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Women increasingly turn to CBD, with or without doc’s blessing
When 42-year-old Danielle Simone Brand started having hormonal migraines, she first turned to cannabidiol (CBD) oil, eventually adding an occasional pull on a prefilled tetrahydrocannabinol (THC) vape for nighttime use. She was careful to avoid THC during work hours. A parenting and cannabis writer, Ms. Brand had more than a cursory background in cannabinoid medicine and had spent time at her local California dispensary discussing various cannabinoid components that might help alleviate her pain.
A self-professed “do-it-yourselfer,” Ms. Brand continues to use cannabinoids for her monthly headaches, forgoing any other pain medication. “There are times for conventional medicine in partnership with your doctor, but when it comes to health and wellness, women should be empowered to make decisions and self-experiment,” she said in an interview.
Ms. Brand is not alone. Significant numbers of women are replacing or supplementing prescription medications with cannabinoids, often without consulting their primary care physician, ob.gyn., or other specialist. At times, women have tried to have these conversations, only to be met with silence or worse.
Take Linda Fuller, a 58-year-old yoga instructor from Long Island who says that she uses CBD and THC for chronic sacroiliac pain after a car accident and to alleviate stress-triggered eczema flares. “I’ve had doctors turn their backs on me; I’ve had nurse practitioners walk out on me in the middle of a sentence,” she said in an interview.
Ms. Fuller said her conversion to cannabinoid medicine is relatively new; she never used cannabis recreationally before her accident but now considers it a gift. She doesn’t keep aspirin in the house and refused pain medication immediately after she injured her back.
Diana Krach, a 34-year-old writer from Maryland, says she’s encountered roadblocks about her decision to use cannabinoids for endometriosis and for pain from Crohn’s disease. When she tried to discuss her CBD use with a gastroenterologist, he interrupted her: “Whatever pot you’re smoking isn’t going to work, you’re going on biologics.”
Ms. Krach had not been smoking anything but had turned to a CBD tincture for symptom relief after prescription pain medications failed to help.
Ms. Brand, Ms. Fuller, and Ms. Krach are the tip of the iceberg when it comes to women seeking symptom relief outside the medicine cabinet. A recent survey in the Journal of Women’s Health of almost 1,000 women show that 90% (most between the ages of 35 and 44) had used cannabis and would consider using it to treat gynecologic pain. Roughly 80% said they would consider using it for procedure-related pain or other conditions. Additionally, women have reported using cannabinoids for PTSD, sleep disturbances or insomnia, anxiety, and migraine headaches.
Observational survey data have likewise shown that 80% of women with advanced or recurrent gynecologic malignancies who were prescribed cannabis reported that it was equivalent or superior to other medications for relieving pain, neuropathy, nausea, insomnia, decreased appetite, and anxiety.
In another survey, almost half (45%) of women with gynecologic malignancies who used nonprescribed cannabis for the same symptoms reported that they had reduced their use of prescription narcotics after initiating use of cannabis.
The gray zone
There has been a surge in self-reported cannabis use among pregnant women in particular. The National Survey on Drug Use and Health findings for the periods 2002-2003 and 2016-2017 highlight increases in adjusted prevalence rates from 3.4% to 7% in past-month use among pregnant women overall and from 5.7% to 12.1% during the first trimester alone.
“The more that you talk to pregnant women, the more that you realize that a lot are using cannabinoids for something that is basically medicinal, for sleep, for anxiety, or for nausea,” Katrina Mark, MD, an ob.gyn. and associate professor of medicine at the University of Maryland, College Park, said in an interview. “I’m not saying it’s fine to use drugs in pregnancy, but it is a grayer conversation than a lot of colleagues want to believe. Telling women to quit seems foolish since the alternative is to be anxious, don’t sleep, don’t eat, or use a medication that also has risks to it.”
One observational study shows that pregnant women themselves are conflicted. Although the majority believe that cannabis is “natural” and “safe,” compared with prescription drugs, they aren’t entirely in the dark about potential risks. They often express frustration with practitioners’ responses when these topics are broached during office visits. An observational survey among women and practitioners published in 2020 highlights that only half of doctors openly discouraged perinatal cannabis use and that others opted out of the discussion entirely.
This is the experience of many of the women that this news organization spoke with. Ms. Krach pointed out that “there’s a big deficit in listening; the doctor is supposed to be working for our behalf, especially when it comes to reproductive health.”
Dr. Mark believed that a lot of the conversation has been clouded by the illegality of the substance but that cannabinoids deserve as much of a fair chance for discussion and consideration as other medicines, which also carry risks in pregnancy. “There’s literally no evidence that it will work in pregnancy [for these symptoms], but there’s no evidence that it doesn’t, either,” she said in an interview. “When I have this conversation with colleagues who do not share my views, I try to encourage them to look at the actual risks versus the benefits versus the alternatives.”
The ‘entourage effect’
Data supporting cannabinoids have been mostly laboratory based, case based, or observational. However, several well-designed (albeit small) trials have demonstrated efficacy for chronic pain conditions, including neuropathic and headache pain, as well as in Crohn’s disease. Most investigators have concluded that dosage is important and that there is a synergistic interaction between compounds (known as the “entourage effect”) that relates to cannabinoid efficacy or lack thereof, as well as possible adverse effects.
In addition to legality issues, the entourage effect is one of the most important factors related to the medical use of cannabinoids. “There are literally thousands of cultivars of cannabis, each with their own phytocannabinoid and terpenic profiles that may produce distinct therapeutic effects, [so] it is misguided to speak of cannabis in monolithic terms. It is like making broad claims about soup,” wrote coauthor Samoon Ahmad, MD, in Medical Marijuana: A Clinical Handbook.
Additionally, the role that reproductive hormones play is not entirely understood. Reproductive-aged women appear to be more susceptible to a “telescoping” (gender-related progression to dependence) effect in comparison with men. Ziva Cooper, PhD, director of the Cannabis Research Initiative at the University of California, Los Angeles, said in an interview. She explained that research has shown that factors such as the degree of exposure, frequency of use, and menses confound this susceptibility.
It’s the data
Frustration over cannabinoid therapeutics abound, especially when it comes to data, legal issues, and lack of training. “The feedback that I hear from providers is that there isn’t enough information; we just don’t know enough about it,” Dr. Mark said, “but there is information that we do have, and ignoring it is not beneficial.”
Dr. Cooper concurred. Although she readily acknowledges that data from randomized, placebo-controlled trials are mostly lacking, she says, “There are signals in the literature providing evidence for the utility of cannabis and cannabinoids for pain and some other effects.”
Other practitioners said in an interview that some patients admit to using cannabinoids but that they lack the ample information to guide these patients. By and large, many women equate “natural” with “safe,” and some will experiment on their own to see what works.
Those experiments are not without risk, which is why “it’s just as important for physicians to talk to their patients about cannabis use as it is for patients to be forthcoming about that use,” said Dr. Cooper. “It could have implications on their overall health as well as interactions with other drugs that they’re using.”
That balance from a clinical perspective on cannabis is crucial, wrote coauthor Kenneth Hill, MD, in Medical Marijuana: A Clinical Handbook. “Without it,” he wrote, “the window of opportunity for a patient to accept treatment that she needs may not be open very long.”
A version of this article first appeared on Medscape.com.
When 42-year-old Danielle Simone Brand started having hormonal migraines, she first turned to cannabidiol (CBD) oil, eventually adding an occasional pull on a prefilled tetrahydrocannabinol (THC) vape for nighttime use. She was careful to avoid THC during work hours. A parenting and cannabis writer, Ms. Brand had more than a cursory background in cannabinoid medicine and had spent time at her local California dispensary discussing various cannabinoid components that might help alleviate her pain.
A self-professed “do-it-yourselfer,” Ms. Brand continues to use cannabinoids for her monthly headaches, forgoing any other pain medication. “There are times for conventional medicine in partnership with your doctor, but when it comes to health and wellness, women should be empowered to make decisions and self-experiment,” she said in an interview.
Ms. Brand is not alone. Significant numbers of women are replacing or supplementing prescription medications with cannabinoids, often without consulting their primary care physician, ob.gyn., or other specialist. At times, women have tried to have these conversations, only to be met with silence or worse.
Take Linda Fuller, a 58-year-old yoga instructor from Long Island who says that she uses CBD and THC for chronic sacroiliac pain after a car accident and to alleviate stress-triggered eczema flares. “I’ve had doctors turn their backs on me; I’ve had nurse practitioners walk out on me in the middle of a sentence,” she said in an interview.
Ms. Fuller said her conversion to cannabinoid medicine is relatively new; she never used cannabis recreationally before her accident but now considers it a gift. She doesn’t keep aspirin in the house and refused pain medication immediately after she injured her back.
Diana Krach, a 34-year-old writer from Maryland, says she’s encountered roadblocks about her decision to use cannabinoids for endometriosis and for pain from Crohn’s disease. When she tried to discuss her CBD use with a gastroenterologist, he interrupted her: “Whatever pot you’re smoking isn’t going to work, you’re going on biologics.”
Ms. Krach had not been smoking anything but had turned to a CBD tincture for symptom relief after prescription pain medications failed to help.
Ms. Brand, Ms. Fuller, and Ms. Krach are the tip of the iceberg when it comes to women seeking symptom relief outside the medicine cabinet. A recent survey in the Journal of Women’s Health of almost 1,000 women show that 90% (most between the ages of 35 and 44) had used cannabis and would consider using it to treat gynecologic pain. Roughly 80% said they would consider using it for procedure-related pain or other conditions. Additionally, women have reported using cannabinoids for PTSD, sleep disturbances or insomnia, anxiety, and migraine headaches.
Observational survey data have likewise shown that 80% of women with advanced or recurrent gynecologic malignancies who were prescribed cannabis reported that it was equivalent or superior to other medications for relieving pain, neuropathy, nausea, insomnia, decreased appetite, and anxiety.
In another survey, almost half (45%) of women with gynecologic malignancies who used nonprescribed cannabis for the same symptoms reported that they had reduced their use of prescription narcotics after initiating use of cannabis.
The gray zone
There has been a surge in self-reported cannabis use among pregnant women in particular. The National Survey on Drug Use and Health findings for the periods 2002-2003 and 2016-2017 highlight increases in adjusted prevalence rates from 3.4% to 7% in past-month use among pregnant women overall and from 5.7% to 12.1% during the first trimester alone.
“The more that you talk to pregnant women, the more that you realize that a lot are using cannabinoids for something that is basically medicinal, for sleep, for anxiety, or for nausea,” Katrina Mark, MD, an ob.gyn. and associate professor of medicine at the University of Maryland, College Park, said in an interview. “I’m not saying it’s fine to use drugs in pregnancy, but it is a grayer conversation than a lot of colleagues want to believe. Telling women to quit seems foolish since the alternative is to be anxious, don’t sleep, don’t eat, or use a medication that also has risks to it.”
One observational study shows that pregnant women themselves are conflicted. Although the majority believe that cannabis is “natural” and “safe,” compared with prescription drugs, they aren’t entirely in the dark about potential risks. They often express frustration with practitioners’ responses when these topics are broached during office visits. An observational survey among women and practitioners published in 2020 highlights that only half of doctors openly discouraged perinatal cannabis use and that others opted out of the discussion entirely.
This is the experience of many of the women that this news organization spoke with. Ms. Krach pointed out that “there’s a big deficit in listening; the doctor is supposed to be working for our behalf, especially when it comes to reproductive health.”
Dr. Mark believed that a lot of the conversation has been clouded by the illegality of the substance but that cannabinoids deserve as much of a fair chance for discussion and consideration as other medicines, which also carry risks in pregnancy. “There’s literally no evidence that it will work in pregnancy [for these symptoms], but there’s no evidence that it doesn’t, either,” she said in an interview. “When I have this conversation with colleagues who do not share my views, I try to encourage them to look at the actual risks versus the benefits versus the alternatives.”
The ‘entourage effect’
Data supporting cannabinoids have been mostly laboratory based, case based, or observational. However, several well-designed (albeit small) trials have demonstrated efficacy for chronic pain conditions, including neuropathic and headache pain, as well as in Crohn’s disease. Most investigators have concluded that dosage is important and that there is a synergistic interaction between compounds (known as the “entourage effect”) that relates to cannabinoid efficacy or lack thereof, as well as possible adverse effects.
In addition to legality issues, the entourage effect is one of the most important factors related to the medical use of cannabinoids. “There are literally thousands of cultivars of cannabis, each with their own phytocannabinoid and terpenic profiles that may produce distinct therapeutic effects, [so] it is misguided to speak of cannabis in monolithic terms. It is like making broad claims about soup,” wrote coauthor Samoon Ahmad, MD, in Medical Marijuana: A Clinical Handbook.
Additionally, the role that reproductive hormones play is not entirely understood. Reproductive-aged women appear to be more susceptible to a “telescoping” (gender-related progression to dependence) effect in comparison with men. Ziva Cooper, PhD, director of the Cannabis Research Initiative at the University of California, Los Angeles, said in an interview. She explained that research has shown that factors such as the degree of exposure, frequency of use, and menses confound this susceptibility.
