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FDA approves first over-the-counter birth control pill
The Food and Drug Administration’s approval today of the first birth control pill for women to be available without a prescription is being hailed by many as a long-needed development, but there remain questions to be resolved, including how much the drug will cost and how it will be used.
The drug, Opill, is expected to be available early next year, and its maker has yet to reveal a retail price. It is the same birth control pill that has been available by prescription for 50 years. But for the first time, women will be able to buy the contraception at a local pharmacy, other retail locations, or online without having to see a doctor first.
Likely to drive debate
Contraception in the United States is not without controversy. The FDA’s approval spurred reactions both for and against making hormonal birth control for women available without a prescription.
“It’s an exciting time, especially right now when reproductive rights are being curtailed in a lot of states. Giving people an additional option for contraception will change people’s lives,” said Beverly Gray, MD, division director of Women’s Community and Population Health at Duke University Medical Center in Durham, N.C.
“It’s a huge win for patients who need better access to contraception,” said Dr. Gray, who is also a spokesperson for the American College of Obstetricians and Gynecologists.
Women who want hormonal birth control but live in areas without convenient access to a doctor, women who cannot easily take time off of work to see a doctor and get a prescription filled, and women without insurance are examples of people who will benefit, she said.
The Catholic Medical Association, in contrast, expressed “deep concern and disappointment” after an FDA advisory committee’s unanimous vote on May 11 recommending the drug be available over the counter. In a statement after the vote, the group cited “extensive medical studies demonstrating the risks and adverse effects of hormonal contraceptives,” adding that “the social impact of [full approval] would be dramatic.”
But doctors largely disagreed.
“It is definitely a huge win for reproductive autonomy. I’m glad that the FDA is prioritizing patient safety and well-being over politics,” said Catherine Cansino, MD, MPH, an ob.gyn. and clinical professor in the University of California Davis department of obstetrics and gynecology. She said the FDA approved the over-the-counter version because the medication is safe.
While opponents like the Catholic Medical Association cite safety concerns and believe doctors should screen all women before prescribing hormonal contraception, Dr. Gray disagreed. “There’s a lot of evidence that patients can figure out if a progestin-only pill is right for them and safe for them. Medical professionals don’t have to be the gatekeepers for contraception,” she said.
Pricing unknown
Whether insurance companies will pay for Opill now that it will be available without a prescription remains unknown. For some medications, paying a copay through insurance can be less expensive than buying at a retail price.
“Although pricing issues will be relevant, the FDA’s decision will enhance women’s access to hormonal birth control,” said Andrew M. Kaunitz, MD, a professor and associate chairman in the department of obstetrics and gynecology at the University of Florida College of Medicine in Jacksonville.
The drugmaker, Perrigo, based in Ireland, has not yet announced how much the pill will cost. The price tag could affect how widely available this form of birth control is. The drug has been shown to be as much as 93% effective for pregnancy prevention. Perrigo says it plans to make the pill available at low or no cost to some women.
Caveats to consider
There are some women for whom hormonal contraceptives have always carried greater risks. For example, women who have breast cancer or a history of breast cancer should not use hormonal contraceptives, the FDA said in a news release announcing the approval. Women with other types of cancer should check with their doctors first, the agency noted.
Women who smoke, who take some medications to lower blood pressure, or who have migraines should also take caution, Dr. Cansino said. “People with migraines may not be suitable for over-the-counter oral contraceptives. But a simple screening through a provider can identify whether you are truly eligible or not.”
Irregular bleeding, headaches, dizziness, nausea, increased appetite, belly pain, cramps, or bloating are the most common side effects of Opill, the FDA said.
The Opill is a progestin-only birth control pill. Similar pills have been available in the United Kingdiom for about 2 years, often referred to as “mini pills” because they contain a single hormone. In contrast, prescription birth control pills in the United States and elsewhere contain more than one hormone, estrogen and progestin, to prevent pregnancy.
Prescription pill packs for combination contraception often feature a week of placebo pills without an active ingredient. While skipping a placebo pill might not make a difference in pregnancy prevention, Opill is different. Every pill in the packet will contain medication, Gray said. “So it’s important to take the pill the same time every day for it to be most effective.”
Even though this may mean one less visit to your doctor, Dr. Kaunitz hopes women will stay up to date on their other medical checkups. “One of our challenges as providers of care to women will be to encourage them to continue to receive important services, including cancer screening and vaccinations, even while they can initiate and continue hormonal contraception without contact with a provider.”
Just the beginning?
The American Medical Association hopes this approval signals more to come.
“While we applaud this move, the AMA continues to urge the FDA and HHS to consider a variety of oral contraceptive options for over-the-counter use,” the association, which has more than 250,000 doctor members, said in a statement. “It is important patients have options when choosing which type of birth control works best for them,”
The American College of Obstetricians and Gynecologists said the FDA’s decision will help many women. “We are glad that more patients will now be empowered to choose when and where they obtain a safe method of contraception without having to wait for a medical appointment or for a prescription to be filled,” Verda J. Hicks, MD, the group’s president, and Christopher M. Zahn, MD, interim chief executive officer, said in a statement.
“Allowing individuals to access birth control at their local pharmacy or drug store will eliminate some barriers,” they said.
A version of this article first appeared on WebMD.com.
This article was updated 7/13/23.
The Food and Drug Administration’s approval today of the first birth control pill for women to be available without a prescription is being hailed by many as a long-needed development, but there remain questions to be resolved, including how much the drug will cost and how it will be used.
The drug, Opill, is expected to be available early next year, and its maker has yet to reveal a retail price. It is the same birth control pill that has been available by prescription for 50 years. But for the first time, women will be able to buy the contraception at a local pharmacy, other retail locations, or online without having to see a doctor first.
Likely to drive debate
Contraception in the United States is not without controversy. The FDA’s approval spurred reactions both for and against making hormonal birth control for women available without a prescription.
“It’s an exciting time, especially right now when reproductive rights are being curtailed in a lot of states. Giving people an additional option for contraception will change people’s lives,” said Beverly Gray, MD, division director of Women’s Community and Population Health at Duke University Medical Center in Durham, N.C.
“It’s a huge win for patients who need better access to contraception,” said Dr. Gray, who is also a spokesperson for the American College of Obstetricians and Gynecologists.
Women who want hormonal birth control but live in areas without convenient access to a doctor, women who cannot easily take time off of work to see a doctor and get a prescription filled, and women without insurance are examples of people who will benefit, she said.
The Catholic Medical Association, in contrast, expressed “deep concern and disappointment” after an FDA advisory committee’s unanimous vote on May 11 recommending the drug be available over the counter. In a statement after the vote, the group cited “extensive medical studies demonstrating the risks and adverse effects of hormonal contraceptives,” adding that “the social impact of [full approval] would be dramatic.”
But doctors largely disagreed.
“It is definitely a huge win for reproductive autonomy. I’m glad that the FDA is prioritizing patient safety and well-being over politics,” said Catherine Cansino, MD, MPH, an ob.gyn. and clinical professor in the University of California Davis department of obstetrics and gynecology. She said the FDA approved the over-the-counter version because the medication is safe.
While opponents like the Catholic Medical Association cite safety concerns and believe doctors should screen all women before prescribing hormonal contraception, Dr. Gray disagreed. “There’s a lot of evidence that patients can figure out if a progestin-only pill is right for them and safe for them. Medical professionals don’t have to be the gatekeepers for contraception,” she said.
Pricing unknown
Whether insurance companies will pay for Opill now that it will be available without a prescription remains unknown. For some medications, paying a copay through insurance can be less expensive than buying at a retail price.
“Although pricing issues will be relevant, the FDA’s decision will enhance women’s access to hormonal birth control,” said Andrew M. Kaunitz, MD, a professor and associate chairman in the department of obstetrics and gynecology at the University of Florida College of Medicine in Jacksonville.
The drugmaker, Perrigo, based in Ireland, has not yet announced how much the pill will cost. The price tag could affect how widely available this form of birth control is. The drug has been shown to be as much as 93% effective for pregnancy prevention. Perrigo says it plans to make the pill available at low or no cost to some women.
Caveats to consider
There are some women for whom hormonal contraceptives have always carried greater risks. For example, women who have breast cancer or a history of breast cancer should not use hormonal contraceptives, the FDA said in a news release announcing the approval. Women with other types of cancer should check with their doctors first, the agency noted.
Women who smoke, who take some medications to lower blood pressure, or who have migraines should also take caution, Dr. Cansino said. “People with migraines may not be suitable for over-the-counter oral contraceptives. But a simple screening through a provider can identify whether you are truly eligible or not.”
Irregular bleeding, headaches, dizziness, nausea, increased appetite, belly pain, cramps, or bloating are the most common side effects of Opill, the FDA said.
The Opill is a progestin-only birth control pill. Similar pills have been available in the United Kingdiom for about 2 years, often referred to as “mini pills” because they contain a single hormone. In contrast, prescription birth control pills in the United States and elsewhere contain more than one hormone, estrogen and progestin, to prevent pregnancy.
Prescription pill packs for combination contraception often feature a week of placebo pills without an active ingredient. While skipping a placebo pill might not make a difference in pregnancy prevention, Opill is different. Every pill in the packet will contain medication, Gray said. “So it’s important to take the pill the same time every day for it to be most effective.”
Even though this may mean one less visit to your doctor, Dr. Kaunitz hopes women will stay up to date on their other medical checkups. “One of our challenges as providers of care to women will be to encourage them to continue to receive important services, including cancer screening and vaccinations, even while they can initiate and continue hormonal contraception without contact with a provider.”
Just the beginning?
The American Medical Association hopes this approval signals more to come.
“While we applaud this move, the AMA continues to urge the FDA and HHS to consider a variety of oral contraceptive options for over-the-counter use,” the association, which has more than 250,000 doctor members, said in a statement. “It is important patients have options when choosing which type of birth control works best for them,”
The American College of Obstetricians and Gynecologists said the FDA’s decision will help many women. “We are glad that more patients will now be empowered to choose when and where they obtain a safe method of contraception without having to wait for a medical appointment or for a prescription to be filled,” Verda J. Hicks, MD, the group’s president, and Christopher M. Zahn, MD, interim chief executive officer, said in a statement.
“Allowing individuals to access birth control at their local pharmacy or drug store will eliminate some barriers,” they said.
A version of this article first appeared on WebMD.com.
This article was updated 7/13/23.
The Food and Drug Administration’s approval today of the first birth control pill for women to be available without a prescription is being hailed by many as a long-needed development, but there remain questions to be resolved, including how much the drug will cost and how it will be used.
The drug, Opill, is expected to be available early next year, and its maker has yet to reveal a retail price. It is the same birth control pill that has been available by prescription for 50 years. But for the first time, women will be able to buy the contraception at a local pharmacy, other retail locations, or online without having to see a doctor first.
Likely to drive debate
Contraception in the United States is not without controversy. The FDA’s approval spurred reactions both for and against making hormonal birth control for women available without a prescription.
“It’s an exciting time, especially right now when reproductive rights are being curtailed in a lot of states. Giving people an additional option for contraception will change people’s lives,” said Beverly Gray, MD, division director of Women’s Community and Population Health at Duke University Medical Center in Durham, N.C.
“It’s a huge win for patients who need better access to contraception,” said Dr. Gray, who is also a spokesperson for the American College of Obstetricians and Gynecologists.
Women who want hormonal birth control but live in areas without convenient access to a doctor, women who cannot easily take time off of work to see a doctor and get a prescription filled, and women without insurance are examples of people who will benefit, she said.
The Catholic Medical Association, in contrast, expressed “deep concern and disappointment” after an FDA advisory committee’s unanimous vote on May 11 recommending the drug be available over the counter. In a statement after the vote, the group cited “extensive medical studies demonstrating the risks and adverse effects of hormonal contraceptives,” adding that “the social impact of [full approval] would be dramatic.”
But doctors largely disagreed.
“It is definitely a huge win for reproductive autonomy. I’m glad that the FDA is prioritizing patient safety and well-being over politics,” said Catherine Cansino, MD, MPH, an ob.gyn. and clinical professor in the University of California Davis department of obstetrics and gynecology. She said the FDA approved the over-the-counter version because the medication is safe.
While opponents like the Catholic Medical Association cite safety concerns and believe doctors should screen all women before prescribing hormonal contraception, Dr. Gray disagreed. “There’s a lot of evidence that patients can figure out if a progestin-only pill is right for them and safe for them. Medical professionals don’t have to be the gatekeepers for contraception,” she said.
Pricing unknown
Whether insurance companies will pay for Opill now that it will be available without a prescription remains unknown. For some medications, paying a copay through insurance can be less expensive than buying at a retail price.
“Although pricing issues will be relevant, the FDA’s decision will enhance women’s access to hormonal birth control,” said Andrew M. Kaunitz, MD, a professor and associate chairman in the department of obstetrics and gynecology at the University of Florida College of Medicine in Jacksonville.
The drugmaker, Perrigo, based in Ireland, has not yet announced how much the pill will cost. The price tag could affect how widely available this form of birth control is. The drug has been shown to be as much as 93% effective for pregnancy prevention. Perrigo says it plans to make the pill available at low or no cost to some women.
Caveats to consider
There are some women for whom hormonal contraceptives have always carried greater risks. For example, women who have breast cancer or a history of breast cancer should not use hormonal contraceptives, the FDA said in a news release announcing the approval. Women with other types of cancer should check with their doctors first, the agency noted.
Women who smoke, who take some medications to lower blood pressure, or who have migraines should also take caution, Dr. Cansino said. “People with migraines may not be suitable for over-the-counter oral contraceptives. But a simple screening through a provider can identify whether you are truly eligible or not.”
Irregular bleeding, headaches, dizziness, nausea, increased appetite, belly pain, cramps, or bloating are the most common side effects of Opill, the FDA said.
The Opill is a progestin-only birth control pill. Similar pills have been available in the United Kingdiom for about 2 years, often referred to as “mini pills” because they contain a single hormone. In contrast, prescription birth control pills in the United States and elsewhere contain more than one hormone, estrogen and progestin, to prevent pregnancy.
Prescription pill packs for combination contraception often feature a week of placebo pills without an active ingredient. While skipping a placebo pill might not make a difference in pregnancy prevention, Opill is different. Every pill in the packet will contain medication, Gray said. “So it’s important to take the pill the same time every day for it to be most effective.”
Even though this may mean one less visit to your doctor, Dr. Kaunitz hopes women will stay up to date on their other medical checkups. “One of our challenges as providers of care to women will be to encourage them to continue to receive important services, including cancer screening and vaccinations, even while they can initiate and continue hormonal contraception without contact with a provider.”
Just the beginning?
The American Medical Association hopes this approval signals more to come.
“While we applaud this move, the AMA continues to urge the FDA and HHS to consider a variety of oral contraceptive options for over-the-counter use,” the association, which has more than 250,000 doctor members, said in a statement. “It is important patients have options when choosing which type of birth control works best for them,”
The American College of Obstetricians and Gynecologists said the FDA’s decision will help many women. “We are glad that more patients will now be empowered to choose when and where they obtain a safe method of contraception without having to wait for a medical appointment or for a prescription to be filled,” Verda J. Hicks, MD, the group’s president, and Christopher M. Zahn, MD, interim chief executive officer, said in a statement.
“Allowing individuals to access birth control at their local pharmacy or drug store will eliminate some barriers,” they said.
A version of this article first appeared on WebMD.com.
This article was updated 7/13/23.
Catch-up HPV screenings help detect cancer in women over 65
The findings, published in PLOS Medicine, included women between ages 65 and 69 years in Denmark who had no record of cervical cancer screening or an HPV test in the previous 5 years.
“It may be valuable to get women above the current screening age to get this one-time catch-up HPV test if they haven’t had one before,” said Mette Tranberg, PhD, a cancer epidemiologist and researcher at Randers Regional Hospital in Denmark and lead author of the study. “That is valuable knowledge for health care providers and policy makers.”
Cervical cancer in the United States is most often diagnosed in women aged 35-44 years, according to the American Cancer Society, with the average age at diagnosis of 50 years. The cancer rarely occurs in women who have undergone regular screenings.
Though current guidelines recommend that clinicians stop screening women for cervical cancer at age 65 years if their previous screening results have been normal, Dr. Tranberg said that many women do not get screened as they get closer to age 65 years.
A study from researchers at the University of California, Davis, found several factors contribute to older women not receiving adequate screening. Some women may think that they no longer need Pap smears after going through menopause, or they might have received a hysterectomy and think that they no longer require screening. And although Pap tests have built-in HPV screenings, these tend to be less accurate in postmenopausal women.
But women older than 65 years account for about 20% of new cervical cancer cases.
According to the Centers for Disease Control and Prevention, until women reach age 80 years, they are as likely to get cervical cancer as are younger women. Jack Cuzick, PhD, professor of epidemiology at Queen Mary University of London, said that the new data should inform patient care and public health efforts.
“People often don’t realize HPV can last even if people haven’t been sexually active,” Dr. Cuzick said. “Even if somebody is nearing 70, it’s probably still worth getting an exit test.”
The intervention group
Study participants were assigned to two groups, one of which was invited to participate in a free HPV screening, either with their general practitioner or by ordering a vaginal self-sampling kit. The control group received standard care, which in Denmark, includes having the opportunity to undergo routine cervical cytology.
Dr. Tranberg and her colleagues found that among women in the intervention group, 62.2% were screened within 1 year. Among the control group, 2.2% had a Pap test. The rate of diagnosed cervical intraepithelial neoplasia grade 2 or worse was 3.9 cases per 1,000 eligible women in the intervention group and 0.3 cases per 1,000 eligible women in the control group (P < .001).
The study also found that women who had been insufficiently screened between ages 50 and 64 years had a higher prevalence of HPV, with more grade 2 cervical intraepithelial neoplasia lesions or worse, than did those who were sufficiently screened.
High-risk HPV tests are replacing the Pap smear as the primary cervical cancer screening test because of superior sensitivity, according to Dr. Tranberg. Though Pap smears detect abnormal cells on the cervix that can lead to cervical cancer, HPV tests specifically look for certain high-risk types of HPV on the cervix.
In the United States, patient histories of screenings, diagnosis, and treatment of HPV are often unavailable because electronic health records between health systems are often not linked, according to Cosette Wheeler, PhD, professor at the University of New Mexico Comprehensive Cancer Center in Albuquerque, and founding director of the New Mexico HPV Pap Registry. Clinicians may not know whether a patient needs a screening.
HPV tests usually have a high threshold of detection in an effort to produce fewer false positives, according to Dr. Wheeler, who was not involved in the latest study. But fewer false positives means that the test could produce more false negatives. Older women could benefit from more sensitive screening, such as the high-risk test that the Danish researchers used, according to Dr. Wheeler.
Dr. Tranberg said that she was surprised and pleased by the high percentage of women who accepted the screening tests in the intervention group, especially those who received at-home tests and followed up with a clinician.
