cancerous tissue, inflammatory adhesion molecules, and factors promoting development of new blood vessels. All of that, she said, explains how a few endometrial cells making their way into the pelvis can attach to ovaries, ligaments, and peritoneal surfaces; proliferate; and acquire a blood supply to ensure their survival.
“We were able to identify a whole host of things that were likely causal to the disease,” Dr. Zondervan said. And that finding led to her next question: “Are there particular genes or areas around them that can be targeted with certain medications?”
The surprising answer was that several of the genes linked to endometriosis share pathways with clinical syndromes that often occur in women with endometriosis. Many of these are chronic pain conditions – such as migraines, headaches, and back pain – but also include inflammatory illnesses such as asthma and osteoarthritis.
As Dr. Zondervan explained, “A lot of the variance that we see for endometriosis is also experienced for low back pain and migraine, and that clearly has something to do with pain perception and pain mechanisms.”
A connection between the development of neural pathways and endometriosis has been proposed before, as researchers have found that endometriotic lesions can develop their own nerve supply, creating a direct interaction between the lesions and the central nervous system. And some clinicians have been employing treatment strategies that employ multimodal therapies – employing physical therapists, mental health practitioners, nutritionists, and pain specialists prior to and following surgical removal of lesions – to improve overall success rates of treatment.
But Dr. Zondervan’s team is the first to uncover an important clue about how this happens.
The study findings also provide solid clues to researchers about which genes and proteins to focus on for drug target discovery. In particular, the gene pathways shared by endometriosis and various pain conditions could allow for repurposing of drugs developed for other conditions for treating endometriosis, reported Dr. Zondervan.
Dr. Zondervan’s other important conclusion, echoed by Dr. Kondo and Dr. Kommagani, is that endometriosis is not one disease. Rather, it appears to be akin to cancer in terms of the heterogeneity of how it presents and the different subtypes of diseases. The Oxford study corroborated this belief, identifying certain genes that were closely associated with cystic lesions in ovaries, but failing to turn up a genetic link to other types of lesions in the pelvis long considered to be part of the spectrum of endometriosis disease.
Dr. Zondervan agreed that the potential link with Fusobacterium is a fascinating area given the critical role of inflammation in the pathogenesis of endometriosis, although she’d like to see the work replicated with larger sample sizes. “From a personal point of view, I’d be really fascinated to see how genetics interplays with this,” she added.
What’s next?
The chief limitation of human studies looking at mechanisms of endometriosis is that they are correlational: Tissue samples are collected from women with and without endometriosis, often through an invasive procedure such as laparoscopy or biopsy, at one point in time. Currently, the best tools for proving causation are animal models of endometriosis, such as the those used by Dr. Kondo’s and Dr. Kommagani’s teams.
Better diagnostic tools would solve that problem. The ultimate goal is a noninvasive test for endometriosis that would allow clinicians to follow women over time and permit the monitoring of disease progression, or regression, without the need for painful procedures. Such a diagnostic tool would facilitate rigorous longitudinal studies evaluating mechanisms of disease, as well as monitoring outcomes of clinical trials of new treatments.
Could stool samples be the answer?
The Japanese team found that women harboring Fusobacterium in endometrial tissue also had Fusobacterium in vaginal samples taken at the time of their hysterectomy – and stool samples can pick up changes in the gut microbiome.
“Vaginal swab or stool tests are probably the best and easiest for noninvasive early detection,” Dr. Kommagani said.
Spit tests for DNA would be even easier to obtain. Polygenic risk scores could be developed to estimate an individual’s risk of disease based on the number of variants, but Dr. Zondervan cautioned that not all the genes that account for endometriosis are known.
“The things that we found altogether explain about 5% of disease variability, basically – which is still not an awful lot,” she said.
Dr. Kondo’s work was supported by the Grant-in-Aid for Scientific Research, the Japan Society for the Promotion of Science, and the Research Grant of the Princess Takamatsu Cancer Research Fund. A patent method for detecting bacteria of genus Fusobacterium in order to diagnose endometriosis (WO2023/ 042714), was submitted (international publication date, March 23, 2023).
Dr. Kommagani’s work was funded, in part, by National Institutes of Health/National Institute of Child Health and Human Development grants R01HD102680, R01HD065435, and R00HD080742. He has no other conflicts of interest. Dr. Zondervan received funding from the Wellcome Trust (216767; 104036; 084766; 212904; 076113 and 085475) and also reported grants from Bayer AG, AbbVie, Volition Rx, MDNA Life Sciences, and Roche Diagnostics outside the submitted work.
Dr. Thomas is a pediatrician and epidemiologist living in Portland, Ore.
A version of this article originally appeared on Medscape.com.
In 1927, American gynecologist John Sampson published his theory of the etiology of endometriosis, postulating that retrograde flow of endometrial debris flows backward through the fallopian tubes during menses into the peritoneal cavity. Dr. Sampson’s notion remains the main paradigm today, mentioned still in recent articles on the topic, but it has a flaw: Although the theory may account for how endometrial tissue escapes the uterus, a 1984 study revealed that this phenomenon occurs in 90% of women. Why, then, do only 10% of women suffer from endometriosis?
Endometriosis describes a condition in which endometrial tissue lining the uterus is found outside the uterus. The disease can be painful, even crippling. As many as 30% of women in their reproductive years who have endometriosis are infertile as a consequence. The hallmarks of the condition are superficial peritoneal lesions of varying color, cysts in the ovaries, deeper nodules accompanied by scarring and adhesion, primarily in the pelvis but sometimes appearing outside the pelvis. The syndrome can be challenging to identify, requiring laparoscopy for definitive diagnosis.
John Sampson aside, scientists have struggled for the past century to identify the cause, or causes, of endometriosis. Hormones clearly play a role in its development, and women with endometriosis have an elevated risk of clear-cell and endometrioid ovarian cancer and autoimmune diseases. Immunodeficiency also could be to blame, if a faulty immune system fails to find and remove endometrial tissue outside of the uterus. A class of chemicals known as endocrine disruptors have been linked to endometriosis, but not definitively. Twin studies have demonstrated that as many as 50% of cases have a genetic basis, while mice with surgically induced endometriosis have been found to have a higher ratio of harmful to beneficial bacteria in their gut.
Several studies published this year point to new insights into the old mystery – with possible implications for ways to treat the disorder.
Perhaps the most surprising came out earlier this year in Science Translational Medicine, as a team of researchers in Japan reported that invasive infection by bacteria of the genus Fusobacterium may cause at least some cases of endometriosis.
Is Fusobacterium the new Helicobacter pylori?
The researchers, from Nagoya University, are the first to suggest that not only might a single bacterial genus cause endometriosis, but that antibiotic treatment could prevent progression of the disease. Using endometrial tissue obtained from 79 women undergoing hysterectomy for endometriosis and 76 women undergoing hysterectomy for other reasons (such as cervical cancer), the team started with gene expression profiling to explore differences between the two sets of samples.
They uncovered an interesting chain of cellular events: macrophages found in endometriotic lesions were secreting transforming growth factor-beta (TGF-beta). TGF-beta in turn stimulated high levels of expression of a gene called TAGLN in fibroblast cells from women with endometriosis but not in fibroblasts from women without endometriosis.
Turning on TAGLN transformed these previously inactive cells into active myofibroblasts, leading to increased proliferation, mobility, and attachment to mesothelial cells, the layer of cells that line body cavities and internal organs. In short, they identified some key players in an environment that seemed very favorable to the development of endometriosis.
“So, the question is: Why are macrophages activated?” said Yutaka Kondo, MD, PhD, the senior author of the study and a professor in the division of cancer biology at the Nagoya (Japan) University Graduate School of Medicine. “We think that there are always bacteria in the endometrium.”
After reviewing data from a previously published study, they used quantitative polymerase chain reaction to rule out one candidate, Erysipelothrix, but scored on their next attempt, identifying Fusobacterium species in endometrial tissue from 64% of the women with endometriosis, compared with fewer than 10% of the controls.
To confirm that the bacteria could cause disease and were not simply bystanders, Dr. Kondo’s team turned to a mouse model for endometriosis, in which endometrial cells are surgically removed from the uteri of mice and injected into the peritoneum of recipient mice, leading to the formation of endometriotic lesions. When mice received further injections of uterine tissue from mice that were infected with F. nucleatum, their lesions were more numerous when compared with mice that received injections of uninfected uterine tissue. Furthermore, antibiotic treatment with metronidazole or chloramphenicol immediately after surgery largely prevented progression to endometriosis, Dr. Kondo and his colleagues reported.
Dr. Kondo likened this relationship between Fusobacterium and endometriosis to that of the link between Helicobacter pylori and peptic ulcers but acknowledged that he doesn’t have all the answers.
“We need more clinical trials, and also we have to know what kind of treatment might be the most effective for the treatment of endometriosis,” Dr. Kondo said, pointing out that other therapies should still be pursued in addition to antibiotics, as not all the samples from women with endometriosis harbored Fusobacterium. “It might be possible that other mechanisms are also involved.”
Don’t write off gut microbiota
Ramakrishna Kommagani, PhD, associate professor of pathology and immunology at Baylor College of Medicine in Houston, agreed. “Endometriosis is a complex disease, which appears to be impacted by many factors, including genetic, epigenetic, and environmental factors,” Dr. Kommagani said.
A key difference between his work and Dr. Kondo’s is his focus on gut microbiota, whereas the Japanese team looked at bacteria in the vagina and endometrium. But Dr. Kommagani said he thinks both could play a role. “Maybe the vaginal microbiome might have a direct impact on disease similar to what we showed on the gut,” he said.
But he said at least part of the answer to why some women develop endometriosis may have to do more with the balance of beneficial and harmful bacteria in the gut rather than because of a single family of microbes like Fusobacterium.
Most recently, by dovetailing a mouse model for inducing endometriosis in mice treated with antibiotics to deplete their gut microbiome, Dr. Kommagani’s lab expanded on its previous work: They showed that the animals developed fewer of the typical lesions seen in endometriosis than those that did not receive antibiotics before all of the mice underwent the surgical procedure used by researchers to induce endometriosis – possibly because they had no bacteria in their gut triggering the inflammatory response required for the development of endometriosis.
But after oral feedings with fecal matter from mice without endometriosis, the microbiota-depleted rodents began developing lesions typical of endometriosis, suggesting that altered gut flora from mice with endometriosis appeared to promote the disorder. Meanwhile, their microbiota-depleted counterparts who were fed fecal matter from mice without endometriosis did not develop the typical lesions.
Dr. Kommagani’s team then compared metabolites from bacteria in stool from mice with and without endometriosis and investigated the in vitro effect of these metabolites on cells from human endometriotic lesions. One of them, quinic acid, increased the proliferation of human endometriotic epithelial cells.
“Some metabolites such as fiber-derived short-chain fatty acids have beneficial effects; they inhibit the disease,” Dr. Kommagani said. “But maybe an amino acid derivative such as quinic acid, [may] promote disease, and these are generated because there is a gut dysbiosis.”
This statement hints at some of the possible therapeutic approaches for endometriosis, such as a high-fiber diet to promote healthy gut flora, or perhaps antibiotics to eradicate unhealthy bacteria. But as with other conditions that have been linked to dysbiosis, like inflammatory bowel disease, use of antibiotics is a bit like balancing on a tightrope; although antibiotics may remove harmful bacteria, their use may negatively affect the beneficial bacteria.
Clues in genetic variants
Krina Zondervan, DPhil, professor and head of the department of reproductive and genomic epidemiology at the University of Oxford (England), focuses on genomic, molecular, and epidemiologic approaches to understanding endometriosis.
“It’s one thing identifying risk variants and the next question is, okay, well, what do those variants actually do in terms of biology?” Dr. Zondervan said. The Oxford team next explored how the identified genetic variants affect gene expression and the proteins generated, drawing on previously collected data on gene expression from samples of human blood and endometrial and uterine tissue.
They found many of the genes implicated in the risk for endometriosis code for proteins that affect sex hormones, uterine development, transformation of healthy cells into cancerous tissue, inflammatory adhesion molecules, and factors promoting development of new blood vessels. All of that, she said, explains how a few endometrial cells making their way into the pelvis can attach to ovaries, ligaments, and peritoneal surfaces; proliferate; and acquire a blood supply to ensure their survival.
“We were able to identify a whole host of things that were likely causal to the disease,” Dr. Zondervan said. And that finding led to her next question: “Are there particular genes or areas around them that can be targeted with certain medications?”
The surprising answer was that several of the genes linked to endometriosis share pathways with clinical syndromes that often occur in women with endometriosis. Many of these are chronic pain conditions – such as migraines, headaches, and back pain – but also include inflammatory illnesses such as asthma and osteoarthritis.
As Dr. Zondervan explained, “A lot of the variance that we see for endometriosis is also experienced for low back pain and migraine, and that clearly has something to do with pain perception and pain mechanisms.”
A connection between the development of neural pathways and endometriosis has been proposed before, as researchers have found that endometriotic lesions can develop their own nerve supply, creating a direct interaction between the lesions and the central nervous system. And some clinicians have been employing treatment strategies that employ multimodal therapies – employing physical therapists, mental health practitioners, nutritionists, and pain specialists prior to and following surgical removal of lesions – to improve overall success rates of treatment.
But Dr. Zondervan’s team is the first to uncover an important clue about how this happens.
The study findings also provide solid clues to researchers about which genes and proteins to focus on for drug target discovery. In particular, the gene pathways shared by endometriosis and various pain conditions could allow for repurposing of drugs developed for other conditions for treating endometriosis, reported Dr. Zondervan.
Dr. Zondervan’s other important conclusion, echoed by Dr. Kondo and Dr. Kommagani, is that endometriosis is not one disease. Rather, it appears to be akin to cancer in terms of the heterogeneity of how it presents and the different subtypes of diseases. The Oxford study corroborated this belief, identifying certain genes that were closely associated with cystic lesions in ovaries, but failing to turn up a genetic link to other types of lesions in the pelvis long considered to be part of the spectrum of endometriosis disease.
Dr. Zondervan agreed that the potential link with Fusobacterium is a fascinating area given the critical role of inflammation in the pathogenesis of endometriosis, although she’d like to see the work replicated with larger sample sizes. “From a personal point of view, I’d be really fascinated to see how genetics interplays with this,” she added.
What’s next?
The chief limitation of human studies looking at mechanisms of endometriosis is that they are correlational: Tissue samples are collected from women with and without endometriosis, often through an invasive procedure such as laparoscopy or biopsy, at one point in time. Currently, the best tools for proving causation are animal models of endometriosis, such as the those used by Dr. Kondo’s and Dr. Kommagani’s teams.
Better diagnostic tools would solve that problem. The ultimate goal is a noninvasive test for endometriosis that would allow clinicians to follow women over time and permit the monitoring of disease progression, or regression, without the need for painful procedures. Such a diagnostic tool would facilitate rigorous longitudinal studies evaluating mechanisms of disease, as well as monitoring outcomes of clinical trials of new treatments.
Could stool samples be the answer?
The Japanese team found that women harboring Fusobacterium in endometrial tissue also had Fusobacterium in vaginal samples taken at the time of their hysterectomy – and stool samples can pick up changes in the gut microbiome.
“Vaginal swab or stool tests are probably the best and easiest for noninvasive early detection,” Dr. Kommagani said.
Spit tests for DNA would be even easier to obtain. Polygenic risk scores could be developed to estimate an individual’s risk of disease based on the number of variants, but Dr. Zondervan cautioned that not all the genes that account for endometriosis are known.
“The things that we found altogether explain about 5% of disease variability, basically – which is still not an awful lot,” she said.
Dr. Kondo’s work was supported by the Grant-in-Aid for Scientific Research, the Japan Society for the Promotion of Science, and the Research Grant of the Princess Takamatsu Cancer Research Fund. A patent method for detecting bacteria of genus Fusobacterium in order to diagnose endometriosis (WO2023/ 042714), was submitted (international publication date, March 23, 2023).
Dr. Kommagani’s work was funded, in part, by National Institutes of Health/National Institute of Child Health and Human Development grants R01HD102680, R01HD065435, and R00HD080742. He has no other conflicts of interest. Dr. Zondervan received funding from the Wellcome Trust (216767; 104036; 084766; 212904; 076113 and 085475) and also reported grants from Bayer AG, AbbVie, Volition Rx, MDNA Life Sciences, and Roche Diagnostics outside the submitted work.
Dr. Thomas is a pediatrician and epidemiologist living in Portland, Ore.
A version of this article originally appeared on Medscape.com.
HPV rates skyrocket despite safe, effective vaccine
An epidemic of sexually transmitted HPV is now swirling around the United States and the United Kingdom, with some serious cases leading to oropharyngeal cancer, which can affect the back of the throat, tonsils, and tongue.
HPV is the leading cause (70%) of this oropharyngeal cancer, according to the CDC. It is the most common sexually transmitted disease in the nation, and around 3.6% of women and 10% of men report oral HPV specifically. But over the past decade, oropharyngeal cases have been steadily falling a little under 4% and 2%, respectively, according to the National Cancer Institute.
HPV is often undetectable and can clear up within a few months. But unfortunately for some, serious disease, such as throat cancer, can develop.
Studies show the HPV vaccine to be extremely effective in lowering sexually transmitted HPV cases. Yet, only 54.5% of young people aged 13-15 have taken the recommended two to three doses, according to the National Cancer Institute.
Why aren’t more young people taking the vaccine?
Low public awareness of the dangers of HPV may be behind young people’s poor vaccination rates, according to Teresa Lee, MD, of the Fox Chase Cancer Center in Philadelphia. “For example, while the link with head and neck cancers has been well-studied, the FDA labeling was not changed to reflect this as an indication until 2020,” she said.