It’s the data
Frustration over cannabinoid therapeutics abound, especially when it comes to data, legal issues, and lack of training. “The feedback that I hear from providers is that there isn’t enough information; we just don’t know enough about it,” Dr. Mark said, “but there is information that we do have, and ignoring it is not beneficial.”
Dr. Cooper concurred. Although she readily acknowledges that data from randomized, placebo-controlled trials are mostly lacking, she says, “There are signals in the literature providing evidence for the utility of cannabis and cannabinoids for pain and some other effects.”
Other practitioners said in an interview that some patients admit to using cannabinoids but that they lack the ample information to guide these patients. By and large, many women equate “natural” with “safe,” and some will experiment on their own to see what works.
Those experiments are not without risk, which is why “it’s just as important for physicians to talk to their patients about cannabis use as it is for patients to be forthcoming about that use,” said Dr. Cooper. “It could have implications on their overall health as well as interactions with other drugs that they’re using.”
That balance from a clinical perspective on cannabis is crucial, wrote coauthor Kenneth Hill, MD, in Medical Marijuana: A Clinical Handbook. “Without it,” he wrote, “the window of opportunity for a patient to accept treatment that she needs may not be open very long.”
A version of this article first appeared on Medscape.com.
When 42-year-old Danielle Simone Brand started having hormonal migraines, she first turned to cannabidiol (CBD) oil, eventually adding an occasional pull on a prefilled tetrahydrocannabinol (THC) vape for nighttime use. She was careful to avoid THC during work hours. A parenting and cannabis writer, Ms. Brand had more than a cursory background in cannabinoid medicine and had spent time at her local California dispensary discussing various cannabinoid components that might help alleviate her pain.
A self-professed “do-it-yourselfer,” Ms. Brand continues to use cannabinoids for her monthly headaches, forgoing any other pain medication. “There are times for conventional medicine in partnership with your doctor, but when it comes to health and wellness, women should be empowered to make decisions and self-experiment,” she said in an interview.
Ms. Brand is not alone. Significant numbers of women are replacing or supplementing prescription medications with cannabinoids, often without consulting their primary care physician, ob.gyn., or other specialist. At times, women have tried to have these conversations, only to be met with silence or worse.
Take Linda Fuller, a 58-year-old yoga instructor from Long Island who says that she uses CBD and THC for chronic sacroiliac pain after a car accident and to alleviate stress-triggered eczema flares. “I’ve had doctors turn their backs on me; I’ve had nurse practitioners walk out on me in the middle of a sentence,” she said in an interview.
Ms. Fuller said her conversion to cannabinoid medicine is relatively new; she never used cannabis recreationally before her accident but now considers it a gift. She doesn’t keep aspirin in the house and refused pain medication immediately after she injured her back.
Diana Krach, a 34-year-old writer from Maryland, says she’s encountered roadblocks about her decision to use cannabinoids for endometriosis and for pain from Crohn’s disease. When she tried to discuss her CBD use with a gastroenterologist, he interrupted her: “Whatever pot you’re smoking isn’t going to work, you’re going on biologics.”
Ms. Krach had not been smoking anything but had turned to a CBD tincture for symptom relief after prescription pain medications failed to help.
Ms. Brand, Ms. Fuller, and Ms. Krach are the tip of the iceberg when it comes to women seeking symptom relief outside the medicine cabinet. A recent survey in the Journal of Women’s Health of almost 1,000 women show that 90% (most between the ages of 35 and 44) had used cannabis and would consider using it to treat gynecologic pain. Roughly 80% said they would consider using it for procedure-related pain or other conditions. Additionally, women have reported using cannabinoids for PTSD, sleep disturbances or insomnia, anxiety, and migraine headaches.
Observational survey data have likewise shown that 80% of women with advanced or recurrent gynecologic malignancies who were prescribed cannabis reported that it was equivalent or superior to other medications for relieving pain, neuropathy, nausea, insomnia, decreased appetite, and anxiety.
In another survey, almost half (45%) of women with gynecologic malignancies who used nonprescribed cannabis for the same symptoms reported that they had reduced their use of prescription narcotics after initiating use of cannabis.
The gray zone
There has been a surge in self-reported cannabis use among pregnant women in particular. The National Survey on Drug Use and Health findings for the periods 2002-2003 and 2016-2017 highlight increases in adjusted prevalence rates from 3.4% to 7% in past-month use among pregnant women overall and from 5.7% to 12.1% during the first trimester alone.
“The more that you talk to pregnant women, the more that you realize that a lot are using cannabinoids for something that is basically medicinal, for sleep, for anxiety, or for nausea,” Katrina Mark, MD, an ob.gyn. and associate professor of medicine at the University of Maryland, College Park, said in an interview. “I’m not saying it’s fine to use drugs in pregnancy, but it is a grayer conversation than a lot of colleagues want to believe. Telling women to quit seems foolish since the alternative is to be anxious, don’t sleep, don’t eat, or use a medication that also has risks to it.”
One observational study shows that pregnant women themselves are conflicted. Although the majority believe that cannabis is “natural” and “safe,” compared with prescription drugs, they aren’t entirely in the dark about potential risks. They often express frustration with practitioners’ responses when these topics are broached during office visits. An observational survey among women and practitioners published in 2020 highlights that only half of doctors openly discouraged perinatal cannabis use and that others opted out of the discussion entirely.
This is the experience of many of the women that this news organization spoke with. Ms. Krach pointed out that “there’s a big deficit in listening; the doctor is supposed to be working for our behalf, especially when it comes to reproductive health.”
Dr. Mark believed that a lot of the conversation has been clouded by the illegality of the substance but that cannabinoids deserve as much of a fair chance for discussion and consideration as other medicines, which also carry risks in pregnancy. “There’s literally no evidence that it will work in pregnancy [for these symptoms], but there’s no evidence that it doesn’t, either,” she said in an interview. “When I have this conversation with colleagues who do not share my views, I try to encourage them to look at the actual risks versus the benefits versus the alternatives.”
The ‘entourage effect’
Data supporting cannabinoids have been mostly laboratory based, case based, or observational. However, several well-designed (albeit small) trials have demonstrated efficacy for chronic pain conditions, including neuropathic and headache pain, as well as in Crohn’s disease. Most investigators have concluded that dosage is important and that there is a synergistic interaction between compounds (known as the “entourage effect”) that relates to cannabinoid efficacy or lack thereof, as well as possible adverse effects.
In addition to legality issues, the entourage effect is one of the most important factors related to the medical use of cannabinoids. “There are literally thousands of cultivars of cannabis, each with their own phytocannabinoid and terpenic profiles that may produce distinct therapeutic effects, [so] it is misguided to speak of cannabis in monolithic terms. It is like making broad claims about soup,” wrote coauthor Samoon Ahmad, MD, in Medical Marijuana: A Clinical Handbook.
Additionally, the role that reproductive hormones play is not entirely understood. Reproductive-aged women appear to be more susceptible to a “telescoping” (gender-related progression to dependence) effect in comparison with men. Ziva Cooper, PhD, director of the Cannabis Research Initiative at the University of California, Los Angeles, said in an interview. She explained that research has shown that factors such as the degree of exposure, frequency of use, and menses confound this susceptibility.
It’s the data
Frustration over cannabinoid therapeutics abound, especially when it comes to data, legal issues, and lack of training. “The feedback that I hear from providers is that there isn’t enough information; we just don’t know enough about it,” Dr. Mark said, “but there is information that we do have, and ignoring it is not beneficial.”
Dr. Cooper concurred. Although she readily acknowledges that data from randomized, placebo-controlled trials are mostly lacking, she says, “There are signals in the literature providing evidence for the utility of cannabis and cannabinoids for pain and some other effects.”
Other practitioners said in an interview that some patients admit to using cannabinoids but that they lack the ample information to guide these patients. By and large, many women equate “natural” with “safe,” and some will experiment on their own to see what works.
Those experiments are not without risk, which is why “it’s just as important for physicians to talk to their patients about cannabis use as it is for patients to be forthcoming about that use,” said Dr. Cooper. “It could have implications on their overall health as well as interactions with other drugs that they’re using.”
That balance from a clinical perspective on cannabis is crucial, wrote coauthor Kenneth Hill, MD, in Medical Marijuana: A Clinical Handbook. “Without it,” he wrote, “the window of opportunity for a patient to accept treatment that she needs may not be open very long.”
A version of this article first appeared on Medscape.com.
Long-term metformin use linked to fewer ER+ breast cancers
.
Conversely, the results also showed higher rates of ER-negative and triple-negative breast cancer among women with type 2 diabetes who received metformin, although case numbers were small.
“Our conclusion that having type 2 diabetes increases the risk of developing breast cancer but taking metformin may protect against developing ER-positive breast cancer – but not other types of breast cancer – is biologically plausible and supported by our results, even though some [endpoints] are not statistically significant,” senior author Dale P. Sandler, PhD, chief of the epidemiology branch, National Institute of Environmental Health Sciences, Research Triangle Park, N.C., said in an interview.
“Among our findings that are not statistically significant are several that helped us get a better picture of the relationships between type 2 diabetes, metformin treatment, and breast cancer risk,” Dr. Sandler added.
The results were published online Jan. 28 in Annals of Oncology by Yong-Moon Mark Park, MD, PhD, now an epidemiologist at the University of Arkansas for Medical Sciences in Little Rock, and colleagues.
Sara P. Cate, MD, a breast cancer surgeon at Mount Sinai Medical Center in New York, who was not involved with the study, said: “Certainly, metformin helps with weight loss, which is linked with estrogen-driven breast cancers, so this may explain why fewer patients on metformin got this type of breast cancer.”
A tangled web ... with no clear conclusions yet
But in an accompanying editorial, Ana E. Lohmann, MD, PhD, and Pamela J. Goodwin, MD, say that, while this is “a large, well-designed prospective cohort study,” it tells a complicated story.
“The report by Park adds to the growing evidence linking type 2 diabetes and its treatment to breast cancer risk, but definitive conclusions regarding these associations are not yet possible,” they observe.
The “largely negative” results of the new study perhaps in part occurred because the cohort included only 277 women with type 2 diabetes diagnosed with incident breast cancer, note Dr. Lohmann, of London Health Sciences Centre, University of Western Ontario, and Dr. Goodwin, of Mount Sinai Hospital, Toronto.
“Clearly, this is an important area, and additional research is needed to untangle the web of inter-related associations of type 2 diabetes, its treatment, and breast cancer risk,” they write.
Examination of the effects of metformin in studies such as the Canadian Cancer Trial Group MA.32, a phase 3 trial of over 3,500 women with hormone receptor–positive early-stage breast cancer who are being randomized to metformin or placebo for up to 5 years in addition to standard adjuvant therapy, will provide further insights, they observe. The trial is slated to be completed in February 2022.
Study followed women whose sisters had breast cancer
The new data come from the Sister Study, which followed more than 50,000 women without a history of breast cancer who had sisters or half-sisters with a breast cancer diagnosis. The study, run by the NIEHS, enrolled women 35-74 years old from all 50 U.S. states and Puerto Rico in 2003-2009.
The current analysis excluded women with a history of any other type of cancer, missing data about diabetes, or an uncertain breast cancer diagnosis during the study, which left 44,541 available for study. At entry, 7% of the women had type 2 diabetes, and another 5% developed new-onset type 2 diabetes during follow-up.
Among those with diabetes, 61% received treatment with metformin either alone or with other antidiabetic drugs.
During a median follow-up of 8.6 years, 2,678 women received a diagnosis of primary breast cancer, either invasive or ductal carcinoma in situ.
In a series of multivariate analyses that adjusted for numerous potential confounders, the authors found that, overall, no association existed between diabetes and breast cancer incidence, with a hazard ratio of 0.99, compared with women without diabetes.
But, said Dr. Sandler, “there is a strong biological rationale to hypothesize that type 2 diabetes increases the risk for breast cancer, and results from earlier studies support this.”
Association of metformin and breast cancer
Women with type 2 diabetes who received metformin had a 14% lower rate of ER-positive breast cancer, compared with women with diabetes not taking metformin, a nonsignificant association.
Among women taking metformin for at least 10 years, the associated reduction in ER-positive breast cancer, compared with those who did not take it, was 38%, a difference that just missed significance, with a 95% confidence interval of 0.38-1.01.
In contrast, cases of ER-negative and triple-negative breast cancers increased in the women with diabetes taking metformin. The hazard ratio for ER-negative tumors showed a nonsignificant 25% relative increase in women taking metformin and a significant 74% increase in triple-negative cancers.
The editorialists note, however, that “the number of patients who were found to have triple-negative breast cancer was small [so] we cannot draw any practice-changing conclusions from it.”
In conclusion, Dr. Park and colleagues reiterate: “Our analysis is consistent with a potential protective effect of metformin and suggests that long-term use of metformin may reduce breast cancer risk associated with type 2 diabetes.”
The study received no commercial funding. Dr. Sandler, Dr. Park, Dr. Lohmann, Dr. Goodwin, and Dr. Cate have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
.
Conversely, the results also showed higher rates of ER-negative and triple-negative breast cancer among women with type 2 diabetes who received metformin, although case numbers were small.
