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New study supports safety of COVID-19 boosters during pregnancy
Doctors and health professionals continue to recommend COVID-19 vaccine boosters or third doses for adolescents and adults more than 5 months after their initial vaccinations with the Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 primary vaccine series or more than 2 months after receiving the Janssen JNJ-78436735 vaccine, Alisa Kachikis, MD, of the University of Washington, Seattle, and colleagues wrote in JAMA Network Open.
Although multiple studies have shown that the COVID-19 primary series is safe and well tolerated in pregnant and lactating women, information on the safety and tolerability of boosters are lacking, the researchers noted.
“COVID-19 will be with us for a while, and it is important to continue to provide data on COVID-19 vaccines in these groups, particularly because there still are many questions about the vaccine, and because pregnant individuals have been, understandably, more hesitant to receive COVID-19 vaccines,” Dr. Kachikis said in an interview. “The findings of this study that COVID-19 booster doses are well tolerated among pregnant and lactating individuals are especially pertinent with the new COVID-19 boosters available this fall.”
In the new study, the researchers reviewed data from 17,014 participants who were part of an ongoing online prospective study of COVID-19 vaccines in pregnant and lactating individuals. Data were collected between October 2021 and April 2022 through an online survey.
The study population included 2,009 participants (11.8%) who were pregnant at the time of their booster or third dose, 10,279 (60.4%) who were lactating, and 4,726 (27.8%) who were neither pregnant nor lactating. The mean age of the participants was 33.3 years; 92.1% self-identified as White, 94.5% self-identified as non-Hispanic, and 99.7% self-identified as female.
The receipt of a booster was similar across trimesters; 26.4%, 36.5%, and 37.1% of participants received boosters or third doses in the first, second, and third trimester, respectively. The primary outcome was self-reported vaccine reactions within 24 hours of the dose.
Overall, 82.8% of the respondents reported a reaction at the site of the injection, such as redness, pain, or swelling, and 67.9% reported at least one systemic symptom, such as aches and pains, headache, chills, or fever. The most frequently reported symptoms across all groups were injection-site pain (82.2%) and fatigue (54.4%).
The pregnant women were significantly more likely than nonpregnant or nonlactating individuals to report any local reaction at the injection site (adjusted odds ratio, 1.2; P = .01), but less likely to report any systemic reaction (aOR, 0.7; P < .001).
The majority (97.6%) of the pregnant respondents and 96.0% of those lactating reported no obstetric or lactation concerns after vaccination.
Overall, a majority of the respondents reported that recommendations from public health authorities were helpful in their decision to receive a COVID-19 booster or third dose (90.0% of pregnant respondents, 89.9% of lactating respondents, and 88.1% of those neither pregnant nor lactating).
Although vaccine uptake in the current study population was high (91.1% overall and 95.0% of those pregnant), “the importance of the health care professional’s recommendation is pertinent given the ongoing increased vaccine hesitancy among pregnant individuals in the context of the COVID-19 vaccine,” the researchers emphasized.
The study findings were limited by several factors including the reliance on self-reports and a convenience sample composed mainly of health care workers because of their vaccine eligibility at the time the study started, which limits generalizability, the researchers noted. Analyses on the pregnancy outcomes of those who were pregnant when vaccinated are in progress.
The results were strengthened by the large study population that included participants from all 50 states and several territories, and ability to compare results between pregnant and lactating individuals with those who were neither pregnant nor lactating, but were of childbearing age, they said.
The results support the safety of COVID-19 boosters for pregnant and breastfeeding individuals, and these data are important to inform discussions between patients and clinicians to boost vaccine uptake and acceptance in this population, they concluded.
“Our earlier data analysis showed that pregnant and lactating individuals did very well with the initial COVID-19 vaccine series, so it was not very surprising that they also did well with COVID-19 booster or third doses,” Dr. Kachikis said in an interview.
There are two takeaway messages for clinicians, she said: “First, pregnant and lactating individuals tolerated the COVID-19 booster well. The second is that clinicians are very important when it comes to vaccine acceptance.”
“In our study, we found that, while pregnant participants were more likely to report that they were hesitant to receive the booster, they also were more likely to have discussed the COVID-19 booster with their health care provider, and to have received a recommendation to receive the booster. So, spending a little bit of extra time with patients discussing COVID-19 boosters and recommending them can make a significant difference,” she said.
The message of the study is highly reassuring for pregnant and lactating individuals, Dr. Kachikis added. “Most of the participants reported that they had fewer symptoms with the COVID-19 booster compared to the primary vaccine series, which is good news, especially since a new COVID-19 booster is being recommended for the fall.”
Reassuring findings for doctors and patients
The current study is especially timely, as updated COVID-19 boosters have now been recommended for most individuals by the Centers for Disease Control and Prevention, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.
The findings support previous studies on the tolerability of COVID-19 vaccinations in pregnant and lactating persons, said Dr. Badell, who was not involved in the study.
The reassuring message for clinicians is that COVID-19 booster vaccinations are similarly well tolerated in pregnancy and lactation as they are in nonpregnant individuals, said Dr. Badell. “Given the risks of COVID infections in pregnancy and neonates, reassuring data on the tolerability and safety of vaccination in this population is very important.” Also, the researchers found that all three cohorts reported that recommendations from public or medical health authorities helped them make a decision about vaccination; “thus the more data to support these recommendations, the better,” she emphasized.
If you are pregnant or breastfeeding, the message from the study is that COVID-19 booster vaccinations are similarly well tolerated by those who are pregnant or breastfeeding and those who are not, said Dr. Badell.
“This study provides additional support for the strong recommendation to encourage not only COVID-19 vaccination in pregnancy and lactation, but booster vaccinations specifically,” and pregnant and breastfeeding individuals should not be excluded from the new CDC recommendations for COVID-19 boosters, she said.
Future research suggestions
Next steps for research include evaluating the obstetrical and neonatal outcomes in pregnancy and lactation following COVID- 19 boosters, Dr. Badell added.
Dr. Kachikis suggested studies try to answer the remaining questions about COVID-19 vaccines and the immunity of pregnant and lactating persons, particularly since they were excluded from the early clinical trials in 2020.
The study was supported by the National Institute of Allergy and Infectious Diseases, a Women’s Reproductive Health Research Award, and the National Center for Advancing Translational Sciences of the National Institutes of Health. \Dr. Kachikis disclosed serving as a research consultant for Pfizer and GlaxoSmithKline and as an unpaid consultant for GlaxoSmithKline unrelated to the current study, as well as grant support from Merck and Pfizer unrelated to the current study. Dr. Badell had no financial conflicts to disclose.
Doctors and health professionals continue to recommend COVID-19 vaccine boosters or third doses for adolescents and adults more than 5 months after their initial vaccinations with the Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 primary vaccine series or more than 2 months after receiving the Janssen JNJ-78436735 vaccine, Alisa Kachikis, MD, of the University of Washington, Seattle, and colleagues wrote in JAMA Network Open.
Although multiple studies have shown that the COVID-19 primary series is safe and well tolerated in pregnant and lactating women, information on the safety and tolerability of boosters are lacking, the researchers noted.
“COVID-19 will be with us for a while, and it is important to continue to provide data on COVID-19 vaccines in these groups, particularly because there still are many questions about the vaccine, and because pregnant individuals have been, understandably, more hesitant to receive COVID-19 vaccines,” Dr. Kachikis said in an interview. “The findings of this study that COVID-19 booster doses are well tolerated among pregnant and lactating individuals are especially pertinent with the new COVID-19 boosters available this fall.”
In the new study, the researchers reviewed data from 17,014 participants who were part of an ongoing online prospective study of COVID-19 vaccines in pregnant and lactating individuals. Data were collected between October 2021 and April 2022 through an online survey.
The study population included 2,009 participants (11.8%) who were pregnant at the time of their booster or third dose, 10,279 (60.4%) who were lactating, and 4,726 (27.8%) who were neither pregnant nor lactating. The mean age of the participants was 33.3 years; 92.1% self-identified as White, 94.5% self-identified as non-Hispanic, and 99.7% self-identified as female.
The receipt of a booster was similar across trimesters; 26.4%, 36.5%, and 37.1% of participants received boosters or third doses in the first, second, and third trimester, respectively. The primary outcome was self-reported vaccine reactions within 24 hours of the dose.
Overall, 82.8% of the respondents reported a reaction at the site of the injection, such as redness, pain, or swelling, and 67.9% reported at least one systemic symptom, such as aches and pains, headache, chills, or fever. The most frequently reported symptoms across all groups were injection-site pain (82.2%) and fatigue (54.4%).
The pregnant women were significantly more likely than nonpregnant or nonlactating individuals to report any local reaction at the injection site (adjusted odds ratio, 1.2; P = .01), but less likely to report any systemic reaction (aOR, 0.7; P < .001).
The majority (97.6%) of the pregnant respondents and 96.0% of those lactating reported no obstetric or lactation concerns after vaccination.
Overall, a majority of the respondents reported that recommendations from public health authorities were helpful in their decision to receive a COVID-19 booster or third dose (90.0% of pregnant respondents, 89.9% of lactating respondents, and 88.1% of those neither pregnant nor lactating).
Although vaccine uptake in the current study population was high (91.1% overall and 95.0% of those pregnant), “the importance of the health care professional’s recommendation is pertinent given the ongoing increased vaccine hesitancy among pregnant individuals in the context of the COVID-19 vaccine,” the researchers emphasized.
The study findings were limited by several factors including the reliance on self-reports and a convenience sample composed mainly of health care workers because of their vaccine eligibility at the time the study started, which limits generalizability, the researchers noted. Analyses on the pregnancy outcomes of those who were pregnant when vaccinated are in progress.
The results were strengthened by the large study population that included participants from all 50 states and several territories, and ability to compare results between pregnant and lactating individuals with those who were neither pregnant nor lactating, but were of childbearing age, they said.
The results support the safety of COVID-19 boosters for pregnant and breastfeeding individuals, and these data are important to inform discussions between patients and clinicians to boost vaccine uptake and acceptance in this population, they concluded.
“Our earlier data analysis showed that pregnant and lactating individuals did very well with the initial COVID-19 vaccine series, so it was not very surprising that they also did well with COVID-19 booster or third doses,” Dr. Kachikis said in an interview.
There are two takeaway messages for clinicians, she said: “First, pregnant and lactating individuals tolerated the COVID-19 booster well. The second is that clinicians are very important when it comes to vaccine acceptance.”
“In our study, we found that, while pregnant participants were more likely to report that they were hesitant to receive the booster, they also were more likely to have discussed the COVID-19 booster with their health care provider, and to have received a recommendation to receive the booster. So, spending a little bit of extra time with patients discussing COVID-19 boosters and recommending them can make a significant difference,” she said.
The message of the study is highly reassuring for pregnant and lactating individuals, Dr. Kachikis added. “Most of the participants reported that they had fewer symptoms with the COVID-19 booster compared to the primary vaccine series, which is good news, especially since a new COVID-19 booster is being recommended for the fall.”
Reassuring findings for doctors and patients
The current study is especially timely, as updated COVID-19 boosters have now been recommended for most individuals by the Centers for Disease Control and Prevention, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.
The findings support previous studies on the tolerability of COVID-19 vaccinations in pregnant and lactating persons, said Dr. Badell, who was not involved in the study.
The reassuring message for clinicians is that COVID-19 booster vaccinations are similarly well tolerated in pregnancy and lactation as they are in nonpregnant individuals, said Dr. Badell. “Given the risks of COVID infections in pregnancy and neonates, reassuring data on the tolerability and safety of vaccination in this population is very important.” Also, the researchers found that all three cohorts reported that recommendations from public or medical health authorities helped them make a decision about vaccination; “thus the more data to support these recommendations, the better,” she emphasized.
If you are pregnant or breastfeeding, the message from the study is that COVID-19 booster vaccinations are similarly well tolerated by those who are pregnant or breastfeeding and those who are not, said Dr. Badell.
“This study provides additional support for the strong recommendation to encourage not only COVID-19 vaccination in pregnancy and lactation, but booster vaccinations specifically,” and pregnant and breastfeeding individuals should not be excluded from the new CDC recommendations for COVID-19 boosters, she said.
Future research suggestions
Next steps for research include evaluating the obstetrical and neonatal outcomes in pregnancy and lactation following COVID- 19 boosters, Dr. Badell added.
Dr. Kachikis suggested studies try to answer the remaining questions about COVID-19 vaccines and the immunity of pregnant and lactating persons, particularly since they were excluded from the early clinical trials in 2020.
The study was supported by the National Institute of Allergy and Infectious Diseases, a Women’s Reproductive Health Research Award, and the National Center for Advancing Translational Sciences of the National Institutes of Health. \Dr. Kachikis disclosed serving as a research consultant for Pfizer and GlaxoSmithKline and as an unpaid consultant for GlaxoSmithKline unrelated to the current study, as well as grant support from Merck and Pfizer unrelated to the current study. Dr. Badell had no financial conflicts to disclose.
Doctors and health professionals continue to recommend COVID-19 vaccine boosters or third doses for adolescents and adults more than 5 months after their initial vaccinations with the Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 primary vaccine series or more than 2 months after receiving the Janssen JNJ-78436735 vaccine, Alisa Kachikis, MD, of the University of Washington, Seattle, and colleagues wrote in JAMA Network Open.
Although multiple studies have shown that the COVID-19 primary series is safe and well tolerated in pregnant and lactating women, information on the safety and tolerability of boosters are lacking, the researchers noted.
“COVID-19 will be with us for a while, and it is important to continue to provide data on COVID-19 vaccines in these groups, particularly because there still are many questions about the vaccine, and because pregnant individuals have been, understandably, more hesitant to receive COVID-19 vaccines,” Dr. Kachikis said in an interview. “The findings of this study that COVID-19 booster doses are well tolerated among pregnant and lactating individuals are especially pertinent with the new COVID-19 boosters available this fall.”
In the new study, the researchers reviewed data from 17,014 participants who were part of an ongoing online prospective study of COVID-19 vaccines in pregnant and lactating individuals. Data were collected between October 2021 and April 2022 through an online survey.
The study population included 2,009 participants (11.8%) who were pregnant at the time of their booster or third dose, 10,279 (60.4%) who were lactating, and 4,726 (27.8%) who were neither pregnant nor lactating. The mean age of the participants was 33.3 years; 92.1% self-identified as White, 94.5% self-identified as non-Hispanic, and 99.7% self-identified as female.
The receipt of a booster was similar across trimesters; 26.4%, 36.5%, and 37.1% of participants received boosters or third doses in the first, second, and third trimester, respectively. The primary outcome was self-reported vaccine reactions within 24 hours of the dose.
Overall, 82.8% of the respondents reported a reaction at the site of the injection, such as redness, pain, or swelling, and 67.9% reported at least one systemic symptom, such as aches and pains, headache, chills, or fever. The most frequently reported symptoms across all groups were injection-site pain (82.2%) and fatigue (54.4%).
The pregnant women were significantly more likely than nonpregnant or nonlactating individuals to report any local reaction at the injection site (adjusted odds ratio, 1.2; P = .01), but less likely to report any systemic reaction (aOR, 0.7; P < .001).
The majority (97.6%) of the pregnant respondents and 96.0% of those lactating reported no obstetric or lactation concerns after vaccination.
Overall, a majority of the respondents reported that recommendations from public health authorities were helpful in their decision to receive a COVID-19 booster or third dose (90.0% of pregnant respondents, 89.9% of lactating respondents, and 88.1% of those neither pregnant nor lactating).
Although vaccine uptake in the current study population was high (91.1% overall and 95.0% of those pregnant), “the importance of the health care professional’s recommendation is pertinent given the ongoing increased vaccine hesitancy among pregnant individuals in the context of the COVID-19 vaccine,” the researchers emphasized.
The study findings were limited by several factors including the reliance on self-reports and a convenience sample composed mainly of health care workers because of their vaccine eligibility at the time the study started, which limits generalizability, the researchers noted. Analyses on the pregnancy outcomes of those who were pregnant when vaccinated are in progress.
The results were strengthened by the large study population that included participants from all 50 states and several territories, and ability to compare results between pregnant and lactating individuals with those who were neither pregnant nor lactating, but were of childbearing age, they said.
The results support the safety of COVID-19 boosters for pregnant and breastfeeding individuals, and these data are important to inform discussions between patients and clinicians to boost vaccine uptake and acceptance in this population, they concluded.
“Our earlier data analysis showed that pregnant and lactating individuals did very well with the initial COVID-19 vaccine series, so it was not very surprising that they also did well with COVID-19 booster or third doses,” Dr. Kachikis said in an interview.
There are two takeaway messages for clinicians, she said: “First, pregnant and lactating individuals tolerated the COVID-19 booster well. The second is that clinicians are very important when it comes to vaccine acceptance.”
“In our study, we found that, while pregnant participants were more likely to report that they were hesitant to receive the booster, they also were more likely to have discussed the COVID-19 booster with their health care provider, and to have received a recommendation to receive the booster. So, spending a little bit of extra time with patients discussing COVID-19 boosters and recommending them can make a significant difference,” she said.
The message of the study is highly reassuring for pregnant and lactating individuals, Dr. Kachikis added. “Most of the participants reported that they had fewer symptoms with the COVID-19 booster compared to the primary vaccine series, which is good news, especially since a new COVID-19 booster is being recommended for the fall.”
Reassuring findings for doctors and patients
The current study is especially timely, as updated COVID-19 boosters have now been recommended for most individuals by the Centers for Disease Control and Prevention, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.
The findings support previous studies on the tolerability of COVID-19 vaccinations in pregnant and lactating persons, said Dr. Badell, who was not involved in the study.
The reassuring message for clinicians is that COVID-19 booster vaccinations are similarly well tolerated in pregnancy and lactation as they are in nonpregnant individuals, said Dr. Badell. “Given the risks of COVID infections in pregnancy and neonates, reassuring data on the tolerability and safety of vaccination in this population is very important.” Also, the researchers found that all three cohorts reported that recommendations from public or medical health authorities helped them make a decision about vaccination; “thus the more data to support these recommendations, the better,” she emphasized.
If you are pregnant or breastfeeding, the message from the study is that COVID-19 booster vaccinations are similarly well tolerated by those who are pregnant or breastfeeding and those who are not, said Dr. Badell.
“This study provides additional support for the strong recommendation to encourage not only COVID-19 vaccination in pregnancy and lactation, but booster vaccinations specifically,” and pregnant and breastfeeding individuals should not be excluded from the new CDC recommendations for COVID-19 boosters, she said.
Future research suggestions
Next steps for research include evaluating the obstetrical and neonatal outcomes in pregnancy and lactation following COVID- 19 boosters, Dr. Badell added.
Dr. Kachikis suggested studies try to answer the remaining questions about COVID-19 vaccines and the immunity of pregnant and lactating persons, particularly since they were excluded from the early clinical trials in 2020.
The study was supported by the National Institute of Allergy and Infectious Diseases, a Women’s Reproductive Health Research Award, and the National Center for Advancing Translational Sciences of the National Institutes of Health. \Dr. Kachikis disclosed serving as a research consultant for Pfizer and GlaxoSmithKline and as an unpaid consultant for GlaxoSmithKline unrelated to the current study, as well as grant support from Merck and Pfizer unrelated to the current study. Dr. Badell had no financial conflicts to disclose.
FROM JAMA NETWORK OPEN
WIC review finds broad benefits, knowledge gaps
How exactly the national program achieves these outcomes, however, remains unclear, and study quality shows room for improvement, reported co–lead authors Maya Venkataramani, MD, MPH and S. Michelle Ogunwole, MD, PhD of Johns Hopkins University, Baltimore, and colleagues.
The WIC program, which has been serving low-income women and young children since 1974, “provides supplemental foods, nutrition education and breastfeeding support, screening and referrals to medical and social services, and support for high-risk pregnancies,” the investigators wrote in Annals of Internal Medicine. The U.S. Food and Nutrition Service administers the program.
The authors conducted a systematic review of 20 observational studies aimed at determining the impacts of WIC participation on maternal, neonatal-birth, and infant-child health outcomes.
All studies included in the review began in or after 2009, when the WIC food package was revised to better address diet-related chronic diseases. For inclusion in the review, studies were required to have a WIC-eligible comparison group. Included research also evaluated the relationship between WIC participation and the prespecified health outcomes.
“We found only 20 studies that fulfilled our rigorous study inclusion criteria for these specific outcomes,” the investigators wrote. “In some areas, the evidence was absent, and in others, the strength of evidence (SOE) was moderate or low.”
Six outcome categories were assessed: maternal morbidity, maternal pregnancy outcomes, maternal health behaviors, maternal health care utilization, child morbidity, and childhood health care utilization. Of these, maternal health care utilization had the most robust body of evidence, while data from studies evaluating maternal morbidity and child morbidity were deemed insufficient.
Based on eligible studies, WIC participation was associated with reduced risks of insufficient weight gain in pregnancy, preterm birth, low infant birthweight, and infant mortality. Participation was also associated with an increased likelihood of infant and child health care utilization, such as routine immunizations.
Growing evidence should drive enrollment
“Growing evidence points to WIC as a way to reduce risk of preterm birth and other adverse outcomes,” said Laura Jelliffe-Pawlowski, PhD, MS, professor at the University of California, San Francisco and a director for the UCSF California Preterm Birth Initiative.