Other reasons can include one’s socioeconomic background, poor health literacy, cultural or religious stigmas around vaccines, and lack of quality, low-cost health care, says Emmanuel Aguh, MD, a board-certified family medicine physician. “Some individuals and families are still resistant to vaccines and the noted lack of uptake.”
Doctors and other health care professionals should also be sure to tell patients of all ages about the risks of HPV infection and how well the vaccine works, Dr. Lee said. “Not everyone who is now eligible may have been offered the vaccine as a child, and the first time young adults may receive counseling on this subject may not be until they are entering a very busy period of their lives with many responsibilities – when it may be hard to fit in things like health maintenance.”
How safe is the HPV vaccine?
The Food and Drug Administration and Centers for Disease Control and Prevention have studied the HPV vaccine for years to find out how safe it is and how well it works, Dr. Aguh said. No major side effects have been reported, and the most common side effect is soreness where you get the shot (which is normal after most vaccines). Some dizziness and fainting in adolescents can also occur, so young people are usually asked to sit or lie down during the shot and for 15 minutes afterward, he said.
“Serious adverse events have not been reported at higher rates than expected following HPV vaccination, meaning there is no clear evidence they are related to the vaccine,” Dr. Lee said. “The vaccine is highly effective in decreasing rates of detectable infection with the high-risk HPV strains responsible for HPV-associated cancers.”
The HPV vaccine is largely recommended for people aged 9-26, and sometimes up to age 45, depending on the individual, Dr. Aguh said. If you are over 26, talk to your doctor about whether you should consider getting the vaccine.
“It is usually given in two doses for complete protection if taken before the 15th birthday,” Dr. Aguh said. “If taken afterward, or in those with a weak immune system, they might require three doses to be fully protected.”
The vaccine produces antibodies that can stop HPV from infecting cells and lowers your chances of catching an HPV-related cancer, such as throat cancer or cancer of the cervix, he said.
While the vaccine is not guaranteed to protect you from the more than 100 strains of HPV, it can protect you from HPV 16 and HPV 18 – two high-risk strains that cause around 70% of cervical cancers.
What is fueling the rise of HPV cases?
A misconception that oral sex is somehow a “safe and risk-free” alternative to anal or vaginal sex could be one reason, Dr. Aguh said.
“It is important to know that, with oral sex, you are exposed to many of the risks associated with vaginal intercourse, especially if you do not take any measures to protect yourself and/or your partner,” Dr. Aguh said. “[With oral sex] it is possible to end up contracting an infection like chlamydia, gonorrhea, and even HPV, leading to an increased risk of HPV-associated oropharyngeal cancers.”
A lack of public awareness of what can cause throat cancer could also explain this phenomenon. The number of people you have oral sex with, along with the age you begin sexual activity, can greatly determine your risk of the disease, according to Dr. Lee. She echoes a report by Hisham Mehanna, PhD, in The Conversation.
“For oropharyngeal cancer, the main risk factor is the number of lifetime sexual partners, especially oral sex,” wrote Dr. Mehanna, a professor at the Institute of Cancer and Genomic Sciences at the University of Birmingham (England). “Those with six or more lifetime oral-sex partners are 8.5 times more likely to develop oropharyngeal cancer than those who do not practice oral sex.”
What are symptoms of oropharyngeal cancer?
Labored breathing or swallowing, a cough that won’t go away, and crackling or hoarseness of your voice could all be signs of throat cancer. Other symptoms include earaches, swelling of the head or neck, and enlarged lymph nodes, among others, Dr. Aguh said.
“The signs and symptoms of HPV-related throat cancers can be difficult to identify and recognize, as they can be vague and are also associated with other medical conditions. Sometimes, there are no signs at all, or they are not easily noticeable due to the location,” he said.
You should go see your doctor if you have any of these ailments for an extended period.
How to reduce your risk
In addition to having six or more oral-sex partners, smoking and drinking heavily could also raise your risk of throat cancer, said Dr. Lee. Proper dental health – like seeing your dentist regularly and practicing proper oral hygiene – can also shave your risk.
“[Good dental health] can help not just with head and neck cancer risk, but with many other inflammation-related diseases,” Dr. Lee said.
Using dental dams and condoms can also be a good method of protection, Dr. Aguh said. A dental dam is a stretchy sheet of latex, or polyurethane plastic, in the shape of a square that is made for blocking body fluid to lower your risk of contracting an STD via oral sex.
Keep in mind: Even with these protections, make sure you and your partner discuss each other’s sexual history, any prior or current STDs and their preferred protection from STDs, said Dr. Aguh.
If you or your partner is being treated for an STD, consider opting out of oral sex and consulting a doctor.
The HPV vaccine is another common method of protection. The shot is “approved for prevention of nine of the most high-risk strains of HPV,” or those that are most commonly linked to cancer, according to Dr. Lee. The vaccine “reduces the frequency of infection” with these viruses, which can ultimately lower the risk of cancers linked to HPV, including cervical, anal, and vulvar and vaginal cancers, she said.
“The best time to receive treatment for prevention of disease is prior to onset of sexual intercourse,” said Dr. Lee.
To get your HPV vaccine, head to your family doctor, school- or community-based health center, or state health department, suggests the CDC.
A version of this article originally appeared on WebMD.com.
An epidemic of sexually transmitted HPV is now swirling around the United States and the United Kingdom, with some serious cases leading to oropharyngeal cancer, which can affect the back of the throat, tonsils, and tongue.
HPV is the leading cause (70%) of this oropharyngeal cancer, according to the CDC. It is the most common sexually transmitted disease in the nation, and around 3.6% of women and 10% of men report oral HPV specifically. But over the past decade, oropharyngeal cases have been steadily falling a little under 4% and 2%, respectively, according to the National Cancer Institute.
HPV is often undetectable and can clear up within a few months. But unfortunately for some, serious disease, such as throat cancer, can develop.
Studies show the HPV vaccine to be extremely effective in lowering sexually transmitted HPV cases. Yet, only 54.5% of young people aged 13-15 have taken the recommended two to three doses, according to the National Cancer Institute.
Why aren’t more young people taking the vaccine?
Low public awareness of the dangers of HPV may be behind young people’s poor vaccination rates, according to Teresa Lee, MD, of the Fox Chase Cancer Center in Philadelphia. “For example, while the link with head and neck cancers has been well-studied, the FDA labeling was not changed to reflect this as an indication until 2020,” she said.
Other reasons can include one’s socioeconomic background, poor health literacy, cultural or religious stigmas around vaccines, and lack of quality, low-cost health care, says Emmanuel Aguh, MD, a board-certified family medicine physician. “Some individuals and families are still resistant to vaccines and the noted lack of uptake.”
Doctors and other health care professionals should also be sure to tell patients of all ages about the risks of HPV infection and how well the vaccine works, Dr. Lee said. “Not everyone who is now eligible may have been offered the vaccine as a child, and the first time young adults may receive counseling on this subject may not be until they are entering a very busy period of their lives with many responsibilities – when it may be hard to fit in things like health maintenance.”
How safe is the HPV vaccine?
The Food and Drug Administration and Centers for Disease Control and Prevention have studied the HPV vaccine for years to find out how safe it is and how well it works, Dr. Aguh said. No major side effects have been reported, and the most common side effect is soreness where you get the shot (which is normal after most vaccines). Some dizziness and fainting in adolescents can also occur, so young people are usually asked to sit or lie down during the shot and for 15 minutes afterward, he said.
“Serious adverse events have not been reported at higher rates than expected following HPV vaccination, meaning there is no clear evidence they are related to the vaccine,” Dr. Lee said. “The vaccine is highly effective in decreasing rates of detectable infection with the high-risk HPV strains responsible for HPV-associated cancers.”
The HPV vaccine is largely recommended for people aged 9-26, and sometimes up to age 45, depending on the individual, Dr. Aguh said. If you are over 26, talk to your doctor about whether you should consider getting the vaccine.
“It is usually given in two doses for complete protection if taken before the 15th birthday,” Dr. Aguh said. “If taken afterward, or in those with a weak immune system, they might require three doses to be fully protected.”
The vaccine produces antibodies that can stop HPV from infecting cells and lowers your chances of catching an HPV-related cancer, such as throat cancer or cancer of the cervix, he said.
While the vaccine is not guaranteed to protect you from the more than 100 strains of HPV, it can protect you from HPV 16 and HPV 18 – two high-risk strains that cause around 70% of cervical cancers.
What is fueling the rise of HPV cases?
A misconception that oral sex is somehow a “safe and risk-free” alternative to anal or vaginal sex could be one reason, Dr. Aguh said.
“It is important to know that, with oral sex, you are exposed to many of the risks associated with vaginal intercourse, especially if you do not take any measures to protect yourself and/or your partner,” Dr. Aguh said. “[With oral sex] it is possible to end up contracting an infection like chlamydia, gonorrhea, and even HPV, leading to an increased risk of HPV-associated oropharyngeal cancers.”
A lack of public awareness of what can cause throat cancer could also explain this phenomenon. The number of people you have oral sex with, along with the age you begin sexual activity, can greatly determine your risk of the disease, according to Dr. Lee. She echoes a report by Hisham Mehanna, PhD, in The Conversation.
“For oropharyngeal cancer, the main risk factor is the number of lifetime sexual partners, especially oral sex,” wrote Dr. Mehanna, a professor at the Institute of Cancer and Genomic Sciences at the University of Birmingham (England). “Those with six or more lifetime oral-sex partners are 8.5 times more likely to develop oropharyngeal cancer than those who do not practice oral sex.”
What are symptoms of oropharyngeal cancer?
Labored breathing or swallowing, a cough that won’t go away, and crackling or hoarseness of your voice could all be signs of throat cancer. Other symptoms include earaches, swelling of the head or neck, and enlarged lymph nodes, among others, Dr. Aguh said.
“The signs and symptoms of HPV-related throat cancers can be difficult to identify and recognize, as they can be vague and are also associated with other medical conditions. Sometimes, there are no signs at all, or they are not easily noticeable due to the location,” he said.
You should go see your doctor if you have any of these ailments for an extended period.
How to reduce your risk
In addition to having six or more oral-sex partners, smoking and drinking heavily could also raise your risk of throat cancer, said Dr. Lee. Proper dental health – like seeing your dentist regularly and practicing proper oral hygiene – can also shave your risk.
“[Good dental health] can help not just with head and neck cancer risk, but with many other inflammation-related diseases,” Dr. Lee said.
Using dental dams and condoms can also be a good method of protection, Dr. Aguh said. A dental dam is a stretchy sheet of latex, or polyurethane plastic, in the shape of a square that is made for blocking body fluid to lower your risk of contracting an STD via oral sex.
Keep in mind: Even with these protections, make sure you and your partner discuss each other’s sexual history, any prior or current STDs and their preferred protection from STDs, said Dr. Aguh.
If you or your partner is being treated for an STD, consider opting out of oral sex and consulting a doctor.
The HPV vaccine is another common method of protection. The shot is “approved for prevention of nine of the most high-risk strains of HPV,” or those that are most commonly linked to cancer, according to Dr. Lee. The vaccine “reduces the frequency of infection” with these viruses, which can ultimately lower the risk of cancers linked to HPV, including cervical, anal, and vulvar and vaginal cancers, she said.
“The best time to receive treatment for prevention of disease is prior to onset of sexual intercourse,” said Dr. Lee.
To get your HPV vaccine, head to your family doctor, school- or community-based health center, or state health department, suggests the CDC.
A version of this article originally appeared on WebMD.com.
An epidemic of sexually transmitted HPV is now swirling around the United States and the United Kingdom, with some serious cases leading to oropharyngeal cancer, which can affect the back of the throat, tonsils, and tongue.
HPV is the leading cause (70%) of this oropharyngeal cancer, according to the CDC. It is the most common sexually transmitted disease in the nation, and around 3.6% of women and 10% of men report oral HPV specifically. But over the past decade, oropharyngeal cases have been steadily falling a little under 4% and 2%, respectively, according to the National Cancer Institute.
HPV is often undetectable and can clear up within a few months. But unfortunately for some, serious disease, such as throat cancer, can develop.
Studies show the HPV vaccine to be extremely effective in lowering sexually transmitted HPV cases. Yet, only 54.5% of young people aged 13-15 have taken the recommended two to three doses, according to the National Cancer Institute.
Why aren’t more young people taking the vaccine?
Low public awareness of the dangers of HPV may be behind young people’s poor vaccination rates, according to Teresa Lee, MD, of the Fox Chase Cancer Center in Philadelphia. “For example, while the link with head and neck cancers has been well-studied, the FDA labeling was not changed to reflect this as an indication until 2020,” she said.
Other reasons can include one’s socioeconomic background, poor health literacy, cultural or religious stigmas around vaccines, and lack of quality, low-cost health care, says Emmanuel Aguh, MD, a board-certified family medicine physician. “Some individuals and families are still resistant to vaccines and the noted lack of uptake.”
Doctors and other health care professionals should also be sure to tell patients of all ages about the risks of HPV infection and how well the vaccine works, Dr. Lee said. “Not everyone who is now eligible may have been offered the vaccine as a child, and the first time young adults may receive counseling on this subject may not be until they are entering a very busy period of their lives with many responsibilities – when it may be hard to fit in things like health maintenance.”
How safe is the HPV vaccine?
The Food and Drug Administration and Centers for Disease Control and Prevention have studied the HPV vaccine for years to find out how safe it is and how well it works, Dr. Aguh said. No major side effects have been reported, and the most common side effect is soreness where you get the shot (which is normal after most vaccines). Some dizziness and fainting in adolescents can also occur, so young people are usually asked to sit or lie down during the shot and for 15 minutes afterward, he said.
“Serious adverse events have not been reported at higher rates than expected following HPV vaccination, meaning there is no clear evidence they are related to the vaccine,” Dr. Lee said. “The vaccine is highly effective in decreasing rates of detectable infection with the high-risk HPV strains responsible for HPV-associated cancers.”
The HPV vaccine is largely recommended for people aged 9-26, and sometimes up to age 45, depending on the individual, Dr. Aguh said. If you are over 26, talk to your doctor about whether you should consider getting the vaccine.
“It is usually given in two doses for complete protection if taken before the 15th birthday,” Dr. Aguh said. “If taken afterward, or in those with a weak immune system, they might require three doses to be fully protected.”
The vaccine produces antibodies that can stop HPV from infecting cells and lowers your chances of catching an HPV-related cancer, such as throat cancer or cancer of the cervix, he said.
While the vaccine is not guaranteed to protect you from the more than 100 strains of HPV, it can protect you from HPV 16 and HPV 18 – two high-risk strains that cause around 70% of cervical cancers.
What is fueling the rise of HPV cases?
A misconception that oral sex is somehow a “safe and risk-free” alternative to anal or vaginal sex could be one reason, Dr. Aguh said.
“It is important to know that, with oral sex, you are exposed to many of the risks associated with vaginal intercourse, especially if you do not take any measures to protect yourself and/or your partner,” Dr. Aguh said. “[With oral sex] it is possible to end up contracting an infection like chlamydia, gonorrhea, and even HPV, leading to an increased risk of HPV-associated oropharyngeal cancers.”
A lack of public awareness of what can cause throat cancer could also explain this phenomenon. The number of people you have oral sex with, along with the age you begin sexual activity, can greatly determine your risk of the disease, according to Dr. Lee. She echoes a report by Hisham Mehanna, PhD, in The Conversation.
“For oropharyngeal cancer, the main risk factor is the number of lifetime sexual partners, especially oral sex,” wrote Dr. Mehanna, a professor at the Institute of Cancer and Genomic Sciences at the University of Birmingham (England). “Those with six or more lifetime oral-sex partners are 8.5 times more likely to develop oropharyngeal cancer than those who do not practice oral sex.”
What are symptoms of oropharyngeal cancer?
Labored breathing or swallowing, a cough that won’t go away, and crackling or hoarseness of your voice could all be signs of throat cancer. Other symptoms include earaches, swelling of the head or neck, and enlarged lymph nodes, among others, Dr. Aguh said.
“The signs and symptoms of HPV-related throat cancers can be difficult to identify and recognize, as they can be vague and are also associated with other medical conditions. Sometimes, there are no signs at all, or they are not easily noticeable due to the location,” he said.
You should go see your doctor if you have any of these ailments for an extended period.
How to reduce your risk
In addition to having six or more oral-sex partners, smoking and drinking heavily could also raise your risk of throat cancer, said Dr. Lee. Proper dental health – like seeing your dentist regularly and practicing proper oral hygiene – can also shave your risk.
“[Good dental health] can help not just with head and neck cancer risk, but with many other inflammation-related diseases,” Dr. Lee said.
Using dental dams and condoms can also be a good method of protection, Dr. Aguh said. A dental dam is a stretchy sheet of latex, or polyurethane plastic, in the shape of a square that is made for blocking body fluid to lower your risk of contracting an STD via oral sex.
Keep in mind: Even with these protections, make sure you and your partner discuss each other’s sexual history, any prior or current STDs and their preferred protection from STDs, said Dr. Aguh.
If you or your partner is being treated for an STD, consider opting out of oral sex and consulting a doctor.
The HPV vaccine is another common method of protection. The shot is “approved for prevention of nine of the most high-risk strains of HPV,” or those that are most commonly linked to cancer, according to Dr. Lee. The vaccine “reduces the frequency of infection” with these viruses, which can ultimately lower the risk of cancers linked to HPV, including cervical, anal, and vulvar and vaginal cancers, she said.
“The best time to receive treatment for prevention of disease is prior to onset of sexual intercourse,” said Dr. Lee.
To get your HPV vaccine, head to your family doctor, school- or community-based health center, or state health department, suggests the CDC.
A version of this article originally appeared on WebMD.com.