“Our conclusion that having type 2 diabetes increases the risk of developing breast cancer but taking metformin may protect against developing ER-positive breast cancer – but not other types of breast cancer – is biologically plausible and supported by our results, even though some [endpoints] are not statistically significant,” senior author Dale P. Sandler, PhD, chief of the epidemiology branch, National Institute of Environmental Health Sciences, Research Triangle Park, N.C., said in an interview.
“Among our findings that are not statistically significant are several that helped us get a better picture of the relationships between type 2 diabetes, metformin treatment, and breast cancer risk,” Dr. Sandler added.
The results were published online Jan. 28 in Annals of Oncology by Yong-Moon Mark Park, MD, PhD, now an epidemiologist at the University of Arkansas for Medical Sciences in Little Rock, and colleagues.
Sara P. Cate, MD, a breast cancer surgeon at Mount Sinai Medical Center in New York, who was not involved with the study, said: “Certainly, metformin helps with weight loss, which is linked with estrogen-driven breast cancers, so this may explain why fewer patients on metformin got this type of breast cancer.”
A tangled web ... with no clear conclusions yet
But in an accompanying editorial, Ana E. Lohmann, MD, PhD, and Pamela J. Goodwin, MD, say that, while this is “a large, well-designed prospective cohort study,” it tells a complicated story.
“The report by Park adds to the growing evidence linking type 2 diabetes and its treatment to breast cancer risk, but definitive conclusions regarding these associations are not yet possible,” they observe.
The “largely negative” results of the new study perhaps in part occurred because the cohort included only 277 women with type 2 diabetes diagnosed with incident breast cancer, note Dr. Lohmann, of London Health Sciences Centre, University of Western Ontario, and Dr. Goodwin, of Mount Sinai Hospital, Toronto.
“Clearly, this is an important area, and additional research is needed to untangle the web of inter-related associations of type 2 diabetes, its treatment, and breast cancer risk,” they write.
Examination of the effects of metformin in studies such as the Canadian Cancer Trial Group MA.32, a phase 3 trial of over 3,500 women with hormone receptor–positive early-stage breast cancer who are being randomized to metformin or placebo for up to 5 years in addition to standard adjuvant therapy, will provide further insights, they observe. The trial is slated to be completed in February 2022.
Study followed women whose sisters had breast cancer
The new data come from the Sister Study, which followed more than 50,000 women without a history of breast cancer who had sisters or half-sisters with a breast cancer diagnosis. The study, run by the NIEHS, enrolled women 35-74 years old from all 50 U.S. states and Puerto Rico in 2003-2009.
The current analysis excluded women with a history of any other type of cancer, missing data about diabetes, or an uncertain breast cancer diagnosis during the study, which left 44,541 available for study. At entry, 7% of the women had type 2 diabetes, and another 5% developed new-onset type 2 diabetes during follow-up.
Among those with diabetes, 61% received treatment with metformin either alone or with other antidiabetic drugs.
During a median follow-up of 8.6 years, 2,678 women received a diagnosis of primary breast cancer, either invasive or ductal carcinoma in situ.
In a series of multivariate analyses that adjusted for numerous potential confounders, the authors found that, overall, no association existed between diabetes and breast cancer incidence, with a hazard ratio of 0.99, compared with women without diabetes.
But, said Dr. Sandler, “there is a strong biological rationale to hypothesize that type 2 diabetes increases the risk for breast cancer, and results from earlier studies support this.”
Association of metformin and breast cancer
Women with type 2 diabetes who received metformin had a 14% lower rate of ER-positive breast cancer, compared with women with diabetes not taking metformin, a nonsignificant association.
Among women taking metformin for at least 10 years, the associated reduction in ER-positive breast cancer, compared with those who did not take it, was 38%, a difference that just missed significance, with a 95% confidence interval of 0.38-1.01.
In contrast, cases of ER-negative and triple-negative breast cancers increased in the women with diabetes taking metformin. The hazard ratio for ER-negative tumors showed a nonsignificant 25% relative increase in women taking metformin and a significant 74% increase in triple-negative cancers.
The editorialists note, however, that “the number of patients who were found to have triple-negative breast cancer was small [so] we cannot draw any practice-changing conclusions from it.”
In conclusion, Dr. Park and colleagues reiterate: “Our analysis is consistent with a potential protective effect of metformin and suggests that long-term use of metformin may reduce breast cancer risk associated with type 2 diabetes.”
The study received no commercial funding. Dr. Sandler, Dr. Park, Dr. Lohmann, Dr. Goodwin, and Dr. Cate have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
.
Conversely, the results also showed higher rates of ER-negative and triple-negative breast cancer among women with type 2 diabetes who received metformin, although case numbers were small.
“Our conclusion that having type 2 diabetes increases the risk of developing breast cancer but taking metformin may protect against developing ER-positive breast cancer – but not other types of breast cancer – is biologically plausible and supported by our results, even though some [endpoints] are not statistically significant,” senior author Dale P. Sandler, PhD, chief of the epidemiology branch, National Institute of Environmental Health Sciences, Research Triangle Park, N.C., said in an interview.
“Among our findings that are not statistically significant are several that helped us get a better picture of the relationships between type 2 diabetes, metformin treatment, and breast cancer risk,” Dr. Sandler added.
The results were published online Jan. 28 in Annals of Oncology by Yong-Moon Mark Park, MD, PhD, now an epidemiologist at the University of Arkansas for Medical Sciences in Little Rock, and colleagues.
Sara P. Cate, MD, a breast cancer surgeon at Mount Sinai Medical Center in New York, who was not involved with the study, said: “Certainly, metformin helps with weight loss, which is linked with estrogen-driven breast cancers, so this may explain why fewer patients on metformin got this type of breast cancer.”
A tangled web ... with no clear conclusions yet
But in an accompanying editorial, Ana E. Lohmann, MD, PhD, and Pamela J. Goodwin, MD, say that, while this is “a large, well-designed prospective cohort study,” it tells a complicated story.
“The report by Park adds to the growing evidence linking type 2 diabetes and its treatment to breast cancer risk, but definitive conclusions regarding these associations are not yet possible,” they observe.
The “largely negative” results of the new study perhaps in part occurred because the cohort included only 277 women with type 2 diabetes diagnosed with incident breast cancer, note Dr. Lohmann, of London Health Sciences Centre, University of Western Ontario, and Dr. Goodwin, of Mount Sinai Hospital, Toronto.
“Clearly, this is an important area, and additional research is needed to untangle the web of inter-related associations of type 2 diabetes, its treatment, and breast cancer risk,” they write.
Examination of the effects of metformin in studies such as the Canadian Cancer Trial Group MA.32, a phase 3 trial of over 3,500 women with hormone receptor–positive early-stage breast cancer who are being randomized to metformin or placebo for up to 5 years in addition to standard adjuvant therapy, will provide further insights, they observe. The trial is slated to be completed in February 2022.
Study followed women whose sisters had breast cancer
The new data come from the Sister Study, which followed more than 50,000 women without a history of breast cancer who had sisters or half-sisters with a breast cancer diagnosis. The study, run by the NIEHS, enrolled women 35-74 years old from all 50 U.S. states and Puerto Rico in 2003-2009.
The current analysis excluded women with a history of any other type of cancer, missing data about diabetes, or an uncertain breast cancer diagnosis during the study, which left 44,541 available for study. At entry, 7% of the women had type 2 diabetes, and another 5% developed new-onset type 2 diabetes during follow-up.
Among those with diabetes, 61% received treatment with metformin either alone or with other antidiabetic drugs.
During a median follow-up of 8.6 years, 2,678 women received a diagnosis of primary breast cancer, either invasive or ductal carcinoma in situ.
In a series of multivariate analyses that adjusted for numerous potential confounders, the authors found that, overall, no association existed between diabetes and breast cancer incidence, with a hazard ratio of 0.99, compared with women without diabetes.
But, said Dr. Sandler, “there is a strong biological rationale to hypothesize that type 2 diabetes increases the risk for breast cancer, and results from earlier studies support this.”
Association of metformin and breast cancer
Women with type 2 diabetes who received metformin had a 14% lower rate of ER-positive breast cancer, compared with women with diabetes not taking metformin, a nonsignificant association.
Among women taking metformin for at least 10 years, the associated reduction in ER-positive breast cancer, compared with those who did not take it, was 38%, a difference that just missed significance, with a 95% confidence interval of 0.38-1.01.
In contrast, cases of ER-negative and triple-negative breast cancers increased in the women with diabetes taking metformin. The hazard ratio for ER-negative tumors showed a nonsignificant 25% relative increase in women taking metformin and a significant 74% increase in triple-negative cancers.
The editorialists note, however, that “the number of patients who were found to have triple-negative breast cancer was small [so] we cannot draw any practice-changing conclusions from it.”
In conclusion, Dr. Park and colleagues reiterate: “Our analysis is consistent with a potential protective effect of metformin and suggests that long-term use of metformin may reduce breast cancer risk associated with type 2 diabetes.”
The study received no commercial funding. Dr. Sandler, Dr. Park, Dr. Lohmann, Dr. Goodwin, and Dr. Cate have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Levonorgestrel IUD effective as emergency contraception
A levonorgestrel 52-mg intrauterine device is noninferior to a copper IUD for emergency contraception, according to randomized trial results published online in the New England Journal of Medicine.
Although the trial didn’t directly compare emergency oral contraception to the hormonal IUD, the authors speculated, on the basis of prior findings, that the levonorgestrel IUD is more effective than oral emergency contraceptive pills. In addition, there is no delay in providing ongoing contraception as there is when ulipristal acetate is used for emergency contraception.
Prior research has found that copper IUDs are a highly effective method of emergency contraception, but studies of the use of other IUDs as emergency contraception have been lacking.
To examine whether the levonorgestrel IUD is noninferior to the copper IUD as emergency contraception after unprotected sexual intercourse during the previous 5 days, David K. Turok, MD, MPH, associate professor of obstetrics and gynecology at the University of Utah Health, Salt Lake City, and colleagues conducted a trial at six Planned Parenthood health centers in Utah.
Researchers enrolled patients between August 2016 and December 2019. Trial sites purchased levonorgestrel 52-mg IUDs (Liletta) and copper T380A IUDs (ParaGard) for the study. The companies that distribute the IUDs were not involved in the trial.
Pregnancy rates were 1 of 317 participants (0.3%) among those who received the levonorgestrel IUD, and 0 of 321 (0%) among those who received the copper IUD. The difference between the two arms was well within the prespecified noninferiority margin of 2.5%.
Adverse event rates were generally similar between the two groups, with 5.2% of participants in the levonorgestrel IUD group seeking medical care in the month after IUD placement, compared with 4.9% in the copper IUD group.
A welcome option
The study “benefits women by allowing us to introduce a new option into the method mix of emergency contraception,” commented Wing Kay Fok, MD, a clinical assistant professor of obstetrics and gynecology at Weill Cornell Medicine, New York.
Specialists in family planning had followed preliminary data from this study and were anticipating the final results. Clinicians who are comfortable placing a copper IUD for emergency contraception are likely to be comfortable placing a levonorgestrel 52-mg IUD, given these data, Dr. Fok said.
“This is definitely – from what we can tell – a more effective method than the pill,” she said.
Gabriela Aguilar, MD, MPH, fellow and clinical instructor in the department of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., said she is reassured by the data and is prepared to offer the 52-mg levonorgestrel IUD as emergency contraception.
The trial is “an important clinical study that has the ability to significantly change clinical practice,” Dr. Aguilar said. She credited the University of Utah and Planned Parenthood for their roles in it.
“Anytime that there are more options, ideally, that means that access is also increased,” Dr. Aguilar said.
Many patients will still prefer oral emergency contraceptive pills, she said. “But for those who are interested in an IUD ... for the immediate and ongoing birth control after that, now they have the two options instead of just the one IUD option.”
One pregnancy
The trial included women aged 18-35 years who requested emergency contraception after unprotected sexual intercourse within the previous 5 days. Other inclusion criteria were that participants had a desire to initiate use of an IUD; a desire to prevent pregnancy for at least 1 year; a negative result on urine pregnancy testing; a history of regular menstrual cycles; and a known date of the last menstrual period. The investigators did not exclude individuals who had unprotected sexual intercourse more than 5 days before IUD placement.
Participants were unaware of their assigned intervention. The nurse practitioners and certified nurse midwives who performed the IUD insertions were aware of the IUD type.
The primary outcome was pregnancy, as determined by a positive result on urine pregnancy testing 1 month after IUD insertion or by a review of survey and health record data.
One pregnancy “occurred in a participant who reported a single episode of unprotected sexual intercourse 48 hours before IUD placement,” the study authors wrote. “Pregnancy dating by an ultrasound examination at 10 weeks was consistent with conception occurring as a result of an emergency contraception failure. The pregnancy ended in a spontaneous abortion at 10 weeks with the IUD still in place.”
“We hope that providers can begin to deliver this method to everyone who wants and needs it and that people considering both emergency contraception and an ongoing method of birth control know that they now have the option of a hormonal IUD in addition to the nonhormonal, copper IUD,” Dr. Turok said in a news release from Planned Parenthood.