Dr. Jelliffe-Pawlowski, who conducted a California-based study included in the paper, said the review is noteworthy because it shows that WIC-associated benefits are observed across locations.
“It’s not just in California; it’s across the country,” she said. “It’s a national call to action – where there’s partnership between national-, state- and community-level WIC programs – to make WIC as accessible as possible, and reflect community wants and needs, so that more people enroll, and more people stay enrolled.”
Dr. Jelliffe-Pawlowski’s coauthor on the California study, Rita Hamad, MD, PhD, associate professor of family & community medicine at UCSF and associate director of the UCSF Center for Health Equity, encouraged health care providers to drive WIC enrollment, noting that, presently, only one in four eligible 4-year-olds participates.
“Physicians and other health care stakeholders can help patients benefit from this program by encouraging them to sign up, and even by providing sign-up support in the form of a social worker or other staff member,” Dr. Hamad said. “There is also literature on the types of interventions that improve take-up of safety net programs that providers can look to.”
Goals of future research
Optimizing WIC operations, however, is only half the battle, considering the evidence gaps revealed by the review.
“We still need stronger studies that use more rigorous study designs ... to provide more convincing evidence to policymakers, as well as more evidence on long-term impacts,” Dr. Hamad said. “We also need to better understand why take-up is low in these programs despite these potential health benefits. Then we can make sure that economically disadvantaged families receive the benefits for which they are eligible through interventions to improve participation rates.”
Ideally, WIC programs would receive additional funding for independent parties to evaluate health outcomes, according to Ashwini Lakshmanan, MD, MS, MPH, associate professor in the department of health systems science at Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, Calif.
Dr. Lakshmanan, who previously evaluated the benefits of WIC participation for high-risk infants, noted that randomized clinical trials would be unethical in this setting, yet data collection can still be “very conscientious and intentional,” with a focus on policy-shaping outcome metrics like immunizations and pediatric health care visits.
“The main point is thinking about it at the forefront, and not retrospectively,” Dr. Lakshmanan said.
Dr. Ogunwole, who led the present review, suggested in a written comment that future studies “could employ robust statistical methods (propensity matching, fixed effects models, etc.) to help reduce bias.”
She also recommended evaluating innovations in WIC programs; for example, adding a health coach, or conducting a cooking skills intervention.
Studies are also needed to better understand the various obstacles to WIC success, such as misconceptions about the program, discrimination, and barriers to enrollment, Dr. Ogunwole added.
“WIC enrollment has been decreasing for a number of years, and this was occurring prepandemic as well,” she said. “More work needs to be done to understand this issue.”
The study was supported by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services. The investigators and interviewees disclosed no conflicts of interest.
How exactly the national program achieves these outcomes, however, remains unclear, and study quality shows room for improvement, reported co–lead authors Maya Venkataramani, MD, MPH and S. Michelle Ogunwole, MD, PhD of Johns Hopkins University, Baltimore, and colleagues.
The WIC program, which has been serving low-income women and young children since 1974, “provides supplemental foods, nutrition education and breastfeeding support, screening and referrals to medical and social services, and support for high-risk pregnancies,” the investigators wrote in Annals of Internal Medicine. The U.S. Food and Nutrition Service administers the program.
The authors conducted a systematic review of 20 observational studies aimed at determining the impacts of WIC participation on maternal, neonatal-birth, and infant-child health outcomes.
All studies included in the review began in or after 2009, when the WIC food package was revised to better address diet-related chronic diseases. For inclusion in the review, studies were required to have a WIC-eligible comparison group. Included research also evaluated the relationship between WIC participation and the prespecified health outcomes.
“We found only 20 studies that fulfilled our rigorous study inclusion criteria for these specific outcomes,” the investigators wrote. “In some areas, the evidence was absent, and in others, the strength of evidence (SOE) was moderate or low.”
Six outcome categories were assessed: maternal morbidity, maternal pregnancy outcomes, maternal health behaviors, maternal health care utilization, child morbidity, and childhood health care utilization. Of these, maternal health care utilization had the most robust body of evidence, while data from studies evaluating maternal morbidity and child morbidity were deemed insufficient.
Based on eligible studies, WIC participation was associated with reduced risks of insufficient weight gain in pregnancy, preterm birth, low infant birthweight, and infant mortality. Participation was also associated with an increased likelihood of infant and child health care utilization, such as routine immunizations.
Growing evidence should drive enrollment
“Growing evidence points to WIC as a way to reduce risk of preterm birth and other adverse outcomes,” said Laura Jelliffe-Pawlowski, PhD, MS, professor at the University of California, San Francisco and a director for the UCSF California Preterm Birth Initiative.
Dr. Jelliffe-Pawlowski, who conducted a California-based study included in the paper, said the review is noteworthy because it shows that WIC-associated benefits are observed across locations.
“It’s not just in California; it’s across the country,” she said. “It’s a national call to action – where there’s partnership between national-, state- and community-level WIC programs – to make WIC as accessible as possible, and reflect community wants and needs, so that more people enroll, and more people stay enrolled.”
Dr. Jelliffe-Pawlowski’s coauthor on the California study, Rita Hamad, MD, PhD, associate professor of family & community medicine at UCSF and associate director of the UCSF Center for Health Equity, encouraged health care providers to drive WIC enrollment, noting that, presently, only one in four eligible 4-year-olds participates.
“Physicians and other health care stakeholders can help patients benefit from this program by encouraging them to sign up, and even by providing sign-up support in the form of a social worker or other staff member,” Dr. Hamad said. “There is also literature on the types of interventions that improve take-up of safety net programs that providers can look to.”
Goals of future research
Optimizing WIC operations, however, is only half the battle, considering the evidence gaps revealed by the review.
“We still need stronger studies that use more rigorous study designs ... to provide more convincing evidence to policymakers, as well as more evidence on long-term impacts,” Dr. Hamad said. “We also need to better understand why take-up is low in these programs despite these potential health benefits. Then we can make sure that economically disadvantaged families receive the benefits for which they are eligible through interventions to improve participation rates.”
Ideally, WIC programs would receive additional funding for independent parties to evaluate health outcomes, according to Ashwini Lakshmanan, MD, MS, MPH, associate professor in the department of health systems science at Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, Calif.
Dr. Lakshmanan, who previously evaluated the benefits of WIC participation for high-risk infants, noted that randomized clinical trials would be unethical in this setting, yet data collection can still be “very conscientious and intentional,” with a focus on policy-shaping outcome metrics like immunizations and pediatric health care visits.
“The main point is thinking about it at the forefront, and not retrospectively,” Dr. Lakshmanan said.
Dr. Ogunwole, who led the present review, suggested in a written comment that future studies “could employ robust statistical methods (propensity matching, fixed effects models, etc.) to help reduce bias.”
She also recommended evaluating innovations in WIC programs; for example, adding a health coach, or conducting a cooking skills intervention.
Studies are also needed to better understand the various obstacles to WIC success, such as misconceptions about the program, discrimination, and barriers to enrollment, Dr. Ogunwole added.
“WIC enrollment has been decreasing for a number of years, and this was occurring prepandemic as well,” she said. “More work needs to be done to understand this issue.”
The study was supported by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services. The investigators and interviewees disclosed no conflicts of interest.
How exactly the national program achieves these outcomes, however, remains unclear, and study quality shows room for improvement, reported co–lead authors Maya Venkataramani, MD, MPH and S. Michelle Ogunwole, MD, PhD of Johns Hopkins University, Baltimore, and colleagues.
The WIC program, which has been serving low-income women and young children since 1974, “provides supplemental foods, nutrition education and breastfeeding support, screening and referrals to medical and social services, and support for high-risk pregnancies,” the investigators wrote in Annals of Internal Medicine. The U.S. Food and Nutrition Service administers the program.
The authors conducted a systematic review of 20 observational studies aimed at determining the impacts of WIC participation on maternal, neonatal-birth, and infant-child health outcomes.
All studies included in the review began in or after 2009, when the WIC food package was revised to better address diet-related chronic diseases. For inclusion in the review, studies were required to have a WIC-eligible comparison group. Included research also evaluated the relationship between WIC participation and the prespecified health outcomes.
“We found only 20 studies that fulfilled our rigorous study inclusion criteria for these specific outcomes,” the investigators wrote. “In some areas, the evidence was absent, and in others, the strength of evidence (SOE) was moderate or low.”
Six outcome categories were assessed: maternal morbidity, maternal pregnancy outcomes, maternal health behaviors, maternal health care utilization, child morbidity, and childhood health care utilization. Of these, maternal health care utilization had the most robust body of evidence, while data from studies evaluating maternal morbidity and child morbidity were deemed insufficient.
Based on eligible studies, WIC participation was associated with reduced risks of insufficient weight gain in pregnancy, preterm birth, low infant birthweight, and infant mortality. Participation was also associated with an increased likelihood of infant and child health care utilization, such as routine immunizations.
Growing evidence should drive enrollment
“Growing evidence points to WIC as a way to reduce risk of preterm birth and other adverse outcomes,” said Laura Jelliffe-Pawlowski, PhD, MS, professor at the University of California, San Francisco and a director for the UCSF California Preterm Birth Initiative.
Dr. Jelliffe-Pawlowski, who conducted a California-based study included in the paper, said the review is noteworthy because it shows that WIC-associated benefits are observed across locations.
“It’s not just in California; it’s across the country,” she said. “It’s a national call to action – where there’s partnership between national-, state- and community-level WIC programs – to make WIC as accessible as possible, and reflect community wants and needs, so that more people enroll, and more people stay enrolled.”
Dr. Jelliffe-Pawlowski’s coauthor on the California study, Rita Hamad, MD, PhD, associate professor of family & community medicine at UCSF and associate director of the UCSF Center for Health Equity, encouraged health care providers to drive WIC enrollment, noting that, presently, only one in four eligible 4-year-olds participates.
“Physicians and other health care stakeholders can help patients benefit from this program by encouraging them to sign up, and even by providing sign-up support in the form of a social worker or other staff member,” Dr. Hamad said. “There is also literature on the types of interventions that improve take-up of safety net programs that providers can look to.”
Goals of future research
Optimizing WIC operations, however, is only half the battle, considering the evidence gaps revealed by the review.
“We still need stronger studies that use more rigorous study designs ... to provide more convincing evidence to policymakers, as well as more evidence on long-term impacts,” Dr. Hamad said. “We also need to better understand why take-up is low in these programs despite these potential health benefits. Then we can make sure that economically disadvantaged families receive the benefits for which they are eligible through interventions to improve participation rates.”
Ideally, WIC programs would receive additional funding for independent parties to evaluate health outcomes, according to Ashwini Lakshmanan, MD, MS, MPH, associate professor in the department of health systems science at Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, Calif.
Dr. Lakshmanan, who previously evaluated the benefits of WIC participation for high-risk infants, noted that randomized clinical trials would be unethical in this setting, yet data collection can still be “very conscientious and intentional,” with a focus on policy-shaping outcome metrics like immunizations and pediatric health care visits.
“The main point is thinking about it at the forefront, and not retrospectively,” Dr. Lakshmanan said.
Dr. Ogunwole, who led the present review, suggested in a written comment that future studies “could employ robust statistical methods (propensity matching, fixed effects models, etc.) to help reduce bias.”
She also recommended evaluating innovations in WIC programs; for example, adding a health coach, or conducting a cooking skills intervention.
Studies are also needed to better understand the various obstacles to WIC success, such as misconceptions about the program, discrimination, and barriers to enrollment, Dr. Ogunwole added.
“WIC enrollment has been decreasing for a number of years, and this was occurring prepandemic as well,” she said. “More work needs to be done to understand this issue.”
The study was supported by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services. The investigators and interviewees disclosed no conflicts of interest.
FROM ANNALS OF INTERNAL MEDICINE
In the rush to curtail abortion, states adopt a jumbled stew of definitions for human life
As life-preserving medical technology advanced in the second half of the 20th century, doctors and families were faced with a thorny decision, one with weighty legal and moral implications: How should we define when life ends? Cardiopulmonary bypass machines could keep the blood pumping and ventilators could maintain breathing long after a patient’s natural ability to perform those vital functions had ceased.
After decades of deliberations involving physicians, bioethicists, attorneys, and theologians, a U.S. presidential commission in 1981 settled on a scientifically derived dividing line between life and death that has endured, more or less, ever since: A person was considered dead when the entire brain – including the brain stem, its most primitive portion – was no longer functioning, even if other vital functions could be maintained indefinitely through artificial life support.
In the decades since, the committee’s criteria have served as a foundation for laws in most states adopting brain death as a standard for legal death.
Now, with the overturning of Roe v. Wade and dozens of states rushing to impose abortion restrictions, At conception, the hint of a heartbeat, a first breath, the ability to survive outside the womb with the help of the latest technology?
That we’ve been able to devise and apply uniform clinical standards for when life ends, but not when it begins, is due largely to the legal and political maelstrom around abortion. And in the 2 months since the U.S. Supreme Court issued its opinion in Dobbs v. Jackson Women’s Health Organization, eliminating a longstanding federal right to abortion, state legislators are eagerly bounding into that void, looking to codify into law assorted definitions of life that carry profound repercussions for abortion rights, birth control, and assisted reproduction, as well as civil and criminal law.
“The court said that when life begins is up to whoever is running your state – whether they are wrong or not, or you agree with them or not,” said Mary Ziegler, a law professor at the University of California, Davis, who has written several books on the history of abortion.
Unlike the debate over death, which delved into exquisite medical and scientific detail, the legislative scramble to determine when life’s building blocks reach a threshold that warrants government protection as human life has generally ignored the input of mainstream medical professionals.
Instead, red states across much of the South and portions of the Midwest are adopting language drafted by elected officials that is informed by conservative Christian doctrine, often with little scientific underpinning.
A handful of Republican-led states, including Arkansas, Kentucky, Missouri, and Oklahoma, have passed laws declaring that life begins at fertilization, a contention that opens the door to a host of pregnancy-related litigation. This includes wrongful death lawsuits brought on behalf of the estate of an embryo by disgruntled ex-partners against physicians and women who end a pregnancy or even miscarry. (One such lawsuit is underway in Arizona. Another reached the Alabama Supreme Court.)
In Kentucky, the law outlawing abortion uses morally explosive terms to define pregnancy as “the human female reproductive condition of having a living unborn human being within her body throughout the entire embryonic and fetal stages of the unborn child from fertilization to full gestation and childbirth.”
Several other states, including Georgia, have adopted measures equating life with the point at which an embryo’s nascent cardiac activity can be detected by an ultrasound, at around 6 weeks of gestation. Many such laws mischaracterize the flickering electrical impulses detectable at that stage as a heartbeat, including in Georgia, whose Department of Revenue recently announced that “any unborn child with a detectable human heartbeat” can be claimed as a dependent.
The Supreme Court’s 1973 decision in Roe v. Wade that established a constitutional right to abortion did not define a moment when life begins. The opinion, written by Justice Harry Blackmun, observed that the Constitution does not provide a definition of “person,” though it extends protections to those born or naturalized in the United States. The court majority made note of the many disparate views among religions and scientists on when life begins, and concluded it was not up to the states to adopt one theory of life.
Instead, Roe created a framework intended to balance a pregnant woman’s right to make decisions about her body with a public interest in protecting potential human life. That decision and a key ruling that followed generally recognized a woman’s right to abortion up to the point medical professionals judge a fetus viable to survive outside the uterus, at about 24 weeks of gestation.
In decisively overturning Roe in June, the Supreme Court’s conservative majority drew on legal arguments that have shaped another contentious end-of-life issue. The legal standard employed in Dobbs – that there is no right to abortion in the federal Constitution and that states can decide on their own – is the same rationale used in 1997 when the Supreme Court said terminally ill people did not have a constitutional right to medically assisted death. That decision, Washington v. Glucksberg, is mentioned 15 times in the majority opinion for Dobbs and a concurrence by Justice Clarence Thomas.
Often, the same groups that have led the fight to outlaw abortion have also challenged medical aid-in-dying laws. Even after Dobbs, so-called right-to-die laws remain far less common than those codifying state abortion rights. Ten states allow physicians to prescribe lethal doses of medicine for terminally ill patients. Doctors are still prohibited from administering the drugs.
James Bopp, general counsel for the National Right to Life Committee who has been central to the efforts to outlaw abortion, said that both abortion and medically assisted death, which he refers to as physician-assisted suicide, endanger society.
“Every individual human life has inherent value and is sacred,” said Mr. Bopp. “The government has the duty to protect that life.”
Both issues raise profound societal questions: Can the government keep a patient on life support against his wishes, or force a woman to give birth? Can states bar their own residents from going to other states to end a pregnancy, or prohibit out-of-state patients from coming in to seek medically assisted death? And who gets to decide, particularly if the answer imposes a singular religious viewpoint?
Just as there are legal implications that flow from determining a person’s death, from organ donation to inheritance, the implied rights held by a legally recognized zygote are potentially vast. Will death certificates be issued for every lost pregnancy? Will miscarriages be investigated? When will Social Security numbers be issued? How will census counts be tallied and congressional districts drawn?
Medical professionals and bioethicists caution that both the beginning and end of life are complicated biological processes that are not defined by a single identifiable moment – and are ill suited to the political arena.
“Unfortunately, biological occurrences are not events, they are processes,” said David Magnus, PhD, director of the Stanford (Calif.) Center for Biomedical Ethics.
Moreover, asking doctors “What is life?” or “What is death?” may miss the point, said Dr. Magnus: “Medicine can answer the question ‘When does a biological organism cease to exist?’ But they can’t answer the question ‘When does a person begin or end?’ because those are metaphysical issues.”
Ben Sarbey, a doctoral candidate in the department of philosophy at Duke University, Durham, N.C., who studies medical ethics, echoed that perspective, recounting the Paradox of the Heap, a thought experiment that involves placing grains of sand one on top of the next. The philosophical quandary is this: At what point do those grains of sand become something more – a heap?
“We’re going to have a rough time placing a dividing line that this counts as a person and this does not count as a person,” he said. “Many things count as life – a sperm counts as life, a person in a persistent vegetative state counts as life – but does that constitute a person that we should be protecting?”
Even as debate over the court’s abortion decision percolates, the 1981 federal statute that grew out of the presidential committee’s findings, the Uniform Determination of Death Act, is also under review. In 2022, the Uniform Law Commission, a nonpartisan group of legal experts that drafts laws intended for adoption in multiple states, has taken up the work to revisit the definition of death.
The group will consider sharpening the medical standards for brain death in light of advances in the understanding of brain function. And they will look to address lingering questions raised in recent years as families and religious groups have waged heated legal battles over terminating artificial life support for patients with no brain wave activity.
Mr. Bopp, with the National Right to Life Committee, is among those serving on advisory panels for the effort, along with an array of doctors, philosophers, and medical ethicists. The concept of “personhood” that infuses the antiabortion movement’s broader push for fetal rights is expected to be an underlying topic, albeit in mirror image: When does a life form cease being a person?
Dr. Magnus, who is also serving on an advisory panel, has no doubt the commission will reach a consensus, a sober resolution rooted in science. What’s less clear, he said, is whether in today’s political environment that updated definition will hold the same sway, an enduring legal standard embraced across states.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
As life-preserving medical technology advanced in the second half of the 20th century, doctors and families were faced with a thorny decision, one with weighty legal and moral implications: How should we define when life ends? Cardiopulmonary bypass machines could keep the blood pumping and ventilators could maintain breathing long after a patient’s natural ability to perform those vital functions had ceased.
After decades of deliberations involving physicians, bioethicists, attorneys, and theologians, a U.S. presidential commission in 1981 settled on a scientifically derived dividing line between life and death that has endured, more or less, ever since: A person was considered dead when the entire brain – including the brain stem, its most primitive portion – was no longer functioning, even if other vital functions could be maintained indefinitely through artificial life support.
In the decades since, the committee’s criteria have served as a foundation for laws in most states adopting brain death as a standard for legal death.
Now, with the overturning of Roe v. Wade and dozens of states rushing to impose abortion restrictions, At conception, the hint of a heartbeat, a first breath, the ability to survive outside the womb with the help of the latest technology?
That we’ve been able to devise and apply uniform clinical standards for when life ends, but not when it begins, is due largely to the legal and political maelstrom around abortion. And in the 2 months since the U.S. Supreme Court issued its opinion in Dobbs v. Jackson Women’s Health Organization, eliminating a longstanding federal right to abortion, state legislators are eagerly bounding into that void, looking to codify into law assorted definitions of life that carry profound repercussions for abortion rights, birth control, and assisted reproduction, as well as civil and criminal law.
“The court said that when life begins is up to whoever is running your state – whether they are wrong or not, or you agree with them or not,” said Mary Ziegler, a law professor at the University of California, Davis, who has written several books on the history of abortion.
Unlike the debate over death, which delved into exquisite medical and scientific detail, the legislative scramble to determine when life’s building blocks reach a threshold that warrants government protection as human life has generally ignored the input of mainstream medical professionals.
Instead, red states across much of the South and portions of the Midwest are adopting language drafted by elected officials that is informed by conservative Christian doctrine, often with little scientific underpinning.
A handful of Republican-led states, including Arkansas, Kentucky, Missouri, and Oklahoma, have passed laws declaring that life begins at fertilization, a contention that opens the door to a host of pregnancy-related litigation. This includes wrongful death lawsuits brought on behalf of the estate of an embryo by disgruntled ex-partners against physicians and women who end a pregnancy or even miscarry. (One such lawsuit is underway in Arizona. Another reached the Alabama Supreme Court.)