Vaginal microbiota transfer may affect neurodevelopment in cesarean infants
Previous studies have shown that gut microbiota in infancy could affect neurodevelopment, and infants delivered by cesarean are not exposed to potentially helpful microbes acquired by infants during vaginal delivery, wrote Lepeng Zhou, MD, of Southern Medical University, Guangdong, China, and colleagues.
“Infants delivered by C-section start life with very different bacteria than those born vaginally,” corresponding author Jose Clemente, PhD, of Icahn School of Medicine at Mount Sinai, New York, said in an interview. “Because this is the first time the newborn is exposed to microbes, we and others have hypothesized for some time that this ‘first encounter’ might be significant to shape the development of the baby,” he said.
“A few years ago, we demonstrated that it is possible to change the microbiome of C-section–delivered infants using an intervention that makes their microbiome more similar to that of a vaginally-delivered infant,” Dr. Clemente told this news organization. “In this study just published, we show that this procedure not only changes the microbiome of C-section infants, but it also modifies a health outcome (in this case, neurodevelopment). This is highly significant because it opens the way to reduce the risk that C-section infants have for certain conditions through a very simple microbial intervention,” he said.
‘Significantly higher’ ASQ-3 scores
In the current study, published in Cell Host & Microbe, the researchers examined the impact of vaginal microbiota transfer (VMT) on the neurodevelopment of cesarean-delivered infants. They randomized 35 women scheduled for cesarean delivery with a single infant to VMT and 41 to a control intervention of saline gauze for their infants immediately after delivery.
The primary outcome of infant neurodevelopment was assessed using the Ages and Stages Questionnaire (ASQ-3) score at 6 months. The researchers also collected fecal samples and assessed safety outcomes for the infants at 3, 7, 30, and 42 days after birth. The final analysis comprised 32 infants in the VMT group and 36 in the control group. The mean age of the mothers was 32 years; the mean gestational age of the infants was 39 weeks, but the difference was significant and slightly less in the VMT group compared with the controls (38.38 weeks vs. 39.13 weeks, P = .007). A group of 33 vaginally-delivered infants (VD) underwent ASQ-3 testing to serve as a reference group.
At 6 months, ASQ-3 scores were significantly higher (10.09%, P = .014) with VMT compared with controls, and the difference remained significant after adjustment for multiple factors including gestational age.
ASQ-3 total scores at 6 months were not significantly different between the VMT group and the VD reference group (mean difference of 8.84 VMT to VD, P = .346); scores between these groups also were similar at 3 months (mean difference of –1.48 VMT to VD, P = .900) and no significant differences appeared in ASQ-3 subdomains between these groups at either time period.
An examination of gut metabolites in stool showed significant differences in fecal metabolites and metabolic function, signs of gut microbiota maturation, the researchers noted.
“Interestingly, all the genera and metabolites that exhibited positive correlations with neurodevelopmental scores were upregulated in the VMT group, whereas the only negative correlation of Klebsiella was downregulated, indicating that VMT may impact neurodevelopment through the modulation of specific gut microbial genera and metabolites,” the researchers wrote.
No serious adverse events occurred in either group during the study period. Nine adverse events were reported; 4 in the VMT group and 5 in the control group. The most common AEs were mild skin disorders, including papules, pustules, and erythema.
The findings were limited by several factors including the potential for transfer not only of vaginal microbiota, but also vaginal metabolites, mycobiome, and virome, which blurs the potential mechanism of VMT, the researchers noted. Other limitations were the relatively short study period, small sample size, and cervical HPV screening within the past 5 years, not during pregnancy, they wrote.
However, the results suggest that VMT is safe, and may help improve the fecal microbiome in cesarean-delivered infants, and the long-term effects merit further studies in larger populations, they concluded.
Limitations and outlook
Dr. Clemente said in an interview that the researchers were “hopeful that the study would demonstrate a health benefit, as it does with some limitations.” The current study findings confirm some previous results showing that modification of the microbiomes of C-section infants is possible through a transfer of maternal vaginal microbes, he said.
“There is also an important aspect that was confirmed here: The lack of serious adverse events associated with the procedure, and the fact that transferring vaginal microbes did not increase the risk of adverse events compared to the control group or to vaginally-delivered infants. This is fundamental to establish that using rigorous exclusion criteria we can perform this procedure safely for infants and mothers,” he added.
“We are at very early stages yet to talk about clinical implications,” said Dr. Clemente. “This is one of the first studies to demonstrate a benefit to the transfer of microbes from mothers to infants, and as such it opens the way for future trials that confirm these findings. The clinical application is still in the future, but this is an important first step towards that goal.”
Interest in restoring gut microbiota to potentially benefit infants persists, but a recent study published in Frontiers and Cellular and Infection Microbiology contradicted the potential association between maternal vaginal microbiome and an infant’s gut microbiome based on an analysis of infant stool.
“There are many reasons why different studies might reach different conclusions: The experimental procedures, the analytical methods, the cohort under study,” Dr. Clemente said when asked to comment on the Frontiers study. “Further studies are needed to establish whether this procedure is equally effective under all conditions and whether health benefits are generalizable or specific to particular populations.”
Several research gaps remain, Dr. Clemente said. “First, neurodevelopment was measured through a questionnaire that captures various aspects such as communication, motor skills, or problem solving. While this is a standard way to establish that an infant is in the correct neurodevelopmental pathway, it is not a ‘hard’ measure of cellular or biochemical processes being impacted by the intervention. Some of our results suggest that there is a change in the metabolome of this infants, particularly an enrichment in GABA, a neurotransmitter, but the exact mechanisms by which the intervention is resulting in a health benefit still remains to be explored,” he said.
“We have an ongoing study here at Mount Sinai to test whether this microbial intervention can be effective in lowering the risk of developing food allergies in newborns who are at high risk, so that is another important future question: What other conditions could benefit from this approach,” said Dr. Clemente.
A third research goal, he added, is “determining what microbes precisely are responsible for the health benefits; this study uses a full microbial community to colonize infants. We show that this is effective and, importantly, that there were no significant adverse events in the treated infants,” he noted. “However, identifying what specific microbes are beneficial would further lower the risk of any potential side effects, while facilitating the development of drugs based on defined microbial consortia,” he said.
Safety and efficacy support further studies
“It is widely accepted that the gut microbiome of neonates varies based on mode of delivery,” Anna K. Knight, PhD, assistant professor of gynecology and obstetrics at Emory University, Atlanta, said in an interview.
“C-sections have been associated with increased risk of asthma and metabolic disease, and have been associated with differences in the development of the immune system,” said Dr. Knight, who was not involved in the study. “There have been small pilot studies examining the use of vaginal microbiome transplants to shift the gut microbiome of neonates born by C-section to be more like the gut microbiome of neonates born via vaginal delivery, but the safety and efficacy of this treatment has not been well established. This study examines both, while also evaluating potential changes in the metabolome and neurodevelopmental trajectories.”
The current study confirmed the impact of the neonatal gut microbe on neurodevelopmental outcomes during a sensitive period, said Dr. Knight. “The fact that these differences persisted at 6 months suggests that even if the microbiome composition between vaginally-delivered and preterm infants converged at 1-2 years old, there may be lasting impacts of mode of delivery,” she said.
“The results of this study suggest that vaginal microbiome transplant may be a safe and effective way to mitigate the negative impacts of C-section delivery on the neonatal gut microbiome, and may be protective for neurodevelopment,” she added.
Regarding the Frontiers in Medicine study, Dr. Knight noted that it examined a very different population, with Zhou and colleagues focusing on Chinese infants, while Dos Santos and colleagues focused on Canadian infants.
“There was also a substantial difference in sample size between the two studies, with Dos Santos and colleagues examining > 500 more infants,” she said. “Additionally, the two studies differed in the sequencing technology used, sample collection methods, and antibiotic exposure, which can all impact microbiome study results.”
Since the current study showed efficacy and safety of VMT in a small clinical trial, larger trials with more diverse participants are needed to further examine the impact of VMT, said Dr. Knight. “The risks of vaginal microbiome transplant in mothers with infections should also be considered, and the mechanisms by which the neonatal gut microbiome impacts neurodevelopment need further investigation,” she said.
The study was funded by the National Key R&D Program of China, the Canadian Institute of Health Research, the National Natural Science Foundation of China, the Clinical Research Startup Program of Southern Medical University, China, and the Top Talent Program of Foshan Women and Children Hospital, China. The researchers and Dr. Knight had no financial conflicts to disclose.
Previous studies have shown that gut microbiota in infancy could affect neurodevelopment, and infants delivered by cesarean are not exposed to potentially helpful microbes acquired by infants during vaginal delivery, wrote Lepeng Zhou, MD, of Southern Medical University, Guangdong, China, and colleagues.
“Infants delivered by C-section start life with very different bacteria than those born vaginally,” corresponding author Jose Clemente, PhD, of Icahn School of Medicine at Mount Sinai, New York, said in an interview. “Because this is the first time the newborn is exposed to microbes, we and others have hypothesized for some time that this ‘first encounter’ might be significant to shape the development of the baby,” he said.
“A few years ago, we demonstrated that it is possible to change the microbiome of C-section–delivered infants using an intervention that makes their microbiome more similar to that of a vaginally-delivered infant,” Dr. Clemente told this news organization. “In this study just published, we show that this procedure not only changes the microbiome of C-section infants, but it also modifies a health outcome (in this case, neurodevelopment). This is highly significant because it opens the way to reduce the risk that C-section infants have for certain conditions through a very simple microbial intervention,” he said.
‘Significantly higher’ ASQ-3 scores
In the current study, published in Cell Host & Microbe, the researchers examined the impact of vaginal microbiota transfer (VMT) on the neurodevelopment of cesarean-delivered infants. They randomized 35 women scheduled for cesarean delivery with a single infant to VMT and 41 to a control intervention of saline gauze for their infants immediately after delivery.
The primary outcome of infant neurodevelopment was assessed using the Ages and Stages Questionnaire (ASQ-3) score at 6 months. The researchers also collected fecal samples and assessed safety outcomes for the infants at 3, 7, 30, and 42 days after birth. The final analysis comprised 32 infants in the VMT group and 36 in the control group. The mean age of the mothers was 32 years; the mean gestational age of the infants was 39 weeks, but the difference was significant and slightly less in the VMT group compared with the controls (38.38 weeks vs. 39.13 weeks, P = .007). A group of 33 vaginally-delivered infants (VD) underwent ASQ-3 testing to serve as a reference group.
At 6 months, ASQ-3 scores were significantly higher (10.09%, P = .014) with VMT compared with controls, and the difference remained significant after adjustment for multiple factors including gestational age.
ASQ-3 total scores at 6 months were not significantly different between the VMT group and the VD reference group (mean difference of 8.84 VMT to VD, P = .346); scores between these groups also were similar at 3 months (mean difference of –1.48 VMT to VD, P = .900) and no significant differences appeared in ASQ-3 subdomains between these groups at either time period.
An examination of gut metabolites in stool showed significant differences in fecal metabolites and metabolic function, signs of gut microbiota maturation, the researchers noted.
“Interestingly, all the genera and metabolites that exhibited positive correlations with neurodevelopmental scores were upregulated in the VMT group, whereas the only negative correlation of Klebsiella was downregulated, indicating that VMT may impact neurodevelopment through the modulation of specific gut microbial genera and metabolites,” the researchers wrote.
No serious adverse events occurred in either group during the study period. Nine adverse events were reported; 4 in the VMT group and 5 in the control group. The most common AEs were mild skin disorders, including papules, pustules, and erythema.
The findings were limited by several factors including the potential for transfer not only of vaginal microbiota, but also vaginal metabolites, mycobiome, and virome, which blurs the potential mechanism of VMT, the researchers noted. Other limitations were the relatively short study period, small sample size, and cervical HPV screening within the past 5 years, not during pregnancy, they wrote.
However, the results suggest that VMT is safe, and may help improve the fecal microbiome in cesarean-delivered infants, and the long-term effects merit further studies in larger populations, they concluded.
Limitations and outlook
Dr. Clemente said in an interview that the researchers were “hopeful that the study would demonstrate a health benefit, as it does with some limitations.” The current study findings confirm some previous results showing that modification of the microbiomes of C-section infants is possible through a transfer of maternal vaginal microbes, he said.
“There is also an important aspect that was confirmed here: The lack of serious adverse events associated with the procedure, and the fact that transferring vaginal microbes did not increase the risk of adverse events compared to the control group or to vaginally-delivered infants. This is fundamental to establish that using rigorous exclusion criteria we can perform this procedure safely for infants and mothers,” he added.
“We are at very early stages yet to talk about clinical implications,” said Dr. Clemente. “This is one of the first studies to demonstrate a benefit to the transfer of microbes from mothers to infants, and as such it opens the way for future trials that confirm these findings. The clinical application is still in the future, but this is an important first step towards that goal.”
Interest in restoring gut microbiota to potentially benefit infants persists, but a recent study published in Frontiers and Cellular and Infection Microbiology contradicted the potential association between maternal vaginal microbiome and an infant’s gut microbiome based on an analysis of infant stool.
“There are many reasons why different studies might reach different conclusions: The experimental procedures, the analytical methods, the cohort under study,” Dr. Clemente said when asked to comment on the Frontiers study. “Further studies are needed to establish whether this procedure is equally effective under all conditions and whether health benefits are generalizable or specific to particular populations.”
Several research gaps remain, Dr. Clemente said. “First, neurodevelopment was measured through a questionnaire that captures various aspects such as communication, motor skills, or problem solving. While this is a standard way to establish that an infant is in the correct neurodevelopmental pathway, it is not a ‘hard’ measure of cellular or biochemical processes being impacted by the intervention. Some of our results suggest that there is a change in the metabolome of this infants, particularly an enrichment in GABA, a neurotransmitter, but the exact mechanisms by which the intervention is resulting in a health benefit still remains to be explored,” he said.
“We have an ongoing study here at Mount Sinai to test whether this microbial intervention can be effective in lowering the risk of developing food allergies in newborns who are at high risk, so that is another important future question: What other conditions could benefit from this approach,” said Dr. Clemente.
A third research goal, he added, is “determining what microbes precisely are responsible for the health benefits; this study uses a full microbial community to colonize infants. We show that this is effective and, importantly, that there were no significant adverse events in the treated infants,” he noted. “However, identifying what specific microbes are beneficial would further lower the risk of any potential side effects, while facilitating the development of drugs based on defined microbial consortia,” he said.
Safety and efficacy support further studies
“It is widely accepted that the gut microbiome of neonates varies based on mode of delivery,” Anna K. Knight, PhD, assistant professor of gynecology and obstetrics at Emory University, Atlanta, said in an interview.
“C-sections have been associated with increased risk of asthma and metabolic disease, and have been associated with differences in the development of the immune system,” said Dr. Knight, who was not involved in the study. “There have been small pilot studies examining the use of vaginal microbiome transplants to shift the gut microbiome of neonates born by C-section to be more like the gut microbiome of neonates born via vaginal delivery, but the safety and efficacy of this treatment has not been well established. This study examines both, while also evaluating potential changes in the metabolome and neurodevelopmental trajectories.”
The current study confirmed the impact of the neonatal gut microbe on neurodevelopmental outcomes during a sensitive period, said Dr. Knight. “The fact that these differences persisted at 6 months suggests that even if the microbiome composition between vaginally-delivered and preterm infants converged at 1-2 years old, there may be lasting impacts of mode of delivery,” she said.
“The results of this study suggest that vaginal microbiome transplant may be a safe and effective way to mitigate the negative impacts of C-section delivery on the neonatal gut microbiome, and may be protective for neurodevelopment,” she added.
Regarding the Frontiers in Medicine study, Dr. Knight noted that it examined a very different population, with Zhou and colleagues focusing on Chinese infants, while Dos Santos and colleagues focused on Canadian infants.
“There was also a substantial difference in sample size between the two studies, with Dos Santos and colleagues examining > 500 more infants,” she said. “Additionally, the two studies differed in the sequencing technology used, sample collection methods, and antibiotic exposure, which can all impact microbiome study results.”
Since the current study showed efficacy and safety of VMT in a small clinical trial, larger trials with more diverse participants are needed to further examine the impact of VMT, said Dr. Knight. “The risks of vaginal microbiome transplant in mothers with infections should also be considered, and the mechanisms by which the neonatal gut microbiome impacts neurodevelopment need further investigation,” she said.
The study was funded by the National Key R&D Program of China, the Canadian Institute of Health Research, the National Natural Science Foundation of China, the Clinical Research Startup Program of Southern Medical University, China, and the Top Talent Program of Foshan Women and Children Hospital, China. The researchers and Dr. Knight had no financial conflicts to disclose.
Previous studies have shown that gut microbiota in infancy could affect neurodevelopment, and infants delivered by cesarean are not exposed to potentially helpful microbes acquired by infants during vaginal delivery, wrote Lepeng Zhou, MD, of Southern Medical University, Guangdong, China, and colleagues.
“Infants delivered by C-section start life with very different bacteria than those born vaginally,” corresponding author Jose Clemente, PhD, of Icahn School of Medicine at Mount Sinai, New York, said in an interview. “Because this is the first time the newborn is exposed to microbes, we and others have hypothesized for some time that this ‘first encounter’ might be significant to shape the development of the baby,” he said.
“A few years ago, we demonstrated that it is possible to change the microbiome of C-section–delivered infants using an intervention that makes their microbiome more similar to that of a vaginally-delivered infant,” Dr. Clemente told this news organization. “In this study just published, we show that this procedure not only changes the microbiome of C-section infants, but it also modifies a health outcome (in this case, neurodevelopment). This is highly significant because it opens the way to reduce the risk that C-section infants have for certain conditions through a very simple microbial intervention,” he said.