“Female life expectancy is really increasing and therefore the number of cervical cancers in women over the age of 65 is expected to rise,” Dr. Tranberg said. “That’s a big reason to rethink whether or not we should do something for these older women.”
The HPV test kits in the intervention region were provided by Roche Diagnostics. According to the contract between Roche and Randers Regional Hospital, Roche had no influence on the scientific process and no editorial rights pertaining to this manuscript.
A version of this article first appeared on Medscape.com.
The findings, published in PLOS Medicine, included women between ages 65 and 69 years in Denmark who had no record of cervical cancer screening or an HPV test in the previous 5 years.
“It may be valuable to get women above the current screening age to get this one-time catch-up HPV test if they haven’t had one before,” said Mette Tranberg, PhD, a cancer epidemiologist and researcher at Randers Regional Hospital in Denmark and lead author of the study. “That is valuable knowledge for health care providers and policy makers.”
Cervical cancer in the United States is most often diagnosed in women aged 35-44 years, according to the American Cancer Society, with the average age at diagnosis of 50 years. The cancer rarely occurs in women who have undergone regular screenings.
Though current guidelines recommend that clinicians stop screening women for cervical cancer at age 65 years if their previous screening results have been normal, Dr. Tranberg said that many women do not get screened as they get closer to age 65 years.
A study from researchers at the University of California, Davis, found several factors contribute to older women not receiving adequate screening. Some women may think that they no longer need Pap smears after going through menopause, or they might have received a hysterectomy and think that they no longer require screening. And although Pap tests have built-in HPV screenings, these tend to be less accurate in postmenopausal women.
But women older than 65 years account for about 20% of new cervical cancer cases.
According to the Centers for Disease Control and Prevention, until women reach age 80 years, they are as likely to get cervical cancer as are younger women. Jack Cuzick, PhD, professor of epidemiology at Queen Mary University of London, said that the new data should inform patient care and public health efforts.
“People often don’t realize HPV can last even if people haven’t been sexually active,” Dr. Cuzick said. “Even if somebody is nearing 70, it’s probably still worth getting an exit test.”
The intervention group
Study participants were assigned to two groups, one of which was invited to participate in a free HPV screening, either with their general practitioner or by ordering a vaginal self-sampling kit. The control group received standard care, which in Denmark, includes having the opportunity to undergo routine cervical cytology.
Dr. Tranberg and her colleagues found that among women in the intervention group, 62.2% were screened within 1 year. Among the control group, 2.2% had a Pap test. The rate of diagnosed cervical intraepithelial neoplasia grade 2 or worse was 3.9 cases per 1,000 eligible women in the intervention group and 0.3 cases per 1,000 eligible women in the control group (P < .001).
The study also found that women who had been insufficiently screened between ages 50 and 64 years had a higher prevalence of HPV, with more grade 2 cervical intraepithelial neoplasia lesions or worse, than did those who were sufficiently screened.
High-risk HPV tests are replacing the Pap smear as the primary cervical cancer screening test because of superior sensitivity, according to Dr. Tranberg. Though Pap smears detect abnormal cells on the cervix that can lead to cervical cancer, HPV tests specifically look for certain high-risk types of HPV on the cervix.
In the United States, patient histories of screenings, diagnosis, and treatment of HPV are often unavailable because electronic health records between health systems are often not linked, according to Cosette Wheeler, PhD, professor at the University of New Mexico Comprehensive Cancer Center in Albuquerque, and founding director of the New Mexico HPV Pap Registry. Clinicians may not know whether a patient needs a screening.
HPV tests usually have a high threshold of detection in an effort to produce fewer false positives, according to Dr. Wheeler, who was not involved in the latest study. But fewer false positives means that the test could produce more false negatives. Older women could benefit from more sensitive screening, such as the high-risk test that the Danish researchers used, according to Dr. Wheeler.
Dr. Tranberg said that she was surprised and pleased by the high percentage of women who accepted the screening tests in the intervention group, especially those who received at-home tests and followed up with a clinician.
“Female life expectancy is really increasing and therefore the number of cervical cancers in women over the age of 65 is expected to rise,” Dr. Tranberg said. “That’s a big reason to rethink whether or not we should do something for these older women.”
The HPV test kits in the intervention region were provided by Roche Diagnostics. According to the contract between Roche and Randers Regional Hospital, Roche had no influence on the scientific process and no editorial rights pertaining to this manuscript.
A version of this article first appeared on Medscape.com.
The findings, published in PLOS Medicine, included women between ages 65 and 69 years in Denmark who had no record of cervical cancer screening or an HPV test in the previous 5 years.
“It may be valuable to get women above the current screening age to get this one-time catch-up HPV test if they haven’t had one before,” said Mette Tranberg, PhD, a cancer epidemiologist and researcher at Randers Regional Hospital in Denmark and lead author of the study. “That is valuable knowledge for health care providers and policy makers.”
Cervical cancer in the United States is most often diagnosed in women aged 35-44 years, according to the American Cancer Society, with the average age at diagnosis of 50 years. The cancer rarely occurs in women who have undergone regular screenings.
Though current guidelines recommend that clinicians stop screening women for cervical cancer at age 65 years if their previous screening results have been normal, Dr. Tranberg said that many women do not get screened as they get closer to age 65 years.
A study from researchers at the University of California, Davis, found several factors contribute to older women not receiving adequate screening. Some women may think that they no longer need Pap smears after going through menopause, or they might have received a hysterectomy and think that they no longer require screening. And although Pap tests have built-in HPV screenings, these tend to be less accurate in postmenopausal women.
But women older than 65 years account for about 20% of new cervical cancer cases.
According to the Centers for Disease Control and Prevention, until women reach age 80 years, they are as likely to get cervical cancer as are younger women. Jack Cuzick, PhD, professor of epidemiology at Queen Mary University of London, said that the new data should inform patient care and public health efforts.
“People often don’t realize HPV can last even if people haven’t been sexually active,” Dr. Cuzick said. “Even if somebody is nearing 70, it’s probably still worth getting an exit test.”
The intervention group
Study participants were assigned to two groups, one of which was invited to participate in a free HPV screening, either with their general practitioner or by ordering a vaginal self-sampling kit. The control group received standard care, which in Denmark, includes having the opportunity to undergo routine cervical cytology.
Dr. Tranberg and her colleagues found that among women in the intervention group, 62.2% were screened within 1 year. Among the control group, 2.2% had a Pap test. The rate of diagnosed cervical intraepithelial neoplasia grade 2 or worse was 3.9 cases per 1,000 eligible women in the intervention group and 0.3 cases per 1,000 eligible women in the control group (P < .001).
The study also found that women who had been insufficiently screened between ages 50 and 64 years had a higher prevalence of HPV, with more grade 2 cervical intraepithelial neoplasia lesions or worse, than did those who were sufficiently screened.
High-risk HPV tests are replacing the Pap smear as the primary cervical cancer screening test because of superior sensitivity, according to Dr. Tranberg. Though Pap smears detect abnormal cells on the cervix that can lead to cervical cancer, HPV tests specifically look for certain high-risk types of HPV on the cervix.
In the United States, patient histories of screenings, diagnosis, and treatment of HPV are often unavailable because electronic health records between health systems are often not linked, according to Cosette Wheeler, PhD, professor at the University of New Mexico Comprehensive Cancer Center in Albuquerque, and founding director of the New Mexico HPV Pap Registry. Clinicians may not know whether a patient needs a screening.
HPV tests usually have a high threshold of detection in an effort to produce fewer false positives, according to Dr. Wheeler, who was not involved in the latest study. But fewer false positives means that the test could produce more false negatives. Older women could benefit from more sensitive screening, such as the high-risk test that the Danish researchers used, according to Dr. Wheeler.
Dr. Tranberg said that she was surprised and pleased by the high percentage of women who accepted the screening tests in the intervention group, especially those who received at-home tests and followed up with a clinician.
“Female life expectancy is really increasing and therefore the number of cervical cancers in women over the age of 65 is expected to rise,” Dr. Tranberg said. “That’s a big reason to rethink whether or not we should do something for these older women.”
The HPV test kits in the intervention region were provided by Roche Diagnostics. According to the contract between Roche and Randers Regional Hospital, Roche had no influence on the scientific process and no editorial rights pertaining to this manuscript.
A version of this article first appeared on Medscape.com.
FROM PLOS MEDICINE
Men and women react differently to acute stress
Topline
Methodology
- The study included 80 healthy participants, mean age 24 years.
- Half the subjects immersed their nondominant hand (including the wrist) in ice water for up to 3 minutes; the other half, which served as the control group, immersed their hand in warm water for 3 minutes.
- Participants were asked to deliberately downregulate emotional responses to high-intensity negative pictures.
- Participants regularly provided saliva samples to check cortisol levels and were monitored for cardiovascular activity.
- Researchers assessed pupil dilation, which along with subject ratings of their affective state served as emotion regulation (ER) outcome measures.
Takeaway
- In men, stress rapidly improved the ability to downregulate emotional arousal via distraction that was fully mediated by cortisol.
- In women, sympathetic nervous system (SNS) reactivity was linked to decreased regulatory performances.
- Direct stress effects on ER were smaller than expected.
In practice
The study contributes to a “better understanding of the neuroendocrinological mechanisms of stress effects on ER that may help to develop adequate preventive and curative interventions of stress- and emotion-related disorders,” the researchers write.
Source
The study was conducted by Katja Langer, Valerie Jentsch, and Oliver Wolf from the Department of Cognitive Psychology, Ruhr University Bochum (Germany). It was published in the May 2023 issue of Psychoneuroendocrinology.
Limitations
The results have some inconsistencies. The ER paradigm is somewhat artificial and not fully comparable with emotional trigger and regulatory requirements in everyday life. The study did not directly assess levels of catecholamines such as adrenaline and noradrenaline.
Disclosures
The study received support from the German Research Foundation (DFG). The authors have no reported conflicts of interest.
A version of this article originally appeared on Medscape.com.
Topline
Methodology
- The study included 80 healthy participants, mean age 24 years.
- Half the subjects immersed their nondominant hand (including the wrist) in ice water for up to 3 minutes; the other half, which served as the control group, immersed their hand in warm water for 3 minutes.
- Participants were asked to deliberately downregulate emotional responses to high-intensity negative pictures.
- Participants regularly provided saliva samples to check cortisol levels and were monitored for cardiovascular activity.
- Researchers assessed pupil dilation, which along with subject ratings of their affective state served as emotion regulation (ER) outcome measures.
Takeaway
- In men, stress rapidly improved the ability to downregulate emotional arousal via distraction that was fully mediated by cortisol.
- In women, sympathetic nervous system (SNS) reactivity was linked to decreased regulatory performances.
- Direct stress effects on ER were smaller than expected.
In practice
The study contributes to a “better understanding of the neuroendocrinological mechanisms of stress effects on ER that may help to develop adequate preventive and curative interventions of stress- and emotion-related disorders,” the researchers write.
Source
The study was conducted by Katja Langer, Valerie Jentsch, and Oliver Wolf from the Department of Cognitive Psychology, Ruhr University Bochum (Germany). It was published in the May 2023 issue of Psychoneuroendocrinology.
Limitations
The results have some inconsistencies. The ER paradigm is somewhat artificial and not fully comparable with emotional trigger and regulatory requirements in everyday life. The study did not directly assess levels of catecholamines such as adrenaline and noradrenaline.
Disclosures
The study received support from the German Research Foundation (DFG). The authors have no reported conflicts of interest.
A version of this article originally appeared on Medscape.com.
Topline
Methodology
- The study included 80 healthy participants, mean age 24 years.
- Half the subjects immersed their nondominant hand (including the wrist) in ice water for up to 3 minutes; the other half, which served as the control group, immersed their hand in warm water for 3 minutes.
- Participants were asked to deliberately downregulate emotional responses to high-intensity negative pictures.
- Participants regularly provided saliva samples to check cortisol levels and were monitored for cardiovascular activity.
- Researchers assessed pupil dilation, which along with subject ratings of their affective state served as emotion regulation (ER) outcome measures.
Takeaway
- In men, stress rapidly improved the ability to downregulate emotional arousal via distraction that was fully mediated by cortisol.
- In women, sympathetic nervous system (SNS) reactivity was linked to decreased regulatory performances.
- Direct stress effects on ER were smaller than expected.
In practice
The study contributes to a “better understanding of the neuroendocrinological mechanisms of stress effects on ER that may help to develop adequate preventive and curative interventions of stress- and emotion-related disorders,” the researchers write.
Source
The study was conducted by Katja Langer, Valerie Jentsch, and Oliver Wolf from the Department of Cognitive Psychology, Ruhr University Bochum (Germany). It was published in the May 2023 issue of Psychoneuroendocrinology.
Limitations
The results have some inconsistencies. The ER paradigm is somewhat artificial and not fully comparable with emotional trigger and regulatory requirements in everyday life. The study did not directly assess levels of catecholamines such as adrenaline and noradrenaline.
Disclosures
The study received support from the German Research Foundation (DFG). The authors have no reported conflicts of interest.
A version of this article originally appeared on Medscape.com.
Does racial bias taint the Apgar score?
Experts say overhaul needed
In 1952, when Dr. Virginia Apgar developed her 10-point scale for assessing neonates’ health, the U.S. obstetrical anesthesiologst may not have foreseen it would one day become one of the commonest medical tests in the world.
Assigned even before the mother first holds her newborn, the score rapidly evaluates neonates with a score of 0-10, which leads to an algorithm of potential medical interventions. The scale evaluates heart rate, respiratory effort, muscle tone, reflex response, and skin coloring (typically described as blue body, pink body/blue limbs, or pink body).
“The Apgar is a very important tool used in millions of babies around the world in the very first minute after birth,” said Amos Grunebaum, MD, a professor of obstetrics and gynecology at Hofstra University, Hempstead, N.Y., and director of perinatal research at Northwell Lenox Hill Hospital in Manhattan.
But recently the venerable system has increasingly come under fire for colorism and racial bias, with some calling for an overhaul. That pressure is due to the 2 out of 10 points allotted to an overall “pink” skin tone, a measure that lowers the scores of non-White newborns and may expose them to unnecessary measures such as resuscitation, neonatal intensive care, and intubation.
“This is their first encounter with systemic racism,” said Dr. Grunebaum in an interview. “The score is prejudiced against Black babies because they can’t get perfect scores.”
Propagating ‘race-based medicine’
Concern about racial bias embedded in the Apgar score is not new, Dr. Grunebaum noted.
“Decades ago, when I was doing my training in Brooklyn, the nurses said that using skin color was ridiculous since Black and brown babies couldn’t be pink. And skin color looks different in different lighting. Dr. Apgar herself recognized the problem.”
Furthermore, men see color differently than women do, and some people are actually color-blind.“But nobody wanted to speak out,” Dr. Grunebaum said. “It was like the emperor’s new clothes scenario.”
In his view, embedding skin color scoring into basic data and health care decisions propagates race-based medicine. “It should not be used for White, Black, or brown babies,” he said.
Removing the skin color portion of the Apgar score – and its racial, colorist, and ethnic bias – will provide more accurate and equitable evaluation of newborn babies worldwide, Dr. Grunebaum said.
“I think there’s a pretty good argument to be made that the skin color measure should be eliminated,” agreed Sara E. Edwards, MD, an obstetrician-gynecologist at the University of Illinois Hospital in Chicago, who has also studied Apgar and racial bias in the clinical care of Black babies.
And such clinical bias may soon be illegal in the United States thanks to a proposed new antidiscrimination provision to the Affordable Care Act regarding the use of clinical algorithms in decision-making. The proposed section, § 92.210, states that a covered entity must not discriminate against any individual on the basis of race, color, national origin, sex, age, or disability through clinical algorithms used in decision-making. Hospitals may soon have to alter clinical algorithms in response.
Dr. Grunebaum’s research in the area of clinical racism includes a large 2022 cohort study of almost 10 million mothers and more than 8 million fathers using 2016-2019 natality data from the National Center for Health Statistics, and Division of Vital Statistics. This study found that Black newborns had a less than 50% chance of having a 5-minute Apgar score of 10, compared with White newborns. White babies, both non-Hispanic and Hispanic, had the highest proportion of perfect 10s.
But can the 2-point skin tone indicator be easily replaced? According to Dr. Grunebaum, substituting indicators such as oral mucosa color or oximetry readings are not satisfactory either. “For one thing, oximetry gives different readings in Black [people],” he said.
In her group’s Apgar research, Dr. Edwards found that care providers applied variable and inaccurate scores based on neonatal race – independently of clinical factors and umbilical-cord gas values.
“In Black neonates umbilical cord gases were not in agreement with lower Apgar scores,” she said. In her view, these inaccuracies point to the existence of colorism and racial bias among health care providers.
Bias ‘creeping in’ to neonatal care
Dr. Edwards’s research was prompted by anecdotal observations that Black babies generally had lower Apgar scores and were more frequently sent to the NICU. “Admission to the NICU can have a negative effect on maternal-child bonding and contribute to PTSD in mothers,” she said.
Her group looked at Apgar scores by race for the year 2019 in an academic hospital cohort of 977 neonates, of whom 56.5% were Black, while controlling for confounding clinical factors.
“Our anecdotal observations of how we score Black neonates were confirmed,” she said. Providers assigned Black babies significantly lower Apgar scores at 1 minute and 5 minutes (odds ratios, .63 and .64) when controlling for umbilical artery gases, gestational age, and maternal-fetal complications.
This difference was specifically associated with lower assigned color Apgar scores at 1 minute (odds ratio, .52). Moreover, full-term Black neonates were sent to neonatal intensive care at higher rates (odds ratio, 1.29) than non-Black neonates when controlling for all the above factors.
Providers applied inaccurate Apgar scores to Black neonates given that the umbilical cord gases were not in agreement with lower Apgar scores, suggesting that colorism and racial biases do exist among health care providers. “We saw bias creeping in because of subjective decisions about color,” Dr. Edwards said. But by the more objective measure of umbilical-cord gas, Black neonates did not have the abnormal values to support NICU admission. The mean umbilical artery pH was 7.259 for Black vs. 7.256 for non-Black neonates.
The solution may lie in switching to an 8 out of 8 score or looking at other indicators such as the eyes and the nail beds, she said. “Or there may be a way to score skin tone accurately when providers are appropriately trained to do so on neonates of all races, to recognize what a well-perfused skin color looks like in all babies.”
New scoring system needed
Interest in this issue continues. In 2022, a population study was conducted by Emma Gillette, MPH, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues in a cohort of almost 7 million singletons born in 2016-2017.
“We found that overall, Apgar scores were highly associated with mortality across the first year of life,” Ms. Gillette said in an interview. “But non-Hispanic Black infants were more likely to be assigned low Apgar scores compared to White infants, and the odds of death in the first year of life are not as strongly correlated with Apgar scores as in White infants.”