In Kentucky, the law outlawing abortion uses morally explosive terms to define pregnancy as “the human female reproductive condition of having a living unborn human being within her body throughout the entire embryonic and fetal stages of the unborn child from fertilization to full gestation and childbirth.”
Several other states, including Georgia, have adopted measures equating life with the point at which an embryo’s nascent cardiac activity can be detected by an ultrasound, at around 6 weeks of gestation. Many such laws mischaracterize the flickering electrical impulses detectable at that stage as a heartbeat, including in Georgia, whose Department of Revenue recently announced that “any unborn child with a detectable human heartbeat” can be claimed as a dependent.
The Supreme Court’s 1973 decision in Roe v. Wade that established a constitutional right to abortion did not define a moment when life begins. The opinion, written by Justice Harry Blackmun, observed that the Constitution does not provide a definition of “person,” though it extends protections to those born or naturalized in the United States. The court majority made note of the many disparate views among religions and scientists on when life begins, and concluded it was not up to the states to adopt one theory of life.
Instead, Roe created a framework intended to balance a pregnant woman’s right to make decisions about her body with a public interest in protecting potential human life. That decision and a key ruling that followed generally recognized a woman’s right to abortion up to the point medical professionals judge a fetus viable to survive outside the uterus, at about 24 weeks of gestation.
In decisively overturning Roe in June, the Supreme Court’s conservative majority drew on legal arguments that have shaped another contentious end-of-life issue. The legal standard employed in Dobbs – that there is no right to abortion in the federal Constitution and that states can decide on their own – is the same rationale used in 1997 when the Supreme Court said terminally ill people did not have a constitutional right to medically assisted death. That decision, Washington v. Glucksberg, is mentioned 15 times in the majority opinion for Dobbs and a concurrence by Justice Clarence Thomas.
Often, the same groups that have led the fight to outlaw abortion have also challenged medical aid-in-dying laws. Even after Dobbs, so-called right-to-die laws remain far less common than those codifying state abortion rights. Ten states allow physicians to prescribe lethal doses of medicine for terminally ill patients. Doctors are still prohibited from administering the drugs.
James Bopp, general counsel for the National Right to Life Committee who has been central to the efforts to outlaw abortion, said that both abortion and medically assisted death, which he refers to as physician-assisted suicide, endanger society.
“Every individual human life has inherent value and is sacred,” said Mr. Bopp. “The government has the duty to protect that life.”
Both issues raise profound societal questions: Can the government keep a patient on life support against his wishes, or force a woman to give birth? Can states bar their own residents from going to other states to end a pregnancy, or prohibit out-of-state patients from coming in to seek medically assisted death? And who gets to decide, particularly if the answer imposes a singular religious viewpoint?
Just as there are legal implications that flow from determining a person’s death, from organ donation to inheritance, the implied rights held by a legally recognized zygote are potentially vast. Will death certificates be issued for every lost pregnancy? Will miscarriages be investigated? When will Social Security numbers be issued? How will census counts be tallied and congressional districts drawn?
Medical professionals and bioethicists caution that both the beginning and end of life are complicated biological processes that are not defined by a single identifiable moment – and are ill suited to the political arena.
“Unfortunately, biological occurrences are not events, they are processes,” said David Magnus, PhD, director of the Stanford (Calif.) Center for Biomedical Ethics.
Moreover, asking doctors “What is life?” or “What is death?” may miss the point, said Dr. Magnus: “Medicine can answer the question ‘When does a biological organism cease to exist?’ But they can’t answer the question ‘When does a person begin or end?’ because those are metaphysical issues.”
Ben Sarbey, a doctoral candidate in the department of philosophy at Duke University, Durham, N.C., who studies medical ethics, echoed that perspective, recounting the Paradox of the Heap, a thought experiment that involves placing grains of sand one on top of the next. The philosophical quandary is this: At what point do those grains of sand become something more – a heap?
“We’re going to have a rough time placing a dividing line that this counts as a person and this does not count as a person,” he said. “Many things count as life – a sperm counts as life, a person in a persistent vegetative state counts as life – but does that constitute a person that we should be protecting?”
Even as debate over the court’s abortion decision percolates, the 1981 federal statute that grew out of the presidential committee’s findings, the Uniform Determination of Death Act, is also under review. In 2022, the Uniform Law Commission, a nonpartisan group of legal experts that drafts laws intended for adoption in multiple states, has taken up the work to revisit the definition of death.
The group will consider sharpening the medical standards for brain death in light of advances in the understanding of brain function. And they will look to address lingering questions raised in recent years as families and religious groups have waged heated legal battles over terminating artificial life support for patients with no brain wave activity.
Mr. Bopp, with the National Right to Life Committee, is among those serving on advisory panels for the effort, along with an array of doctors, philosophers, and medical ethicists. The concept of “personhood” that infuses the antiabortion movement’s broader push for fetal rights is expected to be an underlying topic, albeit in mirror image: When does a life form cease being a person?
Dr. Magnus, who is also serving on an advisory panel, has no doubt the commission will reach a consensus, a sober resolution rooted in science. What’s less clear, he said, is whether in today’s political environment that updated definition will hold the same sway, an enduring legal standard embraced across states.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
As life-preserving medical technology advanced in the second half of the 20th century, doctors and families were faced with a thorny decision, one with weighty legal and moral implications: How should we define when life ends? Cardiopulmonary bypass machines could keep the blood pumping and ventilators could maintain breathing long after a patient’s natural ability to perform those vital functions had ceased.
After decades of deliberations involving physicians, bioethicists, attorneys, and theologians, a U.S. presidential commission in 1981 settled on a scientifically derived dividing line between life and death that has endured, more or less, ever since: A person was considered dead when the entire brain – including the brain stem, its most primitive portion – was no longer functioning, even if other vital functions could be maintained indefinitely through artificial life support.
In the decades since, the committee’s criteria have served as a foundation for laws in most states adopting brain death as a standard for legal death.
Now, with the overturning of Roe v. Wade and dozens of states rushing to impose abortion restrictions, At conception, the hint of a heartbeat, a first breath, the ability to survive outside the womb with the help of the latest technology?
That we’ve been able to devise and apply uniform clinical standards for when life ends, but not when it begins, is due largely to the legal and political maelstrom around abortion. And in the 2 months since the U.S. Supreme Court issued its opinion in Dobbs v. Jackson Women’s Health Organization, eliminating a longstanding federal right to abortion, state legislators are eagerly bounding into that void, looking to codify into law assorted definitions of life that carry profound repercussions for abortion rights, birth control, and assisted reproduction, as well as civil and criminal law.
“The court said that when life begins is up to whoever is running your state – whether they are wrong or not, or you agree with them or not,” said Mary Ziegler, a law professor at the University of California, Davis, who has written several books on the history of abortion.
Unlike the debate over death, which delved into exquisite medical and scientific detail, the legislative scramble to determine when life’s building blocks reach a threshold that warrants government protection as human life has generally ignored the input of mainstream medical professionals.
Instead, red states across much of the South and portions of the Midwest are adopting language drafted by elected officials that is informed by conservative Christian doctrine, often with little scientific underpinning.
A handful of Republican-led states, including Arkansas, Kentucky, Missouri, and Oklahoma, have passed laws declaring that life begins at fertilization, a contention that opens the door to a host of pregnancy-related litigation. This includes wrongful death lawsuits brought on behalf of the estate of an embryo by disgruntled ex-partners against physicians and women who end a pregnancy or even miscarry. (One such lawsuit is underway in Arizona. Another reached the Alabama Supreme Court.)
In Kentucky, the law outlawing abortion uses morally explosive terms to define pregnancy as “the human female reproductive condition of having a living unborn human being within her body throughout the entire embryonic and fetal stages of the unborn child from fertilization to full gestation and childbirth.”
Several other states, including Georgia, have adopted measures equating life with the point at which an embryo’s nascent cardiac activity can be detected by an ultrasound, at around 6 weeks of gestation. Many such laws mischaracterize the flickering electrical impulses detectable at that stage as a heartbeat, including in Georgia, whose Department of Revenue recently announced that “any unborn child with a detectable human heartbeat” can be claimed as a dependent.
The Supreme Court’s 1973 decision in Roe v. Wade that established a constitutional right to abortion did not define a moment when life begins. The opinion, written by Justice Harry Blackmun, observed that the Constitution does not provide a definition of “person,” though it extends protections to those born or naturalized in the United States. The court majority made note of the many disparate views among religions and scientists on when life begins, and concluded it was not up to the states to adopt one theory of life.
Instead, Roe created a framework intended to balance a pregnant woman’s right to make decisions about her body with a public interest in protecting potential human life. That decision and a key ruling that followed generally recognized a woman’s right to abortion up to the point medical professionals judge a fetus viable to survive outside the uterus, at about 24 weeks of gestation.
In decisively overturning Roe in June, the Supreme Court’s conservative majority drew on legal arguments that have shaped another contentious end-of-life issue. The legal standard employed in Dobbs – that there is no right to abortion in the federal Constitution and that states can decide on their own – is the same rationale used in 1997 when the Supreme Court said terminally ill people did not have a constitutional right to medically assisted death. That decision, Washington v. Glucksberg, is mentioned 15 times in the majority opinion for Dobbs and a concurrence by Justice Clarence Thomas.
Often, the same groups that have led the fight to outlaw abortion have also challenged medical aid-in-dying laws. Even after Dobbs, so-called right-to-die laws remain far less common than those codifying state abortion rights. Ten states allow physicians to prescribe lethal doses of medicine for terminally ill patients. Doctors are still prohibited from administering the drugs.
James Bopp, general counsel for the National Right to Life Committee who has been central to the efforts to outlaw abortion, said that both abortion and medically assisted death, which he refers to as physician-assisted suicide, endanger society.
“Every individual human life has inherent value and is sacred,” said Mr. Bopp. “The government has the duty to protect that life.”
Both issues raise profound societal questions: Can the government keep a patient on life support against his wishes, or force a woman to give birth? Can states bar their own residents from going to other states to end a pregnancy, or prohibit out-of-state patients from coming in to seek medically assisted death? And who gets to decide, particularly if the answer imposes a singular religious viewpoint?
Just as there are legal implications that flow from determining a person’s death, from organ donation to inheritance, the implied rights held by a legally recognized zygote are potentially vast. Will death certificates be issued for every lost pregnancy? Will miscarriages be investigated? When will Social Security numbers be issued? How will census counts be tallied and congressional districts drawn?
Medical professionals and bioethicists caution that both the beginning and end of life are complicated biological processes that are not defined by a single identifiable moment – and are ill suited to the political arena.
“Unfortunately, biological occurrences are not events, they are processes,” said David Magnus, PhD, director of the Stanford (Calif.) Center for Biomedical Ethics.
Moreover, asking doctors “What is life?” or “What is death?” may miss the point, said Dr. Magnus: “Medicine can answer the question ‘When does a biological organism cease to exist?’ But they can’t answer the question ‘When does a person begin or end?’ because those are metaphysical issues.”
Ben Sarbey, a doctoral candidate in the department of philosophy at Duke University, Durham, N.C., who studies medical ethics, echoed that perspective, recounting the Paradox of the Heap, a thought experiment that involves placing grains of sand one on top of the next. The philosophical quandary is this: At what point do those grains of sand become something more – a heap?
“We’re going to have a rough time placing a dividing line that this counts as a person and this does not count as a person,” he said. “Many things count as life – a sperm counts as life, a person in a persistent vegetative state counts as life – but does that constitute a person that we should be protecting?”
Even as debate over the court’s abortion decision percolates, the 1981 federal statute that grew out of the presidential committee’s findings, the Uniform Determination of Death Act, is also under review. In 2022, the Uniform Law Commission, a nonpartisan group of legal experts that drafts laws intended for adoption in multiple states, has taken up the work to revisit the definition of death.
The group will consider sharpening the medical standards for brain death in light of advances in the understanding of brain function. And they will look to address lingering questions raised in recent years as families and religious groups have waged heated legal battles over terminating artificial life support for patients with no brain wave activity.
Mr. Bopp, with the National Right to Life Committee, is among those serving on advisory panels for the effort, along with an array of doctors, philosophers, and medical ethicists. The concept of “personhood” that infuses the antiabortion movement’s broader push for fetal rights is expected to be an underlying topic, albeit in mirror image: When does a life form cease being a person?
Dr. Magnus, who is also serving on an advisory panel, has no doubt the commission will reach a consensus, a sober resolution rooted in science. What’s less clear, he said, is whether in today’s political environment that updated definition will hold the same sway, an enduring legal standard embraced across states.
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
VA Amends Rule on Abortions
The US Department of Veterans Affairs (VA) has submitted an interim final rule amending its medical regulations to remove the exclusion on abortion counseling and establish exceptions to the exclusion on abortions.
With this rule, the VA will now offer veterans abortion counseling and abortions—specifically, when the life or health of the pregnant veteran would be endangered if the pregnancy were carried to term, or in cases of rape or incest. Beneficiaries enrolled in CHAMPVA will have the same access to care.
“As abortion bans come into force across the country,” the interim final rule indicates, “veterans in many states are no longer assured access to abortion services in their communities, even when those services are needed… Unless VA removes its existing prohibitions on abortion-related care and makes clear that needed abortion-related care is authorized, these veterans will face serious threats to their life and health.”
“This is a patient safety decision,” said Denis McDonough, Secretary of Veterans Affairs. “Pregnant veterans and VA beneficiaries deserve to have access to world-class reproductive care when they need it most. That’s what our nation owes them, and that’s what we at VA will deliver.”
The rule is the VA’s latest response to the June 24, 2022, Dobbs v Jackson Women’s Health Organization Supreme Court decision, which overruled Roe v Wade and Planned Parenthood of Southeastern Pennsylvania v Casey. “After Dobbs,” according to the rule summary, “certain States have begun to enforce existing abortion bans and restrictions on care, and are proposing and enacting new ones, creating urgent risks to the lives and health of pregnant veterans and CHAMPVA beneficiaries in these states.” The VA is “acting to help to ensure that, irrespective of what laws or policies States may impose” veterans will be able to receive needed care.
Restricting access to abortion care has well-documented adverse health consequences, including a higher risk of loss of future fertility, significant morbidity, or death. Veterans are also at greater risk of experiencing pregnancy-related complications due to increased rates of chronic health conditions. “We came to this decision after listening to VA health care providers and veterans across the country, who sounded the alarm that abortion restrictions are creating a medical emergency for those we serve,” said Under Secretary for Health Shereef Elnahal, MD, MBA. “Offering this care will save veterans’ health and lives, and there is nothing more important than that.”
Services will be authorized immediately after the interim final rule is published. VA is taking steps to guarantee abortion-related care anywhere in the country. VA employees, when working within the scope of their federal employment, may provide authorized services regardless of state restrictions.
The determination of whether the “life and health of the pregnant veteran would be endangered if the pregnancy were carried to term” will be made on a case-by-case basis after “careful consultation” between VA health care professionals and their patients, the VA says. In cases of rape or incest, self-reporting from a veteran or VA beneficiary will constitute sufficient evidence that an act of rape or incest occurred.
The interim final rule will be available for public comment for 30 days after it is published.
The US Department of Veterans Affairs (VA) has submitted an interim final rule amending its medical regulations to remove the exclusion on abortion counseling and establish exceptions to the exclusion on abortions.
With this rule, the VA will now offer veterans abortion counseling and abortions—specifically, when the life or health of the pregnant veteran would be endangered if the pregnancy were carried to term, or in cases of rape or incest. Beneficiaries enrolled in CHAMPVA will have the same access to care.
“As abortion bans come into force across the country,” the interim final rule indicates, “veterans in many states are no longer assured access to abortion services in their communities, even when those services are needed… Unless VA removes its existing prohibitions on abortion-related care and makes clear that needed abortion-related care is authorized, these veterans will face serious threats to their life and health.”
“This is a patient safety decision,” said Denis McDonough, Secretary of Veterans Affairs. “Pregnant veterans and VA beneficiaries deserve to have access to world-class reproductive care when they need it most. That’s what our nation owes them, and that’s what we at VA will deliver.”
The rule is the VA’s latest response to the June 24, 2022, Dobbs v Jackson Women’s Health Organization Supreme Court decision, which overruled Roe v Wade and Planned Parenthood of Southeastern Pennsylvania v Casey. “After Dobbs,” according to the rule summary, “certain States have begun to enforce existing abortion bans and restrictions on care, and are proposing and enacting new ones, creating urgent risks to the lives and health of pregnant veterans and CHAMPVA beneficiaries in these states.” The VA is “acting to help to ensure that, irrespective of what laws or policies States may impose” veterans will be able to receive needed care.
Restricting access to abortion care has well-documented adverse health consequences, including a higher risk of loss of future fertility, significant morbidity, or death. Veterans are also at greater risk of experiencing pregnancy-related complications due to increased rates of chronic health conditions. “We came to this decision after listening to VA health care providers and veterans across the country, who sounded the alarm that abortion restrictions are creating a medical emergency for those we serve,” said Under Secretary for Health Shereef Elnahal, MD, MBA. “Offering this care will save veterans’ health and lives, and there is nothing more important than that.”
Services will be authorized immediately after the interim final rule is published. VA is taking steps to guarantee abortion-related care anywhere in the country. VA employees, when working within the scope of their federal employment, may provide authorized services regardless of state restrictions.
The determination of whether the “life and health of the pregnant veteran would be endangered if the pregnancy were carried to term” will be made on a case-by-case basis after “careful consultation” between VA health care professionals and their patients, the VA says. In cases of rape or incest, self-reporting from a veteran or VA beneficiary will constitute sufficient evidence that an act of rape or incest occurred.
The interim final rule will be available for public comment for 30 days after it is published.
The US Department of Veterans Affairs (VA) has submitted an interim final rule amending its medical regulations to remove the exclusion on abortion counseling and establish exceptions to the exclusion on abortions.
With this rule, the VA will now offer veterans abortion counseling and abortions—specifically, when the life or health of the pregnant veteran would be endangered if the pregnancy were carried to term, or in cases of rape or incest. Beneficiaries enrolled in CHAMPVA will have the same access to care.
“As abortion bans come into force across the country,” the interim final rule indicates, “veterans in many states are no longer assured access to abortion services in their communities, even when those services are needed… Unless VA removes its existing prohibitions on abortion-related care and makes clear that needed abortion-related care is authorized, these veterans will face serious threats to their life and health.”
“This is a patient safety decision,” said Denis McDonough, Secretary of Veterans Affairs. “Pregnant veterans and VA beneficiaries deserve to have access to world-class reproductive care when they need it most. That’s what our nation owes them, and that’s what we at VA will deliver.”
The rule is the VA’s latest response to the June 24, 2022, Dobbs v Jackson Women’s Health Organization Supreme Court decision, which overruled Roe v Wade and Planned Parenthood of Southeastern Pennsylvania v Casey. “After Dobbs,” according to the rule summary, “certain States have begun to enforce existing abortion bans and restrictions on care, and are proposing and enacting new ones, creating urgent risks to the lives and health of pregnant veterans and CHAMPVA beneficiaries in these states.” The VA is “acting to help to ensure that, irrespective of what laws or policies States may impose” veterans will be able to receive needed care.
Restricting access to abortion care has well-documented adverse health consequences, including a higher risk of loss of future fertility, significant morbidity, or death. Veterans are also at greater risk of experiencing pregnancy-related complications due to increased rates of chronic health conditions. “We came to this decision after listening to VA health care providers and veterans across the country, who sounded the alarm that abortion restrictions are creating a medical emergency for those we serve,” said Under Secretary for Health Shereef Elnahal, MD, MBA. “Offering this care will save veterans’ health and lives, and there is nothing more important than that.”
Services will be authorized immediately after the interim final rule is published. VA is taking steps to guarantee abortion-related care anywhere in the country. VA employees, when working within the scope of their federal employment, may provide authorized services regardless of state restrictions.
The determination of whether the “life and health of the pregnant veteran would be endangered if the pregnancy were carried to term” will be made on a case-by-case basis after “careful consultation” between VA health care professionals and their patients, the VA says. In cases of rape or incest, self-reporting from a veteran or VA beneficiary will constitute sufficient evidence that an act of rape or incest occurred.
The interim final rule will be available for public comment for 30 days after it is published.
Exercise may counteract genetics for gestational diabetes
Women giving birth for the first time have significantly higher odds of developing gestational diabetes if they have a high polygenic risk score (PRS) and low physical activity, new data suggest.
Researchers, led by Kymberleigh A. Pagel, PhD, with the department of computer science, Indiana University, Bloomington, concluded that physical activity early in pregnancy is associated with reduced risk of gestational diabetes and may help women who are at high risk because of genetic predisposition, age, family history of diabetes, and body mass index.
The researchers included 3,533 women in the analysis (average age, 28.6 years) which was a subcohort of a larger study. They found that physical activity’s association with lower gestational diabetes risk “was particularly significant in individuals who were genetically predisposed to diabetes through PRS or family history,” the authors wrote.
Women with high PRS and low level of physical activity had three times the odds of developing gestational diabetes (odds ratio, 3.4; 95% confidence interval, 2.3-5.3).
Those with high PRS and moderate to high activity levels in early pregnancy (metabolic equivalents of task [METs] of at least 450) had gestational diabetes risk similar to that of the general population, according to the researchers.