‘Significantly higher’ ASQ-3 scores
In the current study, published in Cell Host & Microbe, the researchers examined the impact of vaginal microbiota transfer (VMT) on the neurodevelopment of cesarean-delivered infants. They randomized 35 women scheduled for cesarean delivery with a single infant to VMT and 41 to a control intervention of saline gauze for their infants immediately after delivery.
The primary outcome of infant neurodevelopment was assessed using the Ages and Stages Questionnaire (ASQ-3) score at 6 months. The researchers also collected fecal samples and assessed safety outcomes for the infants at 3, 7, 30, and 42 days after birth. The final analysis comprised 32 infants in the VMT group and 36 in the control group. The mean age of the mothers was 32 years; the mean gestational age of the infants was 39 weeks, but the difference was significant and slightly less in the VMT group compared with the controls (38.38 weeks vs. 39.13 weeks, P = .007). A group of 33 vaginally-delivered infants (VD) underwent ASQ-3 testing to serve as a reference group.
At 6 months, ASQ-3 scores were significantly higher (10.09%, P = .014) with VMT compared with controls, and the difference remained significant after adjustment for multiple factors including gestational age.
ASQ-3 total scores at 6 months were not significantly different between the VMT group and the VD reference group (mean difference of 8.84 VMT to VD, P = .346); scores between these groups also were similar at 3 months (mean difference of –1.48 VMT to VD, P = .900) and no significant differences appeared in ASQ-3 subdomains between these groups at either time period.
An examination of gut metabolites in stool showed significant differences in fecal metabolites and metabolic function, signs of gut microbiota maturation, the researchers noted.
“Interestingly, all the genera and metabolites that exhibited positive correlations with neurodevelopmental scores were upregulated in the VMT group, whereas the only negative correlation of Klebsiella was downregulated, indicating that VMT may impact neurodevelopment through the modulation of specific gut microbial genera and metabolites,” the researchers wrote.
No serious adverse events occurred in either group during the study period. Nine adverse events were reported; 4 in the VMT group and 5 in the control group. The most common AEs were mild skin disorders, including papules, pustules, and erythema.
The findings were limited by several factors including the potential for transfer not only of vaginal microbiota, but also vaginal metabolites, mycobiome, and virome, which blurs the potential mechanism of VMT, the researchers noted. Other limitations were the relatively short study period, small sample size, and cervical HPV screening within the past 5 years, not during pregnancy, they wrote.
However, the results suggest that VMT is safe, and may help improve the fecal microbiome in cesarean-delivered infants, and the long-term effects merit further studies in larger populations, they concluded.
Limitations and outlook
Dr. Clemente said in an interview that the researchers were “hopeful that the study would demonstrate a health benefit, as it does with some limitations.” The current study findings confirm some previous results showing that modification of the microbiomes of C-section infants is possible through a transfer of maternal vaginal microbes, he said.
“There is also an important aspect that was confirmed here: The lack of serious adverse events associated with the procedure, and the fact that transferring vaginal microbes did not increase the risk of adverse events compared to the control group or to vaginally-delivered infants. This is fundamental to establish that using rigorous exclusion criteria we can perform this procedure safely for infants and mothers,” he added.
“We are at very early stages yet to talk about clinical implications,” said Dr. Clemente. “This is one of the first studies to demonstrate a benefit to the transfer of microbes from mothers to infants, and as such it opens the way for future trials that confirm these findings. The clinical application is still in the future, but this is an important first step towards that goal.”
Interest in restoring gut microbiota to potentially benefit infants persists, but a recent study published in Frontiers and Cellular and Infection Microbiology contradicted the potential association between maternal vaginal microbiome and an infant’s gut microbiome based on an analysis of infant stool.
“There are many reasons why different studies might reach different conclusions: The experimental procedures, the analytical methods, the cohort under study,” Dr. Clemente said when asked to comment on the Frontiers study. “Further studies are needed to establish whether this procedure is equally effective under all conditions and whether health benefits are generalizable or specific to particular populations.”
Several research gaps remain, Dr. Clemente said. “First, neurodevelopment was measured through a questionnaire that captures various aspects such as communication, motor skills, or problem solving. While this is a standard way to establish that an infant is in the correct neurodevelopmental pathway, it is not a ‘hard’ measure of cellular or biochemical processes being impacted by the intervention. Some of our results suggest that there is a change in the metabolome of this infants, particularly an enrichment in GABA, a neurotransmitter, but the exact mechanisms by which the intervention is resulting in a health benefit still remains to be explored,” he said.
“We have an ongoing study here at Mount Sinai to test whether this microbial intervention can be effective in lowering the risk of developing food allergies in newborns who are at high risk, so that is another important future question: What other conditions could benefit from this approach,” said Dr. Clemente.
A third research goal, he added, is “determining what microbes precisely are responsible for the health benefits; this study uses a full microbial community to colonize infants. We show that this is effective and, importantly, that there were no significant adverse events in the treated infants,” he noted. “However, identifying what specific microbes are beneficial would further lower the risk of any potential side effects, while facilitating the development of drugs based on defined microbial consortia,” he said.
Safety and efficacy support further studies
“It is widely accepted that the gut microbiome of neonates varies based on mode of delivery,” Anna K. Knight, PhD, assistant professor of gynecology and obstetrics at Emory University, Atlanta, said in an interview.
“C-sections have been associated with increased risk of asthma and metabolic disease, and have been associated with differences in the development of the immune system,” said Dr. Knight, who was not involved in the study. “There have been small pilot studies examining the use of vaginal microbiome transplants to shift the gut microbiome of neonates born by C-section to be more like the gut microbiome of neonates born via vaginal delivery, but the safety and efficacy of this treatment has not been well established. This study examines both, while also evaluating potential changes in the metabolome and neurodevelopmental trajectories.”
The current study confirmed the impact of the neonatal gut microbe on neurodevelopmental outcomes during a sensitive period, said Dr. Knight. “The fact that these differences persisted at 6 months suggests that even if the microbiome composition between vaginally-delivered and preterm infants converged at 1-2 years old, there may be lasting impacts of mode of delivery,” she said.
“The results of this study suggest that vaginal microbiome transplant may be a safe and effective way to mitigate the negative impacts of C-section delivery on the neonatal gut microbiome, and may be protective for neurodevelopment,” she added.
Regarding the Frontiers in Medicine study, Dr. Knight noted that it examined a very different population, with Zhou and colleagues focusing on Chinese infants, while Dos Santos and colleagues focused on Canadian infants.
“There was also a substantial difference in sample size between the two studies, with Dos Santos and colleagues examining > 500 more infants,” she said. “Additionally, the two studies differed in the sequencing technology used, sample collection methods, and antibiotic exposure, which can all impact microbiome study results.”
Since the current study showed efficacy and safety of VMT in a small clinical trial, larger trials with more diverse participants are needed to further examine the impact of VMT, said Dr. Knight. “The risks of vaginal microbiome transplant in mothers with infections should also be considered, and the mechanisms by which the neonatal gut microbiome impacts neurodevelopment need further investigation,” she said.
The study was funded by the National Key R&D Program of China, the Canadian Institute of Health Research, the National Natural Science Foundation of China, the Clinical Research Startup Program of Southern Medical University, China, and the Top Talent Program of Foshan Women and Children Hospital, China. The researchers and Dr. Knight had no financial conflicts to disclose.
FROM CELL HOST & MICROBE
Malpractice lawsuits over denied abortion care may be on the horizon
Some experts predict those providers could soon face a new legal threat: medical malpractice lawsuits alleging they harmed patients by failing to provide timely, necessary abortion care.
“We will absolutely see medical malpractice cases emerge,” said Diana Nordlund, an emergency physician in Grand Rapids, Mich., and former malpractice defense attorney, who chairs the Medical-Legal Committee of the American College of Emergency Physicians. When physicians decide not to provide treatments widely accepted as the standard of care because of these new laws, “that’s perceived as substandard care and there is increased civil liability.”
To some physicians and malpractice attorneys, the question is when – not if – a pregnant patient will die from lack of care and set the stage for a big-dollar wrongful death claim. Abortion rights supporters said such a case could pressure doctors and hospitals to provide appropriate abortion care, counterbalancing their fears of running afoul of state abortion bans, many of which call for criminal prosecution and revocation of medical licenses as punishment for violations.
“If we want to encourage proper care, there has to be some sort of counter-risk to physicians and hospitals for refusing to provide care that should be legal,” said Greer Donley, an associate professor at the University of Pittsburgh school of law who studies the impact of abortion bans. “But most rational people would be more afraid of going to jail.”
Some supporters of abortion bans said they would welcome malpractice lawsuits. Providers are refusing to use the exceptions in some state laws that allow them to perform abortions to save a patient’s life or health, they said.
“It could help achieve our goal if it clarifies that the law did not contradict standard medical practice,” said John Seago, president of Texas Right to Life, referring to the state’s abortion ban.
A new KFF poll found that 59% of ob.gyns. practicing in states with gestational limits on abortion, and 61% of those in states with bans, are somewhat or very concerned about their legal risk when making decisions about the necessity of an abortion.
Some attorneys are exploring lawsuits on behalf of women who they said have been harmed by a state abortion ban. An attorney for Mylissa Farmer, a Missouri woman who was refused an abortion at two hospitals in August after her water broke about 18 weeks into her pregnancy, said she may sue for malpractice. Missouri’s abortion ban, which took effect last year, makes an exception for medical emergencies.
The federal government recently found that the two hospitals violated a federal emergency care law in denying Ms. Farmer an abortion, which experts said could strengthen a malpractice claim. One of the hospitals, Freeman Health System in Joplin, Mo., did not respond to a request for comment. The other, the University of Kansas Health System in Kansas City, said the care provided “was reviewed by the hospital and found to be in accordance with hospital policy,” according to a spokesperson, Jill Chadwick.
Ms. Farmer “experienced permanent physical and emotional damage,” said Michelle Banker, one of her lawyers at the National Women’s Law Center, who added that Ms. Farmer and her attorneys are “considering all our legal options.”
News reports and medical studies show that some women with pregnancy complications have suffered serious health consequences when doctors and hospitals did not provide once-routine abortion care.
Last month, researchers released a study identifying dozens of cases in 14 states in which physicians said deficiencies in care due to abortion restrictions led to preventable complications and hospitalizations, with some patients nearly dying.
“The patients were sent home and told to come back when they had signs of infection,” said Daniel Grossman, an ob.gyn. at the University of California, San Francisco, who led the study. “Many developed serious infections. And it’s clear many of these cases were very emotionally traumatic.”
He said though the researchers did not track patient outcomes, the lack of timely abortion care in such cases could result in severe health harms including loss of fertility, stroke, or heart attack.
“It’s just a matter of time before there will be a death that comes to light,” Dr. Grossman said.
Still, considering the conflict for doctors between medical ethics and personal risk, some stakeholders said patients may be reluctant to sue doctors and juries may balk at finding them liable.
“It’s a terrible position that providers are being put into, and I don’t think juries will blame the doctor unless it’s a super clear case,” said Morgan Murphy, a malpractice plaintiff’s attorney in Missouri.
She said her firm will not pursue malpractice cases based on abortion denials except in “pretty extreme” situations, such as when a patient dies. “Unless a mother is on her deathbed, it’s pretty hard to fault a provider who thinks if they provide treatment they’re going to be criminally liable or will lose their medical license.”
Another hurdle for malpractice cases is that state abortion bans could undermine the argument that abortion is the legal “standard of care,” meaning that it is a widely accepted and prescribed treatment for pregnancy complications such as miscarriage and for fatal fetal abnormalities.
“I absolutely see a breach of the standard of care in these cases,” said Maria A. Phillis, an ob.gyn. and former lawyer in Cleveland. “But if someone goes to trial in a malpractice case, it will come down to a battle of medical experts about whether it’s no longer the standard of care, and the jury would have to decide.”
An additional justification for physicians not to provide abortions is that medical liability insurers generally do not cover damages from criminal acts, which “puts the finger on the scales even more to not do anything,” Dr. Phillis said.
Stuart Grossman, a prominent malpractice plaintiff’s attorney in Florida, said he would be eager to take an abortion-denial case in which the woman suffered serious health or emotional injuries.
Unlike other states with abortion bans, Florida does not cap damage amounts for pain and suffering in malpractice cases, making it more financially viable to sue there.
Mr. Grossman cited the case of Deborah Dorbert, a Florida woman who reportedly was denied an abortion despite being told by her physicians at 24 weeks of pregnancy that her fetus, with no kidneys and underdeveloped lungs, had a fatal condition called Potter syndrome.
Her doctors and the hospital refused to end the pregnancy even though the state’s abortion ban has an exception for fatal fetal abnormalities. Months later, her baby died in his parents’ arms shortly after birth.
“You can see how she’s been devastated mentally,” Mr. Grossman said. “She has a wrongful death case that I’d take in a minute.” He said the couple could file a malpractice suit for Ms. Dorbert’s physical and emotional damages and a separate malpractice and wrongful death suit for the couple’s suffering over the infant’s death.
Failing to counsel patients about their options and connect them with providers willing to terminate a pregnancy is also possible grounds for a malpractice suit, attorneys said. Katie Watson, an associate professor at Northwestern University, Chicago’s school of medicine who has studied state abortion bans, said counseling and referral are not prohibited under these laws and that physicians have an ethical obligation to offer those services.
“I think breaching the obligation for counseling would make a strong malpractice lawsuit,” she said.
Nancy Davis said she received no counseling or referral assistance last July after her doctors at Woman’s Hospital in Baton Rouge, La., told her 10 weeks into her pregnancy that her fetus would not survive because it was missing the top of its skull, a fatal condition called acrania. She said they recommended that she terminate the pregnancy and she agreed.
Ms. Davis said her doctors then told her a hospital executive had denied permission for the procedure because of Louisiana’s abortion ban, even though the law has an exception for fatal fetal abnormalities. A hospital spokesperson declined to comment.
Ms. Davis, who has three children, contacted Planned Parenthood of Greater New York, which arranged for child care and a flight to New York. She had an abortion performed there in September.
“The whole situation has been mentally and physically draining, and my family and I are receiving counseling,” Ms. Davis said. “I’m still very angry at the hospital and the doctors. I feel like I’m owed compensation for the trauma and the heartbreak.”
She sought the counsel of Benjamin Crump, a prominent attorney known for pursuing high-profile cases like wrongful death lawsuits on behalf of the families of Trayvon Martin and George Floyd.
But Mr. Crump said that after studying Ms. Davis’ legal options, he decided a judge would likely dismiss a malpractice suit and that Ms. Davis could end up paying the defendants’ legal fees and costs.
“The doctor’s lawyers will say, ‘You can’t expect my client to break the law and go to prison for up to 25 years,’ ” Mr. Crump said. “Unless you change the law, there is no option for her to receive compensation.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.
Some experts predict those providers could soon face a new legal threat: medical malpractice lawsuits alleging they harmed patients by failing to provide timely, necessary abortion care.
“We will absolutely see medical malpractice cases emerge,” said Diana Nordlund, an emergency physician in Grand Rapids, Mich., and former malpractice defense attorney, who chairs the Medical-Legal Committee of the American College of Emergency Physicians. When physicians decide not to provide treatments widely accepted as the standard of care because of these new laws, “that’s perceived as substandard care and there is increased civil liability.”
To some physicians and malpractice attorneys, the question is when – not if – a pregnant patient will die from lack of care and set the stage for a big-dollar wrongful death claim. Abortion rights supporters said such a case could pressure doctors and hospitals to provide appropriate abortion care, counterbalancing their fears of running afoul of state abortion bans, many of which call for criminal prosecution and revocation of medical licenses as punishment for violations.
“If we want to encourage proper care, there has to be some sort of counter-risk to physicians and hospitals for refusing to provide care that should be legal,” said Greer Donley, an associate professor at the University of Pittsburgh school of law who studies the impact of abortion bans. “But most rational people would be more afraid of going to jail.”
Some supporters of abortion bans said they would welcome malpractice lawsuits. Providers are refusing to use the exceptions in some state laws that allow them to perform abortions to save a patient’s life or health, they said.
“It could help achieve our goal if it clarifies that the law did not contradict standard medical practice,” said John Seago, president of Texas Right to Life, referring to the state’s abortion ban.
A new KFF poll found that 59% of ob.gyns. practicing in states with gestational limits on abortion, and 61% of those in states with bans, are somewhat or very concerned about their legal risk when making decisions about the necessity of an abortion.
Some attorneys are exploring lawsuits on behalf of women who they said have been harmed by a state abortion ban. An attorney for Mylissa Farmer, a Missouri woman who was refused an abortion at two hospitals in August after her water broke about 18 weeks into her pregnancy, said she may sue for malpractice. Missouri’s abortion ban, which took effect last year, makes an exception for medical emergencies.
The federal government recently found that the two hospitals violated a federal emergency care law in denying Ms. Farmer an abortion, which experts said could strengthen a malpractice claim. One of the hospitals, Freeman Health System in Joplin, Mo., did not respond to a request for comment. The other, the University of Kansas Health System in Kansas City, said the care provided “was reviewed by the hospital and found to be in accordance with hospital policy,” according to a spokesperson, Jill Chadwick.
Ms. Farmer “experienced permanent physical and emotional damage,” said Michelle Banker, one of her lawyers at the National Women’s Law Center, who added that Ms. Farmer and her attorneys are “considering all our legal options.”
News reports and medical studies show that some women with pregnancy complications have suffered serious health consequences when doctors and hospitals did not provide once-routine abortion care.
Last month, researchers released a study identifying dozens of cases in 14 states in which physicians said deficiencies in care due to abortion restrictions led to preventable complications and hospitalizations, with some patients nearly dying.
“The patients were sent home and told to come back when they had signs of infection,” said Daniel Grossman, an ob.gyn. at the University of California, San Francisco, who led the study. “Many developed serious infections. And it’s clear many of these cases were very emotionally traumatic.”