The study used a hormonal IUD manufactured by Liletta; Mirena also manufactures a levonorgestrel 52-mg IUD. The results of the study would apply to Mirena’s product too, according to Planned Parenthood.
“There are various IUDs on the market that are at lower doses, and so those IUDs may not demonstrate similar results,” Dr. Aguilar said.
The research was supported by the National Institutes of Health and the University of Utah. Dr. Turok is the director of surgical services for Planned Parenthood Association of Utah; the trial was conducted at PPAU centers, but Dr. Turok does not work at the sites where the study was conducted. Dr. Turok has consulted for Sebela Pharmaceuticals as the principal investigator for two phase 3 studies that assessed novel IUDs. Dr. Turok and one coauthor received grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Fok and Dr. Aguilar disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A levonorgestrel 52-mg intrauterine device is noninferior to a copper IUD for emergency contraception, according to randomized trial results published online in the New England Journal of Medicine.
Although the trial didn’t directly compare emergency oral contraception to the hormonal IUD, the authors speculated, on the basis of prior findings, that the levonorgestrel IUD is more effective than oral emergency contraceptive pills. In addition, there is no delay in providing ongoing contraception as there is when ulipristal acetate is used for emergency contraception.
Prior research has found that copper IUDs are a highly effective method of emergency contraception, but studies of the use of other IUDs as emergency contraception have been lacking.
To examine whether the levonorgestrel IUD is noninferior to the copper IUD as emergency contraception after unprotected sexual intercourse during the previous 5 days, David K. Turok, MD, MPH, associate professor of obstetrics and gynecology at the University of Utah Health, Salt Lake City, and colleagues conducted a trial at six Planned Parenthood health centers in Utah.
Researchers enrolled patients between August 2016 and December 2019. Trial sites purchased levonorgestrel 52-mg IUDs (Liletta) and copper T380A IUDs (ParaGard) for the study. The companies that distribute the IUDs were not involved in the trial.
Pregnancy rates were 1 of 317 participants (0.3%) among those who received the levonorgestrel IUD, and 0 of 321 (0%) among those who received the copper IUD. The difference between the two arms was well within the prespecified noninferiority margin of 2.5%.
Adverse event rates were generally similar between the two groups, with 5.2% of participants in the levonorgestrel IUD group seeking medical care in the month after IUD placement, compared with 4.9% in the copper IUD group.
A welcome option
The study “benefits women by allowing us to introduce a new option into the method mix of emergency contraception,” commented Wing Kay Fok, MD, a clinical assistant professor of obstetrics and gynecology at Weill Cornell Medicine, New York.
Specialists in family planning had followed preliminary data from this study and were anticipating the final results. Clinicians who are comfortable placing a copper IUD for emergency contraception are likely to be comfortable placing a levonorgestrel 52-mg IUD, given these data, Dr. Fok said.
“This is definitely – from what we can tell – a more effective method than the pill,” she said.
Gabriela Aguilar, MD, MPH, fellow and clinical instructor in the department of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., said she is reassured by the data and is prepared to offer the 52-mg levonorgestrel IUD as emergency contraception.
The trial is “an important clinical study that has the ability to significantly change clinical practice,” Dr. Aguilar said. She credited the University of Utah and Planned Parenthood for their roles in it.
“Anytime that there are more options, ideally, that means that access is also increased,” Dr. Aguilar said.
Many patients will still prefer oral emergency contraceptive pills, she said. “But for those who are interested in an IUD ... for the immediate and ongoing birth control after that, now they have the two options instead of just the one IUD option.”
One pregnancy
The trial included women aged 18-35 years who requested emergency contraception after unprotected sexual intercourse within the previous 5 days. Other inclusion criteria were that participants had a desire to initiate use of an IUD; a desire to prevent pregnancy for at least 1 year; a negative result on urine pregnancy testing; a history of regular menstrual cycles; and a known date of the last menstrual period. The investigators did not exclude individuals who had unprotected sexual intercourse more than 5 days before IUD placement.
Participants were unaware of their assigned intervention. The nurse practitioners and certified nurse midwives who performed the IUD insertions were aware of the IUD type.
The primary outcome was pregnancy, as determined by a positive result on urine pregnancy testing 1 month after IUD insertion or by a review of survey and health record data.
One pregnancy “occurred in a participant who reported a single episode of unprotected sexual intercourse 48 hours before IUD placement,” the study authors wrote. “Pregnancy dating by an ultrasound examination at 10 weeks was consistent with conception occurring as a result of an emergency contraception failure. The pregnancy ended in a spontaneous abortion at 10 weeks with the IUD still in place.”
“We hope that providers can begin to deliver this method to everyone who wants and needs it and that people considering both emergency contraception and an ongoing method of birth control know that they now have the option of a hormonal IUD in addition to the nonhormonal, copper IUD,” Dr. Turok said in a news release from Planned Parenthood.
The study used a hormonal IUD manufactured by Liletta; Mirena also manufactures a levonorgestrel 52-mg IUD. The results of the study would apply to Mirena’s product too, according to Planned Parenthood.
“There are various IUDs on the market that are at lower doses, and so those IUDs may not demonstrate similar results,” Dr. Aguilar said.
The research was supported by the National Institutes of Health and the University of Utah. Dr. Turok is the director of surgical services for Planned Parenthood Association of Utah; the trial was conducted at PPAU centers, but Dr. Turok does not work at the sites where the study was conducted. Dr. Turok has consulted for Sebela Pharmaceuticals as the principal investigator for two phase 3 studies that assessed novel IUDs. Dr. Turok and one coauthor received grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Fok and Dr. Aguilar disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A levonorgestrel 52-mg intrauterine device is noninferior to a copper IUD for emergency contraception, according to randomized trial results published online in the New England Journal of Medicine.
Although the trial didn’t directly compare emergency oral contraception to the hormonal IUD, the authors speculated, on the basis of prior findings, that the levonorgestrel IUD is more effective than oral emergency contraceptive pills. In addition, there is no delay in providing ongoing contraception as there is when ulipristal acetate is used for emergency contraception.
Prior research has found that copper IUDs are a highly effective method of emergency contraception, but studies of the use of other IUDs as emergency contraception have been lacking.
To examine whether the levonorgestrel IUD is noninferior to the copper IUD as emergency contraception after unprotected sexual intercourse during the previous 5 days, David K. Turok, MD, MPH, associate professor of obstetrics and gynecology at the University of Utah Health, Salt Lake City, and colleagues conducted a trial at six Planned Parenthood health centers in Utah.
Researchers enrolled patients between August 2016 and December 2019. Trial sites purchased levonorgestrel 52-mg IUDs (Liletta) and copper T380A IUDs (ParaGard) for the study. The companies that distribute the IUDs were not involved in the trial.
Pregnancy rates were 1 of 317 participants (0.3%) among those who received the levonorgestrel IUD, and 0 of 321 (0%) among those who received the copper IUD. The difference between the two arms was well within the prespecified noninferiority margin of 2.5%.
Adverse event rates were generally similar between the two groups, with 5.2% of participants in the levonorgestrel IUD group seeking medical care in the month after IUD placement, compared with 4.9% in the copper IUD group.
A welcome option
The study “benefits women by allowing us to introduce a new option into the method mix of emergency contraception,” commented Wing Kay Fok, MD, a clinical assistant professor of obstetrics and gynecology at Weill Cornell Medicine, New York.
Specialists in family planning had followed preliminary data from this study and were anticipating the final results. Clinicians who are comfortable placing a copper IUD for emergency contraception are likely to be comfortable placing a levonorgestrel 52-mg IUD, given these data, Dr. Fok said.
“This is definitely – from what we can tell – a more effective method than the pill,” she said.
Gabriela Aguilar, MD, MPH, fellow and clinical instructor in the department of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., said she is reassured by the data and is prepared to offer the 52-mg levonorgestrel IUD as emergency contraception.
The trial is “an important clinical study that has the ability to significantly change clinical practice,” Dr. Aguilar said. She credited the University of Utah and Planned Parenthood for their roles in it.
“Anytime that there are more options, ideally, that means that access is also increased,” Dr. Aguilar said.
Many patients will still prefer oral emergency contraceptive pills, she said. “But for those who are interested in an IUD ... for the immediate and ongoing birth control after that, now they have the two options instead of just the one IUD option.”
One pregnancy
The trial included women aged 18-35 years who requested emergency contraception after unprotected sexual intercourse within the previous 5 days. Other inclusion criteria were that participants had a desire to initiate use of an IUD; a desire to prevent pregnancy for at least 1 year; a negative result on urine pregnancy testing; a history of regular menstrual cycles; and a known date of the last menstrual period. The investigators did not exclude individuals who had unprotected sexual intercourse more than 5 days before IUD placement.
Participants were unaware of their assigned intervention. The nurse practitioners and certified nurse midwives who performed the IUD insertions were aware of the IUD type.
The primary outcome was pregnancy, as determined by a positive result on urine pregnancy testing 1 month after IUD insertion or by a review of survey and health record data.
One pregnancy “occurred in a participant who reported a single episode of unprotected sexual intercourse 48 hours before IUD placement,” the study authors wrote. “Pregnancy dating by an ultrasound examination at 10 weeks was consistent with conception occurring as a result of an emergency contraception failure. The pregnancy ended in a spontaneous abortion at 10 weeks with the IUD still in place.”
“We hope that providers can begin to deliver this method to everyone who wants and needs it and that people considering both emergency contraception and an ongoing method of birth control know that they now have the option of a hormonal IUD in addition to the nonhormonal, copper IUD,” Dr. Turok said in a news release from Planned Parenthood.
The study used a hormonal IUD manufactured by Liletta; Mirena also manufactures a levonorgestrel 52-mg IUD. The results of the study would apply to Mirena’s product too, according to Planned Parenthood.
“There are various IUDs on the market that are at lower doses, and so those IUDs may not demonstrate similar results,” Dr. Aguilar said.
The research was supported by the National Institutes of Health and the University of Utah. Dr. Turok is the director of surgical services for Planned Parenthood Association of Utah; the trial was conducted at PPAU centers, but Dr. Turok does not work at the sites where the study was conducted. Dr. Turok has consulted for Sebela Pharmaceuticals as the principal investigator for two phase 3 studies that assessed novel IUDs. Dr. Turok and one coauthor received grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Fok and Dr. Aguilar disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Survey finds practice gaps in counseling women with hidradenitis suppurativa about pregnancy
that surveyed 59 women with HS.
Previous studies have shown the potential for adverse pregnancy outcomes associated with inflammatory conditions such as systemic vasculitis and lupus, but such data on HS and pregnancy are limited, which makes patient counseling a challenge, Ademide A. Adelekun, MD, of the University of Pennsylvania, Philadelphia, and colleagues wrote.
In a research letter published in JAMA Dermatology, they reported their findings from an email survey of female patients at two academic dermatology departments. A total of 59 women responded to the survey; their average age was 32 years, the majority (76%) had Hurley stage II disease, and 29 (49%) reported having ever been pregnant.
Two of the 29 women (7%) were pregnant at the time of the study survey; 20 of the other 27 pregnant women (74%) said they had full-term births, 4 (15%) reported miscarriages, and 3 (11%) had undergone an abortion.
A total of five patients (9%) reported difficulty getting pregnant after 1 year, and seven (12%) reported undergoing fertility treatments.
Nearly three-quarters of the women (73%) reported that HS had a negative impact on their sexual health, and 54% said they wished their doctors provided more counseling on HS and pregnancy.
A total of 14 patients (24%) said they believed HS affected their ability to become pregnant because of either decreased sexual activity or decreased fertility caused by HS medications, and nearly half (49%) said they believed that discontinuing all HS medications during pregnancy was necessary for safety reasons.
Patients also expressed concern about the possible heritability of HS: 80% said that physicians had not counseled them about HS heritability and 68% expressed concern that their child would have HS.
In addition, 83% said they had not received information about the potential impact of HS on pregnancy, and 22%, or 13 women, were concerned that childbirth would be more difficult; 11 of these 13 women (85%) had HS that affected the vulva and groin, and 4 of the 8 women who reported concerns about difficulty breastfeeding had HS that involved the breast.
Of the 59 patients surveyed, 12 (20%) said they believed HS poses risks to the child, including through transmission of HS in 8 (67%) or through an infection during a vaginal delivery in 7 women (58%).
The prevalence of HS patients’ concerns about pregnancy “may have unfavorable implications for family planning and mental health and may play a role in the inadequate treatment of HS in patients who are pregnant or planning to become pregnant,” the authors noted. “Family planning and prenatal counseling are particularly critical for those with HS given that clinicians weigh the risks of medication use against the benefits of disease control, which is associated with improved pregnancy outcomes for those with inflammatory conditions.”
The study findings were limited by several factors including “recall bias, low response rate, use of a nonvalidated survey, and generalizability to nonacademic settings,” the researchers noted. However, the results emphasize the often-underrecognized concerns of women with HS and the need for improvements in pregnancy-related counseling and systematic evaluation of outcomes.
The researchers had no financial conflicts to disclose. This study was funded by a FOCUS Medical Student Fellowship in Women’s Health grant.
that surveyed 59 women with HS.