The findings were published in JAMA Network Open.
Maisa Feghali, MD, a maternal-fetal specialist at the University of Pittsburgh Medical Center, who was not part of the study, said in an interview she found the link of physical activity and compensation for high predisposition to gestational diabetes most interesting.
“That’s interesting because a lot of studies that have looked at prevention of gestational diabetes either through limited weight gain or through some form of counseling on physical activity have not really shown any benefit,” she noted. “It might just be it’s not just one size fits all and it may be that physical activity is mostly beneficial in those with a high predisposition.”
Research in this area is particularly important as 7% of pregnancies in the United States each year are affected by gestational diabetes and the risk for developing type 2 diabetes “has doubled in the past decade among patients with GD [gestational diabetes],” the authors wrote.
Researchers looked at risks for gestational diabetes in high-risk subgroups, including women who had a body mass index of more than 25 kg/m2 or were at least 35 years old. In that group, women who were either in the in the top 25th percentile for PRS or had low physical activity (METs less than 450) had from 25% to 75% greater risk of developing gestational diabetes.
The findings are consistent with previous research and suggest exercise interventions may be important in improving pregnancy outcomes, the authors wrote.
Christina Han, MD, division director for maternal-fetal medicine at University of California, Los Angeles, who was not part of the study, pointed out several limitations of the study, however.
One of the biggest limitations, she said, was that “they excluded two-thirds of the original study. Essentially, they took only Caucasian [White] patients, which is about one-third of the study.” Additionally, the cohort was made up of people who had never had babies.
“Lots of our gestational diabetes patients are not first-time moms, so this makes the generalizability of the study very limited,” Dr. Han said.
She added that none of the sites where the study was conducted were in the South or Northwest, which also adds questions about generalizability.
Dr. Feghali and Dr. Han reported no relevant financial relationships.
Women giving birth for the first time have significantly higher odds of developing gestational diabetes if they have a high polygenic risk score (PRS) and low physical activity, new data suggest.
Researchers, led by Kymberleigh A. Pagel, PhD, with the department of computer science, Indiana University, Bloomington, concluded that physical activity early in pregnancy is associated with reduced risk of gestational diabetes and may help women who are at high risk because of genetic predisposition, age, family history of diabetes, and body mass index.
The researchers included 3,533 women in the analysis (average age, 28.6 years) which was a subcohort of a larger study. They found that physical activity’s association with lower gestational diabetes risk “was particularly significant in individuals who were genetically predisposed to diabetes through PRS or family history,” the authors wrote.
Women with high PRS and low level of physical activity had three times the odds of developing gestational diabetes (odds ratio, 3.4; 95% confidence interval, 2.3-5.3).
Those with high PRS and moderate to high activity levels in early pregnancy (metabolic equivalents of task [METs] of at least 450) had gestational diabetes risk similar to that of the general population, according to the researchers.
The findings were published in JAMA Network Open.
Maisa Feghali, MD, a maternal-fetal specialist at the University of Pittsburgh Medical Center, who was not part of the study, said in an interview she found the link of physical activity and compensation for high predisposition to gestational diabetes most interesting.
“That’s interesting because a lot of studies that have looked at prevention of gestational diabetes either through limited weight gain or through some form of counseling on physical activity have not really shown any benefit,” she noted. “It might just be it’s not just one size fits all and it may be that physical activity is mostly beneficial in those with a high predisposition.”
Research in this area is particularly important as 7% of pregnancies in the United States each year are affected by gestational diabetes and the risk for developing type 2 diabetes “has doubled in the past decade among patients with GD [gestational diabetes],” the authors wrote.
Researchers looked at risks for gestational diabetes in high-risk subgroups, including women who had a body mass index of more than 25 kg/m2 or were at least 35 years old. In that group, women who were either in the in the top 25th percentile for PRS or had low physical activity (METs less than 450) had from 25% to 75% greater risk of developing gestational diabetes.
The findings are consistent with previous research and suggest exercise interventions may be important in improving pregnancy outcomes, the authors wrote.
Christina Han, MD, division director for maternal-fetal medicine at University of California, Los Angeles, who was not part of the study, pointed out several limitations of the study, however.
One of the biggest limitations, she said, was that “they excluded two-thirds of the original study. Essentially, they took only Caucasian [White] patients, which is about one-third of the study.” Additionally, the cohort was made up of people who had never had babies.
“Lots of our gestational diabetes patients are not first-time moms, so this makes the generalizability of the study very limited,” Dr. Han said.
She added that none of the sites where the study was conducted were in the South or Northwest, which also adds questions about generalizability.
Dr. Feghali and Dr. Han reported no relevant financial relationships.
Women giving birth for the first time have significantly higher odds of developing gestational diabetes if they have a high polygenic risk score (PRS) and low physical activity, new data suggest.
Researchers, led by Kymberleigh A. Pagel, PhD, with the department of computer science, Indiana University, Bloomington, concluded that physical activity early in pregnancy is associated with reduced risk of gestational diabetes and may help women who are at high risk because of genetic predisposition, age, family history of diabetes, and body mass index.
The researchers included 3,533 women in the analysis (average age, 28.6 years) which was a subcohort of a larger study. They found that physical activity’s association with lower gestational diabetes risk “was particularly significant in individuals who were genetically predisposed to diabetes through PRS or family history,” the authors wrote.
Women with high PRS and low level of physical activity had three times the odds of developing gestational diabetes (odds ratio, 3.4; 95% confidence interval, 2.3-5.3).
Those with high PRS and moderate to high activity levels in early pregnancy (metabolic equivalents of task [METs] of at least 450) had gestational diabetes risk similar to that of the general population, according to the researchers.
The findings were published in JAMA Network Open.
Maisa Feghali, MD, a maternal-fetal specialist at the University of Pittsburgh Medical Center, who was not part of the study, said in an interview she found the link of physical activity and compensation for high predisposition to gestational diabetes most interesting.
“That’s interesting because a lot of studies that have looked at prevention of gestational diabetes either through limited weight gain or through some form of counseling on physical activity have not really shown any benefit,” she noted. “It might just be it’s not just one size fits all and it may be that physical activity is mostly beneficial in those with a high predisposition.”
Research in this area is particularly important as 7% of pregnancies in the United States each year are affected by gestational diabetes and the risk for developing type 2 diabetes “has doubled in the past decade among patients with GD [gestational diabetes],” the authors wrote.
Researchers looked at risks for gestational diabetes in high-risk subgroups, including women who had a body mass index of more than 25 kg/m2 or were at least 35 years old. In that group, women who were either in the in the top 25th percentile for PRS or had low physical activity (METs less than 450) had from 25% to 75% greater risk of developing gestational diabetes.
The findings are consistent with previous research and suggest exercise interventions may be important in improving pregnancy outcomes, the authors wrote.
Christina Han, MD, division director for maternal-fetal medicine at University of California, Los Angeles, who was not part of the study, pointed out several limitations of the study, however.
One of the biggest limitations, she said, was that “they excluded two-thirds of the original study. Essentially, they took only Caucasian [White] patients, which is about one-third of the study.” Additionally, the cohort was made up of people who had never had babies.
“Lots of our gestational diabetes patients are not first-time moms, so this makes the generalizability of the study very limited,” Dr. Han said.
She added that none of the sites where the study was conducted were in the South or Northwest, which also adds questions about generalizability.
Dr. Feghali and Dr. Han reported no relevant financial relationships.
FROM JAMA NETWORK OPEN
Hormonal therapy a safe, long term option for older women with recalcitrant acne
PORTLAND, ORE. – During her dermatology residency training at the University of California, Irvine, Medical Center, Jenny Murase, MD, remembers hearing a colleague say that her most angry patients of the day were adult women with recalcitrant acne who present to the clinic with questions like, “My skin has been clear my whole life! What’s going on?”
Such . In fact, 82% fail multiple courses of systemic antibiotics and 32% relapse after using isotretinoin, Dr. Murase, director of medical dermatology consultative services and patch testing at the Palo Alto Foundation Medical Group, said at the annual meeting of the Pacific Dermatologic Association.
In her clinical experience, hormonal therapy is a safe long-term option for recalcitrant acne in postmenarcheal females over the age of 14. “Although oral antibiotics are going to be superior to hormonal therapy in the first month or two, when you get to about six months, they have equivalent efficacy,” she said.
Telltale signs of acne associated with androgen excess include the development of nodulocystic papules along the jawline and small comedones over the forehead. Female patients with acne may request that labs be ordered to check their hormone levels, but that often is not necessary, according to Dr. Murase, who is also associate clinical professor of dermatology at the University of California, San Francisco. “There aren’t strict guidelines to indicate when you should perform hormonal testing, but warning signs that warrant further evaluation include hirsutism, androgenetic alopecia, virilization, infertility, oligomenorrhea or amenorrhea, and sudden onset of severe acne. The most common situation that warrants hormonal testing is polycystic ovary syndrome (PCOS).”
When there is a strong suspicion for hyperandrogenism, essential labs include free and total testosterone. Free testosterone is commonly elevated in patients with PCOS and total testosterone levels over 200 ng/dL is suggestive of an ovarian tumor. Other essential labs include 17-hyydroxyprogesterone (values greater than 200 ng/dL indicate congenital adrenal hyperplasia), and dehydroepiandrosterone sulfate (DHEA-S); levels over 8,000 mcg/dL indicate an adrenal tumor, while levels in the 4,000-8,000 mcg/dL range indicate congenital adrenal hyperplasia.
Helpful lab tests to consider include the ratio of luteinizing hormone to follicle-stimulating hormone; a 3:1 ratio or greater is suggestive for PCOS. “Ordering a prolactin level can also help, especially if patients are describing issues with headaches, which could indicate a pituitary tumor,” Dr. Murase added. Measuring sex hormone binding globulin (SHBG) levels can also be helpful. “If a patient has been on oral contraceptives for a long time, it increases their SHBG,” which, in older women, she said, “is inversely related to the development of type 2 diabetes.”
All labs for hyperandrogenism should be performed early in the morning on day 3 of the patient’s menstrual cycle. “If patients are on some kind of hormonal therapy, they need to be off of it for at least 6 weeks in order for you get a relevant test,” she said. Other relevant labs to consider include fasting glucose and lipids, cortisol, and thyroid-stimulating hormone.
Oral contraceptives
Estrogen contained in oral contraceptives (OCs) provides the most benefit to acne patients. “It reduces sebum production, decreases free testosterone and DHEA-S by stimulating SHBG synthesis in the liver, inhibits 5-alpha-reductase, which decreases peripheral testosterone conversion, and it decreases the production of ovarian and adrenal androgens,” Dr. Murase explained. “On average, you can get about 40%-70% reduction of lesion count, which is pretty good.”
Progestins with low androgenetic activity are the most helpful for acne, including norgestimate, desogestrel, and drospirenone. FDA-approved OC options include Ortho Tri-Cyclen, EstroStep, Yaz, and Beyaz. None has data showing superior efficacy.
No Pap smear or pelvic exam is required when prescribing OCs, but the risk of clotting should be discussed with patients. According to Dr. Murase, the risk of deep vein thrombosis (DVT) at baseline is about 1 per 10,000 woman-years, while the risk of DVT after 1 year on an OC is 3.4 per 10,000 years.
“This is a very mild increased risk that we’re talking about, but it is relevant in smokers, in those with hypertension, and in those who are diabetic,” she said. As for the risk of cancer associated with the use of OCs, a large collaborative study found a relative risk of 1.24 for developing breast cancer (not dose or duration related), but a risk reduction for endometrial, colorectal, and ovarian cancer.
The most common side effects associated with OCs are unscheduled bleeding, nausea, breast tenderness, and possible weight gain. Concomitant antibiotics can be used, with the exception of CYP3A4 inducers, such as rifampin. “That’s the main antibiotic we have to worry about that could affect the efficacy of the birth control pill,” she said. “It accounts for about three-quarters of pregnancies on antibiotics.”
Tetracyclines do not appear to increase the rate of birth defects with incidental first-trimester exposure, and data are reassuring but “tetracycline should be stopped within the first trimester as soon as the patient discovers she is pregnant,” Dr. Murase said.
Contraindications for OCs include being pregnant or breastfeeding; history of stroke, venous thromboembolism, or MI; history of smoking and being over age 35; uncontrolled hypertension; migraines with focal symptoms/aura; current or past breast cancer; hypercholesterolemia; diabetes with end-organ damage or having diabetes over age 35; liver issues such as a tumor, viral hepatitis, or cirrhosis; and a history of major surgery with prolonged immobilization.
Spironolactone
Another treatment option is spironolactone, a potassium-sparing diuretic that blocks aldosterone at a dose of 25 mg/day. At doses of 50-100 mg/day, it blocks androgen. “It can be used in combination with an oral contraceptive, with the rates of efficacy reported to range between 33% and 85%,” Dr. Murase said.
Spironolactone can also reduce hirsutism, improve androgenetic alopecia, and lower blood pressure by about 5 mm Hg systolic and 2.5 mm Hg diastolic. Dr. Murase usually checks blood pressure in patients, and “only if they’re really low I’ll talk about the potential for postural hypotension and the fact that you can get a little bit dizzy when going from a position of lying down to standing up.” Potassium levels should be checked at baseline and 4 weeks in patients older than age 46, in those with cardiac and/or renal disease, or in those on concomitant drospirenone or a third-generation progestin.
Spironolactone is classified as a pregnancy category D drug that could compromise the genital development of a male fetus. “So the onus is on us as providers to have the conversation with our patient,” she said. “If you’re putting a patient on spironolactone and they are of child-bearing age, you need to make sure that you’ve had the conversation with them about the fact that they should not get pregnant while on the medicine.”
Spironolactone also has a boxed warning citing the development of benign tumors in animal studies. That warning is based on studies in rats at doses of 10-150 mg/kg per day, “which is an extremely high dose and would never be given in humans,” said Dr. Murase, who has coauthored CME content regarding the safety of dermatologic medications in pregnancy and lactation.
In humans, there has been no evidence of the development of benign tumors associated with spironolactone therapy, and “there has been a decreased risk of prostate cancer and no association with its use and the development of breast, ovarian, bladder, kidney, gastric, or esophageal cancer,” she said.
Dr. Murase noted that during pregnancy, first-line oral antibiotics include amoxicillin for acne rosacea and cefadroxil for acne vulgaris. Macrolides are a second-line choice because of an increase in atrial/ventricular septal defects and pyloric stenosis that have been reported with first-trimester exposure.
“Erythromycin is the preferred choice over azithromycin and clarithromycin because it has the most data, [but] erythromycin estolate has been associated with increased AST levels in the second trimester,” she said. “It occurs in about 10% of cases and is reversible. Erythromycin base and erythromycin ethylsuccinate do not have this risk, and those are preferable.”
Dr. Murase disclosed that she has been a paid speaker of unbranded medical content for Regeneron and UCB. She is also a member of the advisory board for Leo Pharma, Eli Lilly, UCB, and Genzyme/Sanofi.
PORTLAND, ORE. – During her dermatology residency training at the University of California, Irvine, Medical Center, Jenny Murase, MD, remembers hearing a colleague say that her most angry patients of the day were adult women with recalcitrant acne who present to the clinic with questions like, “My skin has been clear my whole life! What’s going on?”
Such . In fact, 82% fail multiple courses of systemic antibiotics and 32% relapse after using isotretinoin, Dr. Murase, director of medical dermatology consultative services and patch testing at the Palo Alto Foundation Medical Group, said at the annual meeting of the Pacific Dermatologic Association.
In her clinical experience, hormonal therapy is a safe long-term option for recalcitrant acne in postmenarcheal females over the age of 14. “Although oral antibiotics are going to be superior to hormonal therapy in the first month or two, when you get to about six months, they have equivalent efficacy,” she said.
Telltale signs of acne associated with androgen excess include the development of nodulocystic papules along the jawline and small comedones over the forehead. Female patients with acne may request that labs be ordered to check their hormone levels, but that often is not necessary, according to Dr. Murase, who is also associate clinical professor of dermatology at the University of California, San Francisco. “There aren’t strict guidelines to indicate when you should perform hormonal testing, but warning signs that warrant further evaluation include hirsutism, androgenetic alopecia, virilization, infertility, oligomenorrhea or amenorrhea, and sudden onset of severe acne. The most common situation that warrants hormonal testing is polycystic ovary syndrome (PCOS).”
When there is a strong suspicion for hyperandrogenism, essential labs include free and total testosterone. Free testosterone is commonly elevated in patients with PCOS and total testosterone levels over 200 ng/dL is suggestive of an ovarian tumor. Other essential labs include 17-hyydroxyprogesterone (values greater than 200 ng/dL indicate congenital adrenal hyperplasia), and dehydroepiandrosterone sulfate (DHEA-S); levels over 8,000 mcg/dL indicate an adrenal tumor, while levels in the 4,000-8,000 mcg/dL range indicate congenital adrenal hyperplasia.
Helpful lab tests to consider include the ratio of luteinizing hormone to follicle-stimulating hormone; a 3:1 ratio or greater is suggestive for PCOS. “Ordering a prolactin level can also help, especially if patients are describing issues with headaches, which could indicate a pituitary tumor,” Dr. Murase added. Measuring sex hormone binding globulin (SHBG) levels can also be helpful. “If a patient has been on oral contraceptives for a long time, it increases their SHBG,” which, in older women, she said, “is inversely related to the development of type 2 diabetes.”
All labs for hyperandrogenism should be performed early in the morning on day 3 of the patient’s menstrual cycle. “If patients are on some kind of hormonal therapy, they need to be off of it for at least 6 weeks in order for you get a relevant test,” she said. Other relevant labs to consider include fasting glucose and lipids, cortisol, and thyroid-stimulating hormone.
Oral contraceptives
Estrogen contained in oral contraceptives (OCs) provides the most benefit to acne patients. “It reduces sebum production, decreases free testosterone and DHEA-S by stimulating SHBG synthesis in the liver, inhibits 5-alpha-reductase, which decreases peripheral testosterone conversion, and it decreases the production of ovarian and adrenal androgens,” Dr. Murase explained. “On average, you can get about 40%-70% reduction of lesion count, which is pretty good.”
Progestins with low androgenetic activity are the most helpful for acne, including norgestimate, desogestrel, and drospirenone. FDA-approved OC options include Ortho Tri-Cyclen, EstroStep, Yaz, and Beyaz. None has data showing superior efficacy.
No Pap smear or pelvic exam is required when prescribing OCs, but the risk of clotting should be discussed with patients. According to Dr. Murase, the risk of deep vein thrombosis (DVT) at baseline is about 1 per 10,000 woman-years, while the risk of DVT after 1 year on an OC is 3.4 per 10,000 years.
“This is a very mild increased risk that we’re talking about, but it is relevant in smokers, in those with hypertension, and in those who are diabetic,” she said. As for the risk of cancer associated with the use of OCs, a large collaborative study found a relative risk of 1.24 for developing breast cancer (not dose or duration related), but a risk reduction for endometrial, colorectal, and ovarian cancer.
The most common side effects associated with OCs are unscheduled bleeding, nausea, breast tenderness, and possible weight gain. Concomitant antibiotics can be used, with the exception of CYP3A4 inducers, such as rifampin. “That’s the main antibiotic we have to worry about that could affect the efficacy of the birth control pill,” she said. “It accounts for about three-quarters of pregnancies on antibiotics.”
Tetracyclines do not appear to increase the rate of birth defects with incidental first-trimester exposure, and data are reassuring but “tetracycline should be stopped within the first trimester as soon as the patient discovers she is pregnant,” Dr. Murase said.
Contraindications for OCs include being pregnant or breastfeeding; history of stroke, venous thromboembolism, or MI; history of smoking and being over age 35; uncontrolled hypertension; migraines with focal symptoms/aura; current or past breast cancer; hypercholesterolemia; diabetes with end-organ damage or having diabetes over age 35; liver issues such as a tumor, viral hepatitis, or cirrhosis; and a history of major surgery with prolonged immobilization.
Spironolactone
Another treatment option is spironolactone, a potassium-sparing diuretic that blocks aldosterone at a dose of 25 mg/day. At doses of 50-100 mg/day, it blocks androgen. “It can be used in combination with an oral contraceptive, with the rates of efficacy reported to range between 33% and 85%,” Dr. Murase said.
Spironolactone can also reduce hirsutism, improve androgenetic alopecia, and lower blood pressure by about 5 mm Hg systolic and 2.5 mm Hg diastolic. Dr. Murase usually checks blood pressure in patients, and “only if they’re really low I’ll talk about the potential for postural hypotension and the fact that you can get a little bit dizzy when going from a position of lying down to standing up.” Potassium levels should be checked at baseline and 4 weeks in patients older than age 46, in those with cardiac and/or renal disease, or in those on concomitant drospirenone or a third-generation progestin.
Spironolactone is classified as a pregnancy category D drug that could compromise the genital development of a male fetus. “So the onus is on us as providers to have the conversation with our patient,” she said. “If you’re putting a patient on spironolactone and they are of child-bearing age, you need to make sure that you’ve had the conversation with them about the fact that they should not get pregnant while on the medicine.”
Spironolactone also has a boxed warning citing the development of benign tumors in animal studies. That warning is based on studies in rats at doses of 10-150 mg/kg per day, “which is an extremely high dose and would never be given in humans,” said Dr. Murase, who has coauthored CME content regarding the safety of dermatologic medications in pregnancy and lactation.