He said though the researchers did not track patient outcomes, the lack of timely abortion care in such cases could result in severe health harms including loss of fertility, stroke, or heart attack.
“It’s just a matter of time before there will be a death that comes to light,” Dr. Grossman said.
Still, considering the conflict for doctors between medical ethics and personal risk, some stakeholders said patients may be reluctant to sue doctors and juries may balk at finding them liable.
“It’s a terrible position that providers are being put into, and I don’t think juries will blame the doctor unless it’s a super clear case,” said Morgan Murphy, a malpractice plaintiff’s attorney in Missouri.
She said her firm will not pursue malpractice cases based on abortion denials except in “pretty extreme” situations, such as when a patient dies. “Unless a mother is on her deathbed, it’s pretty hard to fault a provider who thinks if they provide treatment they’re going to be criminally liable or will lose their medical license.”
Another hurdle for malpractice cases is that state abortion bans could undermine the argument that abortion is the legal “standard of care,” meaning that it is a widely accepted and prescribed treatment for pregnancy complications such as miscarriage and for fatal fetal abnormalities.
“I absolutely see a breach of the standard of care in these cases,” said Maria A. Phillis, an ob.gyn. and former lawyer in Cleveland. “But if someone goes to trial in a malpractice case, it will come down to a battle of medical experts about whether it’s no longer the standard of care, and the jury would have to decide.”
An additional justification for physicians not to provide abortions is that medical liability insurers generally do not cover damages from criminal acts, which “puts the finger on the scales even more to not do anything,” Dr. Phillis said.
Stuart Grossman, a prominent malpractice plaintiff’s attorney in Florida, said he would be eager to take an abortion-denial case in which the woman suffered serious health or emotional injuries.
Unlike other states with abortion bans, Florida does not cap damage amounts for pain and suffering in malpractice cases, making it more financially viable to sue there.
Mr. Grossman cited the case of Deborah Dorbert, a Florida woman who reportedly was denied an abortion despite being told by her physicians at 24 weeks of pregnancy that her fetus, with no kidneys and underdeveloped lungs, had a fatal condition called Potter syndrome.
Her doctors and the hospital refused to end the pregnancy even though the state’s abortion ban has an exception for fatal fetal abnormalities. Months later, her baby died in his parents’ arms shortly after birth.
“You can see how she’s been devastated mentally,” Mr. Grossman said. “She has a wrongful death case that I’d take in a minute.” He said the couple could file a malpractice suit for Ms. Dorbert’s physical and emotional damages and a separate malpractice and wrongful death suit for the couple’s suffering over the infant’s death.
Failing to counsel patients about their options and connect them with providers willing to terminate a pregnancy is also possible grounds for a malpractice suit, attorneys said. Katie Watson, an associate professor at Northwestern University, Chicago’s school of medicine who has studied state abortion bans, said counseling and referral are not prohibited under these laws and that physicians have an ethical obligation to offer those services.
“I think breaching the obligation for counseling would make a strong malpractice lawsuit,” she said.
Nancy Davis said she received no counseling or referral assistance last July after her doctors at Woman’s Hospital in Baton Rouge, La., told her 10 weeks into her pregnancy that her fetus would not survive because it was missing the top of its skull, a fatal condition called acrania. She said they recommended that she terminate the pregnancy and she agreed.
Ms. Davis said her doctors then told her a hospital executive had denied permission for the procedure because of Louisiana’s abortion ban, even though the law has an exception for fatal fetal abnormalities. A hospital spokesperson declined to comment.
Ms. Davis, who has three children, contacted Planned Parenthood of Greater New York, which arranged for child care and a flight to New York. She had an abortion performed there in September.
“The whole situation has been mentally and physically draining, and my family and I are receiving counseling,” Ms. Davis said. “I’m still very angry at the hospital and the doctors. I feel like I’m owed compensation for the trauma and the heartbreak.”
She sought the counsel of Benjamin Crump, a prominent attorney known for pursuing high-profile cases like wrongful death lawsuits on behalf of the families of Trayvon Martin and George Floyd.
But Mr. Crump said that after studying Ms. Davis’ legal options, he decided a judge would likely dismiss a malpractice suit and that Ms. Davis could end up paying the defendants’ legal fees and costs.
“The doctor’s lawyers will say, ‘You can’t expect my client to break the law and go to prison for up to 25 years,’ ” Mr. Crump said. “Unless you change the law, there is no option for her to receive compensation.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.
Some experts predict those providers could soon face a new legal threat: medical malpractice lawsuits alleging they harmed patients by failing to provide timely, necessary abortion care.
“We will absolutely see medical malpractice cases emerge,” said Diana Nordlund, an emergency physician in Grand Rapids, Mich., and former malpractice defense attorney, who chairs the Medical-Legal Committee of the American College of Emergency Physicians. When physicians decide not to provide treatments widely accepted as the standard of care because of these new laws, “that’s perceived as substandard care and there is increased civil liability.”
To some physicians and malpractice attorneys, the question is when – not if – a pregnant patient will die from lack of care and set the stage for a big-dollar wrongful death claim. Abortion rights supporters said such a case could pressure doctors and hospitals to provide appropriate abortion care, counterbalancing their fears of running afoul of state abortion bans, many of which call for criminal prosecution and revocation of medical licenses as punishment for violations.
“If we want to encourage proper care, there has to be some sort of counter-risk to physicians and hospitals for refusing to provide care that should be legal,” said Greer Donley, an associate professor at the University of Pittsburgh school of law who studies the impact of abortion bans. “But most rational people would be more afraid of going to jail.”
Some supporters of abortion bans said they would welcome malpractice lawsuits. Providers are refusing to use the exceptions in some state laws that allow them to perform abortions to save a patient’s life or health, they said.
“It could help achieve our goal if it clarifies that the law did not contradict standard medical practice,” said John Seago, president of Texas Right to Life, referring to the state’s abortion ban.
A new KFF poll found that 59% of ob.gyns. practicing in states with gestational limits on abortion, and 61% of those in states with bans, are somewhat or very concerned about their legal risk when making decisions about the necessity of an abortion.
Some attorneys are exploring lawsuits on behalf of women who they said have been harmed by a state abortion ban. An attorney for Mylissa Farmer, a Missouri woman who was refused an abortion at two hospitals in August after her water broke about 18 weeks into her pregnancy, said she may sue for malpractice. Missouri’s abortion ban, which took effect last year, makes an exception for medical emergencies.
The federal government recently found that the two hospitals violated a federal emergency care law in denying Ms. Farmer an abortion, which experts said could strengthen a malpractice claim. One of the hospitals, Freeman Health System in Joplin, Mo., did not respond to a request for comment. The other, the University of Kansas Health System in Kansas City, said the care provided “was reviewed by the hospital and found to be in accordance with hospital policy,” according to a spokesperson, Jill Chadwick.
Ms. Farmer “experienced permanent physical and emotional damage,” said Michelle Banker, one of her lawyers at the National Women’s Law Center, who added that Ms. Farmer and her attorneys are “considering all our legal options.”
News reports and medical studies show that some women with pregnancy complications have suffered serious health consequences when doctors and hospitals did not provide once-routine abortion care.
Last month, researchers released a study identifying dozens of cases in 14 states in which physicians said deficiencies in care due to abortion restrictions led to preventable complications and hospitalizations, with some patients nearly dying.
“The patients were sent home and told to come back when they had signs of infection,” said Daniel Grossman, an ob.gyn. at the University of California, San Francisco, who led the study. “Many developed serious infections. And it’s clear many of these cases were very emotionally traumatic.”
He said though the researchers did not track patient outcomes, the lack of timely abortion care in such cases could result in severe health harms including loss of fertility, stroke, or heart attack.
“It’s just a matter of time before there will be a death that comes to light,” Dr. Grossman said.
Still, considering the conflict for doctors between medical ethics and personal risk, some stakeholders said patients may be reluctant to sue doctors and juries may balk at finding them liable.
“It’s a terrible position that providers are being put into, and I don’t think juries will blame the doctor unless it’s a super clear case,” said Morgan Murphy, a malpractice plaintiff’s attorney in Missouri.
She said her firm will not pursue malpractice cases based on abortion denials except in “pretty extreme” situations, such as when a patient dies. “Unless a mother is on her deathbed, it’s pretty hard to fault a provider who thinks if they provide treatment they’re going to be criminally liable or will lose their medical license.”
Another hurdle for malpractice cases is that state abortion bans could undermine the argument that abortion is the legal “standard of care,” meaning that it is a widely accepted and prescribed treatment for pregnancy complications such as miscarriage and for fatal fetal abnormalities.
“I absolutely see a breach of the standard of care in these cases,” said Maria A. Phillis, an ob.gyn. and former lawyer in Cleveland. “But if someone goes to trial in a malpractice case, it will come down to a battle of medical experts about whether it’s no longer the standard of care, and the jury would have to decide.”
An additional justification for physicians not to provide abortions is that medical liability insurers generally do not cover damages from criminal acts, which “puts the finger on the scales even more to not do anything,” Dr. Phillis said.
Stuart Grossman, a prominent malpractice plaintiff’s attorney in Florida, said he would be eager to take an abortion-denial case in which the woman suffered serious health or emotional injuries.
Unlike other states with abortion bans, Florida does not cap damage amounts for pain and suffering in malpractice cases, making it more financially viable to sue there.
Mr. Grossman cited the case of Deborah Dorbert, a Florida woman who reportedly was denied an abortion despite being told by her physicians at 24 weeks of pregnancy that her fetus, with no kidneys and underdeveloped lungs, had a fatal condition called Potter syndrome.
Her doctors and the hospital refused to end the pregnancy even though the state’s abortion ban has an exception for fatal fetal abnormalities. Months later, her baby died in his parents’ arms shortly after birth.
“You can see how she’s been devastated mentally,” Mr. Grossman said. “She has a wrongful death case that I’d take in a minute.” He said the couple could file a malpractice suit for Ms. Dorbert’s physical and emotional damages and a separate malpractice and wrongful death suit for the couple’s suffering over the infant’s death.
Failing to counsel patients about their options and connect them with providers willing to terminate a pregnancy is also possible grounds for a malpractice suit, attorneys said. Katie Watson, an associate professor at Northwestern University, Chicago’s school of medicine who has studied state abortion bans, said counseling and referral are not prohibited under these laws and that physicians have an ethical obligation to offer those services.
“I think breaching the obligation for counseling would make a strong malpractice lawsuit,” she said.
Nancy Davis said she received no counseling or referral assistance last July after her doctors at Woman’s Hospital in Baton Rouge, La., told her 10 weeks into her pregnancy that her fetus would not survive because it was missing the top of its skull, a fatal condition called acrania. She said they recommended that she terminate the pregnancy and she agreed.
Ms. Davis said her doctors then told her a hospital executive had denied permission for the procedure because of Louisiana’s abortion ban, even though the law has an exception for fatal fetal abnormalities. A hospital spokesperson declined to comment.
Ms. Davis, who has three children, contacted Planned Parenthood of Greater New York, which arranged for child care and a flight to New York. She had an abortion performed there in September.
“The whole situation has been mentally and physically draining, and my family and I are receiving counseling,” Ms. Davis said. “I’m still very angry at the hospital and the doctors. I feel like I’m owed compensation for the trauma and the heartbreak.”
She sought the counsel of Benjamin Crump, a prominent attorney known for pursuing high-profile cases like wrongful death lawsuits on behalf of the families of Trayvon Martin and George Floyd.
But Mr. Crump said that after studying Ms. Davis’ legal options, he decided a judge would likely dismiss a malpractice suit and that Ms. Davis could end up paying the defendants’ legal fees and costs.
“The doctor’s lawyers will say, ‘You can’t expect my client to break the law and go to prison for up to 25 years,’ ” Mr. Crump said. “Unless you change the law, there is no option for her to receive compensation.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.
Updates on pregnancy outcomes in transgender men
Despite increased societal gains, transgender individuals are still a medically and socially underserved group. The historic rise of antitransgender legislation and the overturning of Roe v. Wade, further compound existing health care disparities, particularly in the realm of contraception and pregnancy. Obstetrician-gynecologists and midwives are typically first-line providers when discussing family planning and fertility options for all patients assigned female at birth. Unfortunately,
Only individuals who are assigned female at birth and have a uterus are capable of pregnancy. This can include both cisgender women and nonbinary/transgender men. However, societal and medical institutions are struggling with this shift in perspective from a traditionally gendered role to a more inclusive one. Obstetrician-gynecologists and midwives can serve to bridge this gap between these patients and societal misconceptions surrounding transgender men who desire and experience pregnancy.
Providers need to remember that many transmasculine individuals will still retain their uterus and are therefore capable of getting pregnant. While testosterone causes amenorrhea, if patients are engaging in penile-vaginal intercourse, conception is still possible. If a patient does not desire pregnancy, all contraceptive options available for cisgender women, which also include combined oral contraceptives, should be offered.
For patients seeking to become pregnant, testosterone must be discontinued. Testosterone is teratogenic; it can cause abnormal urogenital development in the female fetus and should be avoided even prior to conception.1,2 The timing of testosterone discontinuation is debatable. There are no well-established guidelines dictating how early pregnancy can be attempted after cessation of testosterone, but typically if menses has resumed, the teratogenic effects of testosterone are less likely.
For amenorrheic patients on testosterone, menses will occur, on average, 3-6 months after testosterone is stopped. Of note, the longer that testosterone has been suspended, the greater the likelihood of achieving pregnancy.3 In a study by Light et al., 72% of patients conceived within 6 months of attempting pregnancy, 80% resumed menses within 6 months of stopping testosterone, and 20% of individuals conceived while they were amenorrheic from testosterone.4
Psychosocial support is an essential part of pregnancy care in transgender men. For some patients, pregnancy can worsen gender dysphoria, whereas others are empowered by the experience. Insurance companies may also deny obstetric care services to transgender males who have already changed their gender marker from female to male on insurance policies.
Whether transmasculine individuals are at higher risk for pregnancy complications is largely unknown, although emerging research in this field has yielded interesting results. While testosterone can cause vaginal atrophy, it does not seem to increase a patient’s risk of vaginal lacerations or their ability to have a successful vaginal delivery. For transgender men with significant discomfort around their genitalia, an elective cesarean section may be appropriate.5
More recently, Stroumsa et al. conducted an analysis of all deliveries at a Michigan institution from 2014 to 2018. Patients with male gender at the time of delivery or with the diagnostic code of gender dysphoria were identified as transgender.6 The primary outcome of this study was severe parental morbidity (such as amniotic fluid embolism, acute myocardial infarction, eclampsia, etc.), with secondary outcomes investigating rates of cesarean delivery and preterm birth.
During this time period, the researchers identified 256 transgender patients and 1.3 million cisgender patients in their Medicaid database and 1,651 transgender patients and 1.5 million cisgender patients in the commercial database who had experienced a delivery.6 Compared with cisgender patients, transgender patients in the Medicaid database were younger, less likely to be white, and more likely to have a chronic condition.6 Compared with cisgender patients in the commercial database, transgender patients experienced higher rates of anxiety and depression.6 Both transgender and cisgender patients had similar rates of severe parental morbidity. Ironically, rates of cesarean delivery were lower, compared with cisgender patients, in both the Medicaid and commercial databases, with no differences observed between rates of preterm birth.6
While more research is needed on pregnancy in transgender men, this analysis is not only one of the largest to date, but it also challenges many misconceptions providers have regarding pregnancy outcomes. Even though transmasculine patients may require additional medical interventions to achieve pregnancy, such as assisted reproductive technology, or increased psychosocial support during the process, these initial studies are reassuring. Based on current evidence, these patients are not at greater risk for perinatal complications than their cisgender counterparts.
Despite these encouraging findings, there are still several challenges faced by transgender men when it comes to getting pregnant. For instance, they may have difficulty accessing fertility services because of financial constraints or experience a lack of awareness or prejudice from providers; they might also be subject to discrimination or stigma within health care settings. As front-line providers for obstetrical care, we must lead the way towards improving the care for pregnant transmasculine individuals.
Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.
References
1. Light A et al. Family planning and contraception use in transgender men. Contraception. 2018 Oct. doi: 10.1016/j.contraception.2018.06.006.
2. Krempasky C et al. Contraception across the transmasculine spectrum. Am J Obstet Gynecol. 2020 Feb. doi: 10.1016/j.ajog.2019.07.043.
3. Obedin-Maliver J, De Haan G. “Gynecologic care for transgender patients” in Ferrando C, ed., Comprehensive Care of the Transgender Patient. Philadelphia: Elsevier, 2019. 131-51.
4. Light AD et al. Transgender men who experienced pregnancy after female-to-male gender transitioning. Obstet Gynecol. 2014 Dec. doi: 10.1097/AOG.0000000000000540.
5. Brandt JS et al. Transgender men, pregnancy, and the “new” advanced paternal age: A review of the literature. Maturitas. 2019 Oct. doi: 10.1016/j.maturitas.2019.07.004.
6. Stroumsa D et al. Pregnancy outcomes in a U.S. cohort of transgender people. JAMA. 2023 Jun 6. doi: 10.1001/jama.2023.7688.
Despite increased societal gains, transgender individuals are still a medically and socially underserved group. The historic rise of antitransgender legislation and the overturning of Roe v. Wade, further compound existing health care disparities, particularly in the realm of contraception and pregnancy. Obstetrician-gynecologists and midwives are typically first-line providers when discussing family planning and fertility options for all patients assigned female at birth. Unfortunately,
Only individuals who are assigned female at birth and have a uterus are capable of pregnancy. This can include both cisgender women and nonbinary/transgender men. However, societal and medical institutions are struggling with this shift in perspective from a traditionally gendered role to a more inclusive one. Obstetrician-gynecologists and midwives can serve to bridge this gap between these patients and societal misconceptions surrounding transgender men who desire and experience pregnancy.