Previous studies have shown the potential for adverse pregnancy outcomes associated with inflammatory conditions such as systemic vasculitis and lupus, but such data on HS and pregnancy are limited, which makes patient counseling a challenge, Ademide A. Adelekun, MD, of the University of Pennsylvania, Philadelphia, and colleagues wrote.
In a research letter published in JAMA Dermatology, they reported their findings from an email survey of female patients at two academic dermatology departments. A total of 59 women responded to the survey; their average age was 32 years, the majority (76%) had Hurley stage II disease, and 29 (49%) reported having ever been pregnant.
Two of the 29 women (7%) were pregnant at the time of the study survey; 20 of the other 27 pregnant women (74%) said they had full-term births, 4 (15%) reported miscarriages, and 3 (11%) had undergone an abortion.
A total of five patients (9%) reported difficulty getting pregnant after 1 year, and seven (12%) reported undergoing fertility treatments.
Nearly three-quarters of the women (73%) reported that HS had a negative impact on their sexual health, and 54% said they wished their doctors provided more counseling on HS and pregnancy.
A total of 14 patients (24%) said they believed HS affected their ability to become pregnant because of either decreased sexual activity or decreased fertility caused by HS medications, and nearly half (49%) said they believed that discontinuing all HS medications during pregnancy was necessary for safety reasons.
Patients also expressed concern about the possible heritability of HS: 80% said that physicians had not counseled them about HS heritability and 68% expressed concern that their child would have HS.
In addition, 83% said they had not received information about the potential impact of HS on pregnancy, and 22%, or 13 women, were concerned that childbirth would be more difficult; 11 of these 13 women (85%) had HS that affected the vulva and groin, and 4 of the 8 women who reported concerns about difficulty breastfeeding had HS that involved the breast.
Of the 59 patients surveyed, 12 (20%) said they believed HS poses risks to the child, including through transmission of HS in 8 (67%) or through an infection during a vaginal delivery in 7 women (58%).
The prevalence of HS patients’ concerns about pregnancy “may have unfavorable implications for family planning and mental health and may play a role in the inadequate treatment of HS in patients who are pregnant or planning to become pregnant,” the authors noted. “Family planning and prenatal counseling are particularly critical for those with HS given that clinicians weigh the risks of medication use against the benefits of disease control, which is associated with improved pregnancy outcomes for those with inflammatory conditions.”
The study findings were limited by several factors including “recall bias, low response rate, use of a nonvalidated survey, and generalizability to nonacademic settings,” the researchers noted. However, the results emphasize the often-underrecognized concerns of women with HS and the need for improvements in pregnancy-related counseling and systematic evaluation of outcomes.
The researchers had no financial conflicts to disclose. This study was funded by a FOCUS Medical Student Fellowship in Women’s Health grant.
that surveyed 59 women with HS.
Previous studies have shown the potential for adverse pregnancy outcomes associated with inflammatory conditions such as systemic vasculitis and lupus, but such data on HS and pregnancy are limited, which makes patient counseling a challenge, Ademide A. Adelekun, MD, of the University of Pennsylvania, Philadelphia, and colleagues wrote.
In a research letter published in JAMA Dermatology, they reported their findings from an email survey of female patients at two academic dermatology departments. A total of 59 women responded to the survey; their average age was 32 years, the majority (76%) had Hurley stage II disease, and 29 (49%) reported having ever been pregnant.
Two of the 29 women (7%) were pregnant at the time of the study survey; 20 of the other 27 pregnant women (74%) said they had full-term births, 4 (15%) reported miscarriages, and 3 (11%) had undergone an abortion.
A total of five patients (9%) reported difficulty getting pregnant after 1 year, and seven (12%) reported undergoing fertility treatments.
Nearly three-quarters of the women (73%) reported that HS had a negative impact on their sexual health, and 54% said they wished their doctors provided more counseling on HS and pregnancy.
A total of 14 patients (24%) said they believed HS affected their ability to become pregnant because of either decreased sexual activity or decreased fertility caused by HS medications, and nearly half (49%) said they believed that discontinuing all HS medications during pregnancy was necessary for safety reasons.
Patients also expressed concern about the possible heritability of HS: 80% said that physicians had not counseled them about HS heritability and 68% expressed concern that their child would have HS.
In addition, 83% said they had not received information about the potential impact of HS on pregnancy, and 22%, or 13 women, were concerned that childbirth would be more difficult; 11 of these 13 women (85%) had HS that affected the vulva and groin, and 4 of the 8 women who reported concerns about difficulty breastfeeding had HS that involved the breast.
Of the 59 patients surveyed, 12 (20%) said they believed HS poses risks to the child, including through transmission of HS in 8 (67%) or through an infection during a vaginal delivery in 7 women (58%).
The prevalence of HS patients’ concerns about pregnancy “may have unfavorable implications for family planning and mental health and may play a role in the inadequate treatment of HS in patients who are pregnant or planning to become pregnant,” the authors noted. “Family planning and prenatal counseling are particularly critical for those with HS given that clinicians weigh the risks of medication use against the benefits of disease control, which is associated with improved pregnancy outcomes for those with inflammatory conditions.”
The study findings were limited by several factors including “recall bias, low response rate, use of a nonvalidated survey, and generalizability to nonacademic settings,” the researchers noted. However, the results emphasize the often-underrecognized concerns of women with HS and the need for improvements in pregnancy-related counseling and systematic evaluation of outcomes.
The researchers had no financial conflicts to disclose. This study was funded by a FOCUS Medical Student Fellowship in Women’s Health grant.
FROM JAMA DERMATOLOGY
Higher dietary fiber tied to lower depression risk in young women
Higher fiber intake may be associated with decreased risk of depression in premenopausal women, new research suggests.
Investigators analyzed data from close to 6,000 pre- and postmenopausal women. They found that, in premenopausal women, dietary fiber intake was higher among those without depression versus their counterparts with the disorder in a dose-dependent manner. However, there appeared to be no relationship between higher fiber intake and depression risk in postmenopausal women.
“We think the most important finding of our study is that dietary fiber intake was inversely associated with depression in premenopausal but not postmenopausal women,” lead author Yunsun Kim, MD, resident, department of family medicine, Chung-Ang University Hospital, Seoul, South Korea, said in an interview.
“We hope that the findings of this study could form the basis of future investigations to determine the causal relationship between dietary fiber intake and depression,” she added.
The study was published online Dec. 21, 2020, in Menopause.
Gut-brain interaction
The prevalence of depression is twice as high in women, compared with men, which may be attributable to a number of factors, including hormonal status – especially during menstruation and menopause, the authors wrote.
Previous research suggests a potential association between dietary fiber and depression in premenopausal women and between estrogen and gut microbiota. Fiber intake has an impact on gut microbiota, Dr. Kim said.
“We are motivated by the fact that depression provokes disease burden internationally and we would like to find modifiable factors that could prevent depression, especially in women, who are more vulnerable to depression,” she noted.
To investigate, the researchers drew on data from the Korea National Health and Nutrition Examination Survey for 2014, 2016, and 2018. Of the total number of women who met inclusion criteria (n = 5807; mean age, 47.11), roughly half were premenopausal and half were postmenopausal (n = 2,949 [mean age, 36.23 years] and n = 2,868 [mean age, 62.73], respectively).
Dietary fiber intake was assessed using the 24-hour dietary recall method, while depression was assessed using the Patient Health Questionnaire-9. The researchers used the Dietary Reference Intakes for Koreans to define a sufficient intake of dietary fiber (i.e., 12 g/1,000 kcal).
Covariates included chronic diseases, body mass index, medications, smoking status, alcohol use, physical activity, and sociodemographic factors.
When the researchers looked at all participants, they found that the estimated mean dietary fiber intake was significantly higher in women without depression, compared with those with depression (14.07 g/1,000 kcal/d; 95% confidence interval, 13.85-14.29 vs. 12.67 g/1,000 kcal/d; 95% CI, 11.79-13.55; P = .003).
Although the relationship remained significant in premenopausal women, it lost significance in postmenopausal women.
A 5% decrease in the prevalence of depression in premenopausal (but not postmenopausal) women was found in those with an increased intake of dietary fiber – i..e, there was a 1-g increase for every 1,000 kcal of daily energy intake, after adjusting for potential confounders in premenopausal women (OR, 0.949; 95% CI, 0.906-0.993]).
“The inverse relationship between dietary fiber intake and depression could be explained by the gut-brain interactions,” said Dr. Kim.
“Changes in the gut microbiota composition may affect neurotransmission and various neuropsychiatric phenomena in the brain,” she said, noting that previous studies have suggested that dietary fiber intake “may modulate the richness and diversity of the gut microbiota, and this change may promote brain health by affecting neurotransmission.”
Because postmenopausal women experience estrogen depletion, “the decreased interaction between estrogen and the gut microbiota may be related to the insignificant association between dietary fiber intake and depression in postmenopausal women,” she said.
Despite the lack of a significant association between postmenopausal depression and fiber intake, Dr. Kim said she “advises middle-aged women to have dietary fiber–rich diets, regardless of their menopausal status.”
Link between food and mood
In a comment, Stephanie S. Faubion, MD, MBA, a professor and chair of the department of medicine and the Penny and Bill George director of the Mayo Clinic’s Center for Women’s Health in Rochester, Minn., noted the study was cross-sectional and therefore the direction of the association could not be determined and “causality cannot be assumed.”
It is possible that “depressed women are less likely to eat fiber than women without depression. For example, a depressed woman may be more likely to sit on the couch eating Cheetos than shopping for and preparing a healthy meal,” said Dr. Faubion, who is also the medical director of the North American Menopause Society and was not involved with the study.
She noted that other potential confounders, including access to fresh fruits and vegetables or geographic locations could also “impact the findings and .”
Nevertheless, the study does “add to the body of evidence suggesting a link between diet and overall health, including brain health,” Dr. Faubion said.
One take-home message for practicing clinicians is that a healthy diet that includes fiber may benefit women (and men) for a number of reasons and “appears to be linked to mood.”
More research is needed “to determine the pathophysiologic mechanisms (such as potential brain-gut connection that involves the microbiome) that may explain this association,” Dr. Faubion added.
No source of funding listed. Dr. Kim and coauthors, as well as Dr. Faubion, disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Higher fiber intake may be associated with decreased risk of depression in premenopausal women, new research suggests.
Investigators analyzed data from close to 6,000 pre- and postmenopausal women. They found that, in premenopausal women, dietary fiber intake was higher among those without depression versus their counterparts with the disorder in a dose-dependent manner. However, there appeared to be no relationship between higher fiber intake and depression risk in postmenopausal women.
“We think the most important finding of our study is that dietary fiber intake was inversely associated with depression in premenopausal but not postmenopausal women,” lead author Yunsun Kim, MD, resident, department of family medicine, Chung-Ang University Hospital, Seoul, South Korea, said in an interview.
“We hope that the findings of this study could form the basis of future investigations to determine the causal relationship between dietary fiber intake and depression,” she added.
The study was published online Dec. 21, 2020, in Menopause.
Gut-brain interaction
The prevalence of depression is twice as high in women, compared with men, which may be attributable to a number of factors, including hormonal status – especially during menstruation and menopause, the authors wrote.
Previous research suggests a potential association between dietary fiber and depression in premenopausal women and between estrogen and gut microbiota. Fiber intake has an impact on gut microbiota, Dr. Kim said.
“We are motivated by the fact that depression provokes disease burden internationally and we would like to find modifiable factors that could prevent depression, especially in women, who are more vulnerable to depression,” she noted.
To investigate, the researchers drew on data from the Korea National Health and Nutrition Examination Survey for 2014, 2016, and 2018. Of the total number of women who met inclusion criteria (n = 5807; mean age, 47.11), roughly half were premenopausal and half were postmenopausal (n = 2,949 [mean age, 36.23 years] and n = 2,868 [mean age, 62.73], respectively).
Dietary fiber intake was assessed using the 24-hour dietary recall method, while depression was assessed using the Patient Health Questionnaire-9. The researchers used the Dietary Reference Intakes for Koreans to define a sufficient intake of dietary fiber (i.e., 12 g/1,000 kcal).
Covariates included chronic diseases, body mass index, medications, smoking status, alcohol use, physical activity, and sociodemographic factors.
When the researchers looked at all participants, they found that the estimated mean dietary fiber intake was significantly higher in women without depression, compared with those with depression (14.07 g/1,000 kcal/d; 95% confidence interval, 13.85-14.29 vs. 12.67 g/1,000 kcal/d; 95% CI, 11.79-13.55; P = .003).
Although the relationship remained significant in premenopausal women, it lost significance in postmenopausal women.
A 5% decrease in the prevalence of depression in premenopausal (but not postmenopausal) women was found in those with an increased intake of dietary fiber – i..e, there was a 1-g increase for every 1,000 kcal of daily energy intake, after adjusting for potential confounders in premenopausal women (OR, 0.949; 95% CI, 0.906-0.993]).
“The inverse relationship between dietary fiber intake and depression could be explained by the gut-brain interactions,” said Dr. Kim.