In humans, there has been no evidence of the development of benign tumors associated with spironolactone therapy, and “there has been a decreased risk of prostate cancer and no association with its use and the development of breast, ovarian, bladder, kidney, gastric, or esophageal cancer,” she said.
Dr. Murase noted that during pregnancy, first-line oral antibiotics include amoxicillin for acne rosacea and cefadroxil for acne vulgaris. Macrolides are a second-line choice because of an increase in atrial/ventricular septal defects and pyloric stenosis that have been reported with first-trimester exposure.
“Erythromycin is the preferred choice over azithromycin and clarithromycin because it has the most data, [but] erythromycin estolate has been associated with increased AST levels in the second trimester,” she said. “It occurs in about 10% of cases and is reversible. Erythromycin base and erythromycin ethylsuccinate do not have this risk, and those are preferable.”
Dr. Murase disclosed that she has been a paid speaker of unbranded medical content for Regeneron and UCB. She is also a member of the advisory board for Leo Pharma, Eli Lilly, UCB, and Genzyme/Sanofi.
PORTLAND, ORE. – During her dermatology residency training at the University of California, Irvine, Medical Center, Jenny Murase, MD, remembers hearing a colleague say that her most angry patients of the day were adult women with recalcitrant acne who present to the clinic with questions like, “My skin has been clear my whole life! What’s going on?”
Such . In fact, 82% fail multiple courses of systemic antibiotics and 32% relapse after using isotretinoin, Dr. Murase, director of medical dermatology consultative services and patch testing at the Palo Alto Foundation Medical Group, said at the annual meeting of the Pacific Dermatologic Association.
In her clinical experience, hormonal therapy is a safe long-term option for recalcitrant acne in postmenarcheal females over the age of 14. “Although oral antibiotics are going to be superior to hormonal therapy in the first month or two, when you get to about six months, they have equivalent efficacy,” she said.
Telltale signs of acne associated with androgen excess include the development of nodulocystic papules along the jawline and small comedones over the forehead. Female patients with acne may request that labs be ordered to check their hormone levels, but that often is not necessary, according to Dr. Murase, who is also associate clinical professor of dermatology at the University of California, San Francisco. “There aren’t strict guidelines to indicate when you should perform hormonal testing, but warning signs that warrant further evaluation include hirsutism, androgenetic alopecia, virilization, infertility, oligomenorrhea or amenorrhea, and sudden onset of severe acne. The most common situation that warrants hormonal testing is polycystic ovary syndrome (PCOS).”
When there is a strong suspicion for hyperandrogenism, essential labs include free and total testosterone. Free testosterone is commonly elevated in patients with PCOS and total testosterone levels over 200 ng/dL is suggestive of an ovarian tumor. Other essential labs include 17-hyydroxyprogesterone (values greater than 200 ng/dL indicate congenital adrenal hyperplasia), and dehydroepiandrosterone sulfate (DHEA-S); levels over 8,000 mcg/dL indicate an adrenal tumor, while levels in the 4,000-8,000 mcg/dL range indicate congenital adrenal hyperplasia.
Helpful lab tests to consider include the ratio of luteinizing hormone to follicle-stimulating hormone; a 3:1 ratio or greater is suggestive for PCOS. “Ordering a prolactin level can also help, especially if patients are describing issues with headaches, which could indicate a pituitary tumor,” Dr. Murase added. Measuring sex hormone binding globulin (SHBG) levels can also be helpful. “If a patient has been on oral contraceptives for a long time, it increases their SHBG,” which, in older women, she said, “is inversely related to the development of type 2 diabetes.”
All labs for hyperandrogenism should be performed early in the morning on day 3 of the patient’s menstrual cycle. “If patients are on some kind of hormonal therapy, they need to be off of it for at least 6 weeks in order for you get a relevant test,” she said. Other relevant labs to consider include fasting glucose and lipids, cortisol, and thyroid-stimulating hormone.
Oral contraceptives
Estrogen contained in oral contraceptives (OCs) provides the most benefit to acne patients. “It reduces sebum production, decreases free testosterone and DHEA-S by stimulating SHBG synthesis in the liver, inhibits 5-alpha-reductase, which decreases peripheral testosterone conversion, and it decreases the production of ovarian and adrenal androgens,” Dr. Murase explained. “On average, you can get about 40%-70% reduction of lesion count, which is pretty good.”
Progestins with low androgenetic activity are the most helpful for acne, including norgestimate, desogestrel, and drospirenone. FDA-approved OC options include Ortho Tri-Cyclen, EstroStep, Yaz, and Beyaz. None has data showing superior efficacy.
No Pap smear or pelvic exam is required when prescribing OCs, but the risk of clotting should be discussed with patients. According to Dr. Murase, the risk of deep vein thrombosis (DVT) at baseline is about 1 per 10,000 woman-years, while the risk of DVT after 1 year on an OC is 3.4 per 10,000 years.
“This is a very mild increased risk that we’re talking about, but it is relevant in smokers, in those with hypertension, and in those who are diabetic,” she said. As for the risk of cancer associated with the use of OCs, a large collaborative study found a relative risk of 1.24 for developing breast cancer (not dose or duration related), but a risk reduction for endometrial, colorectal, and ovarian cancer.
The most common side effects associated with OCs are unscheduled bleeding, nausea, breast tenderness, and possible weight gain. Concomitant antibiotics can be used, with the exception of CYP3A4 inducers, such as rifampin. “That’s the main antibiotic we have to worry about that could affect the efficacy of the birth control pill,” she said. “It accounts for about three-quarters of pregnancies on antibiotics.”
Tetracyclines do not appear to increase the rate of birth defects with incidental first-trimester exposure, and data are reassuring but “tetracycline should be stopped within the first trimester as soon as the patient discovers she is pregnant,” Dr. Murase said.
Contraindications for OCs include being pregnant or breastfeeding; history of stroke, venous thromboembolism, or MI; history of smoking and being over age 35; uncontrolled hypertension; migraines with focal symptoms/aura; current or past breast cancer; hypercholesterolemia; diabetes with end-organ damage or having diabetes over age 35; liver issues such as a tumor, viral hepatitis, or cirrhosis; and a history of major surgery with prolonged immobilization.
Spironolactone
Another treatment option is spironolactone, a potassium-sparing diuretic that blocks aldosterone at a dose of 25 mg/day. At doses of 50-100 mg/day, it blocks androgen. “It can be used in combination with an oral contraceptive, with the rates of efficacy reported to range between 33% and 85%,” Dr. Murase said.
Spironolactone can also reduce hirsutism, improve androgenetic alopecia, and lower blood pressure by about 5 mm Hg systolic and 2.5 mm Hg diastolic. Dr. Murase usually checks blood pressure in patients, and “only if they’re really low I’ll talk about the potential for postural hypotension and the fact that you can get a little bit dizzy when going from a position of lying down to standing up.” Potassium levels should be checked at baseline and 4 weeks in patients older than age 46, in those with cardiac and/or renal disease, or in those on concomitant drospirenone or a third-generation progestin.
Spironolactone is classified as a pregnancy category D drug that could compromise the genital development of a male fetus. “So the onus is on us as providers to have the conversation with our patient,” she said. “If you’re putting a patient on spironolactone and they are of child-bearing age, you need to make sure that you’ve had the conversation with them about the fact that they should not get pregnant while on the medicine.”
Spironolactone also has a boxed warning citing the development of benign tumors in animal studies. That warning is based on studies in rats at doses of 10-150 mg/kg per day, “which is an extremely high dose and would never be given in humans,” said Dr. Murase, who has coauthored CME content regarding the safety of dermatologic medications in pregnancy and lactation.
In humans, there has been no evidence of the development of benign tumors associated with spironolactone therapy, and “there has been a decreased risk of prostate cancer and no association with its use and the development of breast, ovarian, bladder, kidney, gastric, or esophageal cancer,” she said.
Dr. Murase noted that during pregnancy, first-line oral antibiotics include amoxicillin for acne rosacea and cefadroxil for acne vulgaris. Macrolides are a second-line choice because of an increase in atrial/ventricular septal defects and pyloric stenosis that have been reported with first-trimester exposure.
“Erythromycin is the preferred choice over azithromycin and clarithromycin because it has the most data, [but] erythromycin estolate has been associated with increased AST levels in the second trimester,” she said. “It occurs in about 10% of cases and is reversible. Erythromycin base and erythromycin ethylsuccinate do not have this risk, and those are preferable.”
Dr. Murase disclosed that she has been a paid speaker of unbranded medical content for Regeneron and UCB. She is also a member of the advisory board for Leo Pharma, Eli Lilly, UCB, and Genzyme/Sanofi.
AT PDA 2022
New ovulatory disorder classifications from FIGO replace 50-year-old system
The first major revision in the systematic description of ovulatory disorders in nearly 50 years has been proposed by a consensus of experts organized by the International Federation of Gynecology and Obstetrics.
“The FIGO HyPO-P system for the classification of ovulatory disorders is submitted for consideration as a worldwide standard,” according to the writing committee, who published their methodology and their proposed applications in the International Journal of Gynecology and Obstetrics.
The classification system was created to replace the much-modified World Health Organization system first described in 1973. Since that time, many modifications have been proposed to accommodate advances in imaging and new information about underlying pathologies, but there has been no subsequent authoritative reference with these modifications or any other newer organizing system.
The new consensus was developed under the aegis of FIGO, but the development group consisted of representatives from national organizations and the major subspecialty societies. Recognized experts in ovulatory disorders and representatives from lay advocacy organizations also participated.
The HyPO-P system is based largely on anatomy. The acronym refers to ovulatory disorders related to the hypothalamus (type I), the pituitary (type II), and the ovary (type III).
Polycystic ovary syndrome (PCOS), one of the most common ovulatory disorders, was given a separate category (type IV) because of its complexity as well as the fact that PCOS is a heterogeneous systemic disorder with manifestations not limited to an impact on ovarian function.
As the first level of classification, three of the four primary categories (I-III) focus attention on the dominant anatomic source of the change in ovulatory function. The original WHO classification system identified as many as seven major groups, but they were based primarily on assays for gonadotropins and estradiol.
The new system “provides a different structure for determining the diagnosis. Blood tests are not a necessary first step,” explained Malcolm G. Munro, MD, clinical professor, department of obstetrics and gynecology, University of California, Los Angeles. Dr. Munro was the first author of the publication.
The classification system “is not as focused on the specific steps for investigation of ovulatory dysfunction as much as it explains how to structure an investigation of the girl or woman with an ovulatory disorder and then how to characterize the underlying cause,” Dr. Munro said in an interview. “It is designed to allow everyone, whether clinicians, researchers, or patients, to speak the same language.”
New system employs four categories
The four primary categories provide just the first level of classification. The next step is encapsulated in the GAIN-FIT-PIE acronym, which frames the presumed or documented categories of etiologies for the primary categories. GAIN stands for genetic, autoimmune, iatrogenic, or neoplasm etiologies. FIT stands for functional, infectious/inflammatory, or trauma and vascular etiologies. PIE stands for physiological, idiopathic, and endocrine etiologies.
By this methodology, a patient with irregular menses, galactorrhea, and elevated prolactin and an MRI showing a pituitary tumor would be identified a type 2-N, signifying pituitary (type 2) involvement with a neoplasm (N).
A third level of classification permits specific diagnostic entities to be named, allowing the patient in the example above to receive a diagnosis of a prolactin-secreting adenoma.
Not all etiologies can be identified with current diagnostic studies, even assuming clinicians have access to the resources, such as advanced imaging, that will increase diagnostic yield. As a result, the authors acknowledged that the classification system will be “aspirational” in at least some patients, but the structure of this system is expected to lead to greater precision in understanding the causes and defining features of ovulatory disorders, which, in turn, might facilitate new research initiatives.
In the published report, diagnostic protocols based on symptoms were described as being “beyond the spectrum” of this initial description. Rather, Dr. Munro explained that the most important contribution of this new classification system are standardization and communication. The system will be amenable for educating trainees and patients, for communicating between clinicians, and as a framework for research where investigators focus on more homogeneous populations of patients.
“There are many causes of ovulatory disorders that are not related to ovarian function. This is one message. Another is that ovulatory disorders are not binary. They occur on a spectrum. These range from transient instances of delayed or failed ovulation to chronic anovulation,” he said.
The new system is “ a welcome update,” according to Mark P. Trolice, MD, director of the IVF Center and professor of obstetrics and gynecology at the University of Central Florida, both in Orlando.
Dr. Trolice pointed to the clinical value of placing PCOS in a separate category. He noted that it affects 8%-13% of women, making it the most common single cause of ovulatory dysfunction.
“Another area that required clarification from prior WHO classifications was hyperprolactinemia, which is now placed in the type II category,” Dr. Trolice said in an interview.
Better terminology can help address a complex set of disorders with multiple causes and variable manifestations.
“In the evaluation of ovulation dysfunction, it is important to remember that regular menstrual intervals do not ensure ovulation,” Dr. Trolice pointed out. Even though a serum progesterone level of higher than 3 ng/mL is one of the simplest laboratory markers for ovulation, this level, he noted, “can vary through the luteal phase and even throughout the day.”
The proposed classification system, while providing a framework for describing ovulatory disorders, is designed to be adaptable, permitting advances in the understanding of the causes of ovulatory dysfunction, in the diagnosis of the causes, and in the treatments to be incorporated.
“No system should be considered permanent,” according to Dr. Munro and his coauthors. “Review and careful modification and revision should be carried out regularly.”
Dr. Munro reports financial relationships with AbbVie, American Regent, Daiichi Sankyo, Hologic, Myovant, and Pharmacosmos. Dr. Trolice reports no potential conflicts of interest.
The first major revision in the systematic description of ovulatory disorders in nearly 50 years has been proposed by a consensus of experts organized by the International Federation of Gynecology and Obstetrics.
“The FIGO HyPO-P system for the classification of ovulatory disorders is submitted for consideration as a worldwide standard,” according to the writing committee, who published their methodology and their proposed applications in the International Journal of Gynecology and Obstetrics.
The classification system was created to replace the much-modified World Health Organization system first described in 1973. Since that time, many modifications have been proposed to accommodate advances in imaging and new information about underlying pathologies, but there has been no subsequent authoritative reference with these modifications or any other newer organizing system.
The new consensus was developed under the aegis of FIGO, but the development group consisted of representatives from national organizations and the major subspecialty societies. Recognized experts in ovulatory disorders and representatives from lay advocacy organizations also participated.
The HyPO-P system is based largely on anatomy. The acronym refers to ovulatory disorders related to the hypothalamus (type I), the pituitary (type II), and the ovary (type III).
Polycystic ovary syndrome (PCOS), one of the most common ovulatory disorders, was given a separate category (type IV) because of its complexity as well as the fact that PCOS is a heterogeneous systemic disorder with manifestations not limited to an impact on ovarian function.
As the first level of classification, three of the four primary categories (I-III) focus attention on the dominant anatomic source of the change in ovulatory function. The original WHO classification system identified as many as seven major groups, but they were based primarily on assays for gonadotropins and estradiol.
The new system “provides a different structure for determining the diagnosis. Blood tests are not a necessary first step,” explained Malcolm G. Munro, MD, clinical professor, department of obstetrics and gynecology, University of California, Los Angeles. Dr. Munro was the first author of the publication.
The classification system “is not as focused on the specific steps for investigation of ovulatory dysfunction as much as it explains how to structure an investigation of the girl or woman with an ovulatory disorder and then how to characterize the underlying cause,” Dr. Munro said in an interview. “It is designed to allow everyone, whether clinicians, researchers, or patients, to speak the same language.”
New system employs four categories
The four primary categories provide just the first level of classification. The next step is encapsulated in the GAIN-FIT-PIE acronym, which frames the presumed or documented categories of etiologies for the primary categories. GAIN stands for genetic, autoimmune, iatrogenic, or neoplasm etiologies. FIT stands for functional, infectious/inflammatory, or trauma and vascular etiologies. PIE stands for physiological, idiopathic, and endocrine etiologies.
By this methodology, a patient with irregular menses, galactorrhea, and elevated prolactin and an MRI showing a pituitary tumor would be identified a type 2-N, signifying pituitary (type 2) involvement with a neoplasm (N).
A third level of classification permits specific diagnostic entities to be named, allowing the patient in the example above to receive a diagnosis of a prolactin-secreting adenoma.
Not all etiologies can be identified with current diagnostic studies, even assuming clinicians have access to the resources, such as advanced imaging, that will increase diagnostic yield. As a result, the authors acknowledged that the classification system will be “aspirational” in at least some patients, but the structure of this system is expected to lead to greater precision in understanding the causes and defining features of ovulatory disorders, which, in turn, might facilitate new research initiatives.
In the published report, diagnostic protocols based on symptoms were described as being “beyond the spectrum” of this initial description. Rather, Dr. Munro explained that the most important contribution of this new classification system are standardization and communication. The system will be amenable for educating trainees and patients, for communicating between clinicians, and as a framework for research where investigators focus on more homogeneous populations of patients.
“There are many causes of ovulatory disorders that are not related to ovarian function. This is one message. Another is that ovulatory disorders are not binary. They occur on a spectrum. These range from transient instances of delayed or failed ovulation to chronic anovulation,” he said.
The new system is “ a welcome update,” according to Mark P. Trolice, MD, director of the IVF Center and professor of obstetrics and gynecology at the University of Central Florida, both in Orlando.
Dr. Trolice pointed to the clinical value of placing PCOS in a separate category. He noted that it affects 8%-13% of women, making it the most common single cause of ovulatory dysfunction.
“Another area that required clarification from prior WHO classifications was hyperprolactinemia, which is now placed in the type II category,” Dr. Trolice said in an interview.
Better terminology can help address a complex set of disorders with multiple causes and variable manifestations.
“In the evaluation of ovulation dysfunction, it is important to remember that regular menstrual intervals do not ensure ovulation,” Dr. Trolice pointed out. Even though a serum progesterone level of higher than 3 ng/mL is one of the simplest laboratory markers for ovulation, this level, he noted, “can vary through the luteal phase and even throughout the day.”
The proposed classification system, while providing a framework for describing ovulatory disorders, is designed to be adaptable, permitting advances in the understanding of the causes of ovulatory dysfunction, in the diagnosis of the causes, and in the treatments to be incorporated.
“No system should be considered permanent,” according to Dr. Munro and his coauthors. “Review and careful modification and revision should be carried out regularly.”
Dr. Munro reports financial relationships with AbbVie, American Regent, Daiichi Sankyo, Hologic, Myovant, and Pharmacosmos. Dr. Trolice reports no potential conflicts of interest.
The first major revision in the systematic description of ovulatory disorders in nearly 50 years has been proposed by a consensus of experts organized by the International Federation of Gynecology and Obstetrics.
“The FIGO HyPO-P system for the classification of ovulatory disorders is submitted for consideration as a worldwide standard,” according to the writing committee, who published their methodology and their proposed applications in the International Journal of Gynecology and Obstetrics.
The classification system was created to replace the much-modified World Health Organization system first described in 1973. Since that time, many modifications have been proposed to accommodate advances in imaging and new information about underlying pathologies, but there has been no subsequent authoritative reference with these modifications or any other newer organizing system.
The new consensus was developed under the aegis of FIGO, but the development group consisted of representatives from national organizations and the major subspecialty societies. Recognized experts in ovulatory disorders and representatives from lay advocacy organizations also participated.
The HyPO-P system is based largely on anatomy. The acronym refers to ovulatory disorders related to the hypothalamus (type I), the pituitary (type II), and the ovary (type III).
Polycystic ovary syndrome (PCOS), one of the most common ovulatory disorders, was given a separate category (type IV) because of its complexity as well as the fact that PCOS is a heterogeneous systemic disorder with manifestations not limited to an impact on ovarian function.
As the first level of classification, three of the four primary categories (I-III) focus attention on the dominant anatomic source of the change in ovulatory function. The original WHO classification system identified as many as seven major groups, but they were based primarily on assays for gonadotropins and estradiol.
The new system “provides a different structure for determining the diagnosis. Blood tests are not a necessary first step,” explained Malcolm G. Munro, MD, clinical professor, department of obstetrics and gynecology, University of California, Los Angeles. Dr. Munro was the first author of the publication.
The classification system “is not as focused on the specific steps for investigation of ovulatory dysfunction as much as it explains how to structure an investigation of the girl or woman with an ovulatory disorder and then how to characterize the underlying cause,” Dr. Munro said in an interview. “It is designed to allow everyone, whether clinicians, researchers, or patients, to speak the same language.”
New system employs four categories
The four primary categories provide just the first level of classification. The next step is encapsulated in the GAIN-FIT-PIE acronym, which frames the presumed or documented categories of etiologies for the primary categories. GAIN stands for genetic, autoimmune, iatrogenic, or neoplasm etiologies. FIT stands for functional, infectious/inflammatory, or trauma and vascular etiologies. PIE stands for physiological, idiopathic, and endocrine etiologies.
By this methodology, a patient with irregular menses, galactorrhea, and elevated prolactin and an MRI showing a pituitary tumor would be identified a type 2-N, signifying pituitary (type 2) involvement with a neoplasm (N).
A third level of classification permits specific diagnostic entities to be named, allowing the patient in the example above to receive a diagnosis of a prolactin-secreting adenoma.