That finding was surprising. “Apgar scores are meant to be an indicator of newborn health and well-being and predictors of infant mortality, and therefore should not vary significantly by race or skin color,” she said. “So I think further study into the component scores of the Apgar score is warranted to try to tease out the reasons behind the differences we’re seeing.”
Ms. Gillette agreed that the skin coloring component of the variable could be inaccurate since variables related to skin color more generally are subjective and difficult to measure. What’s needed is a scoring system that performs equally well across racial groups.
In the meantime, some clinicians may be making practical accommodations. “I hate to tell you, but some people fake the skin score,” said Dr. Grunebaum. “I recently asked a doctor from Ethiopia how they handled it there, and he laughed and said they just automatically give skin color a 2. But faking it is not what you should have to do in medicine.”
Dr. Grunebaum, Dr. Edwards, and Ms. Gillette disclosed no relevant competing interests with respect to their comments.
Experts say overhaul needed
Experts say overhaul needed
In 1952, when Dr. Virginia Apgar developed her 10-point scale for assessing neonates’ health, the U.S. obstetrical anesthesiologst may not have foreseen it would one day become one of the commonest medical tests in the world.
Assigned even before the mother first holds her newborn, the score rapidly evaluates neonates with a score of 0-10, which leads to an algorithm of potential medical interventions. The scale evaluates heart rate, respiratory effort, muscle tone, reflex response, and skin coloring (typically described as blue body, pink body/blue limbs, or pink body).
“The Apgar is a very important tool used in millions of babies around the world in the very first minute after birth,” said Amos Grunebaum, MD, a professor of obstetrics and gynecology at Hofstra University, Hempstead, N.Y., and director of perinatal research at Northwell Lenox Hill Hospital in Manhattan.
But recently the venerable system has increasingly come under fire for colorism and racial bias, with some calling for an overhaul. That pressure is due to the 2 out of 10 points allotted to an overall “pink” skin tone, a measure that lowers the scores of non-White newborns and may expose them to unnecessary measures such as resuscitation, neonatal intensive care, and intubation.
“This is their first encounter with systemic racism,” said Dr. Grunebaum in an interview. “The score is prejudiced against Black babies because they can’t get perfect scores.”
Propagating ‘race-based medicine’
Concern about racial bias embedded in the Apgar score is not new, Dr. Grunebaum noted.
“Decades ago, when I was doing my training in Brooklyn, the nurses said that using skin color was ridiculous since Black and brown babies couldn’t be pink. And skin color looks different in different lighting. Dr. Apgar herself recognized the problem.”
Furthermore, men see color differently than women do, and some people are actually color-blind.“But nobody wanted to speak out,” Dr. Grunebaum said. “It was like the emperor’s new clothes scenario.”
In his view, embedding skin color scoring into basic data and health care decisions propagates race-based medicine. “It should not be used for White, Black, or brown babies,” he said.
Removing the skin color portion of the Apgar score – and its racial, colorist, and ethnic bias – will provide more accurate and equitable evaluation of newborn babies worldwide, Dr. Grunebaum said.
“I think there’s a pretty good argument to be made that the skin color measure should be eliminated,” agreed Sara E. Edwards, MD, an obstetrician-gynecologist at the University of Illinois Hospital in Chicago, who has also studied Apgar and racial bias in the clinical care of Black babies.
And such clinical bias may soon be illegal in the United States thanks to a proposed new antidiscrimination provision to the Affordable Care Act regarding the use of clinical algorithms in decision-making. The proposed section, § 92.210, states that a covered entity must not discriminate against any individual on the basis of race, color, national origin, sex, age, or disability through clinical algorithms used in decision-making. Hospitals may soon have to alter clinical algorithms in response.
Dr. Grunebaum’s research in the area of clinical racism includes a large 2022 cohort study of almost 10 million mothers and more than 8 million fathers using 2016-2019 natality data from the National Center for Health Statistics, and Division of Vital Statistics. This study found that Black newborns had a less than 50% chance of having a 5-minute Apgar score of 10, compared with White newborns. White babies, both non-Hispanic and Hispanic, had the highest proportion of perfect 10s.
But can the 2-point skin tone indicator be easily replaced? According to Dr. Grunebaum, substituting indicators such as oral mucosa color or oximetry readings are not satisfactory either. “For one thing, oximetry gives different readings in Black [people],” he said.
In her group’s Apgar research, Dr. Edwards found that care providers applied variable and inaccurate scores based on neonatal race – independently of clinical factors and umbilical-cord gas values.
“In Black neonates umbilical cord gases were not in agreement with lower Apgar scores,” she said. In her view, these inaccuracies point to the existence of colorism and racial bias among health care providers.
Bias ‘creeping in’ to neonatal care
Dr. Edwards’s research was prompted by anecdotal observations that Black babies generally had lower Apgar scores and were more frequently sent to the NICU. “Admission to the NICU can have a negative effect on maternal-child bonding and contribute to PTSD in mothers,” she said.
Her group looked at Apgar scores by race for the year 2019 in an academic hospital cohort of 977 neonates, of whom 56.5% were Black, while controlling for confounding clinical factors.
“Our anecdotal observations of how we score Black neonates were confirmed,” she said. Providers assigned Black babies significantly lower Apgar scores at 1 minute and 5 minutes (odds ratios, .63 and .64) when controlling for umbilical artery gases, gestational age, and maternal-fetal complications.
This difference was specifically associated with lower assigned color Apgar scores at 1 minute (odds ratio, .52). Moreover, full-term Black neonates were sent to neonatal intensive care at higher rates (odds ratio, 1.29) than non-Black neonates when controlling for all the above factors.
Providers applied inaccurate Apgar scores to Black neonates given that the umbilical cord gases were not in agreement with lower Apgar scores, suggesting that colorism and racial biases do exist among health care providers. “We saw bias creeping in because of subjective decisions about color,” Dr. Edwards said. But by the more objective measure of umbilical-cord gas, Black neonates did not have the abnormal values to support NICU admission. The mean umbilical artery pH was 7.259 for Black vs. 7.256 for non-Black neonates.
The solution may lie in switching to an 8 out of 8 score or looking at other indicators such as the eyes and the nail beds, she said. “Or there may be a way to score skin tone accurately when providers are appropriately trained to do so on neonates of all races, to recognize what a well-perfused skin color looks like in all babies.”
New scoring system needed
Interest in this issue continues. In 2022, a population study was conducted by Emma Gillette, MPH, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues in a cohort of almost 7 million singletons born in 2016-2017.
“We found that overall, Apgar scores were highly associated with mortality across the first year of life,” Ms. Gillette said in an interview. “But non-Hispanic Black infants were more likely to be assigned low Apgar scores compared to White infants, and the odds of death in the first year of life are not as strongly correlated with Apgar scores as in White infants.”
That finding was surprising. “Apgar scores are meant to be an indicator of newborn health and well-being and predictors of infant mortality, and therefore should not vary significantly by race or skin color,” she said. “So I think further study into the component scores of the Apgar score is warranted to try to tease out the reasons behind the differences we’re seeing.”
Ms. Gillette agreed that the skin coloring component of the variable could be inaccurate since variables related to skin color more generally are subjective and difficult to measure. What’s needed is a scoring system that performs equally well across racial groups.
In the meantime, some clinicians may be making practical accommodations. “I hate to tell you, but some people fake the skin score,” said Dr. Grunebaum. “I recently asked a doctor from Ethiopia how they handled it there, and he laughed and said they just automatically give skin color a 2. But faking it is not what you should have to do in medicine.”
Dr. Grunebaum, Dr. Edwards, and Ms. Gillette disclosed no relevant competing interests with respect to their comments.
In 1952, when Dr. Virginia Apgar developed her 10-point scale for assessing neonates’ health, the U.S. obstetrical anesthesiologst may not have foreseen it would one day become one of the commonest medical tests in the world.
Assigned even before the mother first holds her newborn, the score rapidly evaluates neonates with a score of 0-10, which leads to an algorithm of potential medical interventions. The scale evaluates heart rate, respiratory effort, muscle tone, reflex response, and skin coloring (typically described as blue body, pink body/blue limbs, or pink body).
“The Apgar is a very important tool used in millions of babies around the world in the very first minute after birth,” said Amos Grunebaum, MD, a professor of obstetrics and gynecology at Hofstra University, Hempstead, N.Y., and director of perinatal research at Northwell Lenox Hill Hospital in Manhattan.
But recently the venerable system has increasingly come under fire for colorism and racial bias, with some calling for an overhaul. That pressure is due to the 2 out of 10 points allotted to an overall “pink” skin tone, a measure that lowers the scores of non-White newborns and may expose them to unnecessary measures such as resuscitation, neonatal intensive care, and intubation.
“This is their first encounter with systemic racism,” said Dr. Grunebaum in an interview. “The score is prejudiced against Black babies because they can’t get perfect scores.”
Propagating ‘race-based medicine’
Concern about racial bias embedded in the Apgar score is not new, Dr. Grunebaum noted.
“Decades ago, when I was doing my training in Brooklyn, the nurses said that using skin color was ridiculous since Black and brown babies couldn’t be pink. And skin color looks different in different lighting. Dr. Apgar herself recognized the problem.”
Furthermore, men see color differently than women do, and some people are actually color-blind.“But nobody wanted to speak out,” Dr. Grunebaum said. “It was like the emperor’s new clothes scenario.”
In his view, embedding skin color scoring into basic data and health care decisions propagates race-based medicine. “It should not be used for White, Black, or brown babies,” he said.
Removing the skin color portion of the Apgar score – and its racial, colorist, and ethnic bias – will provide more accurate and equitable evaluation of newborn babies worldwide, Dr. Grunebaum said.
“I think there’s a pretty good argument to be made that the skin color measure should be eliminated,” agreed Sara E. Edwards, MD, an obstetrician-gynecologist at the University of Illinois Hospital in Chicago, who has also studied Apgar and racial bias in the clinical care of Black babies.
And such clinical bias may soon be illegal in the United States thanks to a proposed new antidiscrimination provision to the Affordable Care Act regarding the use of clinical algorithms in decision-making. The proposed section, § 92.210, states that a covered entity must not discriminate against any individual on the basis of race, color, national origin, sex, age, or disability through clinical algorithms used in decision-making. Hospitals may soon have to alter clinical algorithms in response.
Dr. Grunebaum’s research in the area of clinical racism includes a large 2022 cohort study of almost 10 million mothers and more than 8 million fathers using 2016-2019 natality data from the National Center for Health Statistics, and Division of Vital Statistics. This study found that Black newborns had a less than 50% chance of having a 5-minute Apgar score of 10, compared with White newborns. White babies, both non-Hispanic and Hispanic, had the highest proportion of perfect 10s.
But can the 2-point skin tone indicator be easily replaced? According to Dr. Grunebaum, substituting indicators such as oral mucosa color or oximetry readings are not satisfactory either. “For one thing, oximetry gives different readings in Black [people],” he said.
In her group’s Apgar research, Dr. Edwards found that care providers applied variable and inaccurate scores based on neonatal race – independently of clinical factors and umbilical-cord gas values.
“In Black neonates umbilical cord gases were not in agreement with lower Apgar scores,” she said. In her view, these inaccuracies point to the existence of colorism and racial bias among health care providers.
Bias ‘creeping in’ to neonatal care
Dr. Edwards’s research was prompted by anecdotal observations that Black babies generally had lower Apgar scores and were more frequently sent to the NICU. “Admission to the NICU can have a negative effect on maternal-child bonding and contribute to PTSD in mothers,” she said.
Her group looked at Apgar scores by race for the year 2019 in an academic hospital cohort of 977 neonates, of whom 56.5% were Black, while controlling for confounding clinical factors.
“Our anecdotal observations of how we score Black neonates were confirmed,” she said. Providers assigned Black babies significantly lower Apgar scores at 1 minute and 5 minutes (odds ratios, .63 and .64) when controlling for umbilical artery gases, gestational age, and maternal-fetal complications.
This difference was specifically associated with lower assigned color Apgar scores at 1 minute (odds ratio, .52). Moreover, full-term Black neonates were sent to neonatal intensive care at higher rates (odds ratio, 1.29) than non-Black neonates when controlling for all the above factors.
Providers applied inaccurate Apgar scores to Black neonates given that the umbilical cord gases were not in agreement with lower Apgar scores, suggesting that colorism and racial biases do exist among health care providers. “We saw bias creeping in because of subjective decisions about color,” Dr. Edwards said. But by the more objective measure of umbilical-cord gas, Black neonates did not have the abnormal values to support NICU admission. The mean umbilical artery pH was 7.259 for Black vs. 7.256 for non-Black neonates.
The solution may lie in switching to an 8 out of 8 score or looking at other indicators such as the eyes and the nail beds, she said. “Or there may be a way to score skin tone accurately when providers are appropriately trained to do so on neonates of all races, to recognize what a well-perfused skin color looks like in all babies.”
New scoring system needed
Interest in this issue continues. In 2022, a population study was conducted by Emma Gillette, MPH, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues in a cohort of almost 7 million singletons born in 2016-2017.
“We found that overall, Apgar scores were highly associated with mortality across the first year of life,” Ms. Gillette said in an interview. “But non-Hispanic Black infants were more likely to be assigned low Apgar scores compared to White infants, and the odds of death in the first year of life are not as strongly correlated with Apgar scores as in White infants.”
That finding was surprising. “Apgar scores are meant to be an indicator of newborn health and well-being and predictors of infant mortality, and therefore should not vary significantly by race or skin color,” she said. “So I think further study into the component scores of the Apgar score is warranted to try to tease out the reasons behind the differences we’re seeing.”
Ms. Gillette agreed that the skin coloring component of the variable could be inaccurate since variables related to skin color more generally are subjective and difficult to measure. What’s needed is a scoring system that performs equally well across racial groups.
In the meantime, some clinicians may be making practical accommodations. “I hate to tell you, but some people fake the skin score,” said Dr. Grunebaum. “I recently asked a doctor from Ethiopia how they handled it there, and he laughed and said they just automatically give skin color a 2. But faking it is not what you should have to do in medicine.”
Dr. Grunebaum, Dr. Edwards, and Ms. Gillette disclosed no relevant competing interests with respect to their comments.
OCD linked to adverse pregnancy and neonatal outcomes
In an observational study that followed almost 3 million pregnancies in two countries over 20 years, children of women with OCD were at increased risk for low Apgar score at 5 minutes in Sweden (adjusted risk ratio [aRR], 1.62) and British Columbia, Canada (aRR, 2.30). The risks for adverse outcomes were greater among women with OCD who were taking serotonin reuptake inhibitors (SRIs), compared with those who were not.
“To me, the most relevant things to consider are the clinical implications of these findings,” lead author Lorena Fernández de la Cruz, PhD, principal researcher at Karolinska Institute in Stockholm, told this news organization. She noted that some of the outcomes, such as preeclampsia, can be prevented or improved with collaboration among clinicians and increased monitoring.
The study was published online in JAMA Network Open.
Increased risk
OCD affects roughly 1%-3% of the population. Although it is sometimes seen as a mild psychiatric disorder, OCD entails a range of adverse outcomes, and this research suggests that the adverse outcomes extend to maternal health, Dr. Fernández de la Cruz stressed.
The researchers drew data from population registers in Sweden and British Columbia for all singleton births over a roughly 20-year period ending in 2019, with subcohorts identified by formal OCD diagnosis and exposure to SRIs within 30 days before conception. Statistical analyses were performed on a range of pregnancy, delivery, and neonatal outcomes.
In an analysis adjusted for common risk factors such as age, BMI, and smoking, Swedish women with OCD had elevated risk for several adverse outcomes, including a 40% increased risk for gestational diabetes. In British Columbia, fewer adverse pregnancy outcomes for women were associated with an OCD diagnosis.
The study, which also tracked neonatal outcomes, found that infants of mothers with OCD in both Sweden and British Columbia had higher rates of preterm birth (Sweden: aRR, 1.33; BC: aRR, 1.58), low birth weight (Sweden: aRR, 1.28; BC: aRR, 1.40), and neonatal respiratory distress (Sweden: aRR, 1.63; BC: aRR, 1.47).
These results, the authors say, show a need for more monitoring of maternal OCD and collaboration among obstetricians and psychologists. “All this evidence shows that OCD should be detected and treated so that adverse outcomes can be prevented or properly handled,” said Dr. Fernández de la Cruz.
SRI medication
SRIs are frequently used to treat OCD. The subclass of selective SRIs, which includes common antidepressants, has been associated with worsened pregnancy outcomes, but it remains unclear whether all SRIs increase pregnancy risks.
To understand the role of SRIs better in this study, the authors compared the outcomes for women taking SRIs and those who were not prescribed the medication, which is a novel aspect of the study, according to Dr. Fernández de la Cruz. Women who took the medication were at greater risk for several adverse outcomes, although all women with an OCD diagnosis were at higher risk than were those without the condition. The investigators hope to continue studying the role of OCD medication during pregnancy in more detail.
The rates of SRI use varied between the two cohorts: 81% of Canadian patients took the medication, compared with 37% of Swedish patients. The disparate rates, along with other clinical practices, may have contributed to differences in outcomes for the two cohorts.
It is also important to bear in mind, however, that patients taking the medication tend to have more severe cases of OCD, said Dr. Fernández de la Cruz. Thus, the increased risk may or may not result from the medication itself. “It is important to understand that there may be other variables besides medication explaining why one group had higher risks than the other,” she said.
‘Multifactorial’ reasons
In addition to medication, other factors may play a role in the association between OCD and adverse pregnancy and neonatal outcomes, including genetics, lifestyle, and psychiatric comorbidities. The authors addressed some of these potential confounders in additional analyses, including sister and cousin comparisons in the Swedish arm of the study, which found weakened associations, compared with population wide statistics.
Commenting on the research, Benicio Frey, PhD, professor of psychiatry and behavioral neurosciences at McMaster University in Hamilton, Ont., said that acknowledging these confounding factors is a strength of the study. Psychiatric conditions such as depression and anxiety are common among patients with OCD. Of the patients with OCD in this study, 72% and 51% had other psychiatric diagnoses in Sweden and British Columbia, respectively. About 7% of the women without OCD had one of these conditions.
However, Dr. Frey said that the effect of adjusting for psychiatric comorbidities on some outcomes should be stated more clearly. “I see a clear difference,” he said. The relative risk for gestational diabetes among the Swedish cohort, for example, drops from a 40% increased risk to 19% increased when adjusted for mood and anxiety disorders.
Regardless of the cause, the results are important and demonstrate a need to provide additional care for pregnant women with psychiatric conditions, said Dr. Frey. “The important take-home message for policymakers and health care providers is to make sure that they assess for OCD and then monitor those individuals very closely. What I would suggest as a caution is that the reasons behind it are multifactorial.”
The study was supported by the Swedish Research Council for Health, Working Life, and Welfare and by the Canadian Institute of Health Research. Dr. Fernández de la Cruz and Dr. Frey reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In an observational study that followed almost 3 million pregnancies in two countries over 20 years, children of women with OCD were at increased risk for low Apgar score at 5 minutes in Sweden (adjusted risk ratio [aRR], 1.62) and British Columbia, Canada (aRR, 2.30). The risks for adverse outcomes were greater among women with OCD who were taking serotonin reuptake inhibitors (SRIs), compared with those who were not.