Providers need to remember that many transmasculine individuals will still retain their uterus and are therefore capable of getting pregnant. While testosterone causes amenorrhea, if patients are engaging in penile-vaginal intercourse, conception is still possible. If a patient does not desire pregnancy, all contraceptive options available for cisgender women, which also include combined oral contraceptives, should be offered.
For patients seeking to become pregnant, testosterone must be discontinued. Testosterone is teratogenic; it can cause abnormal urogenital development in the female fetus and should be avoided even prior to conception.1,2 The timing of testosterone discontinuation is debatable. There are no well-established guidelines dictating how early pregnancy can be attempted after cessation of testosterone, but typically if menses has resumed, the teratogenic effects of testosterone are less likely.
For amenorrheic patients on testosterone, menses will occur, on average, 3-6 months after testosterone is stopped. Of note, the longer that testosterone has been suspended, the greater the likelihood of achieving pregnancy.3 In a study by Light et al., 72% of patients conceived within 6 months of attempting pregnancy, 80% resumed menses within 6 months of stopping testosterone, and 20% of individuals conceived while they were amenorrheic from testosterone.4
Psychosocial support is an essential part of pregnancy care in transgender men. For some patients, pregnancy can worsen gender dysphoria, whereas others are empowered by the experience. Insurance companies may also deny obstetric care services to transgender males who have already changed their gender marker from female to male on insurance policies.
Whether transmasculine individuals are at higher risk for pregnancy complications is largely unknown, although emerging research in this field has yielded interesting results. While testosterone can cause vaginal atrophy, it does not seem to increase a patient’s risk of vaginal lacerations or their ability to have a successful vaginal delivery. For transgender men with significant discomfort around their genitalia, an elective cesarean section may be appropriate.5
More recently, Stroumsa et al. conducted an analysis of all deliveries at a Michigan institution from 2014 to 2018. Patients with male gender at the time of delivery or with the diagnostic code of gender dysphoria were identified as transgender.6 The primary outcome of this study was severe parental morbidity (such as amniotic fluid embolism, acute myocardial infarction, eclampsia, etc.), with secondary outcomes investigating rates of cesarean delivery and preterm birth.
During this time period, the researchers identified 256 transgender patients and 1.3 million cisgender patients in their Medicaid database and 1,651 transgender patients and 1.5 million cisgender patients in the commercial database who had experienced a delivery.6 Compared with cisgender patients, transgender patients in the Medicaid database were younger, less likely to be white, and more likely to have a chronic condition.6 Compared with cisgender patients in the commercial database, transgender patients experienced higher rates of anxiety and depression.6 Both transgender and cisgender patients had similar rates of severe parental morbidity. Ironically, rates of cesarean delivery were lower, compared with cisgender patients, in both the Medicaid and commercial databases, with no differences observed between rates of preterm birth.6
While more research is needed on pregnancy in transgender men, this analysis is not only one of the largest to date, but it also challenges many misconceptions providers have regarding pregnancy outcomes. Even though transmasculine patients may require additional medical interventions to achieve pregnancy, such as assisted reproductive technology, or increased psychosocial support during the process, these initial studies are reassuring. Based on current evidence, these patients are not at greater risk for perinatal complications than their cisgender counterparts.
Despite these encouraging findings, there are still several challenges faced by transgender men when it comes to getting pregnant. For instance, they may have difficulty accessing fertility services because of financial constraints or experience a lack of awareness or prejudice from providers; they might also be subject to discrimination or stigma within health care settings. As front-line providers for obstetrical care, we must lead the way towards improving the care for pregnant transmasculine individuals.
Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.
References
1. Light A et al. Family planning and contraception use in transgender men. Contraception. 2018 Oct. doi: 10.1016/j.contraception.2018.06.006.
2. Krempasky C et al. Contraception across the transmasculine spectrum. Am J Obstet Gynecol. 2020 Feb. doi: 10.1016/j.ajog.2019.07.043.
3. Obedin-Maliver J, De Haan G. “Gynecologic care for transgender patients” in Ferrando C, ed., Comprehensive Care of the Transgender Patient. Philadelphia: Elsevier, 2019. 131-51.
4. Light AD et al. Transgender men who experienced pregnancy after female-to-male gender transitioning. Obstet Gynecol. 2014 Dec. doi: 10.1097/AOG.0000000000000540.
5. Brandt JS et al. Transgender men, pregnancy, and the “new” advanced paternal age: A review of the literature. Maturitas. 2019 Oct. doi: 10.1016/j.maturitas.2019.07.004.
6. Stroumsa D et al. Pregnancy outcomes in a U.S. cohort of transgender people. JAMA. 2023 Jun 6. doi: 10.1001/jama.2023.7688.
Despite increased societal gains, transgender individuals are still a medically and socially underserved group. The historic rise of antitransgender legislation and the overturning of Roe v. Wade, further compound existing health care disparities, particularly in the realm of contraception and pregnancy. Obstetrician-gynecologists and midwives are typically first-line providers when discussing family planning and fertility options for all patients assigned female at birth. Unfortunately,
Only individuals who are assigned female at birth and have a uterus are capable of pregnancy. This can include both cisgender women and nonbinary/transgender men. However, societal and medical institutions are struggling with this shift in perspective from a traditionally gendered role to a more inclusive one. Obstetrician-gynecologists and midwives can serve to bridge this gap between these patients and societal misconceptions surrounding transgender men who desire and experience pregnancy.
Providers need to remember that many transmasculine individuals will still retain their uterus and are therefore capable of getting pregnant. While testosterone causes amenorrhea, if patients are engaging in penile-vaginal intercourse, conception is still possible. If a patient does not desire pregnancy, all contraceptive options available for cisgender women, which also include combined oral contraceptives, should be offered.
For patients seeking to become pregnant, testosterone must be discontinued. Testosterone is teratogenic; it can cause abnormal urogenital development in the female fetus and should be avoided even prior to conception.1,2 The timing of testosterone discontinuation is debatable. There are no well-established guidelines dictating how early pregnancy can be attempted after cessation of testosterone, but typically if menses has resumed, the teratogenic effects of testosterone are less likely.
For amenorrheic patients on testosterone, menses will occur, on average, 3-6 months after testosterone is stopped. Of note, the longer that testosterone has been suspended, the greater the likelihood of achieving pregnancy.3 In a study by Light et al., 72% of patients conceived within 6 months of attempting pregnancy, 80% resumed menses within 6 months of stopping testosterone, and 20% of individuals conceived while they were amenorrheic from testosterone.4
Psychosocial support is an essential part of pregnancy care in transgender men. For some patients, pregnancy can worsen gender dysphoria, whereas others are empowered by the experience. Insurance companies may also deny obstetric care services to transgender males who have already changed their gender marker from female to male on insurance policies.
Whether transmasculine individuals are at higher risk for pregnancy complications is largely unknown, although emerging research in this field has yielded interesting results. While testosterone can cause vaginal atrophy, it does not seem to increase a patient’s risk of vaginal lacerations or their ability to have a successful vaginal delivery. For transgender men with significant discomfort around their genitalia, an elective cesarean section may be appropriate.5
More recently, Stroumsa et al. conducted an analysis of all deliveries at a Michigan institution from 2014 to 2018. Patients with male gender at the time of delivery or with the diagnostic code of gender dysphoria were identified as transgender.6 The primary outcome of this study was severe parental morbidity (such as amniotic fluid embolism, acute myocardial infarction, eclampsia, etc.), with secondary outcomes investigating rates of cesarean delivery and preterm birth.
During this time period, the researchers identified 256 transgender patients and 1.3 million cisgender patients in their Medicaid database and 1,651 transgender patients and 1.5 million cisgender patients in the commercial database who had experienced a delivery.6 Compared with cisgender patients, transgender patients in the Medicaid database were younger, less likely to be white, and more likely to have a chronic condition.6 Compared with cisgender patients in the commercial database, transgender patients experienced higher rates of anxiety and depression.6 Both transgender and cisgender patients had similar rates of severe parental morbidity. Ironically, rates of cesarean delivery were lower, compared with cisgender patients, in both the Medicaid and commercial databases, with no differences observed between rates of preterm birth.6
While more research is needed on pregnancy in transgender men, this analysis is not only one of the largest to date, but it also challenges many misconceptions providers have regarding pregnancy outcomes. Even though transmasculine patients may require additional medical interventions to achieve pregnancy, such as assisted reproductive technology, or increased psychosocial support during the process, these initial studies are reassuring. Based on current evidence, these patients are not at greater risk for perinatal complications than their cisgender counterparts.
Despite these encouraging findings, there are still several challenges faced by transgender men when it comes to getting pregnant. For instance, they may have difficulty accessing fertility services because of financial constraints or experience a lack of awareness or prejudice from providers; they might also be subject to discrimination or stigma within health care settings. As front-line providers for obstetrical care, we must lead the way towards improving the care for pregnant transmasculine individuals.
Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.
References
1. Light A et al. Family planning and contraception use in transgender men. Contraception. 2018 Oct. doi: 10.1016/j.contraception.2018.06.006.
2. Krempasky C et al. Contraception across the transmasculine spectrum. Am J Obstet Gynecol. 2020 Feb. doi: 10.1016/j.ajog.2019.07.043.
3. Obedin-Maliver J, De Haan G. “Gynecologic care for transgender patients” in Ferrando C, ed., Comprehensive Care of the Transgender Patient. Philadelphia: Elsevier, 2019. 131-51.
4. Light AD et al. Transgender men who experienced pregnancy after female-to-male gender transitioning. Obstet Gynecol. 2014 Dec. doi: 10.1097/AOG.0000000000000540.
5. Brandt JS et al. Transgender men, pregnancy, and the “new” advanced paternal age: A review of the literature. Maturitas. 2019 Oct. doi: 10.1016/j.maturitas.2019.07.004.
6. Stroumsa D et al. Pregnancy outcomes in a U.S. cohort of transgender people. JAMA. 2023 Jun 6. doi: 10.1001/jama.2023.7688.
PCOS associated with shorter lifespan
CHICAGO –
In the study, involving nearly 10,000 women with PCOS and matched controls from Finland, women with PCOS died on average a year earlier than their age-matched counterparts, primarily from diseases of the circulatory system, cancer, and diabetes.
PCOS is the most common endocrine disorder of reproductive-age women, of whom about 50%-70% also have obesity.
“I think we need to acknowledge that this is a health burden and not just a reproductive problem. In many cases we deal with the reproductive problem, and then these women are left alone. … So I think the message is we need to look beyond the reproductive outcomes, which are … really good. We can manage that,” said Terhi T. Piltonen, MD, PhD, during a press briefing held June 15 at the annual meeting of the Endocrine Society.
“I think the difficult part is [managing] the lifelong health for these women and supporting them to achieve the best health they can get. We need a multidisciplinary effort and to put more resources into the research,” added Dr. Piltonen, professor in the departments of ob.gyn. and reproductive endocrinology at the University of Oulu, Finland.
Indeed, Punith Kempegowda, MD, PhD, of the University of Birmingham (England) observed: “In our medical schools in the U.K., over 5 years, students get 45 minutes [of education] on PCOS, and they’re expected to learn about it.”
And over the last 20 years, funding for research into the condition has totaled less than a half percent of overall medical funding. “And we’re talking about 10% of all women. …We need to acknowledge it and educate people more. We need more published studies to understand more about it,” he noted.
Asked to comment, Greg Dodell, MD, owner and president of Central Park Endocrinology, New York, said: “PCOS is about a lot more than fertility, and that may not be the goal or on the mind of a woman at the time they start having symptoms of PCOS or get the diagnosis.”
“PCOS is largely a metabolic condition rooted in insulin resistance, and therefore, the potential clinical outcomes, including mortality, are important to recognize.”
Dr. Dodell, who has a special interest in PCOS, advised that, for women with the condition, “focus on reducing insulin resistance with health-promoting behaviors and medications as needed. Data demonstrate that improving fitness, irrespective of a change in weight, can improve metabolic markers.” And, he advised that these women be routinely screened for mental health issues.
He also noted, “PCOS occurs across the size spectrum, but those patients in larger bodies may face weight stigma which has negative health consequences. These patients may avoid going to doctors for routine health screenings, so it is an important issue to continue to address.”
Women with PCOS lose a year of life
The new data come from 9,839 women with PCOS and 70,705 age- and region-matched controls from the Finnish Care Register for Health Care. The group with PCOS had been diagnosed at a mean age of 27 years.
The mean follow-up time was 13.1 years in both groups, during which 1,003 controls and 177 women with PCOS died. The mean age at death was 51.4 years for the PCOS group versus 52.6 years for the control women, a significant difference (P < .001).
Causes of death that were significantly higher among the women with PCOS versus controls after adjustments were cancer (hazard ratio, 1.39), and diseases of the circulatory system (1.68).
In more specific subcategories, after adjustment for education, the women with PCOS had increased mortality from nonischemic diseases, such as hypertensive heart disease, pulmonary embolism, etc. (HR, 2.06), and diabetes (HR, 2.85).
One study limitation was the inability to adjust for body mass index, Dr. Piltonen noted.
Dr. Piltonen, Dr. Kempegowda, and Dr. Dodell have no disclosures.
CHICAGO –
In the study, involving nearly 10,000 women with PCOS and matched controls from Finland, women with PCOS died on average a year earlier than their age-matched counterparts, primarily from diseases of the circulatory system, cancer, and diabetes.
PCOS is the most common endocrine disorder of reproductive-age women, of whom about 50%-70% also have obesity.
“I think we need to acknowledge that this is a health burden and not just a reproductive problem. In many cases we deal with the reproductive problem, and then these women are left alone. … So I think the message is we need to look beyond the reproductive outcomes, which are … really good. We can manage that,” said Terhi T. Piltonen, MD, PhD, during a press briefing held June 15 at the annual meeting of the Endocrine Society.
“I think the difficult part is [managing] the lifelong health for these women and supporting them to achieve the best health they can get. We need a multidisciplinary effort and to put more resources into the research,” added Dr. Piltonen, professor in the departments of ob.gyn. and reproductive endocrinology at the University of Oulu, Finland.
Indeed, Punith Kempegowda, MD, PhD, of the University of Birmingham (England) observed: “In our medical schools in the U.K., over 5 years, students get 45 minutes [of education] on PCOS, and they’re expected to learn about it.”
And over the last 20 years, funding for research into the condition has totaled less than a half percent of overall medical funding. “And we’re talking about 10% of all women. …We need to acknowledge it and educate people more. We need more published studies to understand more about it,” he noted.
Asked to comment, Greg Dodell, MD, owner and president of Central Park Endocrinology, New York, said: “PCOS is about a lot more than fertility, and that may not be the goal or on the mind of a woman at the time they start having symptoms of PCOS or get the diagnosis.”
“PCOS is largely a metabolic condition rooted in insulin resistance, and therefore, the potential clinical outcomes, including mortality, are important to recognize.”
Dr. Dodell, who has a special interest in PCOS, advised that, for women with the condition, “focus on reducing insulin resistance with health-promoting behaviors and medications as needed. Data demonstrate that improving fitness, irrespective of a change in weight, can improve metabolic markers.” And, he advised that these women be routinely screened for mental health issues.
He also noted, “PCOS occurs across the size spectrum, but those patients in larger bodies may face weight stigma which has negative health consequences. These patients may avoid going to doctors for routine health screenings, so it is an important issue to continue to address.”
Women with PCOS lose a year of life
The new data come from 9,839 women with PCOS and 70,705 age- and region-matched controls from the Finnish Care Register for Health Care. The group with PCOS had been diagnosed at a mean age of 27 years.
The mean follow-up time was 13.1 years in both groups, during which 1,003 controls and 177 women with PCOS died. The mean age at death was 51.4 years for the PCOS group versus 52.6 years for the control women, a significant difference (P < .001).
Causes of death that were significantly higher among the women with PCOS versus controls after adjustments were cancer (hazard ratio, 1.39), and diseases of the circulatory system (1.68).
In more specific subcategories, after adjustment for education, the women with PCOS had increased mortality from nonischemic diseases, such as hypertensive heart disease, pulmonary embolism, etc. (HR, 2.06), and diabetes (HR, 2.85).
One study limitation was the inability to adjust for body mass index, Dr. Piltonen noted.
Dr. Piltonen, Dr. Kempegowda, and Dr. Dodell have no disclosures.
CHICAGO –
In the study, involving nearly 10,000 women with PCOS and matched controls from Finland, women with PCOS died on average a year earlier than their age-matched counterparts, primarily from diseases of the circulatory system, cancer, and diabetes.
PCOS is the most common endocrine disorder of reproductive-age women, of whom about 50%-70% also have obesity.
“I think we need to acknowledge that this is a health burden and not just a reproductive problem. In many cases we deal with the reproductive problem, and then these women are left alone. … So I think the message is we need to look beyond the reproductive outcomes, which are … really good. We can manage that,” said Terhi T. Piltonen, MD, PhD, during a press briefing held June 15 at the annual meeting of the Endocrine Society.
“I think the difficult part is [managing] the lifelong health for these women and supporting them to achieve the best health they can get. We need a multidisciplinary effort and to put more resources into the research,” added Dr. Piltonen, professor in the departments of ob.gyn. and reproductive endocrinology at the University of Oulu, Finland.
Indeed, Punith Kempegowda, MD, PhD, of the University of Birmingham (England) observed: “In our medical schools in the U.K., over 5 years, students get 45 minutes [of education] on PCOS, and they’re expected to learn about it.”
And over the last 20 years, funding for research into the condition has totaled less than a half percent of overall medical funding. “And we’re talking about 10% of all women. …We need to acknowledge it and educate people more. We need more published studies to understand more about it,” he noted.