Not all etiologies can be identified with current diagnostic studies, even assuming clinicians have access to the resources, such as advanced imaging, that will increase diagnostic yield. As a result, the authors acknowledged that the classification system will be “aspirational” in at least some patients, but the structure of this system is expected to lead to greater precision in understanding the causes and defining features of ovulatory disorders, which, in turn, might facilitate new research initiatives.
In the published report, diagnostic protocols based on symptoms were described as being “beyond the spectrum” of this initial description. Rather, Dr. Munro explained that the most important contribution of this new classification system are standardization and communication. The system will be amenable for educating trainees and patients, for communicating between clinicians, and as a framework for research where investigators focus on more homogeneous populations of patients.
“There are many causes of ovulatory disorders that are not related to ovarian function. This is one message. Another is that ovulatory disorders are not binary. They occur on a spectrum. These range from transient instances of delayed or failed ovulation to chronic anovulation,” he said.
The new system is “ a welcome update,” according to Mark P. Trolice, MD, director of the IVF Center and professor of obstetrics and gynecology at the University of Central Florida, both in Orlando.
Dr. Trolice pointed to the clinical value of placing PCOS in a separate category. He noted that it affects 8%-13% of women, making it the most common single cause of ovulatory dysfunction.
“Another area that required clarification from prior WHO classifications was hyperprolactinemia, which is now placed in the type II category,” Dr. Trolice said in an interview.
Better terminology can help address a complex set of disorders with multiple causes and variable manifestations.
“In the evaluation of ovulation dysfunction, it is important to remember that regular menstrual intervals do not ensure ovulation,” Dr. Trolice pointed out. Even though a serum progesterone level of higher than 3 ng/mL is one of the simplest laboratory markers for ovulation, this level, he noted, “can vary through the luteal phase and even throughout the day.”
The proposed classification system, while providing a framework for describing ovulatory disorders, is designed to be adaptable, permitting advances in the understanding of the causes of ovulatory dysfunction, in the diagnosis of the causes, and in the treatments to be incorporated.
“No system should be considered permanent,” according to Dr. Munro and his coauthors. “Review and careful modification and revision should be carried out regularly.”
Dr. Munro reports financial relationships with AbbVie, American Regent, Daiichi Sankyo, Hologic, Myovant, and Pharmacosmos. Dr. Trolice reports no potential conflicts of interest.
FROM INTERNATIONAL JOURNAL OF GYNECOLOGY AND OBSTETRICS
Increased risk of dyspareunia following cesarean section
There is no evidence to support postulated associations between mode of delivery and subsequent maternal sexual enjoyment or frequency of intercourse, according to a new study from the University of Bristol (England). However, cesarean section was shown to be associated with a 74% increased risk of dyspareunia, and this was not necessarily due to abdominal scarring, the researchers said.
A team from the University of Bristol and the Karolinska Institutet in Sweden used data from participants in the Avon Longitudinal Study of Parents and Children, a prospective longitudinal birth cohort study also dubbed “Children of the 90s” and involving more than 14,000 women in the United Kingdom who were pregnant in 1991 and 1992. The study has been following the health and development of the parents, their children, and now their grandchildren in detail ever since.
The new study, published in BJOG, aimed to assess whether cesarean section maintains sexual well-being compared with vaginal delivery, as has been suggested to occur because of the reduced risk of genital damage – less chance of tearing – and the maintenance of vaginal tone. There is some evidence that cesarean section is associated with an increased risk of sexual problems such as dyspareunia, but few studies have looked at the postbirth period long term.
Mode of delivery was abstracted from routine obstetric records and recorded as one of either spontaneous vaginal delivery (SVD), cesarean section, assisted breech, breech extraction, forceps, or vacuum extraction. Women whose records showed “other” as mode of delivery or whose notes contained conflicting modes of delivery were excluded.
Self-reported questionnaires asking about general health and lifestyle and including questions relating to sexual enjoyment and frequency were collected at 33 months and at 5, 12, and 18 years postpartum. Women were asked if they enjoyed sexual intercourse, with possible responses of:
- Yes, very much.
- Yes, somewhat.
- No, not a lot.
- No, not at all.
- No sex at the moment.
Possible sexual frequency responses were:
- Not at all.
- Less than once a month.
- 1-3 times a month.
- About once a week.
- 2-4 times a week.
- 5 or more times a week.
First study to look at sexual frequency
The team noted that theirs is the first study investigating the association of mode of delivery with sexual frequency. “Although it may be less important for well-being than sexual enjoyment or sex-related pain, it is an important measure to observe alongside other sexual outcomes,” they said.
Separately, sex-related pain, in the vagina during sex or elsewhere after sex, was assessed once, at 11 years post partum.
The data showed that women who had a cesarean section (11% of the sample) tended to be older than those who had vaginal delivery, with a higher mean body mass index (24.2 versus 22.8 kg/m2), and were more likely to be nulliparous at the time of the index pregnancy (54% versus 44%).
There was no significant difference between cesarean section and vaginal delivery in terms of responses for sexual enjoyment or frequency at any time after childbirth, the authors said. Nor, in adjusted models, was there evidence of associations between the type of vaginal delivery and sexual enjoyment or frequency outcomes.
Pain during sex increased more than a decade after cesarean
However, while the majority of respondents reported no intercourse-related pain, those who delivered via cesarean were more likely than those who gave birth vaginally to report sex-related pain at 11 years post partum. This was specifically an elevated incidence of pain in the vagina during sex, with an odds ratio of 1.74 (95% confidence interval, 1.46-2.08) in the adjusted model. This finding was consistent for emergency and elective cesarean section separately – both types were associated with increased dyspareunia, compared with vaginal delivery.
The dataset did not include measures of individual prenatal sex-related pain and, therefore, “it is unknown from this study whether Caesarean section causes sex-related pain, as suggested by the findings, or whether prenatal sex-related pain predicts both Caesarean section and postnatal sex-related pain,” the researchers said.
“Longitudinal data on sex-related pain need to be collected both before and after parturition,” they recommend, to clarify the direction of a possible effect between cesarean section and dyspareunia.
Cesarean does not protect against sexual dysfunction
Meanwhile, “For women considering a planned Caesarean section in an uncomplicated pregnancy, evidence suggesting that Caesarean section may not protect against sexual dysfunction may help inform their decision-making in the antenatal period.”
Lead author Flo Martin, a PhD student in epidemiology at the University of Bristol, said: “Rates of Caesarean section have been rising over the last 20 years due to many contributing factors and, importantly, it has been suggested that Caesarean section maintains sexual wellbeing compared with vaginal delivery. It is crucial that a whole range of maternal and foetal outcomes following Caesarean section are investigated, including sexual wellbeing, to appropriately inform decision-making both pre- and postnatally.
“This research provides expectant mothers, as well as women who have given birth, with really important information and demonstrates that there was no difference in sexual enjoyment or sexual frequency at any time point postpartum between women who gave birth via Caesarean section and those who delivered vaginally. It also suggests that Caesarean section may not help protect against sexual dysfunction, as previously thought, where sex-related pain was higher among women who gave birth via Caesarean section more than 10 years postpartum.”
Asked to comment on the research, Dr. Leila Frodsham, consultant gynecologist and spokesperson for the Royal College of Obstetricians and Gynaecologists, told this news organization: “Sexual pain disorders affect 7.5% of women of all ages, but there are peaks: during the start of sexual activity, if subfertility is an issue, after childbirth, and in the peri/menopause. It can be up to three times more prevalent at these peak times.
“Many women with sexual pain are worried when they consider starting a family and request a Caesarean birth to reduce risk of worsening their pain. However, this study has demonstrated that a Caesarean birth is associated with increased sexual pain longer term, which is very useful for helping women to plan their births.
“While more research about postpartum sexual wellbeing is needed, the findings of this study are reassuring to those who are pregnant as it found no difference in the enjoyment or frequency of sex in the years after a vaginal or a Caesarean birth.
“Most women in the U.K. recover well whether they have a vaginal or a Caesarean birth. Women should be supported to make informed decisions about how they plan to give birth, and it is vital that health care professionals respect their preferences.”
A version of this article first appeared on Medscape UK.
There is no evidence to support postulated associations between mode of delivery and subsequent maternal sexual enjoyment or frequency of intercourse, according to a new study from the University of Bristol (England). However, cesarean section was shown to be associated with a 74% increased risk of dyspareunia, and this was not necessarily due to abdominal scarring, the researchers said.
A team from the University of Bristol and the Karolinska Institutet in Sweden used data from participants in the Avon Longitudinal Study of Parents and Children, a prospective longitudinal birth cohort study also dubbed “Children of the 90s” and involving more than 14,000 women in the United Kingdom who were pregnant in 1991 and 1992. The study has been following the health and development of the parents, their children, and now their grandchildren in detail ever since.
The new study, published in BJOG, aimed to assess whether cesarean section maintains sexual well-being compared with vaginal delivery, as has been suggested to occur because of the reduced risk of genital damage – less chance of tearing – and the maintenance of vaginal tone. There is some evidence that cesarean section is associated with an increased risk of sexual problems such as dyspareunia, but few studies have looked at the postbirth period long term.
Mode of delivery was abstracted from routine obstetric records and recorded as one of either spontaneous vaginal delivery (SVD), cesarean section, assisted breech, breech extraction, forceps, or vacuum extraction. Women whose records showed “other” as mode of delivery or whose notes contained conflicting modes of delivery were excluded.
Self-reported questionnaires asking about general health and lifestyle and including questions relating to sexual enjoyment and frequency were collected at 33 months and at 5, 12, and 18 years postpartum. Women were asked if they enjoyed sexual intercourse, with possible responses of:
- Yes, very much.
- Yes, somewhat.
- No, not a lot.
- No, not at all.
- No sex at the moment.
Possible sexual frequency responses were:
- Not at all.
- Less than once a month.
- 1-3 times a month.
- About once a week.
- 2-4 times a week.
- 5 or more times a week.
First study to look at sexual frequency
The team noted that theirs is the first study investigating the association of mode of delivery with sexual frequency. “Although it may be less important for well-being than sexual enjoyment or sex-related pain, it is an important measure to observe alongside other sexual outcomes,” they said.
Separately, sex-related pain, in the vagina during sex or elsewhere after sex, was assessed once, at 11 years post partum.
The data showed that women who had a cesarean section (11% of the sample) tended to be older than those who had vaginal delivery, with a higher mean body mass index (24.2 versus 22.8 kg/m2), and were more likely to be nulliparous at the time of the index pregnancy (54% versus 44%).
There was no significant difference between cesarean section and vaginal delivery in terms of responses for sexual enjoyment or frequency at any time after childbirth, the authors said. Nor, in adjusted models, was there evidence of associations between the type of vaginal delivery and sexual enjoyment or frequency outcomes.
Pain during sex increased more than a decade after cesarean
However, while the majority of respondents reported no intercourse-related pain, those who delivered via cesarean were more likely than those who gave birth vaginally to report sex-related pain at 11 years post partum. This was specifically an elevated incidence of pain in the vagina during sex, with an odds ratio of 1.74 (95% confidence interval, 1.46-2.08) in the adjusted model. This finding was consistent for emergency and elective cesarean section separately – both types were associated with increased dyspareunia, compared with vaginal delivery.
The dataset did not include measures of individual prenatal sex-related pain and, therefore, “it is unknown from this study whether Caesarean section causes sex-related pain, as suggested by the findings, or whether prenatal sex-related pain predicts both Caesarean section and postnatal sex-related pain,” the researchers said.
“Longitudinal data on sex-related pain need to be collected both before and after parturition,” they recommend, to clarify the direction of a possible effect between cesarean section and dyspareunia.
Cesarean does not protect against sexual dysfunction
Meanwhile, “For women considering a planned Caesarean section in an uncomplicated pregnancy, evidence suggesting that Caesarean section may not protect against sexual dysfunction may help inform their decision-making in the antenatal period.”
Lead author Flo Martin, a PhD student in epidemiology at the University of Bristol, said: “Rates of Caesarean section have been rising over the last 20 years due to many contributing factors and, importantly, it has been suggested that Caesarean section maintains sexual wellbeing compared with vaginal delivery. It is crucial that a whole range of maternal and foetal outcomes following Caesarean section are investigated, including sexual wellbeing, to appropriately inform decision-making both pre- and postnatally.
“This research provides expectant mothers, as well as women who have given birth, with really important information and demonstrates that there was no difference in sexual enjoyment or sexual frequency at any time point postpartum between women who gave birth via Caesarean section and those who delivered vaginally. It also suggests that Caesarean section may not help protect against sexual dysfunction, as previously thought, where sex-related pain was higher among women who gave birth via Caesarean section more than 10 years postpartum.”
Asked to comment on the research, Dr. Leila Frodsham, consultant gynecologist and spokesperson for the Royal College of Obstetricians and Gynaecologists, told this news organization: “Sexual pain disorders affect 7.5% of women of all ages, but there are peaks: during the start of sexual activity, if subfertility is an issue, after childbirth, and in the peri/menopause. It can be up to three times more prevalent at these peak times.
“Many women with sexual pain are worried when they consider starting a family and request a Caesarean birth to reduce risk of worsening their pain. However, this study has demonstrated that a Caesarean birth is associated with increased sexual pain longer term, which is very useful for helping women to plan their births.
“While more research about postpartum sexual wellbeing is needed, the findings of this study are reassuring to those who are pregnant as it found no difference in the enjoyment or frequency of sex in the years after a vaginal or a Caesarean birth.
“Most women in the U.K. recover well whether they have a vaginal or a Caesarean birth. Women should be supported to make informed decisions about how they plan to give birth, and it is vital that health care professionals respect their preferences.”
A version of this article first appeared on Medscape UK.
There is no evidence to support postulated associations between mode of delivery and subsequent maternal sexual enjoyment or frequency of intercourse, according to a new study from the University of Bristol (England). However, cesarean section was shown to be associated with a 74% increased risk of dyspareunia, and this was not necessarily due to abdominal scarring, the researchers said.
A team from the University of Bristol and the Karolinska Institutet in Sweden used data from participants in the Avon Longitudinal Study of Parents and Children, a prospective longitudinal birth cohort study also dubbed “Children of the 90s” and involving more than 14,000 women in the United Kingdom who were pregnant in 1991 and 1992. The study has been following the health and development of the parents, their children, and now their grandchildren in detail ever since.
The new study, published in BJOG, aimed to assess whether cesarean section maintains sexual well-being compared with vaginal delivery, as has been suggested to occur because of the reduced risk of genital damage – less chance of tearing – and the maintenance of vaginal tone. There is some evidence that cesarean section is associated with an increased risk of sexual problems such as dyspareunia, but few studies have looked at the postbirth period long term.
Mode of delivery was abstracted from routine obstetric records and recorded as one of either spontaneous vaginal delivery (SVD), cesarean section, assisted breech, breech extraction, forceps, or vacuum extraction. Women whose records showed “other” as mode of delivery or whose notes contained conflicting modes of delivery were excluded.
Self-reported questionnaires asking about general health and lifestyle and including questions relating to sexual enjoyment and frequency were collected at 33 months and at 5, 12, and 18 years postpartum. Women were asked if they enjoyed sexual intercourse, with possible responses of:
- Yes, very much.
- Yes, somewhat.
- No, not a lot.
- No, not at all.
- No sex at the moment.
Possible sexual frequency responses were:
- Not at all.
- Less than once a month.
- 1-3 times a month.
- About once a week.
- 2-4 times a week.
- 5 or more times a week.
First study to look at sexual frequency
The team noted that theirs is the first study investigating the association of mode of delivery with sexual frequency. “Although it may be less important for well-being than sexual enjoyment or sex-related pain, it is an important measure to observe alongside other sexual outcomes,” they said.
Separately, sex-related pain, in the vagina during sex or elsewhere after sex, was assessed once, at 11 years post partum.
The data showed that women who had a cesarean section (11% of the sample) tended to be older than those who had vaginal delivery, with a higher mean body mass index (24.2 versus 22.8 kg/m2), and were more likely to be nulliparous at the time of the index pregnancy (54% versus 44%).
There was no significant difference between cesarean section and vaginal delivery in terms of responses for sexual enjoyment or frequency at any time after childbirth, the authors said. Nor, in adjusted models, was there evidence of associations between the type of vaginal delivery and sexual enjoyment or frequency outcomes.
Pain during sex increased more than a decade after cesarean
However, while the majority of respondents reported no intercourse-related pain, those who delivered via cesarean were more likely than those who gave birth vaginally to report sex-related pain at 11 years post partum. This was specifically an elevated incidence of pain in the vagina during sex, with an odds ratio of 1.74 (95% confidence interval, 1.46-2.08) in the adjusted model. This finding was consistent for emergency and elective cesarean section separately – both types were associated with increased dyspareunia, compared with vaginal delivery.
The dataset did not include measures of individual prenatal sex-related pain and, therefore, “it is unknown from this study whether Caesarean section causes sex-related pain, as suggested by the findings, or whether prenatal sex-related pain predicts both Caesarean section and postnatal sex-related pain,” the researchers said.
“Longitudinal data on sex-related pain need to be collected both before and after parturition,” they recommend, to clarify the direction of a possible effect between cesarean section and dyspareunia.
Cesarean does not protect against sexual dysfunction
Meanwhile, “For women considering a planned Caesarean section in an uncomplicated pregnancy, evidence suggesting that Caesarean section may not protect against sexual dysfunction may help inform their decision-making in the antenatal period.”
Lead author Flo Martin, a PhD student in epidemiology at the University of Bristol, said: “Rates of Caesarean section have been rising over the last 20 years due to many contributing factors and, importantly, it has been suggested that Caesarean section maintains sexual wellbeing compared with vaginal delivery. It is crucial that a whole range of maternal and foetal outcomes following Caesarean section are investigated, including sexual wellbeing, to appropriately inform decision-making both pre- and postnatally.
“This research provides expectant mothers, as well as women who have given birth, with really important information and demonstrates that there was no difference in sexual enjoyment or sexual frequency at any time point postpartum between women who gave birth via Caesarean section and those who delivered vaginally. It also suggests that Caesarean section may not help protect against sexual dysfunction, as previously thought, where sex-related pain was higher among women who gave birth via Caesarean section more than 10 years postpartum.”
Asked to comment on the research, Dr. Leila Frodsham, consultant gynecologist and spokesperson for the Royal College of Obstetricians and Gynaecologists, told this news organization: “Sexual pain disorders affect 7.5% of women of all ages, but there are peaks: during the start of sexual activity, if subfertility is an issue, after childbirth, and in the peri/menopause. It can be up to three times more prevalent at these peak times.
“Many women with sexual pain are worried when they consider starting a family and request a Caesarean birth to reduce risk of worsening their pain. However, this study has demonstrated that a Caesarean birth is associated with increased sexual pain longer term, which is very useful for helping women to plan their births.
“While more research about postpartum sexual wellbeing is needed, the findings of this study are reassuring to those who are pregnant as it found no difference in the enjoyment or frequency of sex in the years after a vaginal or a Caesarean birth.
“Most women in the U.K. recover well whether they have a vaginal or a Caesarean birth. Women should be supported to make informed decisions about how they plan to give birth, and it is vital that health care professionals respect their preferences.”
A version of this article first appeared on Medscape UK.
State of the science in PCOS: Emerging neuroendocrine involvement driving research
Polycystic ovary syndrome (PCOS) affects an estimated 8%-13% of women, and yet “it has been quite a black box for many years,” as Margo Hudson, MD, an assistant professor of endocrinology, diabetes, and hypertension at Harvard Medical School, Boston, puts it. That black box encompasses not only uncertainty about the etiology and pathophysiology of the condition but even what constitutes a diagnosis.
Even the international guidelines on PCOS management endorsed by the American Society for Reproductive Medicine – a document developed over 15 months with the input of 37 medical organizations covering 71 countries – notes that PCOS diagnosis is “controversial and assessment and management are inconsistent.” The result, the guidelines note, is that “the needs of women with PCOS are not being adequately met.”
One of the earliest diagnostic criteria, defined in 1990 by the National Institutes of Health, required only hyperandrogenism and irregular menstruation. Then the 2003 Rotterdam Criteria added presence of polycystic ovaries on ultrasound as a third criterion. Then the Androgen Excess Society determined that PCOS required presence of hyperandrogenism with either polycystic ovaries or oligo/amenorrhea anovulation. Yet the Endocrine Society notes that excess androgen levels are seen in 60%-80% of those with PCOS, suggesting it’s not an essential requirement for diagnosis, leaving most to diagnose it in people who have two of the three key criteria. The only real agreement on diagnosis is the need to eliminate other potential diagnoses first, making PCOS always a diagnosis of exclusion.
Further, though PCOS is known as the leading cause of infertility in women, it is more than a reproductive condition, with metabolic and psychological features as well. Then there is the range of comorbidities, none of which occur in all patients with PCOS but all of which occur in a majority and which are themselves interrelated. Insulin resistance is a common feature, occurring in 50%-70% of people with PCOS. Accordingly, metabolic syndrome occurs in at least a third of people with PCOS and type 2 diabetes prevalence is higher in those with PCOS as well.
Obesity occurs in an estimated 80% of women with PCOS in the United States, though it affects only about 50% of women with PCOS outside the United States, and those with PCOS have an increased risk of hypertension. Mood disorders, particularly anxiety and depression but also, to a lesser extent, bipolar disorder and obsessive-compulsive disorder, are more likely in people with PCOS. And given that these comorbidities are all cardiovascular risk factors, it’s unsurprising that recent studies are finding those with PCOS to be at greater risk for cardiometabolic disease and major cardiovascular events.