“To me, the most relevant things to consider are the clinical implications of these findings,” lead author Lorena Fernández de la Cruz, PhD, principal researcher at Karolinska Institute in Stockholm, told this news organization. She noted that some of the outcomes, such as preeclampsia, can be prevented or improved with collaboration among clinicians and increased monitoring.
The study was published online in JAMA Network Open.
Increased risk
OCD affects roughly 1%-3% of the population. Although it is sometimes seen as a mild psychiatric disorder, OCD entails a range of adverse outcomes, and this research suggests that the adverse outcomes extend to maternal health, Dr. Fernández de la Cruz stressed.
The researchers drew data from population registers in Sweden and British Columbia for all singleton births over a roughly 20-year period ending in 2019, with subcohorts identified by formal OCD diagnosis and exposure to SRIs within 30 days before conception. Statistical analyses were performed on a range of pregnancy, delivery, and neonatal outcomes.
In an analysis adjusted for common risk factors such as age, BMI, and smoking, Swedish women with OCD had elevated risk for several adverse outcomes, including a 40% increased risk for gestational diabetes. In British Columbia, fewer adverse pregnancy outcomes for women were associated with an OCD diagnosis.
The study, which also tracked neonatal outcomes, found that infants of mothers with OCD in both Sweden and British Columbia had higher rates of preterm birth (Sweden: aRR, 1.33; BC: aRR, 1.58), low birth weight (Sweden: aRR, 1.28; BC: aRR, 1.40), and neonatal respiratory distress (Sweden: aRR, 1.63; BC: aRR, 1.47).
These results, the authors say, show a need for more monitoring of maternal OCD and collaboration among obstetricians and psychologists. “All this evidence shows that OCD should be detected and treated so that adverse outcomes can be prevented or properly handled,” said Dr. Fernández de la Cruz.
SRI medication
SRIs are frequently used to treat OCD. The subclass of selective SRIs, which includes common antidepressants, has been associated with worsened pregnancy outcomes, but it remains unclear whether all SRIs increase pregnancy risks.
To understand the role of SRIs better in this study, the authors compared the outcomes for women taking SRIs and those who were not prescribed the medication, which is a novel aspect of the study, according to Dr. Fernández de la Cruz. Women who took the medication were at greater risk for several adverse outcomes, although all women with an OCD diagnosis were at higher risk than were those without the condition. The investigators hope to continue studying the role of OCD medication during pregnancy in more detail.
The rates of SRI use varied between the two cohorts: 81% of Canadian patients took the medication, compared with 37% of Swedish patients. The disparate rates, along with other clinical practices, may have contributed to differences in outcomes for the two cohorts.
It is also important to bear in mind, however, that patients taking the medication tend to have more severe cases of OCD, said Dr. Fernández de la Cruz. Thus, the increased risk may or may not result from the medication itself. “It is important to understand that there may be other variables besides medication explaining why one group had higher risks than the other,” she said.
‘Multifactorial’ reasons
In addition to medication, other factors may play a role in the association between OCD and adverse pregnancy and neonatal outcomes, including genetics, lifestyle, and psychiatric comorbidities. The authors addressed some of these potential confounders in additional analyses, including sister and cousin comparisons in the Swedish arm of the study, which found weakened associations, compared with population wide statistics.
Commenting on the research, Benicio Frey, PhD, professor of psychiatry and behavioral neurosciences at McMaster University in Hamilton, Ont., said that acknowledging these confounding factors is a strength of the study. Psychiatric conditions such as depression and anxiety are common among patients with OCD. Of the patients with OCD in this study, 72% and 51% had other psychiatric diagnoses in Sweden and British Columbia, respectively. About 7% of the women without OCD had one of these conditions.
However, Dr. Frey said that the effect of adjusting for psychiatric comorbidities on some outcomes should be stated more clearly. “I see a clear difference,” he said. The relative risk for gestational diabetes among the Swedish cohort, for example, drops from a 40% increased risk to 19% increased when adjusted for mood and anxiety disorders.
Regardless of the cause, the results are important and demonstrate a need to provide additional care for pregnant women with psychiatric conditions, said Dr. Frey. “The important take-home message for policymakers and health care providers is to make sure that they assess for OCD and then monitor those individuals very closely. What I would suggest as a caution is that the reasons behind it are multifactorial.”
The study was supported by the Swedish Research Council for Health, Working Life, and Welfare and by the Canadian Institute of Health Research. Dr. Fernández de la Cruz and Dr. Frey reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In an observational study that followed almost 3 million pregnancies in two countries over 20 years, children of women with OCD were at increased risk for low Apgar score at 5 minutes in Sweden (adjusted risk ratio [aRR], 1.62) and British Columbia, Canada (aRR, 2.30). The risks for adverse outcomes were greater among women with OCD who were taking serotonin reuptake inhibitors (SRIs), compared with those who were not.
“To me, the most relevant things to consider are the clinical implications of these findings,” lead author Lorena Fernández de la Cruz, PhD, principal researcher at Karolinska Institute in Stockholm, told this news organization. She noted that some of the outcomes, such as preeclampsia, can be prevented or improved with collaboration among clinicians and increased monitoring.
The study was published online in JAMA Network Open.
Increased risk
OCD affects roughly 1%-3% of the population. Although it is sometimes seen as a mild psychiatric disorder, OCD entails a range of adverse outcomes, and this research suggests that the adverse outcomes extend to maternal health, Dr. Fernández de la Cruz stressed.
The researchers drew data from population registers in Sweden and British Columbia for all singleton births over a roughly 20-year period ending in 2019, with subcohorts identified by formal OCD diagnosis and exposure to SRIs within 30 days before conception. Statistical analyses were performed on a range of pregnancy, delivery, and neonatal outcomes.
In an analysis adjusted for common risk factors such as age, BMI, and smoking, Swedish women with OCD had elevated risk for several adverse outcomes, including a 40% increased risk for gestational diabetes. In British Columbia, fewer adverse pregnancy outcomes for women were associated with an OCD diagnosis.
The study, which also tracked neonatal outcomes, found that infants of mothers with OCD in both Sweden and British Columbia had higher rates of preterm birth (Sweden: aRR, 1.33; BC: aRR, 1.58), low birth weight (Sweden: aRR, 1.28; BC: aRR, 1.40), and neonatal respiratory distress (Sweden: aRR, 1.63; BC: aRR, 1.47).
These results, the authors say, show a need for more monitoring of maternal OCD and collaboration among obstetricians and psychologists. “All this evidence shows that OCD should be detected and treated so that adverse outcomes can be prevented or properly handled,” said Dr. Fernández de la Cruz.
SRI medication
SRIs are frequently used to treat OCD. The subclass of selective SRIs, which includes common antidepressants, has been associated with worsened pregnancy outcomes, but it remains unclear whether all SRIs increase pregnancy risks.
To understand the role of SRIs better in this study, the authors compared the outcomes for women taking SRIs and those who were not prescribed the medication, which is a novel aspect of the study, according to Dr. Fernández de la Cruz. Women who took the medication were at greater risk for several adverse outcomes, although all women with an OCD diagnosis were at higher risk than were those without the condition. The investigators hope to continue studying the role of OCD medication during pregnancy in more detail.
The rates of SRI use varied between the two cohorts: 81% of Canadian patients took the medication, compared with 37% of Swedish patients. The disparate rates, along with other clinical practices, may have contributed to differences in outcomes for the two cohorts.
It is also important to bear in mind, however, that patients taking the medication tend to have more severe cases of OCD, said Dr. Fernández de la Cruz. Thus, the increased risk may or may not result from the medication itself. “It is important to understand that there may be other variables besides medication explaining why one group had higher risks than the other,” she said.
‘Multifactorial’ reasons
In addition to medication, other factors may play a role in the association between OCD and adverse pregnancy and neonatal outcomes, including genetics, lifestyle, and psychiatric comorbidities. The authors addressed some of these potential confounders in additional analyses, including sister and cousin comparisons in the Swedish arm of the study, which found weakened associations, compared with population wide statistics.
Commenting on the research, Benicio Frey, PhD, professor of psychiatry and behavioral neurosciences at McMaster University in Hamilton, Ont., said that acknowledging these confounding factors is a strength of the study. Psychiatric conditions such as depression and anxiety are common among patients with OCD. Of the patients with OCD in this study, 72% and 51% had other psychiatric diagnoses in Sweden and British Columbia, respectively. About 7% of the women without OCD had one of these conditions.
However, Dr. Frey said that the effect of adjusting for psychiatric comorbidities on some outcomes should be stated more clearly. “I see a clear difference,” he said. The relative risk for gestational diabetes among the Swedish cohort, for example, drops from a 40% increased risk to 19% increased when adjusted for mood and anxiety disorders.
Regardless of the cause, the results are important and demonstrate a need to provide additional care for pregnant women with psychiatric conditions, said Dr. Frey. “The important take-home message for policymakers and health care providers is to make sure that they assess for OCD and then monitor those individuals very closely. What I would suggest as a caution is that the reasons behind it are multifactorial.”
The study was supported by the Swedish Research Council for Health, Working Life, and Welfare and by the Canadian Institute of Health Research. Dr. Fernández de la Cruz and Dr. Frey reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Peripartum cardiomyopathy raises risks at future pregnancy despite LV recovery
, a new study suggests.
Researchers looked at the long-term outcomes in a cohort of women who had developed PPCM and became pregnant again several years later, comparing those with LV function that had “normalized” in the interim against those with persisting LV dysfunction.
In their analysis, adverse maternal outcomes 5 years after an index pregnancy were significantly worse among those in whom LV dysfunction had persisted, compared with those with recovered LV function. The risk of relapsed PPCM persisted out to 8 years. Mortality remained high in both groups through the follow-up.
The study suggests that “women with PPCM need long-term follow-up by cardiology, as mortality does not abate over time,” Kalgi Modi, MD, Louisiana State University, Shreveport, said in an interview.
Women with a history of PPCM, she said, need “multidisciplinary and shared decision-making for family planning, because normalization of left ventricular function after index pregnancy does not guarantee a favorable outcome in the subsequent pregnancies.”
Dr. Modi is senior author on the study published online in the Journal of the American College of Cardiology.
The current findings are important to women with a history of PPCM who are “contemplating future pregnancy,” Afshan Hameed, MD, a maternal-fetal medicine specialist and cardiologist at the University of California, Irvine, said in an interview. The investigators suggest that “complete recovery of cardiac function after PPCM does not guarantee a favorable outcome in future pregnancy,” agreed Dr. Hameed, who was not involved in the current study. Future pregnancies must therefore “be highly discouraged or considered with caution even in patients who have recovered their cardiac function.”
To investigate the impact of PPCM on risk at subsequent pregnancies, the researchers studied 45 patients with PPCM who had gone on to have at least one more pregnancy, the first a median of 28 months later. Their mean age was 27 and 80% were Black; they were followed a median of 8 years.
Peripartum cardiomyopathy, defined as idiopathic heart failure with LV ejection fraction (LVEF) 45% or less in the last month of pregnancy through the following 5 months, was diagnosed post partum in 93.3% and antepartum in the remaining 6.7% (mean time of diagnosis, 6 weeks post partum).
The mean LVEF fell from 45.1% at the index pregnancy to 41.2% (P = .009) at subsequent pregnancies. The “recovery group” included the 30 women with LVEF recovery to 50% or higher after the index pregnancy, and the remaining 15 with persisting LV dysfunction – defined as LVEF < 50% – made up the “nonrecovery group.”
Recovery of LVEF was associated with a reduced risk of persisting LV dysfunction, the report states, at a hazard ratio of 0.08 (95% CI, 0.01-0.64; P = .02) after adjustment for hypertension, diabetes, and history of preeclampsia. But that risk went up sharply in association with illicit drug use, similarly adjusted, with an HR of 9.08 (95% CI, 1.38-59.8; P = .02).
The nonrecovery group, compared with the recovery group, experienced significantly higher rates of adverse maternal outcomes (53.3% vs. 20.0%; P = .04) – a composite endpoint that included relapse PPCM (33.3% vs. 3.3%; P = .01), HF (53.3% vs. 20.0%; P = .03), cardiogenic shock, thromboembolic events, and death – at 5 years. However, all-cause mortality was nonsignificantly different between the two groups (13.3% vs. 3.3%; P = .25)
All-cause mortality was nonsignificantly different between the two groups at a median of 8 years (20.0% vs. 20.0%; P = 1.00), and the difference in overall adverse maternal outcomes had gone from significant to nonsignificant (53.3% vs. 33.3%; P = .20). The difference in relapse PPCM between groups remained significant after 8 years (53.3% vs. 23.3%; P = .04)
The study is limited by its retrospective nature, a relatively small population, and lack of racial diversity, the report notes.
Indeed, most of the study’s subjects were Black, and previous studies have demonstrated a “different phenotypic presentation and outcome in African American women with PPCM, compared with non–African American women,” an accompanying editorial states.
Therefore, applicability of its findings to other populations “needs to be examined by urgently needed national prospective registries with long-term follow-up,” writes Uri Elkayam, MD, University of Southern California, Los Angeles.
Moreover, the study questions “whether the reverse remodeling and improvement of [LVEF] in women with PPCM represent a true recovery.” Prior studies “have shown an impaired contractile reserve as well as abnormal myocardial strain and reduced exercise capacity and even mortality in women with PPCM after RLV,” Dr. Elkayam notes.
It’s therefore possible – as with other forms of dilated cardiomyopathy – that LVEF normalization “does not represent a true recovery but a new steady state with subclinical myocardial dysfunction that is prone to development of recurrent [LV dysfunction] and clinical deterioration in response to various triggers such as long-standing hypertension, obesity, diabetes, illicit drug use,” and, “more importantly,” subsequent pregnancies.
The study points to “the need for a close long-term follow-up of women with PPCM” and provides “a rationale for early initiation of guideline-directed medical therapy after the diagnosis of PPCM and possible continuation even after improvement of LVEF.”
No funding source was reported. Dr. Modi and coauthors, Dr. Elkayam, and Dr. Hameed declare no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a new study suggests.
Researchers looked at the long-term outcomes in a cohort of women who had developed PPCM and became pregnant again several years later, comparing those with LV function that had “normalized” in the interim against those with persisting LV dysfunction.
In their analysis, adverse maternal outcomes 5 years after an index pregnancy were significantly worse among those in whom LV dysfunction had persisted, compared with those with recovered LV function. The risk of relapsed PPCM persisted out to 8 years. Mortality remained high in both groups through the follow-up.
The study suggests that “women with PPCM need long-term follow-up by cardiology, as mortality does not abate over time,” Kalgi Modi, MD, Louisiana State University, Shreveport, said in an interview.
Women with a history of PPCM, she said, need “multidisciplinary and shared decision-making for family planning, because normalization of left ventricular function after index pregnancy does not guarantee a favorable outcome in the subsequent pregnancies.”
Dr. Modi is senior author on the study published online in the Journal of the American College of Cardiology.
The current findings are important to women with a history of PPCM who are “contemplating future pregnancy,” Afshan Hameed, MD, a maternal-fetal medicine specialist and cardiologist at the University of California, Irvine, said in an interview. The investigators suggest that “complete recovery of cardiac function after PPCM does not guarantee a favorable outcome in future pregnancy,” agreed Dr. Hameed, who was not involved in the current study. Future pregnancies must therefore “be highly discouraged or considered with caution even in patients who have recovered their cardiac function.”
To investigate the impact of PPCM on risk at subsequent pregnancies, the researchers studied 45 patients with PPCM who had gone on to have at least one more pregnancy, the first a median of 28 months later. Their mean age was 27 and 80% were Black; they were followed a median of 8 years.
Peripartum cardiomyopathy, defined as idiopathic heart failure with LV ejection fraction (LVEF) 45% or less in the last month of pregnancy through the following 5 months, was diagnosed post partum in 93.3% and antepartum in the remaining 6.7% (mean time of diagnosis, 6 weeks post partum).
The mean LVEF fell from 45.1% at the index pregnancy to 41.2% (P = .009) at subsequent pregnancies. The “recovery group” included the 30 women with LVEF recovery to 50% or higher after the index pregnancy, and the remaining 15 with persisting LV dysfunction – defined as LVEF < 50% – made up the “nonrecovery group.”
Recovery of LVEF was associated with a reduced risk of persisting LV dysfunction, the report states, at a hazard ratio of 0.08 (95% CI, 0.01-0.64; P = .02) after adjustment for hypertension, diabetes, and history of preeclampsia. But that risk went up sharply in association with illicit drug use, similarly adjusted, with an HR of 9.08 (95% CI, 1.38-59.8; P = .02).
The nonrecovery group, compared with the recovery group, experienced significantly higher rates of adverse maternal outcomes (53.3% vs. 20.0%; P = .04) – a composite endpoint that included relapse PPCM (33.3% vs. 3.3%; P = .01), HF (53.3% vs. 20.0%; P = .03), cardiogenic shock, thromboembolic events, and death – at 5 years. However, all-cause mortality was nonsignificantly different between the two groups (13.3% vs. 3.3%; P = .25)
All-cause mortality was nonsignificantly different between the two groups at a median of 8 years (20.0% vs. 20.0%; P = 1.00), and the difference in overall adverse maternal outcomes had gone from significant to nonsignificant (53.3% vs. 33.3%; P = .20). The difference in relapse PPCM between groups remained significant after 8 years (53.3% vs. 23.3%; P = .04)
The study is limited by its retrospective nature, a relatively small population, and lack of racial diversity, the report notes.
Indeed, most of the study’s subjects were Black, and previous studies have demonstrated a “different phenotypic presentation and outcome in African American women with PPCM, compared with non–African American women,” an accompanying editorial states.
Therefore, applicability of its findings to other populations “needs to be examined by urgently needed national prospective registries with long-term follow-up,” writes Uri Elkayam, MD, University of Southern California, Los Angeles.
Moreover, the study questions “whether the reverse remodeling and improvement of [LVEF] in women with PPCM represent a true recovery.” Prior studies “have shown an impaired contractile reserve as well as abnormal myocardial strain and reduced exercise capacity and even mortality in women with PPCM after RLV,” Dr. Elkayam notes.
It’s therefore possible – as with other forms of dilated cardiomyopathy – that LVEF normalization “does not represent a true recovery but a new steady state with subclinical myocardial dysfunction that is prone to development of recurrent [LV dysfunction] and clinical deterioration in response to various triggers such as long-standing hypertension, obesity, diabetes, illicit drug use,” and, “more importantly,” subsequent pregnancies.
The study points to “the need for a close long-term follow-up of women with PPCM” and provides “a rationale for early initiation of guideline-directed medical therapy after the diagnosis of PPCM and possible continuation even after improvement of LVEF.”