“Changes in the gut microbiota composition may affect neurotransmission and various neuropsychiatric phenomena in the brain,” she said, noting that previous studies have suggested that dietary fiber intake “may modulate the richness and diversity of the gut microbiota, and this change may promote brain health by affecting neurotransmission.”
Because postmenopausal women experience estrogen depletion, “the decreased interaction between estrogen and the gut microbiota may be related to the insignificant association between dietary fiber intake and depression in postmenopausal women,” she said.
Despite the lack of a significant association between postmenopausal depression and fiber intake, Dr. Kim said she “advises middle-aged women to have dietary fiber–rich diets, regardless of their menopausal status.”
Link between food and mood
In a comment, Stephanie S. Faubion, MD, MBA, a professor and chair of the department of medicine and the Penny and Bill George director of the Mayo Clinic’s Center for Women’s Health in Rochester, Minn., noted the study was cross-sectional and therefore the direction of the association could not be determined and “causality cannot be assumed.”
It is possible that “depressed women are less likely to eat fiber than women without depression. For example, a depressed woman may be more likely to sit on the couch eating Cheetos than shopping for and preparing a healthy meal,” said Dr. Faubion, who is also the medical director of the North American Menopause Society and was not involved with the study.
She noted that other potential confounders, including access to fresh fruits and vegetables or geographic locations could also “impact the findings and .”
Nevertheless, the study does “add to the body of evidence suggesting a link between diet and overall health, including brain health,” Dr. Faubion said.
One take-home message for practicing clinicians is that a healthy diet that includes fiber may benefit women (and men) for a number of reasons and “appears to be linked to mood.”
More research is needed “to determine the pathophysiologic mechanisms (such as potential brain-gut connection that involves the microbiome) that may explain this association,” Dr. Faubion added.
No source of funding listed. Dr. Kim and coauthors, as well as Dr. Faubion, disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Higher fiber intake may be associated with decreased risk of depression in premenopausal women, new research suggests.
Investigators analyzed data from close to 6,000 pre- and postmenopausal women. They found that, in premenopausal women, dietary fiber intake was higher among those without depression versus their counterparts with the disorder in a dose-dependent manner. However, there appeared to be no relationship between higher fiber intake and depression risk in postmenopausal women.
“We think the most important finding of our study is that dietary fiber intake was inversely associated with depression in premenopausal but not postmenopausal women,” lead author Yunsun Kim, MD, resident, department of family medicine, Chung-Ang University Hospital, Seoul, South Korea, said in an interview.
“We hope that the findings of this study could form the basis of future investigations to determine the causal relationship between dietary fiber intake and depression,” she added.
The study was published online Dec. 21, 2020, in Menopause.
Gut-brain interaction
The prevalence of depression is twice as high in women, compared with men, which may be attributable to a number of factors, including hormonal status – especially during menstruation and menopause, the authors wrote.
Previous research suggests a potential association between dietary fiber and depression in premenopausal women and between estrogen and gut microbiota. Fiber intake has an impact on gut microbiota, Dr. Kim said.
“We are motivated by the fact that depression provokes disease burden internationally and we would like to find modifiable factors that could prevent depression, especially in women, who are more vulnerable to depression,” she noted.
To investigate, the researchers drew on data from the Korea National Health and Nutrition Examination Survey for 2014, 2016, and 2018. Of the total number of women who met inclusion criteria (n = 5807; mean age, 47.11), roughly half were premenopausal and half were postmenopausal (n = 2,949 [mean age, 36.23 years] and n = 2,868 [mean age, 62.73], respectively).
Dietary fiber intake was assessed using the 24-hour dietary recall method, while depression was assessed using the Patient Health Questionnaire-9. The researchers used the Dietary Reference Intakes for Koreans to define a sufficient intake of dietary fiber (i.e., 12 g/1,000 kcal).
Covariates included chronic diseases, body mass index, medications, smoking status, alcohol use, physical activity, and sociodemographic factors.
When the researchers looked at all participants, they found that the estimated mean dietary fiber intake was significantly higher in women without depression, compared with those with depression (14.07 g/1,000 kcal/d; 95% confidence interval, 13.85-14.29 vs. 12.67 g/1,000 kcal/d; 95% CI, 11.79-13.55; P = .003).
Although the relationship remained significant in premenopausal women, it lost significance in postmenopausal women.
A 5% decrease in the prevalence of depression in premenopausal (but not postmenopausal) women was found in those with an increased intake of dietary fiber – i..e, there was a 1-g increase for every 1,000 kcal of daily energy intake, after adjusting for potential confounders in premenopausal women (OR, 0.949; 95% CI, 0.906-0.993]).
“The inverse relationship between dietary fiber intake and depression could be explained by the gut-brain interactions,” said Dr. Kim.
“Changes in the gut microbiota composition may affect neurotransmission and various neuropsychiatric phenomena in the brain,” she said, noting that previous studies have suggested that dietary fiber intake “may modulate the richness and diversity of the gut microbiota, and this change may promote brain health by affecting neurotransmission.”
Because postmenopausal women experience estrogen depletion, “the decreased interaction between estrogen and the gut microbiota may be related to the insignificant association between dietary fiber intake and depression in postmenopausal women,” she said.
Despite the lack of a significant association between postmenopausal depression and fiber intake, Dr. Kim said she “advises middle-aged women to have dietary fiber–rich diets, regardless of their menopausal status.”
Link between food and mood
In a comment, Stephanie S. Faubion, MD, MBA, a professor and chair of the department of medicine and the Penny and Bill George director of the Mayo Clinic’s Center for Women’s Health in Rochester, Minn., noted the study was cross-sectional and therefore the direction of the association could not be determined and “causality cannot be assumed.”
It is possible that “depressed women are less likely to eat fiber than women without depression. For example, a depressed woman may be more likely to sit on the couch eating Cheetos than shopping for and preparing a healthy meal,” said Dr. Faubion, who is also the medical director of the North American Menopause Society and was not involved with the study.
She noted that other potential confounders, including access to fresh fruits and vegetables or geographic locations could also “impact the findings and .”
Nevertheless, the study does “add to the body of evidence suggesting a link between diet and overall health, including brain health,” Dr. Faubion said.
One take-home message for practicing clinicians is that a healthy diet that includes fiber may benefit women (and men) for a number of reasons and “appears to be linked to mood.”
More research is needed “to determine the pathophysiologic mechanisms (such as potential brain-gut connection that involves the microbiome) that may explain this association,” Dr. Faubion added.
No source of funding listed. Dr. Kim and coauthors, as well as Dr. Faubion, disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Metformin tied to longer gestation in women with preterm preeclampsia
Metformin extended gestation by nearly a week in women with preterm preeclampsia and was also linked to a shorter neonatal hospital stay, according to findings from a study presented Jan. 28 at the virtual Society for Maternal-Fetal Medicine 2021 Annual Pregnancy Meeting.
The causes of preeclampsia have continued to elude researchers, but most agree the placenta plays a key role, explained Cathy Cluver, PhD, director of the preeclampsia research unit and an associate professor at Stellenbosch University, Cape Town. Past trials have tested sildenafil, antithrombin, pravastatin, and esomeprazole, but the drugs either did not show promise, had unacceptable side effects, or need further study.
“This trial provides proof of concept that preterm preeclampsia can be treated and that we can slow the progression of preterm preeclampsia,” Dr. Cluver said.
In this trial, the researchers enrolled 180 women with preterm preeclampsia between 26 and 31 weeks of gestation. All the women were taking hypertensives. They were randomly assigned to receive 3 g oral metformin XR or placebo daily. The intention-to-treat analysis included 87 women who received metformin and 84 who received placebo, with baseline characteristics similar in both groups.
Women in the metformin group gave birth a median 16.2 days after randomization, which was 6.7 days longer than the 9.5 days postrandomization delivery of women in the placebo group. The differences, however, narrowly missed statistical significance (P =.056).
But when the researchers took compliance and dose into account, the effect of the metformin increased, showing a dose-dependent effect, and did reach statistical significance. Among the 147 women who continued treatment until delivery, those in the metformin group delivered a median 8.4 days later than those in the placebo group (16.2 vs. 7.4 days; P =.026). Further, when the analysis was further restricted to just the 100 women who continued taking the full dose until delivery, the difference was even greater (16.2 vs. 4.8 days; P =.008). In accordance with the safety profile of metformin, women taking the drug had more diarrhea and a trend toward more nausea than those taking the placebo.
There were no differences between the groups in composite maternal or neonatal outcomes, but the infants were an average 136 g (4.8 ounces) heavier in the metformin group, albeit the difference did not reach statistical significance. The 6-day–shorter neonatal stay at the study site facility for infants of the metformin group also did not reach statistical significance, but there was a significant difference between the groups on overall stay, including transfers to other facilities. Infants in the metformin group averaged 26 days vs. 34 days for infants in the placebo group (P =.007).
“We have shown that metformin XR may be a treatment for preterm preeclampsia. We now plan to do a larger study to hopefully confirm these findings, which will be powered to both prolongation of pregnancy and neonatal outcomes,” Dr. Cluver told this news organization. “We have also shown that one can prolong pregnancy in preterm preeclampsia, and we hope that this will encourage others in our field to continue researching therapeutics for preterm preeclampsia.”
In response to questions from attendees, Dr. Cluver reported that her team did not collect histological data from placentas in this study, and lack of funding is limiting their ability to evaluate longer-term outcomes.
The findings of prolonged gestation were certainly exciting, but they warrant caution before any changes in clinical practice, Michelle Y. Owens, MD, professor and chief of maternal-fetal medicine at the University of Mississippi Medical Center, Jackson, said in an interview.
“While the findings of this study are promising, the sample size was small, the dosing exceeds what we typically use in the U.S., and this was undertaken in Cape Town, South Africa, all of which may render this study less generalizable to our population and others across the globe,” said Dr. Owens, who moderated the oral abstract session.
She also pointed out a possible conflicting effect on birth weight brought on by using metformin to extend gestation.
“If larger studies are undertaken, I believe it is quite possible that, with extended gestation, there will be bigger babies,” she said. “However, metformin also helps control blood glucose and in so doing, may contribute to lower birth weights over time, compared with women not exposed to the drug.”
Dr. Cluver and Dr. Owens have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
*This story was updated on 2/9/2021.
Metformin extended gestation by nearly a week in women with preterm preeclampsia and was also linked to a shorter neonatal hospital stay, according to findings from a study presented Jan. 28 at the virtual Society for Maternal-Fetal Medicine 2021 Annual Pregnancy Meeting.
The causes of preeclampsia have continued to elude researchers, but most agree the placenta plays a key role, explained Cathy Cluver, PhD, director of the preeclampsia research unit and an associate professor at Stellenbosch University, Cape Town. Past trials have tested sildenafil, antithrombin, pravastatin, and esomeprazole, but the drugs either did not show promise, had unacceptable side effects, or need further study.
“This trial provides proof of concept that preterm preeclampsia can be treated and that we can slow the progression of preterm preeclampsia,” Dr. Cluver said.
In this trial, the researchers enrolled 180 women with preterm preeclampsia between 26 and 31 weeks of gestation. All the women were taking hypertensives. They were randomly assigned to receive 3 g oral metformin XR or placebo daily. The intention-to-treat analysis included 87 women who received metformin and 84 who received placebo, with baseline characteristics similar in both groups.
Women in the metformin group gave birth a median 16.2 days after randomization, which was 6.7 days longer than the 9.5 days postrandomization delivery of women in the placebo group. The differences, however, narrowly missed statistical significance (P =.056).
But when the researchers took compliance and dose into account, the effect of the metformin increased, showing a dose-dependent effect, and did reach statistical significance. Among the 147 women who continued treatment until delivery, those in the metformin group delivered a median 8.4 days later than those in the placebo group (16.2 vs. 7.4 days; P =.026). Further, when the analysis was further restricted to just the 100 women who continued taking the full dose until delivery, the difference was even greater (16.2 vs. 4.8 days; P =.008). In accordance with the safety profile of metformin, women taking the drug had more diarrhea and a trend toward more nausea than those taking the placebo.
There were no differences between the groups in composite maternal or neonatal outcomes, but the infants were an average 136 g (4.8 ounces) heavier in the metformin group, albeit the difference did not reach statistical significance. The 6-day–shorter neonatal stay at the study site facility for infants of the metformin group also did not reach statistical significance, but there was a significant difference between the groups on overall stay, including transfers to other facilities. Infants in the metformin group averaged 26 days vs. 34 days for infants in the placebo group (P =.007).
“We have shown that metformin XR may be a treatment for preterm preeclampsia. We now plan to do a larger study to hopefully confirm these findings, which will be powered to both prolongation of pregnancy and neonatal outcomes,” Dr. Cluver told this news organization. “We have also shown that one can prolong pregnancy in preterm preeclampsia, and we hope that this will encourage others in our field to continue researching therapeutics for preterm preeclampsia.”
In response to questions from attendees, Dr. Cluver reported that her team did not collect histological data from placentas in this study, and lack of funding is limiting their ability to evaluate longer-term outcomes.
The findings of prolonged gestation were certainly exciting, but they warrant caution before any changes in clinical practice, Michelle Y. Owens, MD, professor and chief of maternal-fetal medicine at the University of Mississippi Medical Center, Jackson, said in an interview.