“The reality is that PCOS is a heterogenous entity. It’s not one thing – it’s a syndrome,” Lubna Pal, MBBS, a professor of ob.gyn. and director of the PCOS Program at Yale University, New Haven, Conn., said in an interview. A whole host of factors are likely playing a role in the causes of PCOS, and those factors interact differently within different people. “We’re looking at things like lipid metabolism, fetal origins, the gut microbiome, genetics, epigenetics, and then dietary and environmental factors,” Nichole Tyson, MD, division chief of pediatric and adolescent gynecology and a clinical associate professor at Stanford (Calif.) Medicine Children’s Health, said in an interview. And most studies have identified associations that may or may not be causal. Take, for example, endocrine disruptors. BPA levels have been shown to be higher in women with PCOS than women without, but that correlation may or may not be related to the etiology of the condition.
The hypothalamic-pituitary-gonadal axis
In trying to understand the pathophysiology of the condition, much of the latest research has zeroed in on potential mechanisms in the hypothalamic-pituitary-gonadal axis. “A consistent feature of PCOS is disordered gonadotropin secretion with elevated mean LH [luteinizing hormone], low or low normal FSH [follicle-stimulating hormone], and a persistently rapid frequency of GnRH [gonadotropin-releasing hormone] pulse secretion,” wrote authors of a scientific statement on aspects of PCOS.
“I think the balance is heading more to central neurologic control of the reproductive system and that disturbances there impact the GnRH cells in the hypothalamus, which then go on to give us the findings that we can measure peripherally with the LH-FSH ratio,” Dr. Hudson said in an interview.
The increased LH levels are thought to be a major driver of increased androgen levels. Current thinking suggests that the primary driver of increased LH is GnRH pulsatility, supported not only by human studies but by animal models as well. This leads to the question of what drives GnRH dysregulation. One hypothesis posits that GABA neurons play a role here, given findings that GABA levels in cerebrospinal fluid were higher in women with PCOS than those with normal ovulation.
But the culprit garnering the most attention is kisspeptin, a protein encoded by the KISS1 gene that stimulates GnRH neurons and has been linked to regulation of LH and FSH secretion. Kisspeptin, along with neurokinin B and dynorphin, is part of the triumvirate that comprises KNDy neurons, also recently implicated in menopausal vasomotor symptoms. Multiple systematic reviewsand meta-analyses have found a correlation between higher kisspeptin levels in the blood and higher circulating LH levels, regardless of body mass index. While kisspeptin is expressed in several tissues, including liver, pancreas, gonad, and adipose, it’s neural kisspeptin signaling that appears most likely to play a role in activating GnRH hormones and disrupting normal function of the hypothalamic-pituitary-gonadal axis.
But as noted, in at least one systematic review of kisspeptin and PCOS, “findings from animal studies suggest that kisspeptin levels are not increased in all subtypes of PCOS.” And another review found “altered” levels of kisspeptin levels in non-PCOS patients who had obesity, potentially raising questions about any associations between kisspeptin and obesity or insulin resistance.
Remaining chicken-and-egg questions
A hallmark of PCOS has long been, and continues to be, the string of chicken-or-egg questions that plague understanding of it. One of these is how depression and anxiety fit into the etiology of PCOS. Exploring the role of specific neurons that may overstimulate GnRH pulsatility may hold clues to a common underlying mechanism for the involvement of depression and anxiety in patients with PCOS, Dr. Hudson speculated. While previous assumptions often attributed depression and anxiety in PCOS to the symptoms – such as thin scalp hair and increased facial hair, excess weight, acne, and irregular periods – Dr. Hudson pointed out that women can address many of these symptoms with laser hair removal, weight loss, acne treatment, and similar interventions, yet they still have a lot of underlying mental health issues.
It’s also unclear whether metabolic factors so common with PCOS, particularly insulin resistance and obesity, are a result of the condition or are contributors to it. Is insulin resistance contributing to dysregulation in the neurons that interferes with normal functioning of the hypothalamic-pituitary-adrenal axis? Is abnormal functioning along this axis contributing to insulin resistance? Or neither? Or both? Or does it depend? The authors of one paper wrote that “insulin may play both direct and indirect roles in the pathogenesis of androgen excess in PCOS,” since insulin can “stimulate ovarian androgen production” and “enhance ovarian growth and follicular cyst formation in rats.”
Dr. Pal noted that “obesity itself can evolve into a PCOS-like picture,” raising questions about whether obesity or insulin resistance might be part of the causal pathway to PCOS, or whether either can trigger its development in those genetically predisposed.
“Obesity does appear to exacerbate many aspects of the PCOS phenotype, particularly those risk factors related to metabolic syndrome,” wrote the authors of a scientific statement on aspects of PCOS, but they add that “it is currently debated whether obesity per se can cause PCOS.” While massive weight loss in those with PCOS and obesity has improved multiple reproductive and metabolic issues, it hasn’t resolved all of them, they write.
Dr. Hudson said she expects there’s “some degree of appetite dysregulation and metabolic dysregulation” that contributes, but then there are other women who don’t have much of an appetite or overeat and still struggle with their weight. Evidence has also found insulin resistance in women of normal weight with PCOS. “There may be some kind of metabolic dysregulation that they have at some level, and others are clearly bothered by overeating,” Dr. Hudson said.
Similarly, it’s not clear whether the recent discovery of increased cardiovascular risks in people with PCOS is a result of the comorbidities so common with PCOS, such as obesity, or whether an underlying mechanism links the cardiovascular risk and the dysregulation of hormones. Dr. Pal would argue that, again, it’s probably both, depending on the patient.
Then there is the key feature of hyperandrogenemia. “An outstanding debate is whether the elevated androgens in PCOS women are merely a downstream endocrine response to hyperactive GnRH and LH secretion driving the ovary, or do the elevated androgens themselves act in the brain (or pituitary) during development and/or adulthood to sculpt and maintain the hypersecretion of GnRH and LH?” wrote Eulalia A. Coutinho, PhD, and Alexander S. Kauffman, PhD, in a 2019 review of the brain’s role in PCOS.
These problems may be bidirectional or part of various feedback loops. Sleep apnea is more common in people with PCOS, Dr. Tyson noted, but sleep apnea is also linked to cardiovascular, metabolic, and depression risks, and depression can play a role in obesity, which increases the risk of obstructive sleep apnea. “So you’re in this vicious cycle,” Dr. Tyson said. That’s why she also believes it’s important to change the dialogue and perspective on PCOS, to reduce the stigma attached to it, and work with patients to empower them in treating its symptoms and reducing their risk of comorbidities.
Recent and upcoming changes in treatment
Current treatment of PCOS already changes according to the symptoms posing the greatest problems at each stage of a person’s life, Dr. Hudson said. Younger women tend to be more bothered about the cosmetic effects of PCOS, including hair growth patterns and acne, but as they grow out of adolescence and into their 20s and 30s, infertility becomes a bigger concern for many. Then, as they start approaching menopause, metabolic and cardiovascular issues take the lead, with more of a focus on lipids, diabetes risk, and heart health.
In some ways, management of PCOS hasn’t changed much in the past several decades, except in an increased awareness of the metabolic and cardiovascular risks, which has led to more frequent screening to catch potential conditions earlier in life. What has changed, however, is improvements in the treatments used for symptoms, such as expanded bariatric surgery options and GLP-1 agonists for treating obesity. Other examples include better options for menstrual management, such as new progesterone IUDs, and optimized fertility treatments, Dr. Tyson said.
“I think with more of these large-scale studies about the pathophysiology of PCOS and how it may look in different people and the different outcomes, we may be able to tailor our treatments even further,” Dr. Tyson said. She emphasized the importance of identifying the condition early, particularly in adolescents, even if it’s identifying young people at risk for the condition rather than actually having it yet.
Early identification “gives us this chance to do a lot of preventative care and motivate older teens to have a great lifestyle, work on their diet and exercise, and manage cardiovascular” risk factors, Dr. Tyson said.
“What we do know and recognize is that there’s so many spokes to this PCOS wheel that there really should be a multidisciplinary approach to care,” Dr. Tyson said. “When I think about who would be the real doctors for patients with PCOS, these would be gynecologists, endocrinologists, dermatologists, nutritionists, psychologists, sleep specialists, and primary care at a minimum.”
Dr. Pal worries that the label of PCOS leaves it in the laps of ob.gyns. whereas, “if it was called something else, everybody would be involved in being vigilant and managing those patients.” She frequently reiterated that the label of PCOS is less important than ensuring clinicians treat the symptoms that most bother the patient.
And even if kisspeptin does play a causal role in PCOS for some patients, it’s only a subset of individuals with PCOS who would benefit from therapies developed to target it. Given the complexity of the syndrome and its many manifestations, a “galaxy of pathways” are involved in different potential subtypes of the condition. “You can’t treat PCOS as one entity,” Dr. Pal said.
Still, Dr. Hudson is optimistic that the research into potential neuroendocrine contributions to PCOS will yield therapies that go beyond just managing symptoms.
“There aren’t a lot of treatments available yet, but there may be some on the horizon,” Dr. Hudson said. “We’re still in this very primitive stage in terms of therapeutics, where we’re only addressing specific symptoms, and we haven’t been able to really address the underlying cause because we haven’t understood it as well and because we don’t have therapies that can target it,” Dr. Hudson said. “But once there are therapies developed that will target some of these central mechanisms, I think it will change completely the approach to treating PCOS for patients.”
This story was updated on Sept. 6, 2022.
Polycystic ovary syndrome (PCOS) affects an estimated 8%-13% of women, and yet “it has been quite a black box for many years,” as Margo Hudson, MD, an assistant professor of endocrinology, diabetes, and hypertension at Harvard Medical School, Boston, puts it. That black box encompasses not only uncertainty about the etiology and pathophysiology of the condition but even what constitutes a diagnosis.
Even the international guidelines on PCOS management endorsed by the American Society for Reproductive Medicine – a document developed over 15 months with the input of 37 medical organizations covering 71 countries – notes that PCOS diagnosis is “controversial and assessment and management are inconsistent.” The result, the guidelines note, is that “the needs of women with PCOS are not being adequately met.”
One of the earliest diagnostic criteria, defined in 1990 by the National Institutes of Health, required only hyperandrogenism and irregular menstruation. Then the 2003 Rotterdam Criteria added presence of polycystic ovaries on ultrasound as a third criterion. Then the Androgen Excess Society determined that PCOS required presence of hyperandrogenism with either polycystic ovaries or oligo/amenorrhea anovulation. Yet the Endocrine Society notes that excess androgen levels are seen in 60%-80% of those with PCOS, suggesting it’s not an essential requirement for diagnosis, leaving most to diagnose it in people who have two of the three key criteria. The only real agreement on diagnosis is the need to eliminate other potential diagnoses first, making PCOS always a diagnosis of exclusion.
Further, though PCOS is known as the leading cause of infertility in women, it is more than a reproductive condition, with metabolic and psychological features as well. Then there is the range of comorbidities, none of which occur in all patients with PCOS but all of which occur in a majority and which are themselves interrelated. Insulin resistance is a common feature, occurring in 50%-70% of people with PCOS. Accordingly, metabolic syndrome occurs in at least a third of people with PCOS and type 2 diabetes prevalence is higher in those with PCOS as well.
Obesity occurs in an estimated 80% of women with PCOS in the United States, though it affects only about 50% of women with PCOS outside the United States, and those with PCOS have an increased risk of hypertension. Mood disorders, particularly anxiety and depression but also, to a lesser extent, bipolar disorder and obsessive-compulsive disorder, are more likely in people with PCOS. And given that these comorbidities are all cardiovascular risk factors, it’s unsurprising that recent studies are finding those with PCOS to be at greater risk for cardiometabolic disease and major cardiovascular events.
“The reality is that PCOS is a heterogenous entity. It’s not one thing – it’s a syndrome,” Lubna Pal, MBBS, a professor of ob.gyn. and director of the PCOS Program at Yale University, New Haven, Conn., said in an interview. A whole host of factors are likely playing a role in the causes of PCOS, and those factors interact differently within different people. “We’re looking at things like lipid metabolism, fetal origins, the gut microbiome, genetics, epigenetics, and then dietary and environmental factors,” Nichole Tyson, MD, division chief of pediatric and adolescent gynecology and a clinical associate professor at Stanford (Calif.) Medicine Children’s Health, said in an interview. And most studies have identified associations that may or may not be causal. Take, for example, endocrine disruptors. BPA levels have been shown to be higher in women with PCOS than women without, but that correlation may or may not be related to the etiology of the condition.
The hypothalamic-pituitary-gonadal axis
In trying to understand the pathophysiology of the condition, much of the latest research has zeroed in on potential mechanisms in the hypothalamic-pituitary-gonadal axis. “A consistent feature of PCOS is disordered gonadotropin secretion with elevated mean LH [luteinizing hormone], low or low normal FSH [follicle-stimulating hormone], and a persistently rapid frequency of GnRH [gonadotropin-releasing hormone] pulse secretion,” wrote authors of a scientific statement on aspects of PCOS.
“I think the balance is heading more to central neurologic control of the reproductive system and that disturbances there impact the GnRH cells in the hypothalamus, which then go on to give us the findings that we can measure peripherally with the LH-FSH ratio,” Dr. Hudson said in an interview.
The increased LH levels are thought to be a major driver of increased androgen levels. Current thinking suggests that the primary driver of increased LH is GnRH pulsatility, supported not only by human studies but by animal models as well. This leads to the question of what drives GnRH dysregulation. One hypothesis posits that GABA neurons play a role here, given findings that GABA levels in cerebrospinal fluid were higher in women with PCOS than those with normal ovulation.
But the culprit garnering the most attention is kisspeptin, a protein encoded by the KISS1 gene that stimulates GnRH neurons and has been linked to regulation of LH and FSH secretion. Kisspeptin, along with neurokinin B and dynorphin, is part of the triumvirate that comprises KNDy neurons, also recently implicated in menopausal vasomotor symptoms. Multiple systematic reviewsand meta-analyses have found a correlation between higher kisspeptin levels in the blood and higher circulating LH levels, regardless of body mass index. While kisspeptin is expressed in several tissues, including liver, pancreas, gonad, and adipose, it’s neural kisspeptin signaling that appears most likely to play a role in activating GnRH hormones and disrupting normal function of the hypothalamic-pituitary-gonadal axis.
But as noted, in at least one systematic review of kisspeptin and PCOS, “findings from animal studies suggest that kisspeptin levels are not increased in all subtypes of PCOS.” And another review found “altered” levels of kisspeptin levels in non-PCOS patients who had obesity, potentially raising questions about any associations between kisspeptin and obesity or insulin resistance.
Remaining chicken-and-egg questions
A hallmark of PCOS has long been, and continues to be, the string of chicken-or-egg questions that plague understanding of it. One of these is how depression and anxiety fit into the etiology of PCOS. Exploring the role of specific neurons that may overstimulate GnRH pulsatility may hold clues to a common underlying mechanism for the involvement of depression and anxiety in patients with PCOS, Dr. Hudson speculated. While previous assumptions often attributed depression and anxiety in PCOS to the symptoms – such as thin scalp hair and increased facial hair, excess weight, acne, and irregular periods – Dr. Hudson pointed out that women can address many of these symptoms with laser hair removal, weight loss, acne treatment, and similar interventions, yet they still have a lot of underlying mental health issues.
It’s also unclear whether metabolic factors so common with PCOS, particularly insulin resistance and obesity, are a result of the condition or are contributors to it. Is insulin resistance contributing to dysregulation in the neurons that interferes with normal functioning of the hypothalamic-pituitary-adrenal axis? Is abnormal functioning along this axis contributing to insulin resistance? Or neither? Or both? Or does it depend? The authors of one paper wrote that “insulin may play both direct and indirect roles in the pathogenesis of androgen excess in PCOS,” since insulin can “stimulate ovarian androgen production” and “enhance ovarian growth and follicular cyst formation in rats.”
Dr. Pal noted that “obesity itself can evolve into a PCOS-like picture,” raising questions about whether obesity or insulin resistance might be part of the causal pathway to PCOS, or whether either can trigger its development in those genetically predisposed.
“Obesity does appear to exacerbate many aspects of the PCOS phenotype, particularly those risk factors related to metabolic syndrome,” wrote the authors of a scientific statement on aspects of PCOS, but they add that “it is currently debated whether obesity per se can cause PCOS.” While massive weight loss in those with PCOS and obesity has improved multiple reproductive and metabolic issues, it hasn’t resolved all of them, they write.
Dr. Hudson said she expects there’s “some degree of appetite dysregulation and metabolic dysregulation” that contributes, but then there are other women who don’t have much of an appetite or overeat and still struggle with their weight. Evidence has also found insulin resistance in women of normal weight with PCOS. “There may be some kind of metabolic dysregulation that they have at some level, and others are clearly bothered by overeating,” Dr. Hudson said.
Similarly, it’s not clear whether the recent discovery of increased cardiovascular risks in people with PCOS is a result of the comorbidities so common with PCOS, such as obesity, or whether an underlying mechanism links the cardiovascular risk and the dysregulation of hormones. Dr. Pal would argue that, again, it’s probably both, depending on the patient.
Then there is the key feature of hyperandrogenemia. “An outstanding debate is whether the elevated androgens in PCOS women are merely a downstream endocrine response to hyperactive GnRH and LH secretion driving the ovary, or do the elevated androgens themselves act in the brain (or pituitary) during development and/or adulthood to sculpt and maintain the hypersecretion of GnRH and LH?” wrote Eulalia A. Coutinho, PhD, and Alexander S. Kauffman, PhD, in a 2019 review of the brain’s role in PCOS.
These problems may be bidirectional or part of various feedback loops. Sleep apnea is more common in people with PCOS, Dr. Tyson noted, but sleep apnea is also linked to cardiovascular, metabolic, and depression risks, and depression can play a role in obesity, which increases the risk of obstructive sleep apnea. “So you’re in this vicious cycle,” Dr. Tyson said. That’s why she also believes it’s important to change the dialogue and perspective on PCOS, to reduce the stigma attached to it, and work with patients to empower them in treating its symptoms and reducing their risk of comorbidities.
Recent and upcoming changes in treatment
Current treatment of PCOS already changes according to the symptoms posing the greatest problems at each stage of a person’s life, Dr. Hudson said. Younger women tend to be more bothered about the cosmetic effects of PCOS, including hair growth patterns and acne, but as they grow out of adolescence and into their 20s and 30s, infertility becomes a bigger concern for many. Then, as they start approaching menopause, metabolic and cardiovascular issues take the lead, with more of a focus on lipids, diabetes risk, and heart health.
In some ways, management of PCOS hasn’t changed much in the past several decades, except in an increased awareness of the metabolic and cardiovascular risks, which has led to more frequent screening to catch potential conditions earlier in life. What has changed, however, is improvements in the treatments used for symptoms, such as expanded bariatric surgery options and GLP-1 agonists for treating obesity. Other examples include better options for menstrual management, such as new progesterone IUDs, and optimized fertility treatments, Dr. Tyson said.
“I think with more of these large-scale studies about the pathophysiology of PCOS and how it may look in different people and the different outcomes, we may be able to tailor our treatments even further,” Dr. Tyson said. She emphasized the importance of identifying the condition early, particularly in adolescents, even if it’s identifying young people at risk for the condition rather than actually having it yet.
Early identification “gives us this chance to do a lot of preventative care and motivate older teens to have a great lifestyle, work on their diet and exercise, and manage cardiovascular” risk factors, Dr. Tyson said.
“What we do know and recognize is that there’s so many spokes to this PCOS wheel that there really should be a multidisciplinary approach to care,” Dr. Tyson said. “When I think about who would be the real doctors for patients with PCOS, these would be gynecologists, endocrinologists, dermatologists, nutritionists, psychologists, sleep specialists, and primary care at a minimum.”
Dr. Pal worries that the label of PCOS leaves it in the laps of ob.gyns. whereas, “if it was called something else, everybody would be involved in being vigilant and managing those patients.” She frequently reiterated that the label of PCOS is less important than ensuring clinicians treat the symptoms that most bother the patient.
And even if kisspeptin does play a causal role in PCOS for some patients, it’s only a subset of individuals with PCOS who would benefit from therapies developed to target it. Given the complexity of the syndrome and its many manifestations, a “galaxy of pathways” are involved in different potential subtypes of the condition. “You can’t treat PCOS as one entity,” Dr. Pal said.
Still, Dr. Hudson is optimistic that the research into potential neuroendocrine contributions to PCOS will yield therapies that go beyond just managing symptoms.
“There aren’t a lot of treatments available yet, but there may be some on the horizon,” Dr. Hudson said. “We’re still in this very primitive stage in terms of therapeutics, where we’re only addressing specific symptoms, and we haven’t been able to really address the underlying cause because we haven’t understood it as well and because we don’t have therapies that can target it,” Dr. Hudson said. “But once there are therapies developed that will target some of these central mechanisms, I think it will change completely the approach to treating PCOS for patients.”
This story was updated on Sept. 6, 2022.
Polycystic ovary syndrome (PCOS) affects an estimated 8%-13% of women, and yet “it has been quite a black box for many years,” as Margo Hudson, MD, an assistant professor of endocrinology, diabetes, and hypertension at Harvard Medical School, Boston, puts it. That black box encompasses not only uncertainty about the etiology and pathophysiology of the condition but even what constitutes a diagnosis.