Asked to comment, Greg Dodell, MD, owner and president of Central Park Endocrinology, New York, said: “PCOS is about a lot more than fertility, and that may not be the goal or on the mind of a woman at the time they start having symptoms of PCOS or get the diagnosis.”
“PCOS is largely a metabolic condition rooted in insulin resistance, and therefore, the potential clinical outcomes, including mortality, are important to recognize.”
Dr. Dodell, who has a special interest in PCOS, advised that, for women with the condition, “focus on reducing insulin resistance with health-promoting behaviors and medications as needed. Data demonstrate that improving fitness, irrespective of a change in weight, can improve metabolic markers.” And, he advised that these women be routinely screened for mental health issues.
He also noted, “PCOS occurs across the size spectrum, but those patients in larger bodies may face weight stigma which has negative health consequences. These patients may avoid going to doctors for routine health screenings, so it is an important issue to continue to address.”
Women with PCOS lose a year of life
The new data come from 9,839 women with PCOS and 70,705 age- and region-matched controls from the Finnish Care Register for Health Care. The group with PCOS had been diagnosed at a mean age of 27 years.
The mean follow-up time was 13.1 years in both groups, during which 1,003 controls and 177 women with PCOS died. The mean age at death was 51.4 years for the PCOS group versus 52.6 years for the control women, a significant difference (P < .001).
Causes of death that were significantly higher among the women with PCOS versus controls after adjustments were cancer (hazard ratio, 1.39), and diseases of the circulatory system (1.68).
In more specific subcategories, after adjustment for education, the women with PCOS had increased mortality from nonischemic diseases, such as hypertensive heart disease, pulmonary embolism, etc. (HR, 2.06), and diabetes (HR, 2.85).
One study limitation was the inability to adjust for body mass index, Dr. Piltonen noted.
Dr. Piltonen, Dr. Kempegowda, and Dr. Dodell have no disclosures.
AT ENDO 2023
Vulvodynia: A little-known and treatable condition
Vulvodynia is a little-known condition that, according to some U.S. studies, affects 3%-14% of the female population. It is defined as chronic pain, present for at least 3 months, that generally involves the vulva or some of its specific areas such as the clitoris or vestibule and is not attributable to causes of an infectious, inflammatory, oncologic, or endocrine nature; skin trauma; or damage to nerve fibers.
“There are probably many more women who suffer from it who don’t talk about it out of shame, because they feel ‘wrong,’ ” said gynecologist Pina Belfiore, MD, chair of the Italian Interdisciplinary Society of Vulvology, at the annual conference of the Italian Society of Gender Medicine in Neurosciences. “It is a treatable condition, or at the very least, a patient’s quality of life can be significantly improved with a personalized therapeutic approach.”
The correct diagnosis
The first step for setting the patient on the right course toward recovery is to offer welcome and empathy, recognizing that the suffering, which can have psychological causes, is not imaginary. “We need to explain to patients that their condition has a name, that they are not alone in this situation, and, above all, that there is hope for solving the problem. They can get through it,” said Dr. Belfiore.
First, an accurate history of the pain is needed to correctly diagnose vulvodynia. How long has the pain been going on? Is it continuous or is it triggered by an environmental factor, for example by sexual intercourse or contact with underwear? Is it a burning or stinging sensation? Did it first occur after an infection or after a physical or psychological trauma? Does the patient suffer from other forms of chronic pain such as recurring headaches or fibromyalgia?
“It is then necessary to inspect the vulva to exclude other systematic conditions or injuries that may be responsible for the pain, as well as to locate hypersensitive areas and evaluate the intensity of the symptoms,” said Dr. Belfiore.” A swab test is performed for this purpose, which is carried out by applying light pressure on different points of the vulva with a cotton swab.”
CNS dysfunction
, which confuses signals coming from the peripheral area, interpreting signals of a different nature as painful stimuli.
“The origin of this dysfunction is an individual predisposition. In fact, often the women who suffer from it are also affected by other forms of chronic pain,” said Dr. Belfiore. “Triggers for vulvodynia can be bacterial infections, candidiasis, or traumatic events such as surgically assisted birth or psychological trauma.”
Because inflammatory mechanisms are not involved, anti-inflammatory drugs are not helpful in treating the problem. “Instead, it is necessary to reduce the sensitivity of the CNS. For this purpose, low-dose antidepressant or antiepileptic drugs are used,” said Dr. Belfiore. “Pelvic floor rehabilitation is another treatment that can be beneficial when combined with pharmacologic treatment. This should be conducted by a professional with specific experience in vulvodynia, because an excessive increase in the tone of the levator ani muscle can make the situation worse. Psychotherapy and the adoption of certain hygienic and behavioral measures can also help, such as using lubricant during sexual intercourse, wearing pure cotton underwear, and using gentle intimate body washes.”
“It is important that family doctors who see women with this problem refer them to an experienced specialist,” said Dr. Belfiore.
A version of this article first appeared on Medscape.com.
This article was translated from Univadis Italy, which is part of the Medscape Professional Network.
Vulvodynia is a little-known condition that, according to some U.S. studies, affects 3%-14% of the female population. It is defined as chronic pain, present for at least 3 months, that generally involves the vulva or some of its specific areas such as the clitoris or vestibule and is not attributable to causes of an infectious, inflammatory, oncologic, or endocrine nature; skin trauma; or damage to nerve fibers.
“There are probably many more women who suffer from it who don’t talk about it out of shame, because they feel ‘wrong,’ ” said gynecologist Pina Belfiore, MD, chair of the Italian Interdisciplinary Society of Vulvology, at the annual conference of the Italian Society of Gender Medicine in Neurosciences. “It is a treatable condition, or at the very least, a patient’s quality of life can be significantly improved with a personalized therapeutic approach.”
The correct diagnosis
The first step for setting the patient on the right course toward recovery is to offer welcome and empathy, recognizing that the suffering, which can have psychological causes, is not imaginary. “We need to explain to patients that their condition has a name, that they are not alone in this situation, and, above all, that there is hope for solving the problem. They can get through it,” said Dr. Belfiore.
First, an accurate history of the pain is needed to correctly diagnose vulvodynia. How long has the pain been going on? Is it continuous or is it triggered by an environmental factor, for example by sexual intercourse or contact with underwear? Is it a burning or stinging sensation? Did it first occur after an infection or after a physical or psychological trauma? Does the patient suffer from other forms of chronic pain such as recurring headaches or fibromyalgia?
“It is then necessary to inspect the vulva to exclude other systematic conditions or injuries that may be responsible for the pain, as well as to locate hypersensitive areas and evaluate the intensity of the symptoms,” said Dr. Belfiore.” A swab test is performed for this purpose, which is carried out by applying light pressure on different points of the vulva with a cotton swab.”
CNS dysfunction
, which confuses signals coming from the peripheral area, interpreting signals of a different nature as painful stimuli.
“The origin of this dysfunction is an individual predisposition. In fact, often the women who suffer from it are also affected by other forms of chronic pain,” said Dr. Belfiore. “Triggers for vulvodynia can be bacterial infections, candidiasis, or traumatic events such as surgically assisted birth or psychological trauma.”
Because inflammatory mechanisms are not involved, anti-inflammatory drugs are not helpful in treating the problem. “Instead, it is necessary to reduce the sensitivity of the CNS. For this purpose, low-dose antidepressant or antiepileptic drugs are used,” said Dr. Belfiore. “Pelvic floor rehabilitation is another treatment that can be beneficial when combined with pharmacologic treatment. This should be conducted by a professional with specific experience in vulvodynia, because an excessive increase in the tone of the levator ani muscle can make the situation worse. Psychotherapy and the adoption of certain hygienic and behavioral measures can also help, such as using lubricant during sexual intercourse, wearing pure cotton underwear, and using gentle intimate body washes.”
“It is important that family doctors who see women with this problem refer them to an experienced specialist,” said Dr. Belfiore.
A version of this article first appeared on Medscape.com.
This article was translated from Univadis Italy, which is part of the Medscape Professional Network.
Vulvodynia is a little-known condition that, according to some U.S. studies, affects 3%-14% of the female population. It is defined as chronic pain, present for at least 3 months, that generally involves the vulva or some of its specific areas such as the clitoris or vestibule and is not attributable to causes of an infectious, inflammatory, oncologic, or endocrine nature; skin trauma; or damage to nerve fibers.
“There are probably many more women who suffer from it who don’t talk about it out of shame, because they feel ‘wrong,’ ” said gynecologist Pina Belfiore, MD, chair of the Italian Interdisciplinary Society of Vulvology, at the annual conference of the Italian Society of Gender Medicine in Neurosciences. “It is a treatable condition, or at the very least, a patient’s quality of life can be significantly improved with a personalized therapeutic approach.”
The correct diagnosis
The first step for setting the patient on the right course toward recovery is to offer welcome and empathy, recognizing that the suffering, which can have psychological causes, is not imaginary. “We need to explain to patients that their condition has a name, that they are not alone in this situation, and, above all, that there is hope for solving the problem. They can get through it,” said Dr. Belfiore.
First, an accurate history of the pain is needed to correctly diagnose vulvodynia. How long has the pain been going on? Is it continuous or is it triggered by an environmental factor, for example by sexual intercourse or contact with underwear? Is it a burning or stinging sensation? Did it first occur after an infection or after a physical or psychological trauma? Does the patient suffer from other forms of chronic pain such as recurring headaches or fibromyalgia?
“It is then necessary to inspect the vulva to exclude other systematic conditions or injuries that may be responsible for the pain, as well as to locate hypersensitive areas and evaluate the intensity of the symptoms,” said Dr. Belfiore.” A swab test is performed for this purpose, which is carried out by applying light pressure on different points of the vulva with a cotton swab.”
CNS dysfunction
, which confuses signals coming from the peripheral area, interpreting signals of a different nature as painful stimuli.
“The origin of this dysfunction is an individual predisposition. In fact, often the women who suffer from it are also affected by other forms of chronic pain,” said Dr. Belfiore. “Triggers for vulvodynia can be bacterial infections, candidiasis, or traumatic events such as surgically assisted birth or psychological trauma.”
Because inflammatory mechanisms are not involved, anti-inflammatory drugs are not helpful in treating the problem. “Instead, it is necessary to reduce the sensitivity of the CNS. For this purpose, low-dose antidepressant or antiepileptic drugs are used,” said Dr. Belfiore. “Pelvic floor rehabilitation is another treatment that can be beneficial when combined with pharmacologic treatment. This should be conducted by a professional with specific experience in vulvodynia, because an excessive increase in the tone of the levator ani muscle can make the situation worse. Psychotherapy and the adoption of certain hygienic and behavioral measures can also help, such as using lubricant during sexual intercourse, wearing pure cotton underwear, and using gentle intimate body washes.”
“It is important that family doctors who see women with this problem refer them to an experienced specialist,” said Dr. Belfiore.
A version of this article first appeared on Medscape.com.
This article was translated from Univadis Italy, which is part of the Medscape Professional Network.
Surgical de-escalation passes clinical test in low-risk cervical cancer
CHICAGO –
“Following adequate and rigorous preoperative assessment, and that’s key – very careful [patient selection] – simple hysterectomies can now be considered the new standard of care for patients with low-risk early-stage cervical cancer,” said Marie Plante, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. A simple hysterectomy removes the uterus and cervix, while a radical hysterectomy also removes the parametrium and upper vagina.
Cervical cancer incidence has gone down over the past 2 decades as a result of improved screening, and patients tend to be lower in age and are more likely to have low-risk, early-stage disease, according to Dr. Plante. “Although radical surgery is highly effective for the treatment of low-risk disease, women are at risk of suffering survivorship issues related to long-term surgical side effects including compromised bladder, bowel, and sexual function,” said Dr. Plante, who is a professor of obstetrics and gynecology at Laval University and head of clinical research at l’Hôtel-Dieu de Québec, both in Quebec City.
Retrospective studies found that infiltration of the parametrium is quite rare in low-risk cases, “suggesting that less radical surgery may be a safe option associated with decreased morbidity – what we call surgical de-escalation,” said Dr. Plante.
To test that idea more rigorously, the researchers designed the SHAPE trial, which randomized 700 women to a simple hysterectomy or radical hysterectomy. Patients were carefully selected to be low risk, having squamous cell, adenocarcinoma, or adenosquamous carcinoma, stage IA2 or IB2 tumors, fewer than 10 mm of stromal invasion on loop electrosurgical excision procedure or cone biopsy, less than 50% stromal invasion seen in MRI, and a maximum tumor dimension of 20 mm or less. Tumors were grade I-III or not assessable.
Over a median follow-up of 4.5 years, pelvic recurrence was 2.52% in the simple hysterectomy group and 2.17% in the radical hysterectomy group. The difference between the recurrence rate between the two groups was 0.35%, with an upper 95% confidence limit of 2.32%, below the threshold of 4% which had been predetermined as a benchmark for similar outcomes between the two groups. “Therefore, noninferiority of simple hysterectomy to radical hysterectomy could be concluded,” said Dr. Plante.
There were no statistically significant differences in intraoperative complications or mortality between the groups.
Surgery-related adverse events greater in radical hysterectomy group
There were some differences between the groups with respect to surgery-related adverse events. Within 4 weeks of surgery, there was a greater incidence of any adverse event in the radical hysterectomy group (50.6% vs. 42.6%; P = .04), as well as greater incidences of urinary incontinence (5.5% vs. 2.4%; P = .048) and urinary retention (11.0% vs. 0.6%; P < .0001). In the 4 weeks following surgery, there was a trend toward more surgery-related adverse events in the radical hysterectomy group (60.5% vs. 53.6%; P = .08) and higher incidences of urinary incontinence (11.0% vs. 4.7%; P = .003) and urinary retention (9.9% vs. 0.6%; P < .0001).
“Urinary incontinence and urinary retention are statistically worse in the radical hysterectomy group – both acutely, as well as [during] the following four weeks after surgery, suggesting that the problem persisted over time,” said Dr. Plante.
Dr. Plante also presented the study at a premeeting virtual press conference, during which Kathleen Moore, MD, provided comments on the study. She expressed enthusiasm about the results.
“Amongst those carefully selected tumors, radical hysterectomy can be converted to a simple hysterectomy, including minimally invasive. You still have to do nodes – that’s an important thing to remember – but you can do this without loss of oncologic control. And importantly, with reduction in surgical complications, postop morbidity, specifically neurologic morbidity. The moment this is presented [at the ASCO conference] this will be the new standard of care, and it represents a huge step forward in the care of women with early-stage cervical cancer,” said Dr. Moore, who is a professor of gynecologic oncology at the University of Oklahoma Health Sciences Center, Oklahoma City.
Also in the press conference, Dr. Plante emphasized the importance of a thorough understanding of the tumor, including size, imaging, and pathology. “The more conservative one wants to be, the more meticulous, the more careful one has to be to make sure that we’re truly dealing with low-risk patients.”
During the question-and-answer session following her presentation at the ASCO session, a moderator asked Dr. Plante if the presence of lymph vascular space invasion (LVSI) should prompt a radical hysterectomy.
Dr. Plante noted that about 13% of both radical and simple hysterectomy groups had LVSI present. “I think the key thing is careful selection, but I’m not sure that we should exclude LVSI [from consideration for simple hysterectomy] de facto,” she said.
Dr. Plante has consulted or advised Merck Serono and has received travel, accommodations, or other expenses from AstraZeneca. Dr. Moore has consulted, advised, and received research funding and travel expenses from numerous pharmaceutical companies.
CHICAGO –
“Following adequate and rigorous preoperative assessment, and that’s key – very careful [patient selection] – simple hysterectomies can now be considered the new standard of care for patients with low-risk early-stage cervical cancer,” said Marie Plante, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. A simple hysterectomy removes the uterus and cervix, while a radical hysterectomy also removes the parametrium and upper vagina.
Cervical cancer incidence has gone down over the past 2 decades as a result of improved screening, and patients tend to be lower in age and are more likely to have low-risk, early-stage disease, according to Dr. Plante. “Although radical surgery is highly effective for the treatment of low-risk disease, women are at risk of suffering survivorship issues related to long-term surgical side effects including compromised bladder, bowel, and sexual function,” said Dr. Plante, who is a professor of obstetrics and gynecology at Laval University and head of clinical research at l’Hôtel-Dieu de Québec, both in Quebec City.
Retrospective studies found that infiltration of the parametrium is quite rare in low-risk cases, “suggesting that less radical surgery may be a safe option associated with decreased morbidity – what we call surgical de-escalation,” said Dr. Plante.
To test that idea more rigorously, the researchers designed the SHAPE trial, which randomized 700 women to a simple hysterectomy or radical hysterectomy. Patients were carefully selected to be low risk, having squamous cell, adenocarcinoma, or adenosquamous carcinoma, stage IA2 or IB2 tumors, fewer than 10 mm of stromal invasion on loop electrosurgical excision procedure or cone biopsy, less than 50% stromal invasion seen in MRI, and a maximum tumor dimension of 20 mm or less. Tumors were grade I-III or not assessable.
Over a median follow-up of 4.5 years, pelvic recurrence was 2.52% in the simple hysterectomy group and 2.17% in the radical hysterectomy group. The difference between the recurrence rate between the two groups was 0.35%, with an upper 95% confidence limit of 2.32%, below the threshold of 4% which had been predetermined as a benchmark for similar outcomes between the two groups. “Therefore, noninferiority of simple hysterectomy to radical hysterectomy could be concluded,” said Dr. Plante.
There were no statistically significant differences in intraoperative complications or mortality between the groups.