“While the findings of this study are promising, the sample size was small, the dosing exceeds what we typically use in the U.S., and this was undertaken in Cape Town, South Africa, all of which may render this study less generalizable to our population and others across the globe,” said Dr. Owens, who moderated the oral abstract session.
She also pointed out a possible conflicting effect on birth weight brought on by using metformin to extend gestation.
“If larger studies are undertaken, I believe it is quite possible that, with extended gestation, there will be bigger babies,” she said. “However, metformin also helps control blood glucose and in so doing, may contribute to lower birth weights over time, compared with women not exposed to the drug.”
Dr. Cluver and Dr. Owens have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
*This story was updated on 2/9/2021.
Metformin extended gestation by nearly a week in women with preterm preeclampsia and was also linked to a shorter neonatal hospital stay, according to findings from a study presented Jan. 28 at the virtual Society for Maternal-Fetal Medicine 2021 Annual Pregnancy Meeting.
The causes of preeclampsia have continued to elude researchers, but most agree the placenta plays a key role, explained Cathy Cluver, PhD, director of the preeclampsia research unit and an associate professor at Stellenbosch University, Cape Town. Past trials have tested sildenafil, antithrombin, pravastatin, and esomeprazole, but the drugs either did not show promise, had unacceptable side effects, or need further study.
“This trial provides proof of concept that preterm preeclampsia can be treated and that we can slow the progression of preterm preeclampsia,” Dr. Cluver said.
In this trial, the researchers enrolled 180 women with preterm preeclampsia between 26 and 31 weeks of gestation. All the women were taking hypertensives. They were randomly assigned to receive 3 g oral metformin XR or placebo daily. The intention-to-treat analysis included 87 women who received metformin and 84 who received placebo, with baseline characteristics similar in both groups.
Women in the metformin group gave birth a median 16.2 days after randomization, which was 6.7 days longer than the 9.5 days postrandomization delivery of women in the placebo group. The differences, however, narrowly missed statistical significance (P =.056).
But when the researchers took compliance and dose into account, the effect of the metformin increased, showing a dose-dependent effect, and did reach statistical significance. Among the 147 women who continued treatment until delivery, those in the metformin group delivered a median 8.4 days later than those in the placebo group (16.2 vs. 7.4 days; P =.026). Further, when the analysis was further restricted to just the 100 women who continued taking the full dose until delivery, the difference was even greater (16.2 vs. 4.8 days; P =.008). In accordance with the safety profile of metformin, women taking the drug had more diarrhea and a trend toward more nausea than those taking the placebo.
There were no differences between the groups in composite maternal or neonatal outcomes, but the infants were an average 136 g (4.8 ounces) heavier in the metformin group, albeit the difference did not reach statistical significance. The 6-day–shorter neonatal stay at the study site facility for infants of the metformin group also did not reach statistical significance, but there was a significant difference between the groups on overall stay, including transfers to other facilities. Infants in the metformin group averaged 26 days vs. 34 days for infants in the placebo group (P =.007).
“We have shown that metformin XR may be a treatment for preterm preeclampsia. We now plan to do a larger study to hopefully confirm these findings, which will be powered to both prolongation of pregnancy and neonatal outcomes,” Dr. Cluver told this news organization. “We have also shown that one can prolong pregnancy in preterm preeclampsia, and we hope that this will encourage others in our field to continue researching therapeutics for preterm preeclampsia.”
In response to questions from attendees, Dr. Cluver reported that her team did not collect histological data from placentas in this study, and lack of funding is limiting their ability to evaluate longer-term outcomes.
The findings of prolonged gestation were certainly exciting, but they warrant caution before any changes in clinical practice, Michelle Y. Owens, MD, professor and chief of maternal-fetal medicine at the University of Mississippi Medical Center, Jackson, said in an interview.
“While the findings of this study are promising, the sample size was small, the dosing exceeds what we typically use in the U.S., and this was undertaken in Cape Town, South Africa, all of which may render this study less generalizable to our population and others across the globe,” said Dr. Owens, who moderated the oral abstract session.
She also pointed out a possible conflicting effect on birth weight brought on by using metformin to extend gestation.
“If larger studies are undertaken, I believe it is quite possible that, with extended gestation, there will be bigger babies,” she said. “However, metformin also helps control blood glucose and in so doing, may contribute to lower birth weights over time, compared with women not exposed to the drug.”
Dr. Cluver and Dr. Owens have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
*This story was updated on 2/9/2021.
COVID-19 in pregnancy tied to hypertension, preeclampsia
Having COVID-19 during pregnancy is linked to a significantly increased risk for gestational hypertension and preeclampsia compared with not having COVID-19 while pregnant, according to findings from a retrospective study presented Jan. 28 at the Society for Maternal-Fetal Medicine 2021 Annual Pregnancy Meeting.
“This was not entirely surprising given that inflammation has been implicated in the pathogenesis of both hypertensive disorders of pregnancy and COVID-19 infection and thus may serve to exacerbate each other,” Nigel Madden, MD, a resident physician in the ob.gyn. department at Columbia University, New York. , told this news organization after she presented the results.
Hypertensive disorders of pregnancy occur in 10%-15% of all pregnancies and are the leading cause of maternal and perinatal morbidity and mortality worldwide, Dr. Madden told attendees of the meeting. Although it’s not clear what causes hypertensive diseases in pregnancy generally, “it is possible that the acute inflammatory state of the COVID infection may incite or exacerbate hypertensive disease of pregnancy,” Dr. Madden said.
The researchers conducted a retrospective chart review of 1,715 patients who had a singleton pregnancy and who underwent routine nasal polymerase chain reaction testing at admission to one institution’s labor and delivery department between March and June 2020. The researchers excluded patients who had a history of chronic hypertension.
Overall, 10% of the patients tested positive for COVID-19 (n = 167), and 90% tested negative (n = 1,548). There were several differences at baseline between the groups. Those who tested positive tended to be younger, with an average age of 28, compared with an average age of 31 years for the group that tested negative. The group that tested negative also had a higher proportion of mothers aged 35 and older (P < .01). There were also significant differences in the racial makeup of the groups. Half of those in the COVID-positive group reported “other” for their race. The biggest baseline disparity between the groups was with regard to insurance type: 73% of those who tested positive for COVID-19 used Medicaid; only 36% of patients in the COVID-negative group used Medicaid. Those with private insurance were more likely to test negative (43%) than positive (25%) (P < .01).
The researchers defined gestational hypertension as having a systolic blood pressure greater than or equal to 140 mm Hg or a diastolic blood pressure greater than or equal to 90 mm Hg on two occasions at least 4 hours apart. A preeclampsia diagnosis required elevated blood pressure (using the same definition as for hypertension) as well as proteinuria, characterized by a protein/creatine ratio greater than or equal to 0.3 mg/dL or greater than or equal to 300 mg of protein on a 24-hour urine collection. Preeclampsia with severe features required prespecified laboratory abnormalities, pulmonary edema, or symptoms of headache, vision changes, chest pain, shortness of breath, or right upper quadrant pain.
More than twice as many patients with COVID had a hypertensive disorder of pregnancy (18%) as those who tested negative (8%). The patients who were COVID positive were significantly more likely than those who tested negative to have gestational hypertension and preeclampsia without severe features. Rates of preeclampsia with severe features were not significantly different between the groups.
The severity of hypertensive disease did not differ between the groups. Limitations of the study included its retrospective design, the small number of COVID-positive patients, and the fact that it was conducted at a single institution in New York. However, the study population was diverse, and it was conducted during the height of infections at the epicenter of the COVID-19 pandemic.
“This was a study of great clinical significance,” said Kim Boggess, MD, of the University of North Carolina at Chapel Hill, while moderating the session. “I would argue that you guys in New York are the best poised to answer some of the questions that need to be answered as it relates to the effect of coronavirus infection in pregnancy.”
Dr. Boggess asked whether the study examined associations related to the severity of COVID-19. Only 10 of the patients were symptomatic, Dr. Madden said, and only one of those patients developed preeclampsia with severe features.
Michelle Y. Owens, MD, professor and chief of maternal fetal medicine at the University of Mississippi Medical Center, Jackson, who also moderated the session, said in an interview that the findings call for physicians to remain vigilant about evaluating patients who test positive for COVID-19 for hypertensive disease and disorders.
“Additionally, these women should be educated about hypertensive disorders and the common symptoms to facilitate early diagnosis and treatment when indicated,” Dr. Owens said. “I believe this is of particular interest in those women who are not severely affected by COVID, as these changes may occur while they are undergoing quarantine or being monitored remotely. This amplifies the need for remote assessment or home monitoring of maternal blood pressures.”
Dr. Madden, Dr. Boggess, and Dr. Owens have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Having COVID-19 during pregnancy is linked to a significantly increased risk for gestational hypertension and preeclampsia compared with not having COVID-19 while pregnant, according to findings from a retrospective study presented Jan. 28 at the Society for Maternal-Fetal Medicine 2021 Annual Pregnancy Meeting.
“This was not entirely surprising given that inflammation has been implicated in the pathogenesis of both hypertensive disorders of pregnancy and COVID-19 infection and thus may serve to exacerbate each other,” Nigel Madden, MD, a resident physician in the ob.gyn. department at Columbia University, New York. , told this news organization after she presented the results.
Hypertensive disorders of pregnancy occur in 10%-15% of all pregnancies and are the leading cause of maternal and perinatal morbidity and mortality worldwide, Dr. Madden told attendees of the meeting. Although it’s not clear what causes hypertensive diseases in pregnancy generally, “it is possible that the acute inflammatory state of the COVID infection may incite or exacerbate hypertensive disease of pregnancy,” Dr. Madden said.
The researchers conducted a retrospective chart review of 1,715 patients who had a singleton pregnancy and who underwent routine nasal polymerase chain reaction testing at admission to one institution’s labor and delivery department between March and June 2020. The researchers excluded patients who had a history of chronic hypertension.
Overall, 10% of the patients tested positive for COVID-19 (n = 167), and 90% tested negative (n = 1,548). There were several differences at baseline between the groups. Those who tested positive tended to be younger, with an average age of 28, compared with an average age of 31 years for the group that tested negative. The group that tested negative also had a higher proportion of mothers aged 35 and older (P < .01). There were also significant differences in the racial makeup of the groups. Half of those in the COVID-positive group reported “other” for their race. The biggest baseline disparity between the groups was with regard to insurance type: 73% of those who tested positive for COVID-19 used Medicaid; only 36% of patients in the COVID-negative group used Medicaid. Those with private insurance were more likely to test negative (43%) than positive (25%) (P < .01).
The researchers defined gestational hypertension as having a systolic blood pressure greater than or equal to 140 mm Hg or a diastolic blood pressure greater than or equal to 90 mm Hg on two occasions at least 4 hours apart. A preeclampsia diagnosis required elevated blood pressure (using the same definition as for hypertension) as well as proteinuria, characterized by a protein/creatine ratio greater than or equal to 0.3 mg/dL or greater than or equal to 300 mg of protein on a 24-hour urine collection. Preeclampsia with severe features required prespecified laboratory abnormalities, pulmonary edema, or symptoms of headache, vision changes, chest pain, shortness of breath, or right upper quadrant pain.
More than twice as many patients with COVID had a hypertensive disorder of pregnancy (18%) as those who tested negative (8%). The patients who were COVID positive were significantly more likely than those who tested negative to have gestational hypertension and preeclampsia without severe features. Rates of preeclampsia with severe features were not significantly different between the groups.
The severity of hypertensive disease did not differ between the groups. Limitations of the study included its retrospective design, the small number of COVID-positive patients, and the fact that it was conducted at a single institution in New York. However, the study population was diverse, and it was conducted during the height of infections at the epicenter of the COVID-19 pandemic.
“This was a study of great clinical significance,” said Kim Boggess, MD, of the University of North Carolina at Chapel Hill, while moderating the session. “I would argue that you guys in New York are the best poised to answer some of the questions that need to be answered as it relates to the effect of coronavirus infection in pregnancy.”
Dr. Boggess asked whether the study examined associations related to the severity of COVID-19. Only 10 of the patients were symptomatic, Dr. Madden said, and only one of those patients developed preeclampsia with severe features.
Michelle Y. Owens, MD, professor and chief of maternal fetal medicine at the University of Mississippi Medical Center, Jackson, who also moderated the session, said in an interview that the findings call for physicians to remain vigilant about evaluating patients who test positive for COVID-19 for hypertensive disease and disorders.
“Additionally, these women should be educated about hypertensive disorders and the common symptoms to facilitate early diagnosis and treatment when indicated,” Dr. Owens said. “I believe this is of particular interest in those women who are not severely affected by COVID, as these changes may occur while they are undergoing quarantine or being monitored remotely. This amplifies the need for remote assessment or home monitoring of maternal blood pressures.”
Dr. Madden, Dr. Boggess, and Dr. Owens have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Having COVID-19 during pregnancy is linked to a significantly increased risk for gestational hypertension and preeclampsia compared with not having COVID-19 while pregnant, according to findings from a retrospective study presented Jan. 28 at the Society for Maternal-Fetal Medicine 2021 Annual Pregnancy Meeting.