Even the international guidelines on PCOS management endorsed by the American Society for Reproductive Medicine – a document developed over 15 months with the input of 37 medical organizations covering 71 countries – notes that PCOS diagnosis is “controversial and assessment and management are inconsistent.” The result, the guidelines note, is that “the needs of women with PCOS are not being adequately met.”
One of the earliest diagnostic criteria, defined in 1990 by the National Institutes of Health, required only hyperandrogenism and irregular menstruation. Then the 2003 Rotterdam Criteria added presence of polycystic ovaries on ultrasound as a third criterion. Then the Androgen Excess Society determined that PCOS required presence of hyperandrogenism with either polycystic ovaries or oligo/amenorrhea anovulation. Yet the Endocrine Society notes that excess androgen levels are seen in 60%-80% of those with PCOS, suggesting it’s not an essential requirement for diagnosis, leaving most to diagnose it in people who have two of the three key criteria. The only real agreement on diagnosis is the need to eliminate other potential diagnoses first, making PCOS always a diagnosis of exclusion.
Further, though PCOS is known as the leading cause of infertility in women, it is more than a reproductive condition, with metabolic and psychological features as well. Then there is the range of comorbidities, none of which occur in all patients with PCOS but all of which occur in a majority and which are themselves interrelated. Insulin resistance is a common feature, occurring in 50%-70% of people with PCOS. Accordingly, metabolic syndrome occurs in at least a third of people with PCOS and type 2 diabetes prevalence is higher in those with PCOS as well.
Obesity occurs in an estimated 80% of women with PCOS in the United States, though it affects only about 50% of women with PCOS outside the United States, and those with PCOS have an increased risk of hypertension. Mood disorders, particularly anxiety and depression but also, to a lesser extent, bipolar disorder and obsessive-compulsive disorder, are more likely in people with PCOS. And given that these comorbidities are all cardiovascular risk factors, it’s unsurprising that recent studies are finding those with PCOS to be at greater risk for cardiometabolic disease and major cardiovascular events.
“The reality is that PCOS is a heterogenous entity. It’s not one thing – it’s a syndrome,” Lubna Pal, MBBS, a professor of ob.gyn. and director of the PCOS Program at Yale University, New Haven, Conn., said in an interview. A whole host of factors are likely playing a role in the causes of PCOS, and those factors interact differently within different people. “We’re looking at things like lipid metabolism, fetal origins, the gut microbiome, genetics, epigenetics, and then dietary and environmental factors,” Nichole Tyson, MD, division chief of pediatric and adolescent gynecology and a clinical associate professor at Stanford (Calif.) Medicine Children’s Health, said in an interview. And most studies have identified associations that may or may not be causal. Take, for example, endocrine disruptors. BPA levels have been shown to be higher in women with PCOS than women without, but that correlation may or may not be related to the etiology of the condition.
The hypothalamic-pituitary-gonadal axis
In trying to understand the pathophysiology of the condition, much of the latest research has zeroed in on potential mechanisms in the hypothalamic-pituitary-gonadal axis. “A consistent feature of PCOS is disordered gonadotropin secretion with elevated mean LH [luteinizing hormone], low or low normal FSH [follicle-stimulating hormone], and a persistently rapid frequency of GnRH [gonadotropin-releasing hormone] pulse secretion,” wrote authors of a scientific statement on aspects of PCOS.
“I think the balance is heading more to central neurologic control of the reproductive system and that disturbances there impact the GnRH cells in the hypothalamus, which then go on to give us the findings that we can measure peripherally with the LH-FSH ratio,” Dr. Hudson said in an interview.
The increased LH levels are thought to be a major driver of increased androgen levels. Current thinking suggests that the primary driver of increased LH is GnRH pulsatility, supported not only by human studies but by animal models as well. This leads to the question of what drives GnRH dysregulation. One hypothesis posits that GABA neurons play a role here, given findings that GABA levels in cerebrospinal fluid were higher in women with PCOS than those with normal ovulation.
But the culprit garnering the most attention is kisspeptin, a protein encoded by the KISS1 gene that stimulates GnRH neurons and has been linked to regulation of LH and FSH secretion. Kisspeptin, along with neurokinin B and dynorphin, is part of the triumvirate that comprises KNDy neurons, also recently implicated in menopausal vasomotor symptoms. Multiple systematic reviewsand meta-analyses have found a correlation between higher kisspeptin levels in the blood and higher circulating LH levels, regardless of body mass index. While kisspeptin is expressed in several tissues, including liver, pancreas, gonad, and adipose, it’s neural kisspeptin signaling that appears most likely to play a role in activating GnRH hormones and disrupting normal function of the hypothalamic-pituitary-gonadal axis.
But as noted, in at least one systematic review of kisspeptin and PCOS, “findings from animal studies suggest that kisspeptin levels are not increased in all subtypes of PCOS.” And another review found “altered” levels of kisspeptin levels in non-PCOS patients who had obesity, potentially raising questions about any associations between kisspeptin and obesity or insulin resistance.
Remaining chicken-and-egg questions
A hallmark of PCOS has long been, and continues to be, the string of chicken-or-egg questions that plague understanding of it. One of these is how depression and anxiety fit into the etiology of PCOS. Exploring the role of specific neurons that may overstimulate GnRH pulsatility may hold clues to a common underlying mechanism for the involvement of depression and anxiety in patients with PCOS, Dr. Hudson speculated. While previous assumptions often attributed depression and anxiety in PCOS to the symptoms – such as thin scalp hair and increased facial hair, excess weight, acne, and irregular periods – Dr. Hudson pointed out that women can address many of these symptoms with laser hair removal, weight loss, acne treatment, and similar interventions, yet they still have a lot of underlying mental health issues.
It’s also unclear whether metabolic factors so common with PCOS, particularly insulin resistance and obesity, are a result of the condition or are contributors to it. Is insulin resistance contributing to dysregulation in the neurons that interferes with normal functioning of the hypothalamic-pituitary-adrenal axis? Is abnormal functioning along this axis contributing to insulin resistance? Or neither? Or both? Or does it depend? The authors of one paper wrote that “insulin may play both direct and indirect roles in the pathogenesis of androgen excess in PCOS,” since insulin can “stimulate ovarian androgen production” and “enhance ovarian growth and follicular cyst formation in rats.”
Dr. Pal noted that “obesity itself can evolve into a PCOS-like picture,” raising questions about whether obesity or insulin resistance might be part of the causal pathway to PCOS, or whether either can trigger its development in those genetically predisposed.
“Obesity does appear to exacerbate many aspects of the PCOS phenotype, particularly those risk factors related to metabolic syndrome,” wrote the authors of a scientific statement on aspects of PCOS, but they add that “it is currently debated whether obesity per se can cause PCOS.” While massive weight loss in those with PCOS and obesity has improved multiple reproductive and metabolic issues, it hasn’t resolved all of them, they write.
Dr. Hudson said she expects there’s “some degree of appetite dysregulation and metabolic dysregulation” that contributes, but then there are other women who don’t have much of an appetite or overeat and still struggle with their weight. Evidence has also found insulin resistance in women of normal weight with PCOS. “There may be some kind of metabolic dysregulation that they have at some level, and others are clearly bothered by overeating,” Dr. Hudson said.
Similarly, it’s not clear whether the recent discovery of increased cardiovascular risks in people with PCOS is a result of the comorbidities so common with PCOS, such as obesity, or whether an underlying mechanism links the cardiovascular risk and the dysregulation of hormones. Dr. Pal would argue that, again, it’s probably both, depending on the patient.
Then there is the key feature of hyperandrogenemia. “An outstanding debate is whether the elevated androgens in PCOS women are merely a downstream endocrine response to hyperactive GnRH and LH secretion driving the ovary, or do the elevated androgens themselves act in the brain (or pituitary) during development and/or adulthood to sculpt and maintain the hypersecretion of GnRH and LH?” wrote Eulalia A. Coutinho, PhD, and Alexander S. Kauffman, PhD, in a 2019 review of the brain’s role in PCOS.
These problems may be bidirectional or part of various feedback loops. Sleep apnea is more common in people with PCOS, Dr. Tyson noted, but sleep apnea is also linked to cardiovascular, metabolic, and depression risks, and depression can play a role in obesity, which increases the risk of obstructive sleep apnea. “So you’re in this vicious cycle,” Dr. Tyson said. That’s why she also believes it’s important to change the dialogue and perspective on PCOS, to reduce the stigma attached to it, and work with patients to empower them in treating its symptoms and reducing their risk of comorbidities.
Recent and upcoming changes in treatment
Current treatment of PCOS already changes according to the symptoms posing the greatest problems at each stage of a person’s life, Dr. Hudson said. Younger women tend to be more bothered about the cosmetic effects of PCOS, including hair growth patterns and acne, but as they grow out of adolescence and into their 20s and 30s, infertility becomes a bigger concern for many. Then, as they start approaching menopause, metabolic and cardiovascular issues take the lead, with more of a focus on lipids, diabetes risk, and heart health.
In some ways, management of PCOS hasn’t changed much in the past several decades, except in an increased awareness of the metabolic and cardiovascular risks, which has led to more frequent screening to catch potential conditions earlier in life. What has changed, however, is improvements in the treatments used for symptoms, such as expanded bariatric surgery options and GLP-1 agonists for treating obesity. Other examples include better options for menstrual management, such as new progesterone IUDs, and optimized fertility treatments, Dr. Tyson said.
“I think with more of these large-scale studies about the pathophysiology of PCOS and how it may look in different people and the different outcomes, we may be able to tailor our treatments even further,” Dr. Tyson said. She emphasized the importance of identifying the condition early, particularly in adolescents, even if it’s identifying young people at risk for the condition rather than actually having it yet.
Early identification “gives us this chance to do a lot of preventative care and motivate older teens to have a great lifestyle, work on their diet and exercise, and manage cardiovascular” risk factors, Dr. Tyson said.
“What we do know and recognize is that there’s so many spokes to this PCOS wheel that there really should be a multidisciplinary approach to care,” Dr. Tyson said. “When I think about who would be the real doctors for patients with PCOS, these would be gynecologists, endocrinologists, dermatologists, nutritionists, psychologists, sleep specialists, and primary care at a minimum.”
Dr. Pal worries that the label of PCOS leaves it in the laps of ob.gyns. whereas, “if it was called something else, everybody would be involved in being vigilant and managing those patients.” She frequently reiterated that the label of PCOS is less important than ensuring clinicians treat the symptoms that most bother the patient.
And even if kisspeptin does play a causal role in PCOS for some patients, it’s only a subset of individuals with PCOS who would benefit from therapies developed to target it. Given the complexity of the syndrome and its many manifestations, a “galaxy of pathways” are involved in different potential subtypes of the condition. “You can’t treat PCOS as one entity,” Dr. Pal said.
Still, Dr. Hudson is optimistic that the research into potential neuroendocrine contributions to PCOS will yield therapies that go beyond just managing symptoms.
“There aren’t a lot of treatments available yet, but there may be some on the horizon,” Dr. Hudson said. “We’re still in this very primitive stage in terms of therapeutics, where we’re only addressing specific symptoms, and we haven’t been able to really address the underlying cause because we haven’t understood it as well and because we don’t have therapies that can target it,” Dr. Hudson said. “But once there are therapies developed that will target some of these central mechanisms, I think it will change completely the approach to treating PCOS for patients.”
This story was updated on Sept. 6, 2022.
Early menopause linked with increased risk of heart problems
SEOUL, South Korea – Menopause before age 40 is associated with elevated risk of heart failure and atrial fibrillation, according to a study published in European Heart Journal, from the European Society of Cardiology (ESC). The study of more than 1.4 million women revealed that the younger the age at menopause, the higher the risk of heart failure and atrial fibrillation.
“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Ga Eun Nam, MD, PhD, of Korea University College of Medicine, Seoul. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”
Cardiovascular disease typically occurs up to 10 years later in women than men. Premenopausal women are thought to benefit from estrogen’s protective effect on the cardiovascular system. The cessation of menstruation and subsequent decline of estrogen levels may make women more vulnerable to cardiovascular disease.
A national population
Premature menopause affects 1% of women younger than 40 years, the ESC press release stated. Prior studies have found a link between premature (before age 40 years) and early (before age 45 years) menopause and cardiovascular disease overall, but the evidence for heart failure or atrial fibrillation alone is limited. This study examined the associations between premature menopause, age at menopause, and incident heart failure and atrial fibrillation. Data were obtained from the Korean National Health Insurance System (NHIS), which provides health screening at least every 2 years and includes 97% of the population.
The study included 1,401,175 postmenopausal women aged 30 years and older who completed the NHIS health checkup in 2009. Participants were monitored until the end of 2018 for new-onset heart failure and atrial fibrillation. Information was collected on demographics, health behaviors, and reproductive factors, including age at menopause and use of hormone replacement therapy (HRT). Age at menopause was split into four categories: younger than 40 years, 40-44 years, 45-49 years, and 50 years or older. Premature menopause was defined as having the final menstrual period before age 40 years.
Some 28,111 (2%) participants had a history of premature menopause. For these women, the average age at menopause was 36.7 years. The average age at study enrollment for women with and for those without a history of premature menopause was 60 and 61.5 years, respectively. During an average follow-up of 9.1 years, 42,699 (3.0%) developed heart failure, and 44,834 (3.2%) developed atrial fibrillation.
The researchers analyzed the association between history of premature menopause and incident heart failure and atrial fibrillation after adjusting for age, smoking, alcohol use, physical activity, income, body mass index, hypertension, type 2 diabetes, dyslipidemia, chronic kidney disease, coronary heart disease, HRT, and age at menarche. Women who experienced premature menopause had a 33% higher risk for heart failure and 9% higher risk for atrial fibrillation, compared with those who did not.
Reproductive history
The researchers then analyzed the associations between age at menopause and incidence of heart failure and atrial fibrillation after adjusting for the same factors as in the previous analyses. The risk for incident heart failure increased as the age at menopause decreased. Compared with women aged 50 years and older at menopause, those aged 45-49 years, 40-44 years, and younger than 40 years at menopause had 11%, 23%, and 39% greater risk for incident heart failure, respectively. Similarly, the risk for incident atrial fibrillation increased as the age at menopause decreased; the risk was 4%, 10%, and 11% higher for those aged 45-49 years, 40-44 years, and younger than 40 years at menopause, respectively, compared with women aged 50 years and older at menopause.
The authors said that several factors may explain the associations between menopausal age, heart failure, and atrial fibrillation, such as the drop in estrogen levels and changes in body fat distribution.
Dr. Nam concluded, “The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is growing that undergoing menopause before the age of 40 years may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”
A version of this article appeared on Medscape.com. This article was translated from the Medscape French edition.
SEOUL, South Korea – Menopause before age 40 is associated with elevated risk of heart failure and atrial fibrillation, according to a study published in European Heart Journal, from the European Society of Cardiology (ESC). The study of more than 1.4 million women revealed that the younger the age at menopause, the higher the risk of heart failure and atrial fibrillation.
“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Ga Eun Nam, MD, PhD, of Korea University College of Medicine, Seoul. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”
Cardiovascular disease typically occurs up to 10 years later in women than men. Premenopausal women are thought to benefit from estrogen’s protective effect on the cardiovascular system. The cessation of menstruation and subsequent decline of estrogen levels may make women more vulnerable to cardiovascular disease.
A national population
Premature menopause affects 1% of women younger than 40 years, the ESC press release stated. Prior studies have found a link between premature (before age 40 years) and early (before age 45 years) menopause and cardiovascular disease overall, but the evidence for heart failure or atrial fibrillation alone is limited. This study examined the associations between premature menopause, age at menopause, and incident heart failure and atrial fibrillation. Data were obtained from the Korean National Health Insurance System (NHIS), which provides health screening at least every 2 years and includes 97% of the population.
The study included 1,401,175 postmenopausal women aged 30 years and older who completed the NHIS health checkup in 2009. Participants were monitored until the end of 2018 for new-onset heart failure and atrial fibrillation. Information was collected on demographics, health behaviors, and reproductive factors, including age at menopause and use of hormone replacement therapy (HRT). Age at menopause was split into four categories: younger than 40 years, 40-44 years, 45-49 years, and 50 years or older. Premature menopause was defined as having the final menstrual period before age 40 years.
Some 28,111 (2%) participants had a history of premature menopause. For these women, the average age at menopause was 36.7 years. The average age at study enrollment for women with and for those without a history of premature menopause was 60 and 61.5 years, respectively. During an average follow-up of 9.1 years, 42,699 (3.0%) developed heart failure, and 44,834 (3.2%) developed atrial fibrillation.
The researchers analyzed the association between history of premature menopause and incident heart failure and atrial fibrillation after adjusting for age, smoking, alcohol use, physical activity, income, body mass index, hypertension, type 2 diabetes, dyslipidemia, chronic kidney disease, coronary heart disease, HRT, and age at menarche. Women who experienced premature menopause had a 33% higher risk for heart failure and 9% higher risk for atrial fibrillation, compared with those who did not.
Reproductive history
The researchers then analyzed the associations between age at menopause and incidence of heart failure and atrial fibrillation after adjusting for the same factors as in the previous analyses. The risk for incident heart failure increased as the age at menopause decreased. Compared with women aged 50 years and older at menopause, those aged 45-49 years, 40-44 years, and younger than 40 years at menopause had 11%, 23%, and 39% greater risk for incident heart failure, respectively. Similarly, the risk for incident atrial fibrillation increased as the age at menopause decreased; the risk was 4%, 10%, and 11% higher for those aged 45-49 years, 40-44 years, and younger than 40 years at menopause, respectively, compared with women aged 50 years and older at menopause.
The authors said that several factors may explain the associations between menopausal age, heart failure, and atrial fibrillation, such as the drop in estrogen levels and changes in body fat distribution.
Dr. Nam concluded, “The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is growing that undergoing menopause before the age of 40 years may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”
A version of this article appeared on Medscape.com. This article was translated from the Medscape French edition.
SEOUL, South Korea – Menopause before age 40 is associated with elevated risk of heart failure and atrial fibrillation, according to a study published in European Heart Journal, from the European Society of Cardiology (ESC). The study of more than 1.4 million women revealed that the younger the age at menopause, the higher the risk of heart failure and atrial fibrillation.
“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Ga Eun Nam, MD, PhD, of Korea University College of Medicine, Seoul. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”
Cardiovascular disease typically occurs up to 10 years later in women than men. Premenopausal women are thought to benefit from estrogen’s protective effect on the cardiovascular system. The cessation of menstruation and subsequent decline of estrogen levels may make women more vulnerable to cardiovascular disease.
A national population
Premature menopause affects 1% of women younger than 40 years, the ESC press release stated. Prior studies have found a link between premature (before age 40 years) and early (before age 45 years) menopause and cardiovascular disease overall, but the evidence for heart failure or atrial fibrillation alone is limited. This study examined the associations between premature menopause, age at menopause, and incident heart failure and atrial fibrillation. Data were obtained from the Korean National Health Insurance System (NHIS), which provides health screening at least every 2 years and includes 97% of the population.
The study included 1,401,175 postmenopausal women aged 30 years and older who completed the NHIS health checkup in 2009. Participants were monitored until the end of 2018 for new-onset heart failure and atrial fibrillation. Information was collected on demographics, health behaviors, and reproductive factors, including age at menopause and use of hormone replacement therapy (HRT). Age at menopause was split into four categories: younger than 40 years, 40-44 years, 45-49 years, and 50 years or older. Premature menopause was defined as having the final menstrual period before age 40 years.
Some 28,111 (2%) participants had a history of premature menopause. For these women, the average age at menopause was 36.7 years. The average age at study enrollment for women with and for those without a history of premature menopause was 60 and 61.5 years, respectively. During an average follow-up of 9.1 years, 42,699 (3.0%) developed heart failure, and 44,834 (3.2%) developed atrial fibrillation.
The researchers analyzed the association between history of premature menopause and incident heart failure and atrial fibrillation after adjusting for age, smoking, alcohol use, physical activity, income, body mass index, hypertension, type 2 diabetes, dyslipidemia, chronic kidney disease, coronary heart disease, HRT, and age at menarche. Women who experienced premature menopause had a 33% higher risk for heart failure and 9% higher risk for atrial fibrillation, compared with those who did not.
Reproductive history
The researchers then analyzed the associations between age at menopause and incidence of heart failure and atrial fibrillation after adjusting for the same factors as in the previous analyses. The risk for incident heart failure increased as the age at menopause decreased. Compared with women aged 50 years and older at menopause, those aged 45-49 years, 40-44 years, and younger than 40 years at menopause had 11%, 23%, and 39% greater risk for incident heart failure, respectively. Similarly, the risk for incident atrial fibrillation increased as the age at menopause decreased; the risk was 4%, 10%, and 11% higher for those aged 45-49 years, 40-44 years, and younger than 40 years at menopause, respectively, compared with women aged 50 years and older at menopause.
The authors said that several factors may explain the associations between menopausal age, heart failure, and atrial fibrillation, such as the drop in estrogen levels and changes in body fat distribution.
Dr. Nam concluded, “The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is growing that undergoing menopause before the age of 40 years may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”
A version of this article appeared on Medscape.com. This article was translated from the Medscape French edition.