Surgery-related adverse events greater in radical hysterectomy group
There were some differences between the groups with respect to surgery-related adverse events. Within 4 weeks of surgery, there was a greater incidence of any adverse event in the radical hysterectomy group (50.6% vs. 42.6%; P = .04), as well as greater incidences of urinary incontinence (5.5% vs. 2.4%; P = .048) and urinary retention (11.0% vs. 0.6%; P < .0001). In the 4 weeks following surgery, there was a trend toward more surgery-related adverse events in the radical hysterectomy group (60.5% vs. 53.6%; P = .08) and higher incidences of urinary incontinence (11.0% vs. 4.7%; P = .003) and urinary retention (9.9% vs. 0.6%; P < .0001).
“Urinary incontinence and urinary retention are statistically worse in the radical hysterectomy group – both acutely, as well as [during] the following four weeks after surgery, suggesting that the problem persisted over time,” said Dr. Plante.
Dr. Plante also presented the study at a premeeting virtual press conference, during which Kathleen Moore, MD, provided comments on the study. She expressed enthusiasm about the results.
“Amongst those carefully selected tumors, radical hysterectomy can be converted to a simple hysterectomy, including minimally invasive. You still have to do nodes – that’s an important thing to remember – but you can do this without loss of oncologic control. And importantly, with reduction in surgical complications, postop morbidity, specifically neurologic morbidity. The moment this is presented [at the ASCO conference] this will be the new standard of care, and it represents a huge step forward in the care of women with early-stage cervical cancer,” said Dr. Moore, who is a professor of gynecologic oncology at the University of Oklahoma Health Sciences Center, Oklahoma City.
Also in the press conference, Dr. Plante emphasized the importance of a thorough understanding of the tumor, including size, imaging, and pathology. “The more conservative one wants to be, the more meticulous, the more careful one has to be to make sure that we’re truly dealing with low-risk patients.”
During the question-and-answer session following her presentation at the ASCO session, a moderator asked Dr. Plante if the presence of lymph vascular space invasion (LVSI) should prompt a radical hysterectomy.
Dr. Plante noted that about 13% of both radical and simple hysterectomy groups had LVSI present. “I think the key thing is careful selection, but I’m not sure that we should exclude LVSI [from consideration for simple hysterectomy] de facto,” she said.
Dr. Plante has consulted or advised Merck Serono and has received travel, accommodations, or other expenses from AstraZeneca. Dr. Moore has consulted, advised, and received research funding and travel expenses from numerous pharmaceutical companies.
CHICAGO –
“Following adequate and rigorous preoperative assessment, and that’s key – very careful [patient selection] – simple hysterectomies can now be considered the new standard of care for patients with low-risk early-stage cervical cancer,” said Marie Plante, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. A simple hysterectomy removes the uterus and cervix, while a radical hysterectomy also removes the parametrium and upper vagina.
Cervical cancer incidence has gone down over the past 2 decades as a result of improved screening, and patients tend to be lower in age and are more likely to have low-risk, early-stage disease, according to Dr. Plante. “Although radical surgery is highly effective for the treatment of low-risk disease, women are at risk of suffering survivorship issues related to long-term surgical side effects including compromised bladder, bowel, and sexual function,” said Dr. Plante, who is a professor of obstetrics and gynecology at Laval University and head of clinical research at l’Hôtel-Dieu de Québec, both in Quebec City.
Retrospective studies found that infiltration of the parametrium is quite rare in low-risk cases, “suggesting that less radical surgery may be a safe option associated with decreased morbidity – what we call surgical de-escalation,” said Dr. Plante.
To test that idea more rigorously, the researchers designed the SHAPE trial, which randomized 700 women to a simple hysterectomy or radical hysterectomy. Patients were carefully selected to be low risk, having squamous cell, adenocarcinoma, or adenosquamous carcinoma, stage IA2 or IB2 tumors, fewer than 10 mm of stromal invasion on loop electrosurgical excision procedure or cone biopsy, less than 50% stromal invasion seen in MRI, and a maximum tumor dimension of 20 mm or less. Tumors were grade I-III or not assessable.
Over a median follow-up of 4.5 years, pelvic recurrence was 2.52% in the simple hysterectomy group and 2.17% in the radical hysterectomy group. The difference between the recurrence rate between the two groups was 0.35%, with an upper 95% confidence limit of 2.32%, below the threshold of 4% which had been predetermined as a benchmark for similar outcomes between the two groups. “Therefore, noninferiority of simple hysterectomy to radical hysterectomy could be concluded,” said Dr. Plante.
There were no statistically significant differences in intraoperative complications or mortality between the groups.
Surgery-related adverse events greater in radical hysterectomy group
There were some differences between the groups with respect to surgery-related adverse events. Within 4 weeks of surgery, there was a greater incidence of any adverse event in the radical hysterectomy group (50.6% vs. 42.6%; P = .04), as well as greater incidences of urinary incontinence (5.5% vs. 2.4%; P = .048) and urinary retention (11.0% vs. 0.6%; P < .0001). In the 4 weeks following surgery, there was a trend toward more surgery-related adverse events in the radical hysterectomy group (60.5% vs. 53.6%; P = .08) and higher incidences of urinary incontinence (11.0% vs. 4.7%; P = .003) and urinary retention (9.9% vs. 0.6%; P < .0001).
“Urinary incontinence and urinary retention are statistically worse in the radical hysterectomy group – both acutely, as well as [during] the following four weeks after surgery, suggesting that the problem persisted over time,” said Dr. Plante.
Dr. Plante also presented the study at a premeeting virtual press conference, during which Kathleen Moore, MD, provided comments on the study. She expressed enthusiasm about the results.
“Amongst those carefully selected tumors, radical hysterectomy can be converted to a simple hysterectomy, including minimally invasive. You still have to do nodes – that’s an important thing to remember – but you can do this without loss of oncologic control. And importantly, with reduction in surgical complications, postop morbidity, specifically neurologic morbidity. The moment this is presented [at the ASCO conference] this will be the new standard of care, and it represents a huge step forward in the care of women with early-stage cervical cancer,” said Dr. Moore, who is a professor of gynecologic oncology at the University of Oklahoma Health Sciences Center, Oklahoma City.
Also in the press conference, Dr. Plante emphasized the importance of a thorough understanding of the tumor, including size, imaging, and pathology. “The more conservative one wants to be, the more meticulous, the more careful one has to be to make sure that we’re truly dealing with low-risk patients.”
During the question-and-answer session following her presentation at the ASCO session, a moderator asked Dr. Plante if the presence of lymph vascular space invasion (LVSI) should prompt a radical hysterectomy.
Dr. Plante noted that about 13% of both radical and simple hysterectomy groups had LVSI present. “I think the key thing is careful selection, but I’m not sure that we should exclude LVSI [from consideration for simple hysterectomy] de facto,” she said.
Dr. Plante has consulted or advised Merck Serono and has received travel, accommodations, or other expenses from AstraZeneca. Dr. Moore has consulted, advised, and received research funding and travel expenses from numerous pharmaceutical companies.
AT ASCO 2023
The diagnostic and therapeutic challenges of syringoma
Pain and pruritus are the most common complaints in patients who present to vulvar clinics.1 These symptoms can be related to a variety of conditions, including vulvar lesions. There are both common and uncommon vulvar lesions. Vulvar lesions can be skin colored, yellow, and red. Certain lesions can be diagnosed with history and physical examination alone. Some more common lesions include acrochordons (skin tags), benign growths that are common in patients with diabetes, obesity, and pregnancy.2,3 Other common vulvar lesions are papillomatosis, lichen simplex chronicus, and epidermoid cysts. Other lesions include low- and high-grade squamous intraepithelial lesions (HSIL).4 These lesions require biopsy for diagnosis as high-grade lesions require treatment. HSIL of the vulva is considered a premalignancy that necessitates treatment.5 Other lesions that can present with vulvar complaints are molluscum contagiosum, Bartholin gland duct cyst, intradermal melanocytic nevus, and squamous cell carcinoma.
Rarely, other less common conditions can present as vulvar lesions. Syringomas are benign eccrine sweat gland neoplasms. They are more commonly found on the face, neck, or chest.6 On the vulva they are generally small subcutaneous skin-colored papules.7 They may be asymptomatic and noted only on routine examination.
Vulvar syringomas also may present with symptoms. On the vulva, syringomas often present as pruritic papules that can be isolated or multifocal. Often on the labia majora they range in size from 2 to 20 mm.8
They can coalesce to form a larger lesion. They also may be described as painful. When syringomas are pruritic, the overlying skin may appear thickened from rubbing or scratching, and excoriations may be present.
Since vulvar syringomas are rare, there is no standard treatment. Biopsy is necessary for definitive diagnosis. For asymptomatic cases, expectant management is warranted. In symptomatic cases treatment can be considered. Treatment options include cryotherapy, laser ablation, and intralesional electrodissection.8 Intralesional electrodissection and curettage also has been described as treatment.9 Other treatment options include surgical excision of individual lesions or larger excisions if multifocal.
The case study described in "Case letter: Vulvar syringoma" highlights the diagnostic and therapeutic challenges associated with rare lesions of the vulva. Referral to a specialty clinic may be warranted in these challenging cases. ●
- Hansen A, Carr K, Jensen JT. Characteristics and initial diagnoses in women presenting to a referral center for vulvovaginal disorders in 1996–2000. J Reprod Med. 2002; 47: 854-860.
- Boza JC, Trindade EN, Peruzzo J, et al. Skin manifestations of obesity: a comparative study. J Eur Acad Dermatol Venereol. 2012;26:1220-1223.
- Winton GB, Lewis CW. Dermatoses of pregnancy. J Am Acad Dermatol. 1982;6:977-998.
- Bornstein J, Bogliatto F, Haefner HK, et al; ISSVD Terminology Committee. The 2015 International Society for the Study of Vulvovaginal Disease (ISSVD) terminology of vulvar squamous intraepithelial lesions. J Low Genit Tract Dis. 2016;20:11-14.
- American College of Obstetricians and Gynecologists. Committee opinion no. 675: management of vulvar intraepithelial neoplasia. Obstet Gynecol. 2016;128:e178-e182.
- Heller DS. Benign tumors and tumor-like lesions of the vulva. Clin Obstet Gynecol. 2015;58:526-535.
- Shalabi MMK, Homan K, Bicknell L. Vulvar syringomas. Proc (Bayl Univer Med Cent). 2022;35:113-114.
- Ozdemir O, Sari ME, Sen E, et al. Vulvar syringoma in a postmenopausal woman: a case report. J Reprod Med. 2015;60:452-454.
- Stevenson TR, Swanson NA. Syringoma: removal by electrodesiccation and curettage. Ann Plast Surg. 1985;15:151-154.
Pain and pruritus are the most common complaints in patients who present to vulvar clinics.1 These symptoms can be related to a variety of conditions, including vulvar lesions. There are both common and uncommon vulvar lesions. Vulvar lesions can be skin colored, yellow, and red. Certain lesions can be diagnosed with history and physical examination alone. Some more common lesions include acrochordons (skin tags), benign growths that are common in patients with diabetes, obesity, and pregnancy.2,3 Other common vulvar lesions are papillomatosis, lichen simplex chronicus, and epidermoid cysts. Other lesions include low- and high-grade squamous intraepithelial lesions (HSIL).4 These lesions require biopsy for diagnosis as high-grade lesions require treatment. HSIL of the vulva is considered a premalignancy that necessitates treatment.5 Other lesions that can present with vulvar complaints are molluscum contagiosum, Bartholin gland duct cyst, intradermal melanocytic nevus, and squamous cell carcinoma.
Rarely, other less common conditions can present as vulvar lesions. Syringomas are benign eccrine sweat gland neoplasms. They are more commonly found on the face, neck, or chest.6 On the vulva they are generally small subcutaneous skin-colored papules.7 They may be asymptomatic and noted only on routine examination.
Vulvar syringomas also may present with symptoms. On the vulva, syringomas often present as pruritic papules that can be isolated or multifocal. Often on the labia majora they range in size from 2 to 20 mm.8
They can coalesce to form a larger lesion. They also may be described as painful. When syringomas are pruritic, the overlying skin may appear thickened from rubbing or scratching, and excoriations may be present.
Since vulvar syringomas are rare, there is no standard treatment. Biopsy is necessary for definitive diagnosis. For asymptomatic cases, expectant management is warranted. In symptomatic cases treatment can be considered. Treatment options include cryotherapy, laser ablation, and intralesional electrodissection.8 Intralesional electrodissection and curettage also has been described as treatment.9 Other treatment options include surgical excision of individual lesions or larger excisions if multifocal.
The case study described in "Case letter: Vulvar syringoma" highlights the diagnostic and therapeutic challenges associated with rare lesions of the vulva. Referral to a specialty clinic may be warranted in these challenging cases. ●
Pain and pruritus are the most common complaints in patients who present to vulvar clinics.1 These symptoms can be related to a variety of conditions, including vulvar lesions. There are both common and uncommon vulvar lesions. Vulvar lesions can be skin colored, yellow, and red. Certain lesions can be diagnosed with history and physical examination alone. Some more common lesions include acrochordons (skin tags), benign growths that are common in patients with diabetes, obesity, and pregnancy.2,3 Other common vulvar lesions are papillomatosis, lichen simplex chronicus, and epidermoid cysts. Other lesions include low- and high-grade squamous intraepithelial lesions (HSIL).4 These lesions require biopsy for diagnosis as high-grade lesions require treatment. HSIL of the vulva is considered a premalignancy that necessitates treatment.5 Other lesions that can present with vulvar complaints are molluscum contagiosum, Bartholin gland duct cyst, intradermal melanocytic nevus, and squamous cell carcinoma.
Rarely, other less common conditions can present as vulvar lesions. Syringomas are benign eccrine sweat gland neoplasms. They are more commonly found on the face, neck, or chest.6 On the vulva they are generally small subcutaneous skin-colored papules.7 They may be asymptomatic and noted only on routine examination.
Vulvar syringomas also may present with symptoms. On the vulva, syringomas often present as pruritic papules that can be isolated or multifocal. Often on the labia majora they range in size from 2 to 20 mm.8
They can coalesce to form a larger lesion. They also may be described as painful. When syringomas are pruritic, the overlying skin may appear thickened from rubbing or scratching, and excoriations may be present.
Since vulvar syringomas are rare, there is no standard treatment. Biopsy is necessary for definitive diagnosis. For asymptomatic cases, expectant management is warranted. In symptomatic cases treatment can be considered. Treatment options include cryotherapy, laser ablation, and intralesional electrodissection.8 Intralesional electrodissection and curettage also has been described as treatment.9 Other treatment options include surgical excision of individual lesions or larger excisions if multifocal.
The case study described in "Case letter: Vulvar syringoma" highlights the diagnostic and therapeutic challenges associated with rare lesions of the vulva. Referral to a specialty clinic may be warranted in these challenging cases. ●
- Hansen A, Carr K, Jensen JT. Characteristics and initial diagnoses in women presenting to a referral center for vulvovaginal disorders in 1996–2000. J Reprod Med. 2002; 47: 854-860.
- Boza JC, Trindade EN, Peruzzo J, et al. Skin manifestations of obesity: a comparative study. J Eur Acad Dermatol Venereol. 2012;26:1220-1223.
- Winton GB, Lewis CW. Dermatoses of pregnancy. J Am Acad Dermatol. 1982;6:977-998.
- Bornstein J, Bogliatto F, Haefner HK, et al; ISSVD Terminology Committee. The 2015 International Society for the Study of Vulvovaginal Disease (ISSVD) terminology of vulvar squamous intraepithelial lesions. J Low Genit Tract Dis. 2016;20:11-14.
- American College of Obstetricians and Gynecologists. Committee opinion no. 675: management of vulvar intraepithelial neoplasia. Obstet Gynecol. 2016;128:e178-e182.
- Heller DS. Benign tumors and tumor-like lesions of the vulva. Clin Obstet Gynecol. 2015;58:526-535.
- Shalabi MMK, Homan K, Bicknell L. Vulvar syringomas. Proc (Bayl Univer Med Cent). 2022;35:113-114.
- Ozdemir O, Sari ME, Sen E, et al. Vulvar syringoma in a postmenopausal woman: a case report. J Reprod Med. 2015;60:452-454.
- Stevenson TR, Swanson NA. Syringoma: removal by electrodesiccation and curettage. Ann Plast Surg. 1985;15:151-154.
- Hansen A, Carr K, Jensen JT. Characteristics and initial diagnoses in women presenting to a referral center for vulvovaginal disorders in 1996–2000. J Reprod Med. 2002; 47: 854-860.
- Boza JC, Trindade EN, Peruzzo J, et al. Skin manifestations of obesity: a comparative study. J Eur Acad Dermatol Venereol. 2012;26:1220-1223.
- Winton GB, Lewis CW. Dermatoses of pregnancy. J Am Acad Dermatol. 1982;6:977-998.
- Bornstein J, Bogliatto F, Haefner HK, et al; ISSVD Terminology Committee. The 2015 International Society for the Study of Vulvovaginal Disease (ISSVD) terminology of vulvar squamous intraepithelial lesions. J Low Genit Tract Dis. 2016;20:11-14.
- American College of Obstetricians and Gynecologists. Committee opinion no. 675: management of vulvar intraepithelial neoplasia. Obstet Gynecol. 2016;128:e178-e182.
- Heller DS. Benign tumors and tumor-like lesions of the vulva. Clin Obstet Gynecol. 2015;58:526-535.
- Shalabi MMK, Homan K, Bicknell L. Vulvar syringomas. Proc (Bayl Univer Med Cent). 2022;35:113-114.
- Ozdemir O, Sari ME, Sen E, et al. Vulvar syringoma in a postmenopausal woman: a case report. J Reprod Med. 2015;60:452-454.
- Stevenson TR, Swanson NA. Syringoma: removal by electrodesiccation and curettage. Ann Plast Surg. 1985;15:151-154.