No funding source was reported. Dr. Modi and coauthors, Dr. Elkayam, and Dr. Hameed declare no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a new study suggests.
Researchers looked at the long-term outcomes in a cohort of women who had developed PPCM and became pregnant again several years later, comparing those with LV function that had “normalized” in the interim against those with persisting LV dysfunction.
In their analysis, adverse maternal outcomes 5 years after an index pregnancy were significantly worse among those in whom LV dysfunction had persisted, compared with those with recovered LV function. The risk of relapsed PPCM persisted out to 8 years. Mortality remained high in both groups through the follow-up.
The study suggests that “women with PPCM need long-term follow-up by cardiology, as mortality does not abate over time,” Kalgi Modi, MD, Louisiana State University, Shreveport, said in an interview.
Women with a history of PPCM, she said, need “multidisciplinary and shared decision-making for family planning, because normalization of left ventricular function after index pregnancy does not guarantee a favorable outcome in the subsequent pregnancies.”
Dr. Modi is senior author on the study published online in the Journal of the American College of Cardiology.
The current findings are important to women with a history of PPCM who are “contemplating future pregnancy,” Afshan Hameed, MD, a maternal-fetal medicine specialist and cardiologist at the University of California, Irvine, said in an interview. The investigators suggest that “complete recovery of cardiac function after PPCM does not guarantee a favorable outcome in future pregnancy,” agreed Dr. Hameed, who was not involved in the current study. Future pregnancies must therefore “be highly discouraged or considered with caution even in patients who have recovered their cardiac function.”
To investigate the impact of PPCM on risk at subsequent pregnancies, the researchers studied 45 patients with PPCM who had gone on to have at least one more pregnancy, the first a median of 28 months later. Their mean age was 27 and 80% were Black; they were followed a median of 8 years.
Peripartum cardiomyopathy, defined as idiopathic heart failure with LV ejection fraction (LVEF) 45% or less in the last month of pregnancy through the following 5 months, was diagnosed post partum in 93.3% and antepartum in the remaining 6.7% (mean time of diagnosis, 6 weeks post partum).
The mean LVEF fell from 45.1% at the index pregnancy to 41.2% (P = .009) at subsequent pregnancies. The “recovery group” included the 30 women with LVEF recovery to 50% or higher after the index pregnancy, and the remaining 15 with persisting LV dysfunction – defined as LVEF < 50% – made up the “nonrecovery group.”
Recovery of LVEF was associated with a reduced risk of persisting LV dysfunction, the report states, at a hazard ratio of 0.08 (95% CI, 0.01-0.64; P = .02) after adjustment for hypertension, diabetes, and history of preeclampsia. But that risk went up sharply in association with illicit drug use, similarly adjusted, with an HR of 9.08 (95% CI, 1.38-59.8; P = .02).
The nonrecovery group, compared with the recovery group, experienced significantly higher rates of adverse maternal outcomes (53.3% vs. 20.0%; P = .04) – a composite endpoint that included relapse PPCM (33.3% vs. 3.3%; P = .01), HF (53.3% vs. 20.0%; P = .03), cardiogenic shock, thromboembolic events, and death – at 5 years. However, all-cause mortality was nonsignificantly different between the two groups (13.3% vs. 3.3%; P = .25)
All-cause mortality was nonsignificantly different between the two groups at a median of 8 years (20.0% vs. 20.0%; P = 1.00), and the difference in overall adverse maternal outcomes had gone from significant to nonsignificant (53.3% vs. 33.3%; P = .20). The difference in relapse PPCM between groups remained significant after 8 years (53.3% vs. 23.3%; P = .04)
The study is limited by its retrospective nature, a relatively small population, and lack of racial diversity, the report notes.
Indeed, most of the study’s subjects were Black, and previous studies have demonstrated a “different phenotypic presentation and outcome in African American women with PPCM, compared with non–African American women,” an accompanying editorial states.
Therefore, applicability of its findings to other populations “needs to be examined by urgently needed national prospective registries with long-term follow-up,” writes Uri Elkayam, MD, University of Southern California, Los Angeles.
Moreover, the study questions “whether the reverse remodeling and improvement of [LVEF] in women with PPCM represent a true recovery.” Prior studies “have shown an impaired contractile reserve as well as abnormal myocardial strain and reduced exercise capacity and even mortality in women with PPCM after RLV,” Dr. Elkayam notes.
It’s therefore possible – as with other forms of dilated cardiomyopathy – that LVEF normalization “does not represent a true recovery but a new steady state with subclinical myocardial dysfunction that is prone to development of recurrent [LV dysfunction] and clinical deterioration in response to various triggers such as long-standing hypertension, obesity, diabetes, illicit drug use,” and, “more importantly,” subsequent pregnancies.
The study points to “the need for a close long-term follow-up of women with PPCM” and provides “a rationale for early initiation of guideline-directed medical therapy after the diagnosis of PPCM and possible continuation even after improvement of LVEF.”
No funding source was reported. Dr. Modi and coauthors, Dr. Elkayam, and Dr. Hameed declare no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
‘Artificial pancreas’ for all type 1 diabetes pregnancies?
In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.
Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.
The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.
CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”
The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.
Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”
However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
Two experts weigh in
Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.
“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.
“If a woman is on an AID system – except for DIY loop – I have them stop the automation and adjust manually,” she said in an email. “My [patients] do amazingly well in pregnancy – most can get their A1cs below 6%,” she noted. “But if someone can’t do that and their A1cs are higher, automation can help.
“It is always about individualizing care,” said Dr. Peters. “The one thing that helps the most is continuous glucose monitoring (CGM). And I do have patients who remain on [insulin] injections throughout pregnancy.”
And Sarit Polsky, MD, MPH, who was also not involved with the current study, agrees that “AID with CamAPS, which has an option to customize the glucose target in the pregnancy-specific range, appears to be safe and effective in pregnancy and should be offered” to patients in Europe and the United Kingdom.
“Whether other AID systems should be recommended in pregnancy is still unclear, said Dr. Polsky, associate professor of medicine and pediatrics at Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus.
“Around 48% of [global] pregnancies are unplanned,” Dr. Polsky said in an interview. “Many women do indeed become pregnant while using AID systems and many opt to continue use of these systems.
“Off-label use of these products can be beneficial in pregnancy in select cases, but the systems generally need the use of assistive techniques, which we previously published, to help get glucose levels to pregnancy-specific targets,” she noted in an email.
Study rationale, method, and findings
Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.
“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.
Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin.
As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.
Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.
They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.
A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).
Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.
The effect was consistent across clinical sites and maternal age and A1c categories.
Ongoing studies, off-label use
Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”
There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.
The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.
“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.
“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.
The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.
A version of this article first appeared on Medscape.com.
In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.
Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.
The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.
CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”
The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.
Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”
However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
Two experts weigh in
Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.
“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.
“If a woman is on an AID system – except for DIY loop – I have them stop the automation and adjust manually,” she said in an email. “My [patients] do amazingly well in pregnancy – most can get their A1cs below 6%,” she noted. “But if someone can’t do that and their A1cs are higher, automation can help.
“It is always about individualizing care,” said Dr. Peters. “The one thing that helps the most is continuous glucose monitoring (CGM). And I do have patients who remain on [insulin] injections throughout pregnancy.”
And Sarit Polsky, MD, MPH, who was also not involved with the current study, agrees that “AID with CamAPS, which has an option to customize the glucose target in the pregnancy-specific range, appears to be safe and effective in pregnancy and should be offered” to patients in Europe and the United Kingdom.
“Whether other AID systems should be recommended in pregnancy is still unclear, said Dr. Polsky, associate professor of medicine and pediatrics at Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus.
“Around 48% of [global] pregnancies are unplanned,” Dr. Polsky said in an interview. “Many women do indeed become pregnant while using AID systems and many opt to continue use of these systems.
“Off-label use of these products can be beneficial in pregnancy in select cases, but the systems generally need the use of assistive techniques, which we previously published, to help get glucose levels to pregnancy-specific targets,” she noted in an email.
Study rationale, method, and findings
Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.
“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.
Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin.
As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.
Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.
They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.
A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).
Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.
The effect was consistent across clinical sites and maternal age and A1c categories.
Ongoing studies, off-label use
Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”
There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.
The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.
“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.
“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.
The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.
A version of this article first appeared on Medscape.com.
In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.
Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.
The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.
CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”
The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.
Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”
However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
Two experts weigh in
Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.
“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.
“If a woman is on an AID system – except for DIY loop – I have them stop the automation and adjust manually,” she said in an email. “My [patients] do amazingly well in pregnancy – most can get their A1cs below 6%,” she noted. “But if someone can’t do that and their A1cs are higher, automation can help.
“It is always about individualizing care,” said Dr. Peters. “The one thing that helps the most is continuous glucose monitoring (CGM). And I do have patients who remain on [insulin] injections throughout pregnancy.”
And Sarit Polsky, MD, MPH, who was also not involved with the current study, agrees that “AID with CamAPS, which has an option to customize the glucose target in the pregnancy-specific range, appears to be safe and effective in pregnancy and should be offered” to patients in Europe and the United Kingdom.
“Whether other AID systems should be recommended in pregnancy is still unclear, said Dr. Polsky, associate professor of medicine and pediatrics at Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus.
“Around 48% of [global] pregnancies are unplanned,” Dr. Polsky said in an interview. “Many women do indeed become pregnant while using AID systems and many opt to continue use of these systems.
“Off-label use of these products can be beneficial in pregnancy in select cases, but the systems generally need the use of assistive techniques, which we previously published, to help get glucose levels to pregnancy-specific targets,” she noted in an email.
Study rationale, method, and findings
Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.
“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.
Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin.
As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.
Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.
They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.
A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).
Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.
The effect was consistent across clinical sites and maternal age and A1c categories.
Ongoing studies, off-label use
Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”
There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.
The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.
“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.
“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.
The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.
A version of this article first appeared on Medscape.com.
FROM ADA 2023
Do oral contraceptives increase depression risk?
In addition, OC use in adolescence has been tied to an increased risk for depression later in life. However, some experts believe the study’s methodology may be flawed.
The investigators tracked more than 250,000 women from birth to menopause, gathering information about their use of combined contraceptive pills (progesterone and estrogen), the timing of the initial depression diagnosis, and the onset of depressive symptoms that were not formally diagnosed.
Women who began using these OCs before or at the age of 20 experienced a 130% higher incidence of depressive symptoms, whereas adult users saw a 92% increase. But the higher occurrence of depression tended to decline after the first 2 years of use, except in teenagers, who maintained an increased incidence of depression even after discontinuation.
This effect remained, even after analysis of potential familial confounding.
“Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life,” Therese Johansson, of the department of immunology, genetics, and pathology, Science for Life Laboratory, Uppsala (Sweden) University, and colleagues wrote.
The study was published online in Epidemiology and Psychiatric Sciences.
Inconsistent findings
Previous studies suggest an association between adolescent use of hormonal contraceptives (HCs) and increased depression risk, but it’s “less clear” whether these effects are similar in adults, the authors wrote. Randomized clinical trials have “shown little or no effect” of HCs on mood. However, most of these studies didn’t consider previous use of HC.
The researchers wanted to estimate the incidence rate of depression associated with first initiation of OC use as well as the lifetime risk associated with use.
They studied 264,557 female participants in the UK Biobank (aged 37-71 years), collecting data from questionnaires, interviews, physical health measures, biological samples, imaging, and linked health records.
Most participants taking OCs had initiated use during the 1970s/early 1980s when second-generation OCs were predominantly used, consisting of levonorgestrel and ethinyl estradiol.
The researchers conducted a secondary outcome analysis on women who completed the UK Biobank Mental Health Questionnaire (MHQ) to evaluate depressive symptoms.
They estimated the associated risk for depression within 2 years after starting OCs in all women, as well as in groups stratified by age at initiation: before age 20 (adolescents) and age 20 and older (adults). In addition, the investigators estimated the lifetime risk for depression.
Time-dependent analysis compared the effect of OC use at initiation to the effect during the remaining years of use in recent and previous users.
They analyzed a subcohort of female siblings, utilizing “inference about causation from examination of familial confounding,” defined by the authors as a “regression-based approach for determining causality through the use of paired observational data collected from related individuals.”
Adolescents at highest risk
Of the participants, 80.6% had used OCs at some point.
The first 2 years of use were associated with a higher rate of depression among users, compared with never-users (hazard ration, 1.79; 95% confidence interval, 1.63-1.96). Although the risk became less pronounced after that, ever-use was still associated with increased lifetime risk for depression (HR, 1.05; 95% CI, 1.01-1.09).
Adolescents and adult OC users both experienced higher rates of depression during the first 2 years, with a more marked effect in adolescents than in adults (HR, 1.95; 95% CI, 1.64-2.32; and HR, 1.74; 95% CI, 1.54-1.95, respectively).
Previous users of OCs had a higher lifetime risk for depression, compared with never-users (HR, 1.05; 95% CI, 1.01-1.09).
Of the subcohort of women who completed the MHQ (n = 82,232), about half reported experiencing at least one of the core depressive symptoms.
OC initiation was associated with an increased risk for depressive symptoms during the first 2 years in ever- versus never-users (HR, 2.00; 95% CI, 1.91-2.10).
Those who began using OCs during adolescence had a dramatically higher rate of depressive symptoms, compared with never-users (HR, 2.30; 95% CI, 2.11-2.51), as did adult initiators (HR, 1.92; 95% CI, 2.11-2.51).
In the analysis of 7,354 first-degree sister pairs, 81% had initiated OCs. A sibling’s OC use was positively associated with a depression diagnosis, and the cosibling’s OC use was also associated with the sibling’s depression diagnosis. “These results support the hypothesis of a causal relationship between OC use and depression, such that OC use increases the risk of depression,” the authors wrote.
The main limitation is the potential for recall bias in the self-reported data, and that the UK Biobank sample consists of a healthier population than the overall U.K. population, which “hampers the generalizability” of the findings, the authors stated.
Flawed study
In a comment, Natalie Rasgon, MD, founder and director of the Stanford (Calif.) Center for Neuroscience in Women’s Health, said the study was “well researched” and “well written” but had “methodological issues.”
She questioned the sibling component, “which the researchers regard as confirming causality.” The effect may be “important but not causative.” Causality in people who are recalling retrospectively “is highly questionable by any adept researcher because it’s subject to memory. Different siblings may have different recall.”
The authors also didn’t study the indication for OC use. Several medical conditions are treated with OCs, including premenstrual dysphoric disorder, the “number one mood disorder among women of reproductive age.” Including this “could have made a huge difference in outcome data,” said Dr. Rasgon, who was not involved with the study.
Anne-Marie Amies Oelschlager, MD, professor of obstetrics and gynecology, University of Washington, Seattle, noted participants were asked to recall depressive symptoms and OC use as far back as 20-30 years ago, which lends itself to inaccurate recall.
And the researchers didn’t ascertain whether the contraceptives had been used continuously or had been started, stopped, and restarted. Nor did they look at different formulations and doses. And the observational nature of the study “limits the ability to infer causation,” continued Dr. Oelschlager, chair of the American College of Obstetrics and Gynecology Clinical Consensus Gynecology Committee. She was not involved with the study.
“This study is too flawed to use meaningfully in clinical practice,” Dr. Oelschlager concluded.
The study was primarily funded by the Swedish Research Council, the Swedish Brain Foundation, and the Uppsala University Center for Women ‘s Mental Health during the Reproductive Lifespan. The authors, Dr. Rasgon, and Dr. Oelschlager declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In addition, OC use in adolescence has been tied to an increased risk for depression later in life. However, some experts believe the study’s methodology may be flawed.
The investigators tracked more than 250,000 women from birth to menopause, gathering information about their use of combined contraceptive pills (progesterone and estrogen), the timing of the initial depression diagnosis, and the onset of depressive symptoms that were not formally diagnosed.
Women who began using these OCs before or at the age of 20 experienced a 130% higher incidence of depressive symptoms, whereas adult users saw a 92% increase. But the higher occurrence of depression tended to decline after the first 2 years of use, except in teenagers, who maintained an increased incidence of depression even after discontinuation.
This effect remained, even after analysis of potential familial confounding.
“Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life,” Therese Johansson, of the department of immunology, genetics, and pathology, Science for Life Laboratory, Uppsala (Sweden) University, and colleagues wrote.
The study was published online in Epidemiology and Psychiatric Sciences.
Inconsistent findings
Previous studies suggest an association between adolescent use of hormonal contraceptives (HCs) and increased depression risk, but it’s “less clear” whether these effects are similar in adults, the authors wrote. Randomized clinical trials have “shown little or no effect” of HCs on mood. However, most of these studies didn’t consider previous use of HC.
The researchers wanted to estimate the incidence rate of depression associated with first initiation of OC use as well as the lifetime risk associated with use.
They studied 264,557 female participants in the UK Biobank (aged 37-71 years), collecting data from questionnaires, interviews, physical health measures, biological samples, imaging, and linked health records.
Most participants taking OCs had initiated use during the 1970s/early 1980s when second-generation OCs were predominantly used, consisting of levonorgestrel and ethinyl estradiol.
The researchers conducted a secondary outcome analysis on women who completed the UK Biobank Mental Health Questionnaire (MHQ) to evaluate depressive symptoms.
They estimated the associated risk for depression within 2 years after starting OCs in all women, as well as in groups stratified by age at initiation: before age 20 (adolescents) and age 20 and older (adults). In addition, the investigators estimated the lifetime risk for depression.
Time-dependent analysis compared the effect of OC use at initiation to the effect during the remaining years of use in recent and previous users.
They analyzed a subcohort of female siblings, utilizing “inference about causation from examination of familial confounding,” defined by the authors as a “regression-based approach for determining causality through the use of paired observational data collected from related individuals.”
Adolescents at highest risk
Of the participants, 80.6% had used OCs at some point.
The first 2 years of use were associated with a higher rate of depression among users, compared with never-users (hazard ration, 1.79; 95% confidence interval, 1.63-1.96). Although the risk became less pronounced after that, ever-use was still associated with increased lifetime risk for depression (HR, 1.05; 95% CI, 1.01-1.09).
Adolescents and adult OC users both experienced higher rates of depression during the first 2 years, with a more marked effect in adolescents than in adults (HR, 1.95; 95% CI, 1.64-2.32; and HR, 1.74; 95% CI, 1.54-1.95, respectively).
Previous users of OCs had a higher lifetime risk for depression, compared with never-users (HR, 1.05; 95% CI, 1.01-1.09).
Of the subcohort of women who completed the MHQ (n = 82,232), about half reported experiencing at least one of the core depressive symptoms.
OC initiation was associated with an increased risk for depressive symptoms during the first 2 years in ever- versus never-users (HR, 2.00; 95% CI, 1.91-2.10).
Those who began using OCs during adolescence had a dramatically higher rate of depressive symptoms, compared with never-users (HR, 2.30; 95% CI, 2.11-2.51), as did adult initiators (HR, 1.92; 95% CI, 2.11-2.51).
In the analysis of 7,354 first-degree sister pairs, 81% had initiated OCs. A sibling’s OC use was positively associated with a depression diagnosis, and the cosibling’s OC use was also associated with the sibling’s depression diagnosis. “These results support the hypothesis of a causal relationship between OC use and depression, such that OC use increases the risk of depression,” the authors wrote.
The main limitation is the potential for recall bias in the self-reported data, and that the UK Biobank sample consists of a healthier population than the overall U.K. population, which “hampers the generalizability” of the findings, the authors stated.
Flawed study
In a comment, Natalie Rasgon, MD, founder and director of the Stanford (Calif.) Center for Neuroscience in Women’s Health, said the study was “well researched” and “well written” but had “methodological issues.”
She questioned the sibling component, “which the researchers regard as confirming causality.” The effect may be “important but not causative.” Causality in people who are recalling retrospectively “is highly questionable by any adept researcher because it’s subject to memory. Different siblings may have different recall.”
The authors also didn’t study the indication for OC use. Several medical conditions are treated with OCs, including premenstrual dysphoric disorder, the “number one mood disorder among women of reproductive age.” Including this “could have made a huge difference in outcome data,” said Dr. Rasgon, who was not involved with the study.
Anne-Marie Amies Oelschlager, MD, professor of obstetrics and gynecology, University of Washington, Seattle, noted participants were asked to recall depressive symptoms and OC use as far back as 20-30 years ago, which lends itself to inaccurate recall.
And the researchers didn’t ascertain whether the contraceptives had been used continuously or had been started, stopped, and restarted. Nor did they look at different formulations and doses. And the observational nature of the study “limits the ability to infer causation,” continued Dr. Oelschlager, chair of the American College of Obstetrics and Gynecology Clinical Consensus Gynecology Committee. She was not involved with the study.
“This study is too flawed to use meaningfully in clinical practice,” Dr. Oelschlager concluded.
The study was primarily funded by the Swedish Research Council, the Swedish Brain Foundation, and the Uppsala University Center for Women ‘s Mental Health during the Reproductive Lifespan. The authors, Dr. Rasgon, and Dr. Oelschlager declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In addition, OC use in adolescence has been tied to an increased risk for depression later in life. However, some experts believe the study’s methodology may be flawed.
The investigators tracked more than 250,000 women from birth to menopause, gathering information about their use of combined contraceptive pills (progesterone and estrogen), the timing of the initial depression diagnosis, and the onset of depressive symptoms that were not formally diagnosed.
Women who began using these OCs before or at the age of 20 experienced a 130% higher incidence of depressive symptoms, whereas adult users saw a 92% increase. But the higher occurrence of depression tended to decline after the first 2 years of use, except in teenagers, who maintained an increased incidence of depression even after discontinuation.
This effect remained, even after analysis of potential familial confounding.
“Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life,” Therese Johansson, of the department of immunology, genetics, and pathology, Science for Life Laboratory, Uppsala (Sweden) University, and colleagues wrote.
The study was published online in Epidemiology and Psychiatric Sciences.
Inconsistent findings
Previous studies suggest an association between adolescent use of hormonal contraceptives (HCs) and increased depression risk, but it’s “less clear” whether these effects are similar in adults, the authors wrote. Randomized clinical trials have “shown little or no effect” of HCs on mood. However, most of these studies didn’t consider previous use of HC.
The researchers wanted to estimate the incidence rate of depression associated with first initiation of OC use as well as the lifetime risk associated with use.
They studied 264,557 female participants in the UK Biobank (aged 37-71 years), collecting data from questionnaires, interviews, physical health measures, biological samples, imaging, and linked health records.
Most participants taking OCs had initiated use during the 1970s/early 1980s when second-generation OCs were predominantly used, consisting of levonorgestrel and ethinyl estradiol.
The researchers conducted a secondary outcome analysis on women who completed the UK Biobank Mental Health Questionnaire (MHQ) to evaluate depressive symptoms.
They estimated the associated risk for depression within 2 years after starting OCs in all women, as well as in groups stratified by age at initiation: before age 20 (adolescents) and age 20 and older (adults). In addition, the investigators estimated the lifetime risk for depression.
Time-dependent analysis compared the effect of OC use at initiation to the effect during the remaining years of use in recent and previous users.
They analyzed a subcohort of female siblings, utilizing “inference about causation from examination of familial confounding,” defined by the authors as a “regression-based approach for determining causality through the use of paired observational data collected from related individuals.”
Adolescents at highest risk
Of the participants, 80.6% had used OCs at some point.
The first 2 years of use were associated with a higher rate of depression among users, compared with never-users (hazard ration, 1.79; 95% confidence interval, 1.63-1.96). Although the risk became less pronounced after that, ever-use was still associated with increased lifetime risk for depression (HR, 1.05; 95% CI, 1.01-1.09).
Adolescents and adult OC users both experienced higher rates of depression during the first 2 years, with a more marked effect in adolescents than in adults (HR, 1.95; 95% CI, 1.64-2.32; and HR, 1.74; 95% CI, 1.54-1.95, respectively).
Previous users of OCs had a higher lifetime risk for depression, compared with never-users (HR, 1.05; 95% CI, 1.01-1.09).
Of the subcohort of women who completed the MHQ (n = 82,232), about half reported experiencing at least one of the core depressive symptoms.
OC initiation was associated with an increased risk for depressive symptoms during the first 2 years in ever- versus never-users (HR, 2.00; 95% CI, 1.91-2.10).
Those who began using OCs during adolescence had a dramatically higher rate of depressive symptoms, compared with never-users (HR, 2.30; 95% CI, 2.11-2.51), as did adult initiators (HR, 1.92; 95% CI, 2.11-2.51).
In the analysis of 7,354 first-degree sister pairs, 81% had initiated OCs. A sibling’s OC use was positively associated with a depression diagnosis, and the cosibling’s OC use was also associated with the sibling’s depression diagnosis. “These results support the hypothesis of a causal relationship between OC use and depression, such that OC use increases the risk of depression,” the authors wrote.
The main limitation is the potential for recall bias in the self-reported data, and that the UK Biobank sample consists of a healthier population than the overall U.K. population, which “hampers the generalizability” of the findings, the authors stated.
Flawed study
In a comment, Natalie Rasgon, MD, founder and director of the Stanford (Calif.) Center for Neuroscience in Women’s Health, said the study was “well researched” and “well written” but had “methodological issues.”
She questioned the sibling component, “which the researchers regard as confirming causality.” The effect may be “important but not causative.” Causality in people who are recalling retrospectively “is highly questionable by any adept researcher because it’s subject to memory. Different siblings may have different recall.”
The authors also didn’t study the indication for OC use. Several medical conditions are treated with OCs, including premenstrual dysphoric disorder, the “number one mood disorder among women of reproductive age.” Including this “could have made a huge difference in outcome data,” said Dr. Rasgon, who was not involved with the study.
Anne-Marie Amies Oelschlager, MD, professor of obstetrics and gynecology, University of Washington, Seattle, noted participants were asked to recall depressive symptoms and OC use as far back as 20-30 years ago, which lends itself to inaccurate recall.
And the researchers didn’t ascertain whether the contraceptives had been used continuously or had been started, stopped, and restarted. Nor did they look at different formulations and doses. And the observational nature of the study “limits the ability to infer causation,” continued Dr. Oelschlager, chair of the American College of Obstetrics and Gynecology Clinical Consensus Gynecology Committee. She was not involved with the study.
“This study is too flawed to use meaningfully in clinical practice,” Dr. Oelschlager concluded.
The study was primarily funded by the Swedish Research Council, the Swedish Brain Foundation, and the Uppsala University Center for Women ‘s Mental Health during the Reproductive Lifespan. The authors, Dr. Rasgon, and Dr. Oelschlager declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM EPIDEMIOLOGY AND PSYCHIATRIC SCIENCES
New clues to an old mystery: Recent gains in endometriosis
In 1927, American gynecologist John Sampson published his theory of the etiology of endometriosis, postulating that retrograde flow of endometrial debris flows backward through the fallopian tubes during menses into the peritoneal cavity. Dr. Sampson’s notion remains the main paradigm today, mentioned still in recent articles on the topic, but it has a flaw: Although the theory may account for how endometrial tissue escapes the uterus, a 1984 study revealed that this phenomenon occurs in 90% of women. Why, then, do only 10% of women suffer from endometriosis?
Endometriosis describes a condition in which endometrial tissue lining the uterus is found outside the uterus. The disease can be painful, even crippling. As many as 30% of women in their reproductive years who have endometriosis are infertile as a consequence. The hallmarks of the condition are superficial peritoneal lesions of varying color, cysts in the ovaries, deeper nodules accompanied by scarring and adhesion, primarily in the pelvis but sometimes appearing outside the pelvis. The syndrome can be challenging to identify, requiring laparoscopy for definitive diagnosis.
John Sampson aside, scientists have struggled for the past century to identify the cause, or causes, of endometriosis. Hormones clearly play a role in its development, and women with endometriosis have an elevated risk of clear-cell and endometrioid ovarian cancer and autoimmune diseases. Immunodeficiency also could be to blame, if a faulty immune system fails to find and remove endometrial tissue outside of the uterus. A class of chemicals known as endocrine disruptors have been linked to endometriosis, but not definitively. Twin studies have demonstrated that as many as 50% of cases have a genetic basis, while mice with surgically induced endometriosis have been found to have a higher ratio of harmful to beneficial bacteria in their gut.
Several studies published this year point to new insights into the old mystery – with possible implications for ways to treat the disorder.
Perhaps the most surprising came out earlier this year in Science Translational Medicine, as a team of researchers in Japan reported that invasive infection by bacteria of the genus Fusobacterium may cause at least some cases of endometriosis.
Is Fusobacterium the new Helicobacter pylori?
The researchers, from Nagoya University, are the first to suggest that not only might a single bacterial genus cause endometriosis, but that antibiotic treatment could prevent progression of the disease. Using endometrial tissue obtained from 79 women undergoing hysterectomy for endometriosis and 76 women undergoing hysterectomy for other reasons (such as cervical cancer), the team started with gene expression profiling to explore differences between the two sets of samples.
They uncovered an interesting chain of cellular events: macrophages found in endometriotic lesions were secreting transforming growth factor-beta (TGF-beta). TGF-beta in turn stimulated high levels of expression of a gene called TAGLN in fibroblast cells from women with endometriosis but not in fibroblasts from women without endometriosis.
Turning on TAGLN transformed these previously inactive cells into active myofibroblasts, leading to increased proliferation, mobility, and attachment to mesothelial cells, the layer of cells that line body cavities and internal organs. In short, they identified some key players in an environment that seemed very favorable to the development of endometriosis.
“So, the question is: Why are macrophages activated?” said Yutaka Kondo, MD, PhD, the senior author of the study and a professor in the division of cancer biology at the Nagoya (Japan) University Graduate School of Medicine. “We think that there are always bacteria in the endometrium.”
After reviewing data from a previously published study, they used quantitative polymerase chain reaction to rule out one candidate, Erysipelothrix, but scored on their next attempt, identifying Fusobacterium species in endometrial tissue from 64% of the women with endometriosis, compared with fewer than 10% of the controls.
To confirm that the bacteria could cause disease and were not simply bystanders, Dr. Kondo’s team turned to a mouse model for endometriosis, in which endometrial cells are surgically removed from the uteri of mice and injected into the peritoneum of recipient mice, leading to the formation of endometriotic lesions. When mice received further injections of uterine tissue from mice that were infected with F. nucleatum, their lesions were more numerous when compared with mice that received injections of uninfected uterine tissue. Furthermore, antibiotic treatment with metronidazole or chloramphenicol immediately after surgery largely prevented progression to endometriosis, Dr. Kondo and his colleagues reported.
Dr. Kondo likened this relationship between Fusobacterium and endometriosis to that of the link between Helicobacter pylori and peptic ulcers but acknowledged that he doesn’t have all the answers.
“We need more clinical trials, and also we have to know what kind of treatment might be the most effective for the treatment of endometriosis,” Dr. Kondo said, pointing out that other therapies should still be pursued in addition to antibiotics, as not all the samples from women with endometriosis harbored Fusobacterium. “It might be possible that other mechanisms are also involved.”
Don’t write off gut microbiota
Ramakrishna Kommagani, PhD, associate professor of pathology and immunology at Baylor College of Medicine in Houston, agreed. “Endometriosis is a complex disease, which appears to be impacted by many factors, including genetic, epigenetic, and environmental factors,” Dr. Kommagani said.
A key difference between his work and Dr. Kondo’s is his focus on gut microbiota, whereas the Japanese team looked at bacteria in the vagina and endometrium. But Dr. Kommagani said he thinks both could play a role. “Maybe the vaginal microbiome might have a direct impact on disease similar to what we showed on the gut,” he said.
But he said at least part of the answer to why some women develop endometriosis may have to do more with the balance of beneficial and harmful bacteria in the gut rather than because of a single family of microbes like Fusobacterium.
Most recently, by dovetailing a mouse model for inducing endometriosis in mice treated with antibiotics to deplete their gut microbiome, Dr. Kommagani’s lab expanded on its previous work: They showed that the animals developed fewer of the typical lesions seen in endometriosis than those that did not receive antibiotics before all of the mice underwent the surgical procedure used by researchers to induce endometriosis – possibly because they had no bacteria in their gut triggering the inflammatory response required for the development of endometriosis.
But after oral feedings with fecal matter from mice without endometriosis, the microbiota-depleted rodents began developing lesions typical of endometriosis, suggesting that altered gut flora from mice with endometriosis appeared to promote the disorder. Meanwhile, their microbiota-depleted counterparts who were fed fecal matter from mice without endometriosis did not develop the typical lesions.
Dr. Kommagani’s team then compared metabolites from bacteria in stool from mice with and without endometriosis and investigated the in vitro effect of these metabolites on cells from human endometriotic lesions. One of them, quinic acid, increased the proliferation of human endometriotic epithelial cells.
“Some metabolites such as fiber-derived short-chain fatty acids have beneficial effects; they inhibit the disease,” Dr. Kommagani said. “But maybe an amino acid derivative such as quinic acid, [may] promote disease, and these are generated because there is a gut dysbiosis.”
This statement hints at some of the possible therapeutic approaches for endometriosis, such as a high-fiber diet to promote healthy gut flora, or perhaps antibiotics to eradicate unhealthy bacteria. But as with other conditions that have been linked to dysbiosis, like inflammatory bowel disease, use of antibiotics is a bit like balancing on a tightrope; although antibiotics may remove harmful bacteria, their use may negatively affect the beneficial bacteria.
Clues in genetic variants
Krina Zondervan, DPhil, professor and head of the department of reproductive and genomic epidemiology at the University of Oxford (England), focuses on genomic, molecular, and epidemiologic approaches to understanding endometriosis.
“It’s one thing identifying risk variants and the next question is, okay, well, what do those variants actually do in terms of biology?” Dr. Zondervan said. The Oxford team next explored how the identified genetic variants affect gene expression and the proteins generated, drawing on previously collected data on gene expression from samples of human blood and endometrial and uterine tissue.
They found many of the genes implicated in the risk for endometriosis code for proteins that affect sex hormones, uterine development, transformation of healthy cells into cancerous tissue, inflammatory adhesion molecules, and factors promoting development of new blood vessels. All of that, she said, explains how a few endometrial cells making their way into the pelvis can attach to ovaries, ligaments, and peritoneal surfaces; proliferate; and acquire a blood supply to ensure their survival.
“We were able to identify a whole host of things that were likely causal to the disease,” Dr. Zondervan said. And that finding led to her next question: “Are there particular genes or areas around them that can be targeted with certain medications?”
The surprising answer was that several of the genes linked to endometriosis share pathways with clinical syndromes that often occur in women with endometriosis. Many of these are chronic pain conditions – such as migraines, headaches, and back pain – but also include inflammatory illnesses such as asthma and osteoarthritis.
As Dr. Zondervan explained, “A lot of the variance that we see for endometriosis is also experienced for low back pain and migraine, and that clearly has something to do with pain perception and pain mechanisms.”
A connection between the development of neural pathways and endometriosis has been proposed before, as researchers have found that endometriotic lesions can develop their own nerve supply, creating a direct interaction between the lesions and the central nervous system. And some clinicians have been employing treatment strategies that employ multimodal therapies – employing physical therapists, mental health practitioners, nutritionists, and pain specialists prior to and following surgical removal of lesions – to improve overall success rates of treatment.
But Dr. Zondervan’s team is the first to uncover an important clue about how this happens.
The study findings also provide solid clues to researchers about which genes and proteins to focus on for drug target discovery. In particular, the gene pathways shared by endometriosis and various pain conditions could allow for repurposing of drugs developed for other conditions for treating endometriosis, reported Dr. Zondervan.
Dr. Zondervan’s other important conclusion, echoed by Dr. Kondo and Dr. Kommagani, is that endometriosis is not one disease. Rather, it appears to be akin to cancer in terms of the heterogeneity of how it presents and the different subtypes of diseases. The Oxford study corroborated this belief, identifying certain genes that were closely associated with cystic lesions in ovaries, but failing to turn up a genetic link to other types of lesions in the pelvis long considered to be part of the spectrum of endometriosis disease.
Dr. Zondervan agreed that the potential link with Fusobacterium is a fascinating area given the critical role of inflammation in the pathogenesis of endometriosis, although she’d like to see the work replicated with larger sample sizes. “From a personal point of view, I’d be really fascinated to see how genetics interplays with this,” she added.
What’s next?
The chief limitation of human studies looking at mechanisms of endometriosis is that they are correlational: Tissue samples are collected from women with and without endometriosis, often through an invasive procedure such as laparoscopy or biopsy, at one point in time. Currently, the best tools for proving causation are animal models of endometriosis, such as the those used by Dr. Kondo’s and Dr. Kommagani’s teams.
Better diagnostic tools would solve that problem. The ultimate goal is a noninvasive test for endometriosis that would allow clinicians to follow women over time and permit the monitoring of disease progression, or regression, without the need for painful procedures. Such a diagnostic tool would facilitate rigorous longitudinal studies evaluating mechanisms of disease, as well as monitoring outcomes of clinical trials of new treatments.
Could stool samples be the answer?
The Japanese team found that women harboring Fusobacterium in endometrial tissue also had Fusobacterium in vaginal samples taken at the time of their hysterectomy – and stool samples can pick up changes in the gut microbiome.
“Vaginal swab or stool tests are probably the best and easiest for noninvasive early detection,” Dr. Kommagani said.
Spit tests for DNA would be even easier to obtain. Polygenic risk scores could be developed to estimate an individual’s risk of disease based on the number of variants, but Dr. Zondervan cautioned that not all the genes that account for endometriosis are known.
“The things that we found altogether explain about 5% of disease variability, basically – which is still not an awful lot,” she said.
Dr. Kondo’s work was supported by the Grant-in-Aid for Scientific Research, the Japan Society for the Promotion of Science, and the Research Grant of the Princess Takamatsu Cancer Research Fund. A patent method for detecting bacteria of genus Fusobacterium in order to diagnose endometriosis (WO2023/ 042714), was submitted (international publication date, March 23, 2023).
Dr. Kommagani’s work was funded, in part, by National Institutes of Health/National Institute of Child Health and Human Development grants R01HD102680, R01HD065435, and R00HD080742. He has no other conflicts of interest. Dr. Zondervan received funding from the Wellcome Trust (216767; 104036; 084766; 212904; 076113 and 085475) and also reported grants from Bayer AG, AbbVie, Volition Rx, MDNA Life Sciences, and Roche Diagnostics outside the submitted work.
Dr. Thomas is a pediatrician and epidemiologist living in Portland, Ore.
A version of this article originally appeared on Medscape.com.
In 1927, American gynecologist John Sampson published his theory of the etiology of endometriosis, postulating that retrograde flow of endometrial debris flows backward through the fallopian tubes during menses into the peritoneal cavity. Dr. Sampson’s notion remains the main paradigm today, mentioned still in recent articles on the topic, but it has a flaw: Although the theory may account for how endometrial tissue escapes the uterus, a 1984 study revealed that this phenomenon occurs in 90% of women. Why, then, do only 10% of women suffer from endometriosis?
Endometriosis describes a condition in which endometrial tissue lining the uterus is found outside the uterus. The disease can be painful, even crippling. As many as 30% of women in their reproductive years who have endometriosis are infertile as a consequence. The hallmarks of the condition are superficial peritoneal lesions of varying color, cysts in the ovaries, deeper nodules accompanied by scarring and adhesion, primarily in the pelvis but sometimes appearing outside the pelvis. The syndrome can be challenging to identify, requiring laparoscopy for definitive diagnosis.
John Sampson aside, scientists have struggled for the past century to identify the cause, or causes, of endometriosis. Hormones clearly play a role in its development, and women with endometriosis have an elevated risk of clear-cell and endometrioid ovarian cancer and autoimmune diseases. Immunodeficiency also could be to blame, if a faulty immune system fails to find and remove endometrial tissue outside of the uterus. A class of chemicals known as endocrine disruptors have been linked to endometriosis, but not definitively. Twin studies have demonstrated that as many as 50% of cases have a genetic basis, while mice with surgically induced endometriosis have been found to have a higher ratio of harmful to beneficial bacteria in their gut.
Several studies published this year point to new insights into the old mystery – with possible implications for ways to treat the disorder.
Perhaps the most surprising came out earlier this year in Science Translational Medicine, as a team of researchers in Japan reported that invasive infection by bacteria of the genus Fusobacterium may cause at least some cases of endometriosis.
Is Fusobacterium the new Helicobacter pylori?
The researchers, from Nagoya University, are the first to suggest that not only might a single bacterial genus cause endometriosis, but that antibiotic treatment could prevent progression of the disease. Using endometrial tissue obtained from 79 women undergoing hysterectomy for endometriosis and 76 women undergoing hysterectomy for other reasons (such as cervical cancer), the team started with gene expression profiling to explore differences between the two sets of samples.
They uncovered an interesting chain of cellular events: macrophages found in endometriotic lesions were secreting transforming growth factor-beta (TGF-beta). TGF-beta in turn stimulated high levels of expression of a gene called TAGLN in fibroblast cells from women with endometriosis but not in fibroblasts from women without endometriosis.
Turning on TAGLN transformed these previously inactive cells into active myofibroblasts, leading to increased proliferation, mobility, and attachment to mesothelial cells, the layer of cells that line body cavities and internal organs. In short, they identified some key players in an environment that seemed very favorable to the development of endometriosis.
“So, the question is: Why are macrophages activated?” said Yutaka Kondo, MD, PhD, the senior author of the study and a professor in the division of cancer biology at the Nagoya (Japan) University Graduate School of Medicine. “We think that there are always bacteria in the endometrium.”
After reviewing data from a previously published study, they used quantitative polymerase chain reaction to rule out one candidate, Erysipelothrix, but scored on their next attempt, identifying Fusobacterium species in endometrial tissue from 64% of the women with endometriosis, compared with fewer than 10% of the controls.
To confirm that the bacteria could cause disease and were not simply bystanders, Dr. Kondo’s team turned to a mouse model for endometriosis, in which endometrial cells are surgically removed from the uteri of mice and injected into the peritoneum of recipient mice, leading to the formation of endometriotic lesions. When mice received further injections of uterine tissue from mice that were infected with F. nucleatum, their lesions were more numerous when compared with mice that received injections of uninfected uterine tissue. Furthermore, antibiotic treatment with metronidazole or chloramphenicol immediately after surgery largely prevented progression to endometriosis, Dr. Kondo and his colleagues reported.
Dr. Kondo likened this relationship between Fusobacterium and endometriosis to that of the link between Helicobacter pylori and peptic ulcers but acknowledged that he doesn’t have all the answers.
“We need more clinical trials, and also we have to know what kind of treatment might be the most effective for the treatment of endometriosis,” Dr. Kondo said, pointing out that other therapies should still be pursued in addition to antibiotics, as not all the samples from women with endometriosis harbored Fusobacterium. “It might be possible that other mechanisms are also involved.”
Don’t write off gut microbiota
Ramakrishna Kommagani, PhD, associate professor of pathology and immunology at Baylor College of Medicine in Houston, agreed. “Endometriosis is a complex disease, which appears to be impacted by many factors, including genetic, epigenetic, and environmental factors,” Dr. Kommagani said.
A key difference between his work and Dr. Kondo’s is his focus on gut microbiota, whereas the Japanese team looked at bacteria in the vagina and endometrium. But Dr. Kommagani said he thinks both could play a role. “Maybe the vaginal microbiome might have a direct impact on disease similar to what we showed on the gut,” he said.
But he said at least part of the answer to why some women develop endometriosis may have to do more with the balance of beneficial and harmful bacteria in the gut rather than because of a single family of microbes like Fusobacterium.
Most recently, by dovetailing a mouse model for inducing endometriosis in mice treated with antibiotics to deplete their gut microbiome, Dr. Kommagani’s lab expanded on its previous work: They showed that the animals developed fewer of the typical lesions seen in endometriosis than those that did not receive antibiotics before all of the mice underwent the surgical procedure used by researchers to induce endometriosis – possibly because they had no bacteria in their gut triggering the inflammatory response required for the development of endometriosis.
But after oral feedings with fecal matter from mice without endometriosis, the microbiota-depleted rodents began developing lesions typical of endometriosis, suggesting that altered gut flora from mice with endometriosis appeared to promote the disorder. Meanwhile, their microbiota-depleted counterparts who were fed fecal matter from mice without endometriosis did not develop the typical lesions.
Dr. Kommagani’s team then compared metabolites from bacteria in stool from mice with and without endometriosis and investigated the in vitro effect of these metabolites on cells from human endometriotic lesions. One of them, quinic acid, increased the proliferation of human endometriotic epithelial cells.
“Some metabolites such as fiber-derived short-chain fatty acids have beneficial effects; they inhibit the disease,” Dr. Kommagani said. “But maybe an amino acid derivative such as quinic acid, [may] promote disease, and these are generated because there is a gut dysbiosis.”
This statement hints at some of the possible therapeutic approaches for endometriosis, such as a high-fiber diet to promote healthy gut flora, or perhaps antibiotics to eradicate unhealthy bacteria. But as with other conditions that have been linked to dysbiosis, like inflammatory bowel disease, use of antibiotics is a bit like balancing on a tightrope; although antibiotics may remove harmful bacteria, their use may negatively affect the beneficial bacteria.
Clues in genetic variants
Krina Zondervan, DPhil, professor and head of the department of reproductive and genomic epidemiology at the University of Oxford (England), focuses on genomic, molecular, and epidemiologic approaches to understanding endometriosis.
“It’s one thing identifying risk variants and the next question is, okay, well, what do those variants actually do in terms of biology?” Dr. Zondervan said. The Oxford team next explored how the identified genetic variants affect gene expression and the proteins generated, drawing on previously collected data on gene expression from samples of human blood and endometrial and uterine tissue.
They found many of the genes implicated in the risk for endometriosis code for proteins that affect sex hormones, uterine development, transformation of healthy cells into cancerous tissue, inflammatory adhesion molecules, and factors promoting development of new blood vessels. All of that, she said, explains how a few endometrial cells making their way into the pelvis can attach to ovaries, ligaments, and peritoneal surfaces; proliferate; and acquire a blood supply to ensure their survival.
“We were able to identify a whole host of things that were likely causal to the disease,” Dr. Zondervan said. And that finding led to her next question: “Are there particular genes or areas around them that can be targeted with certain medications?”
The surprising answer was that several of the genes linked to endometriosis share pathways with clinical syndromes that often occur in women with endometriosis. Many of these are chronic pain conditions – such as migraines, headaches, and back pain – but also include inflammatory illnesses such as asthma and osteoarthritis.
As Dr. Zondervan explained, “A lot of the variance that we see for endometriosis is also experienced for low back pain and migraine, and that clearly has something to do with pain perception and pain mechanisms.”
A connection between the development of neural pathways and endometriosis has been proposed before, as researchers have found that endometriotic lesions can develop their own nerve supply, creating a direct interaction between the lesions and the central nervous system. And some clinicians have been employing treatment strategies that employ multimodal therapies – employing physical therapists, mental health practitioners, nutritionists, and pain specialists prior to and following surgical removal of lesions – to improve overall success rates of treatment.
But Dr. Zondervan’s team is the first to uncover an important clue about how this happens.
The study findings also provide solid clues to researchers about which genes and proteins to focus on for drug target discovery. In particular, the gene pathways shared by endometriosis and various pain conditions could allow for repurposing of drugs developed for other conditions for treating endometriosis, reported Dr. Zondervan.
Dr. Zondervan’s other important conclusion, echoed by Dr. Kondo and Dr. Kommagani, is that endometriosis is not one disease. Rather, it appears to be akin to cancer in terms of the heterogeneity of how it presents and the different subtypes of diseases. The Oxford study corroborated this belief, identifying certain genes that were closely associated with cystic lesions in ovaries, but failing to turn up a genetic link to other types of lesions in the pelvis long considered to be part of the spectrum of endometriosis disease.
Dr. Zondervan agreed that the potential link with Fusobacterium is a fascinating area given the critical role of inflammation in the pathogenesis of endometriosis, although she’d like to see the work replicated with larger sample sizes. “From a personal point of view, I’d be really fascinated to see how genetics interplays with this,” she added.
What’s next?
The chief limitation of human studies looking at mechanisms of endometriosis is that they are correlational: Tissue samples are collected from women with and without endometriosis, often through an invasive procedure such as laparoscopy or biopsy, at one point in time. Currently, the best tools for proving causation are animal models of endometriosis, such as the those used by Dr. Kondo’s and Dr. Kommagani’s teams.
Better diagnostic tools would solve that problem. The ultimate goal is a noninvasive test for endometriosis that would allow clinicians to follow women over time and permit the monitoring of disease progression, or regression, without the need for painful procedures. Such a diagnostic tool would facilitate rigorous longitudinal studies evaluating mechanisms of disease, as well as monitoring outcomes of clinical trials of new treatments.
Could stool samples be the answer?
The Japanese team found that women harboring Fusobacterium in endometrial tissue also had Fusobacterium in vaginal samples taken at the time of their hysterectomy – and stool samples can pick up changes in the gut microbiome.
“Vaginal swab or stool tests are probably the best and easiest for noninvasive early detection,” Dr. Kommagani said.
Spit tests for DNA would be even easier to obtain. Polygenic risk scores could be developed to estimate an individual’s risk of disease based on the number of variants, but Dr. Zondervan cautioned that not all the genes that account for endometriosis are known.
“The things that we found altogether explain about 5% of disease variability, basically – which is still not an awful lot,” she said.
Dr. Kondo’s work was supported by the Grant-in-Aid for Scientific Research, the Japan Society for the Promotion of Science, and the Research Grant of the Princess Takamatsu Cancer Research Fund. A patent method for detecting bacteria of genus Fusobacterium in order to diagnose endometriosis (WO2023/ 042714), was submitted (international publication date, March 23, 2023).
Dr. Kommagani’s work was funded, in part, by National Institutes of Health/National Institute of Child Health and Human Development grants R01HD102680, R01HD065435, and R00HD080742. He has no other conflicts of interest. Dr. Zondervan received funding from the Wellcome Trust (216767; 104036; 084766; 212904; 076113 and 085475) and also reported grants from Bayer AG, AbbVie, Volition Rx, MDNA Life Sciences, and Roche Diagnostics outside the submitted work.
Dr. Thomas is a pediatrician and epidemiologist living in Portland, Ore.
A version of this article originally appeared on Medscape.com.
In 1927, American gynecologist John Sampson published his theory of the etiology of endometriosis, postulating that retrograde flow of endometrial debris flows backward through the fallopian tubes during menses into the peritoneal cavity. Dr. Sampson’s notion remains the main paradigm today, mentioned still in recent articles on the topic, but it has a flaw: Although the theory may account for how endometrial tissue escapes the uterus, a 1984 study revealed that this phenomenon occurs in 90% of women. Why, then, do only 10% of women suffer from endometriosis?
Endometriosis describes a condition in which endometrial tissue lining the uterus is found outside the uterus. The disease can be painful, even crippling. As many as 30% of women in their reproductive years who have endometriosis are infertile as a consequence. The hallmarks of the condition are superficial peritoneal lesions of varying color, cysts in the ovaries, deeper nodules accompanied by scarring and adhesion, primarily in the pelvis but sometimes appearing outside the pelvis. The syndrome can be challenging to identify, requiring laparoscopy for definitive diagnosis.
John Sampson aside, scientists have struggled for the past century to identify the cause, or causes, of endometriosis. Hormones clearly play a role in its development, and women with endometriosis have an elevated risk of clear-cell and endometrioid ovarian cancer and autoimmune diseases. Immunodeficiency also could be to blame, if a faulty immune system fails to find and remove endometrial tissue outside of the uterus. A class of chemicals known as endocrine disruptors have been linked to endometriosis, but not definitively. Twin studies have demonstrated that as many as 50% of cases have a genetic basis, while mice with surgically induced endometriosis have been found to have a higher ratio of harmful to beneficial bacteria in their gut.
Several studies published this year point to new insights into the old mystery – with possible implications for ways to treat the disorder.
Perhaps the most surprising came out earlier this year in Science Translational Medicine, as a team of researchers in Japan reported that invasive infection by bacteria of the genus Fusobacterium may cause at least some cases of endometriosis.
Is Fusobacterium the new Helicobacter pylori?
The researchers, from Nagoya University, are the first to suggest that not only might a single bacterial genus cause endometriosis, but that antibiotic treatment could prevent progression of the disease. Using endometrial tissue obtained from 79 women undergoing hysterectomy for endometriosis and 76 women undergoing hysterectomy for other reasons (such as cervical cancer), the team started with gene expression profiling to explore differences between the two sets of samples.
They uncovered an interesting chain of cellular events: macrophages found in endometriotic lesions were secreting transforming growth factor-beta (TGF-beta). TGF-beta in turn stimulated high levels of expression of a gene called TAGLN in fibroblast cells from women with endometriosis but not in fibroblasts from women without endometriosis.
Turning on TAGLN transformed these previously inactive cells into active myofibroblasts, leading to increased proliferation, mobility, and attachment to mesothelial cells, the layer of cells that line body cavities and internal organs. In short, they identified some key players in an environment that seemed very favorable to the development of endometriosis.
“So, the question is: Why are macrophages activated?” said Yutaka Kondo, MD, PhD, the senior author of the study and a professor in the division of cancer biology at the Nagoya (Japan) University Graduate School of Medicine. “We think that there are always bacteria in the endometrium.”
After reviewing data from a previously published study, they used quantitative polymerase chain reaction to rule out one candidate, Erysipelothrix, but scored on their next attempt, identifying Fusobacterium species in endometrial tissue from 64% of the women with endometriosis, compared with fewer than 10% of the controls.
To confirm that the bacteria could cause disease and were not simply bystanders, Dr. Kondo’s team turned to a mouse model for endometriosis, in which endometrial cells are surgically removed from the uteri of mice and injected into the peritoneum of recipient mice, leading to the formation of endometriotic lesions. When mice received further injections of uterine tissue from mice that were infected with F. nucleatum, their lesions were more numerous when compared with mice that received injections of uninfected uterine tissue. Furthermore, antibiotic treatment with metronidazole or chloramphenicol immediately after surgery largely prevented progression to endometriosis, Dr. Kondo and his colleagues reported.
Dr. Kondo likened this relationship between Fusobacterium and endometriosis to that of the link between Helicobacter pylori and peptic ulcers but acknowledged that he doesn’t have all the answers.
“We need more clinical trials, and also we have to know what kind of treatment might be the most effective for the treatment of endometriosis,” Dr. Kondo said, pointing out that other therapies should still be pursued in addition to antibiotics, as not all the samples from women with endometriosis harbored Fusobacterium. “It might be possible that other mechanisms are also involved.”
Don’t write off gut microbiota
Ramakrishna Kommagani, PhD, associate professor of pathology and immunology at Baylor College of Medicine in Houston, agreed. “Endometriosis is a complex disease, which appears to be impacted by many factors, including genetic, epigenetic, and environmental factors,” Dr. Kommagani said.
A key difference between his work and Dr. Kondo’s is his focus on gut microbiota, whereas the Japanese team looked at bacteria in the vagina and endometrium. But Dr. Kommagani said he thinks both could play a role. “Maybe the vaginal microbiome might have a direct impact on disease similar to what we showed on the gut,” he said.
But he said at least part of the answer to why some women develop endometriosis may have to do more with the balance of beneficial and harmful bacteria in the gut rather than because of a single family of microbes like Fusobacterium.
Most recently, by dovetailing a mouse model for inducing endometriosis in mice treated with antibiotics to deplete their gut microbiome, Dr. Kommagani’s lab expanded on its previous work: They showed that the animals developed fewer of the typical lesions seen in endometriosis than those that did not receive antibiotics before all of the mice underwent the surgical procedure used by researchers to induce endometriosis – possibly because they had no bacteria in their gut triggering the inflammatory response required for the development of endometriosis.
But after oral feedings with fecal matter from mice without endometriosis, the microbiota-depleted rodents began developing lesions typical of endometriosis, suggesting that altered gut flora from mice with endometriosis appeared to promote the disorder. Meanwhile, their microbiota-depleted counterparts who were fed fecal matter from mice without endometriosis did not develop the typical lesions.
Dr. Kommagani’s team then compared metabolites from bacteria in stool from mice with and without endometriosis and investigated the in vitro effect of these metabolites on cells from human endometriotic lesions. One of them, quinic acid, increased the proliferation of human endometriotic epithelial cells.
“Some metabolites such as fiber-derived short-chain fatty acids have beneficial effects; they inhibit the disease,” Dr. Kommagani said. “But maybe an amino acid derivative such as quinic acid, [may] promote disease, and these are generated because there is a gut dysbiosis.”
This statement hints at some of the possible therapeutic approaches for endometriosis, such as a high-fiber diet to promote healthy gut flora, or perhaps antibiotics to eradicate unhealthy bacteria. But as with other conditions that have been linked to dysbiosis, like inflammatory bowel disease, use of antibiotics is a bit like balancing on a tightrope; although antibiotics may remove harmful bacteria, their use may negatively affect the beneficial bacteria.
Clues in genetic variants
Krina Zondervan, DPhil, professor and head of the department of reproductive and genomic epidemiology at the University of Oxford (England), focuses on genomic, molecular, and epidemiologic approaches to understanding endometriosis.
“It’s one thing identifying risk variants and the next question is, okay, well, what do those variants actually do in terms of biology?” Dr. Zondervan said. The Oxford team next explored how the identified genetic variants affect gene expression and the proteins generated, drawing on previously collected data on gene expression from samples of human blood and endometrial and uterine tissue.
They found many of the genes implicated in the risk for endometriosis code for proteins that affect sex hormones, uterine development, transformation of healthy cells into cancerous tissue, inflammatory adhesion molecules, and factors promoting development of new blood vessels. All of that, she said, explains how a few endometrial cells making their way into the pelvis can attach to ovaries, ligaments, and peritoneal surfaces; proliferate; and acquire a blood supply to ensure their survival.
“We were able to identify a whole host of things that were likely causal to the disease,” Dr. Zondervan said. And that finding led to her next question: “Are there particular genes or areas around them that can be targeted with certain medications?”
The surprising answer was that several of the genes linked to endometriosis share pathways with clinical syndromes that often occur in women with endometriosis. Many of these are chronic pain conditions – such as migraines, headaches, and back pain – but also include inflammatory illnesses such as asthma and osteoarthritis.
As Dr. Zondervan explained, “A lot of the variance that we see for endometriosis is also experienced for low back pain and migraine, and that clearly has something to do with pain perception and pain mechanisms.”
A connection between the development of neural pathways and endometriosis has been proposed before, as researchers have found that endometriotic lesions can develop their own nerve supply, creating a direct interaction between the lesions and the central nervous system. And some clinicians have been employing treatment strategies that employ multimodal therapies – employing physical therapists, mental health practitioners, nutritionists, and pain specialists prior to and following surgical removal of lesions – to improve overall success rates of treatment.
But Dr. Zondervan’s team is the first to uncover an important clue about how this happens.
The study findings also provide solid clues to researchers about which genes and proteins to focus on for drug target discovery. In particular, the gene pathways shared by endometriosis and various pain conditions could allow for repurposing of drugs developed for other conditions for treating endometriosis, reported Dr. Zondervan.
Dr. Zondervan’s other important conclusion, echoed by Dr. Kondo and Dr. Kommagani, is that endometriosis is not one disease. Rather, it appears to be akin to cancer in terms of the heterogeneity of how it presents and the different subtypes of diseases. The Oxford study corroborated this belief, identifying certain genes that were closely associated with cystic lesions in ovaries, but failing to turn up a genetic link to other types of lesions in the pelvis long considered to be part of the spectrum of endometriosis disease.
Dr. Zondervan agreed that the potential link with Fusobacterium is a fascinating area given the critical role of inflammation in the pathogenesis of endometriosis, although she’d like to see the work replicated with larger sample sizes. “From a personal point of view, I’d be really fascinated to see how genetics interplays with this,” she added.
What’s next?
The chief limitation of human studies looking at mechanisms of endometriosis is that they are correlational: Tissue samples are collected from women with and without endometriosis, often through an invasive procedure such as laparoscopy or biopsy, at one point in time. Currently, the best tools for proving causation are animal models of endometriosis, such as the those used by Dr. Kondo’s and Dr. Kommagani’s teams.
Better diagnostic tools would solve that problem. The ultimate goal is a noninvasive test for endometriosis that would allow clinicians to follow women over time and permit the monitoring of disease progression, or regression, without the need for painful procedures. Such a diagnostic tool would facilitate rigorous longitudinal studies evaluating mechanisms of disease, as well as monitoring outcomes of clinical trials of new treatments.
Could stool samples be the answer?
The Japanese team found that women harboring Fusobacterium in endometrial tissue also had Fusobacterium in vaginal samples taken at the time of their hysterectomy – and stool samples can pick up changes in the gut microbiome.
“Vaginal swab or stool tests are probably the best and easiest for noninvasive early detection,” Dr. Kommagani said.
Spit tests for DNA would be even easier to obtain. Polygenic risk scores could be developed to estimate an individual’s risk of disease based on the number of variants, but Dr. Zondervan cautioned that not all the genes that account for endometriosis are known.
“The things that we found altogether explain about 5% of disease variability, basically – which is still not an awful lot,” she said.
Dr. Kondo’s work was supported by the Grant-in-Aid for Scientific Research, the Japan Society for the Promotion of Science, and the Research Grant of the Princess Takamatsu Cancer Research Fund. A patent method for detecting bacteria of genus Fusobacterium in order to diagnose endometriosis (WO2023/ 042714), was submitted (international publication date, March 23, 2023).
Dr. Kommagani’s work was funded, in part, by National Institutes of Health/National Institute of Child Health and Human Development grants R01HD102680, R01HD065435, and R00HD080742. He has no other conflicts of interest. Dr. Zondervan received funding from the Wellcome Trust (216767; 104036; 084766; 212904; 076113 and 085475) and also reported grants from Bayer AG, AbbVie, Volition Rx, MDNA Life Sciences, and Roche Diagnostics outside the submitted work.
Dr. Thomas is a pediatrician and epidemiologist living in Portland, Ore.
A version of this article originally appeared on Medscape.com.
HT, even short-term use, linked to dementia risk in women
Short-term and cyclical use of estrogen and progestin therapy for menopausal symptoms is linked to an increased risk of dementia, results of a large observational study show.
(AD) 20 years later, compared with those who didn’t use HT. The risk was present even in women who used HT for brief periods at menopause onset.
However, both the investigators and experts not involved in the research caution that further studies are needed to explore whether the increased risk of dementia stems from HT use or whether women in need of HT have other underlying dementia risk factors.
“We cannot guarantee that our findings illustrate a causal relationship or if they represent underlying disposition to dementia in women in need of [HT],” lead investigator Nelsan Pourhadi, MD, from the Danish Dementia Research Centre at Copenhagen University Hospital Rigshospitalet, told this news organization.
Still, he added, the findings supported evidence from the Women’s Health Initiative Memory Study (WHIMS), the largest randomized trial on menopausal hormone therapy and dementia.
The findings were published online in BMJ.
Conflicting findings
Before WHIMS was published in 2003, HT was widely prescribed to relieve menopausal symptoms. However, WHIMS, which included more than 4,000 women aged 65 years or older, revealed that HT was associated with a twofold increased risk of dementia.
Studies published since then have yielded mixed results, adding to the controversy surrounding the safety of HT.
To discover whether age of initiation or length of duration of HT affects health outcomes, Dr. Pourhadi and his team undertook the observational study.
Between 2000 and 2018, the researchers tracked more than 60,000 Danish women aged 50-60 years using diagnosis and prescription information from Denmark’s National Registry of Patients.
The registry records showed that nearly 5,600 women developed dementia and 56,000 did not develop dementia. Of the 5,600 women with dementia, 1,460 had a diagnosis of AD.
Nearly 18,000 participants in the study sample received HT – 1,790 (29%) in the dementia group and 16,150 (32%) in the control group. Half started treatment before age 53 years and half stopped within 4 years. Roughly 90% used oral medications, which included a combination of estrogen and progestin.
The median age at which participants started HT was 53 years for both cases and controls, and the median duration of use was 4 years.
Longer use equals greater risk
Compared with those who did not use HT, those who used estrogen-progestin therapy had a 24% increased risk of developing all-cause dementia (hazard ratio, 1.24; 95% confidence interval, 1.17-1.44).
The increased dementia risk was similar between continuous (estrogen and progestin taken daily) and cyclic (daily estrogen with progestin taken 10-14 days a month) treatment regimens.
Longer durations of HT use were associated with increased risk, ranging from a 21% increased risk (HR, 1.21; 95% CI, 1.09-1.35) for those who used it for 1 year or less to a 74% increased risk (HR, 1.74; 95% CI, 1.45-2.10) for use lasting 12 years or more.
Women who started HT between the age of 45 and 50 had a 26% increased risk of developing all-cause dementia (HR, 1.26; 95% CI, 1.13-1.41) while women who initiated HT between age 51 and 60 had a 21% greater risk (HR, 1.21; 95% CI, 1.12-1.29).
Progestin-only or vaginal-estrogen-only therapy was not associated with the development of dementia.
The investigators noted that because this is an observational study, “further studies are warranted to explore if the observed association in this study between menopausal hormone therapy use and increased risk of dementia illustrates a causal effect.”
No causal relationship
In an accompanying editorial, Kejal Kantarci, MD, a professor of radiology at the Mayo Clinic, Rochester, Minn., noted that three clinical trials, including the WHIMS of Younger Women (WHIMS-Y) in 2013, did not show a link between cognitive function and HT.
“Although [Dr.] Pourhadi and colleagues’ study was done carefully using national registries, the observed associations could be artefactual and should not be used to infer a causal relationship between hormone therapy and dementia risk. These findings cannot inform shared decision-making about use of hormone therapy for menopausal symptoms,” she states in the editorial.
Also commenting on the findings, Amanda Heslegrave, PhD, a senior research fellow at the U.K. Dementia Research Institute, London, said in a release from the U.K.’s Science Media Centre that while the study “may cause alarm for women taking [HT], it highlights just how much we still don’t know about the effects of hormones on women’s brain health, and with promising treatments on the horizon, it should be a call to action to make this a priority area of research.”
There was no specific funding for the study. Dr. Kantarci reported working on an unpaid educational activity on Alzheimer’s disease for Biogen and is the PI on a study of a PET imaging ligand for Alzheimer’s disease, to which Eli Lilly and Avid Radiopharmaceuticals donated supplies.
A version of this article originally appeared on Medscape.com.
Short-term and cyclical use of estrogen and progestin therapy for menopausal symptoms is linked to an increased risk of dementia, results of a large observational study show.
(AD) 20 years later, compared with those who didn’t use HT. The risk was present even in women who used HT for brief periods at menopause onset.
However, both the investigators and experts not involved in the research caution that further studies are needed to explore whether the increased risk of dementia stems from HT use or whether women in need of HT have other underlying dementia risk factors.
“We cannot guarantee that our findings illustrate a causal relationship or if they represent underlying disposition to dementia in women in need of [HT],” lead investigator Nelsan Pourhadi, MD, from the Danish Dementia Research Centre at Copenhagen University Hospital Rigshospitalet, told this news organization.
Still, he added, the findings supported evidence from the Women’s Health Initiative Memory Study (WHIMS), the largest randomized trial on menopausal hormone therapy and dementia.
The findings were published online in BMJ.
Conflicting findings
Before WHIMS was published in 2003, HT was widely prescribed to relieve menopausal symptoms. However, WHIMS, which included more than 4,000 women aged 65 years or older, revealed that HT was associated with a twofold increased risk of dementia.
Studies published since then have yielded mixed results, adding to the controversy surrounding the safety of HT.
To discover whether age of initiation or length of duration of HT affects health outcomes, Dr. Pourhadi and his team undertook the observational study.
Between 2000 and 2018, the researchers tracked more than 60,000 Danish women aged 50-60 years using diagnosis and prescription information from Denmark’s National Registry of Patients.
The registry records showed that nearly 5,600 women developed dementia and 56,000 did not develop dementia. Of the 5,600 women with dementia, 1,460 had a diagnosis of AD.
Nearly 18,000 participants in the study sample received HT – 1,790 (29%) in the dementia group and 16,150 (32%) in the control group. Half started treatment before age 53 years and half stopped within 4 years. Roughly 90% used oral medications, which included a combination of estrogen and progestin.
The median age at which participants started HT was 53 years for both cases and controls, and the median duration of use was 4 years.
Longer use equals greater risk
Compared with those who did not use HT, those who used estrogen-progestin therapy had a 24% increased risk of developing all-cause dementia (hazard ratio, 1.24; 95% confidence interval, 1.17-1.44).
The increased dementia risk was similar between continuous (estrogen and progestin taken daily) and cyclic (daily estrogen with progestin taken 10-14 days a month) treatment regimens.
Longer durations of HT use were associated with increased risk, ranging from a 21% increased risk (HR, 1.21; 95% CI, 1.09-1.35) for those who used it for 1 year or less to a 74% increased risk (HR, 1.74; 95% CI, 1.45-2.10) for use lasting 12 years or more.
Women who started HT between the age of 45 and 50 had a 26% increased risk of developing all-cause dementia (HR, 1.26; 95% CI, 1.13-1.41) while women who initiated HT between age 51 and 60 had a 21% greater risk (HR, 1.21; 95% CI, 1.12-1.29).
Progestin-only or vaginal-estrogen-only therapy was not associated with the development of dementia.
The investigators noted that because this is an observational study, “further studies are warranted to explore if the observed association in this study between menopausal hormone therapy use and increased risk of dementia illustrates a causal effect.”
No causal relationship
In an accompanying editorial, Kejal Kantarci, MD, a professor of radiology at the Mayo Clinic, Rochester, Minn., noted that three clinical trials, including the WHIMS of Younger Women (WHIMS-Y) in 2013, did not show a link between cognitive function and HT.
“Although [Dr.] Pourhadi and colleagues’ study was done carefully using national registries, the observed associations could be artefactual and should not be used to infer a causal relationship between hormone therapy and dementia risk. These findings cannot inform shared decision-making about use of hormone therapy for menopausal symptoms,” she states in the editorial.
Also commenting on the findings, Amanda Heslegrave, PhD, a senior research fellow at the U.K. Dementia Research Institute, London, said in a release from the U.K.’s Science Media Centre that while the study “may cause alarm for women taking [HT], it highlights just how much we still don’t know about the effects of hormones on women’s brain health, and with promising treatments on the horizon, it should be a call to action to make this a priority area of research.”
There was no specific funding for the study. Dr. Kantarci reported working on an unpaid educational activity on Alzheimer’s disease for Biogen and is the PI on a study of a PET imaging ligand for Alzheimer’s disease, to which Eli Lilly and Avid Radiopharmaceuticals donated supplies.
A version of this article originally appeared on Medscape.com.
Short-term and cyclical use of estrogen and progestin therapy for menopausal symptoms is linked to an increased risk of dementia, results of a large observational study show.
(AD) 20 years later, compared with those who didn’t use HT. The risk was present even in women who used HT for brief periods at menopause onset.
However, both the investigators and experts not involved in the research caution that further studies are needed to explore whether the increased risk of dementia stems from HT use or whether women in need of HT have other underlying dementia risk factors.
“We cannot guarantee that our findings illustrate a causal relationship or if they represent underlying disposition to dementia in women in need of [HT],” lead investigator Nelsan Pourhadi, MD, from the Danish Dementia Research Centre at Copenhagen University Hospital Rigshospitalet, told this news organization.
Still, he added, the findings supported evidence from the Women’s Health Initiative Memory Study (WHIMS), the largest randomized trial on menopausal hormone therapy and dementia.
The findings were published online in BMJ.
Conflicting findings
Before WHIMS was published in 2003, HT was widely prescribed to relieve menopausal symptoms. However, WHIMS, which included more than 4,000 women aged 65 years or older, revealed that HT was associated with a twofold increased risk of dementia.
Studies published since then have yielded mixed results, adding to the controversy surrounding the safety of HT.
To discover whether age of initiation or length of duration of HT affects health outcomes, Dr. Pourhadi and his team undertook the observational study.
Between 2000 and 2018, the researchers tracked more than 60,000 Danish women aged 50-60 years using diagnosis and prescription information from Denmark’s National Registry of Patients.
The registry records showed that nearly 5,600 women developed dementia and 56,000 did not develop dementia. Of the 5,600 women with dementia, 1,460 had a diagnosis of AD.
Nearly 18,000 participants in the study sample received HT – 1,790 (29%) in the dementia group and 16,150 (32%) in the control group. Half started treatment before age 53 years and half stopped within 4 years. Roughly 90% used oral medications, which included a combination of estrogen and progestin.
The median age at which participants started HT was 53 years for both cases and controls, and the median duration of use was 4 years.
Longer use equals greater risk
Compared with those who did not use HT, those who used estrogen-progestin therapy had a 24% increased risk of developing all-cause dementia (hazard ratio, 1.24; 95% confidence interval, 1.17-1.44).
The increased dementia risk was similar between continuous (estrogen and progestin taken daily) and cyclic (daily estrogen with progestin taken 10-14 days a month) treatment regimens.
Longer durations of HT use were associated with increased risk, ranging from a 21% increased risk (HR, 1.21; 95% CI, 1.09-1.35) for those who used it for 1 year or less to a 74% increased risk (HR, 1.74; 95% CI, 1.45-2.10) for use lasting 12 years or more.
Women who started HT between the age of 45 and 50 had a 26% increased risk of developing all-cause dementia (HR, 1.26; 95% CI, 1.13-1.41) while women who initiated HT between age 51 and 60 had a 21% greater risk (HR, 1.21; 95% CI, 1.12-1.29).
Progestin-only or vaginal-estrogen-only therapy was not associated with the development of dementia.
The investigators noted that because this is an observational study, “further studies are warranted to explore if the observed association in this study between menopausal hormone therapy use and increased risk of dementia illustrates a causal effect.”
No causal relationship
In an accompanying editorial, Kejal Kantarci, MD, a professor of radiology at the Mayo Clinic, Rochester, Minn., noted that three clinical trials, including the WHIMS of Younger Women (WHIMS-Y) in 2013, did not show a link between cognitive function and HT.
“Although [Dr.] Pourhadi and colleagues’ study was done carefully using national registries, the observed associations could be artefactual and should not be used to infer a causal relationship between hormone therapy and dementia risk. These findings cannot inform shared decision-making about use of hormone therapy for menopausal symptoms,” she states in the editorial.
Also commenting on the findings, Amanda Heslegrave, PhD, a senior research fellow at the U.K. Dementia Research Institute, London, said in a release from the U.K.’s Science Media Centre that while the study “may cause alarm for women taking [HT], it highlights just how much we still don’t know about the effects of hormones on women’s brain health, and with promising treatments on the horizon, it should be a call to action to make this a priority area of research.”
There was no specific funding for the study. Dr. Kantarci reported working on an unpaid educational activity on Alzheimer’s disease for Biogen and is the PI on a study of a PET imaging ligand for Alzheimer’s disease, to which Eli Lilly and Avid Radiopharmaceuticals donated supplies.
A version of this article originally appeared on Medscape.com.