“This was not entirely surprising given that inflammation has been implicated in the pathogenesis of both hypertensive disorders of pregnancy and COVID-19 infection and thus may serve to exacerbate each other,” Nigel Madden, MD, a resident physician in the ob.gyn. department at Columbia University, New York. , told this news organization after she presented the results.
Hypertensive disorders of pregnancy occur in 10%-15% of all pregnancies and are the leading cause of maternal and perinatal morbidity and mortality worldwide, Dr. Madden told attendees of the meeting. Although it’s not clear what causes hypertensive diseases in pregnancy generally, “it is possible that the acute inflammatory state of the COVID infection may incite or exacerbate hypertensive disease of pregnancy,” Dr. Madden said.
The researchers conducted a retrospective chart review of 1,715 patients who had a singleton pregnancy and who underwent routine nasal polymerase chain reaction testing at admission to one institution’s labor and delivery department between March and June 2020. The researchers excluded patients who had a history of chronic hypertension.
Overall, 10% of the patients tested positive for COVID-19 (n = 167), and 90% tested negative (n = 1,548). There were several differences at baseline between the groups. Those who tested positive tended to be younger, with an average age of 28, compared with an average age of 31 years for the group that tested negative. The group that tested negative also had a higher proportion of mothers aged 35 and older (P < .01). There were also significant differences in the racial makeup of the groups. Half of those in the COVID-positive group reported “other” for their race. The biggest baseline disparity between the groups was with regard to insurance type: 73% of those who tested positive for COVID-19 used Medicaid; only 36% of patients in the COVID-negative group used Medicaid. Those with private insurance were more likely to test negative (43%) than positive (25%) (P < .01).
The researchers defined gestational hypertension as having a systolic blood pressure greater than or equal to 140 mm Hg or a diastolic blood pressure greater than or equal to 90 mm Hg on two occasions at least 4 hours apart. A preeclampsia diagnosis required elevated blood pressure (using the same definition as for hypertension) as well as proteinuria, characterized by a protein/creatine ratio greater than or equal to 0.3 mg/dL or greater than or equal to 300 mg of protein on a 24-hour urine collection. Preeclampsia with severe features required prespecified laboratory abnormalities, pulmonary edema, or symptoms of headache, vision changes, chest pain, shortness of breath, or right upper quadrant pain.
More than twice as many patients with COVID had a hypertensive disorder of pregnancy (18%) as those who tested negative (8%). The patients who were COVID positive were significantly more likely than those who tested negative to have gestational hypertension and preeclampsia without severe features. Rates of preeclampsia with severe features were not significantly different between the groups.
The severity of hypertensive disease did not differ between the groups. Limitations of the study included its retrospective design, the small number of COVID-positive patients, and the fact that it was conducted at a single institution in New York. However, the study population was diverse, and it was conducted during the height of infections at the epicenter of the COVID-19 pandemic.
“This was a study of great clinical significance,” said Kim Boggess, MD, of the University of North Carolina at Chapel Hill, while moderating the session. “I would argue that you guys in New York are the best poised to answer some of the questions that need to be answered as it relates to the effect of coronavirus infection in pregnancy.”
Dr. Boggess asked whether the study examined associations related to the severity of COVID-19. Only 10 of the patients were symptomatic, Dr. Madden said, and only one of those patients developed preeclampsia with severe features.
Michelle Y. Owens, MD, professor and chief of maternal fetal medicine at the University of Mississippi Medical Center, Jackson, who also moderated the session, said in an interview that the findings call for physicians to remain vigilant about evaluating patients who test positive for COVID-19 for hypertensive disease and disorders.
“Additionally, these women should be educated about hypertensive disorders and the common symptoms to facilitate early diagnosis and treatment when indicated,” Dr. Owens said. “I believe this is of particular interest in those women who are not severely affected by COVID, as these changes may occur while they are undergoing quarantine or being monitored remotely. This amplifies the need for remote assessment or home monitoring of maternal blood pressures.”
Dr. Madden, Dr. Boggess, and Dr. Owens have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Oral contraceptives may reduce ovarian and endometrial cancer risk 35 years after discontinuation
At the same time, oral contraceptive use is associated with a short-term increased risk of breast cancer after discontinuation, although the lifetime risk of breast cancer is not significantly different, the researchers found.
The absolute risk of breast cancer after discontinuation is “extremely small” and should be a limited factor when deciding whether to start oral contraceptive pills (OCPs), a doctor said.
The study was conducted by Torgny Karlsson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala (Sweden) University, and colleagues and published online in Cancer Research.
Reinforcing and extending knowledge
“These findings are generally consistent with what is known, but extend that knowledge, most notably by the longer-term follow-up for the cohort,” commented Nancy L. Keating, MD, MPH, professor of health care policy and medicine at Harvard Medical School and a physician at Brigham and Women’s Hospital, both in Boston. “Other studies have also shown that OCPs lower risk of ovarian and endometrial cancer. This study suggests that this protective benefit extends up to 30-35 years after discontinuing OCPs.”
The results “reinforce the message to patients of the protective effect of OCPs on risk of ovarian and endometrial cancer,” Dr. Keating said. “Women concerned about these cancers can be reassured that this protective effect appears to persist for decades after discontinuing use.”
Prior studies have indicated that oral contraceptives may be associated with an increased risk of breast cancer.
In terms of breast cancer risk, the study “again extends follow-up and shows that risk of breast cancer was higher for current and ever users through age 50,” although the lifetime risk was not elevated, Dr. Keating said.
“The counseling regarding the effect on breast cancer is more complex,” she said. “I tell women about the very small increased risk of breast cancer during and immediately after use. Because cancer is very rare among women at the ages when OCPs are typically prescribed, the absolute risk increase is extremely small. This paper adds reassurance that this small increase in risk does not persist.”
For certain patients, the association may be more relevant.
“For most women, this risk is so small that it should be a limited factor in their decision to start OCPs,” Dr. Keating said. “However, for women with a substantially higher risk of breast cancer, or a family history of breast cancer at a young age, the small increased risk of breast cancer during and immediately after OCP use is more relevant, and counseling should include carefully weighing the benefits and harms of OCPs with other forms of contraception (and no contraception).”
Although the protective effects of oral contraceptives on ovarian and endometrial cancer were well known, the study describes long-term outcomes that can further inform patient counseling, said Samuel S. Badalian, MD, PhD, chief of the department of obstetrics and gynecology at Bassett Medical Center in Cooperstown, N.Y., and clinical professor of obstetrics and gynecology at the State University of New York, Syracuse.
“Women with individual or family risk factors of ovarian or endometrial cancers will need to know about the protective effects of oral contraceptives and long-term benefits related with their use (30-35 years after discontinuation),” Dr. Badalian said. “Women with family history of breast cancer need to know that lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”
Data from the U.K. Biobank
To examine the time-dependent effects between long-term oral contraceptive use and cancer risk, the researchers examined data from 256,661 women from the U.K. Biobank who were born between 1939 and 1970. The researchers identified cancer diagnoses using information from national registers and self-reported data until March 2019.
Of the women included in the study, 82% had used or still were using oral contraceptives, whereas 18% had never used oral contraceptives. Overall, ever users were younger, more frequently smokers, and had a lower body mass index, compared with never users. Most women started using oral contraceptives between 1969 and 1978. Last use of oral contraceptives occurred on average 10.7 years after starting.
The researchers adjusted for covariates and used logistic regression analyses to measure the cumulative risk of cancer. They used Cox regression analysis to examine instantaneous risk, measured using hazard ratios.
In all, there were 17,739 cases of breast cancer (6.9%), 1,966 cases of ovarian cancer (0.76%), and 2,462 cases of endometrial cancer (0.96%).
Among ever users, the likelihood of ovarian cancer (OR, 0.72) and endometrial cancer (OR, 0.68) was lower, compared with never users. “However, we did not see a significant association between oral contraceptive use and breast cancer” for the study period as a whole, the researchers reported. When the researchers limited follow-up to age 50 years, however, the odds ratio for breast cancer was increased (OR, 1.09).
“Surprisingly, we only found a small increased risk of breast cancer among oral contraceptive users, and the increased risk disappeared within a few years after discontinuation,” Åsa Johansson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala University and one of the study authors, said in a news release. “Our results suggest that the lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”
Oral contraceptives today typically use lower doses of estrogen and other types of progesterone, compared with formulas commonly used when participants in the study started taking them, so the results may not directly apply to patients currently taking oral contraceptives, the researchers noted.
The study was supported by the Swedish Research Council, the Swedish Cancer Society, and the Kjell and Märta Beijers, the Marcus Borgström, the Åke Wiberg, and the A and M Rudbergs foundations. The authors, Dr. Keating, and Dr. Badalian had no conflicts of interest.
At the same time, oral contraceptive use is associated with a short-term increased risk of breast cancer after discontinuation, although the lifetime risk of breast cancer is not significantly different, the researchers found.
The absolute risk of breast cancer after discontinuation is “extremely small” and should be a limited factor when deciding whether to start oral contraceptive pills (OCPs), a doctor said.
The study was conducted by Torgny Karlsson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala (Sweden) University, and colleagues and published online in Cancer Research.
Reinforcing and extending knowledge
“These findings are generally consistent with what is known, but extend that knowledge, most notably by the longer-term follow-up for the cohort,” commented Nancy L. Keating, MD, MPH, professor of health care policy and medicine at Harvard Medical School and a physician at Brigham and Women’s Hospital, both in Boston. “Other studies have also shown that OCPs lower risk of ovarian and endometrial cancer. This study suggests that this protective benefit extends up to 30-35 years after discontinuing OCPs.”
The results “reinforce the message to patients of the protective effect of OCPs on risk of ovarian and endometrial cancer,” Dr. Keating said. “Women concerned about these cancers can be reassured that this protective effect appears to persist for decades after discontinuing use.”
Prior studies have indicated that oral contraceptives may be associated with an increased risk of breast cancer.
In terms of breast cancer risk, the study “again extends follow-up and shows that risk of breast cancer was higher for current and ever users through age 50,” although the lifetime risk was not elevated, Dr. Keating said.
“The counseling regarding the effect on breast cancer is more complex,” she said. “I tell women about the very small increased risk of breast cancer during and immediately after use. Because cancer is very rare among women at the ages when OCPs are typically prescribed, the absolute risk increase is extremely small. This paper adds reassurance that this small increase in risk does not persist.”
For certain patients, the association may be more relevant.
“For most women, this risk is so small that it should be a limited factor in their decision to start OCPs,” Dr. Keating said. “However, for women with a substantially higher risk of breast cancer, or a family history of breast cancer at a young age, the small increased risk of breast cancer during and immediately after OCP use is more relevant, and counseling should include carefully weighing the benefits and harms of OCPs with other forms of contraception (and no contraception).”
Although the protective effects of oral contraceptives on ovarian and endometrial cancer were well known, the study describes long-term outcomes that can further inform patient counseling, said Samuel S. Badalian, MD, PhD, chief of the department of obstetrics and gynecology at Bassett Medical Center in Cooperstown, N.Y., and clinical professor of obstetrics and gynecology at the State University of New York, Syracuse.
“Women with individual or family risk factors of ovarian or endometrial cancers will need to know about the protective effects of oral contraceptives and long-term benefits related with their use (30-35 years after discontinuation),” Dr. Badalian said. “Women with family history of breast cancer need to know that lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”
Data from the U.K. Biobank
To examine the time-dependent effects between long-term oral contraceptive use and cancer risk, the researchers examined data from 256,661 women from the U.K. Biobank who were born between 1939 and 1970. The researchers identified cancer diagnoses using information from national registers and self-reported data until March 2019.
Of the women included in the study, 82% had used or still were using oral contraceptives, whereas 18% had never used oral contraceptives. Overall, ever users were younger, more frequently smokers, and had a lower body mass index, compared with never users. Most women started using oral contraceptives between 1969 and 1978. Last use of oral contraceptives occurred on average 10.7 years after starting.
The researchers adjusted for covariates and used logistic regression analyses to measure the cumulative risk of cancer. They used Cox regression analysis to examine instantaneous risk, measured using hazard ratios.
In all, there were 17,739 cases of breast cancer (6.9%), 1,966 cases of ovarian cancer (0.76%), and 2,462 cases of endometrial cancer (0.96%).
Among ever users, the likelihood of ovarian cancer (OR, 0.72) and endometrial cancer (OR, 0.68) was lower, compared with never users. “However, we did not see a significant association between oral contraceptive use and breast cancer” for the study period as a whole, the researchers reported. When the researchers limited follow-up to age 50 years, however, the odds ratio for breast cancer was increased (OR, 1.09).
“Surprisingly, we only found a small increased risk of breast cancer among oral contraceptive users, and the increased risk disappeared within a few years after discontinuation,” Åsa Johansson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala University and one of the study authors, said in a news release. “Our results suggest that the lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”
Oral contraceptives today typically use lower doses of estrogen and other types of progesterone, compared with formulas commonly used when participants in the study started taking them, so the results may not directly apply to patients currently taking oral contraceptives, the researchers noted.
The study was supported by the Swedish Research Council, the Swedish Cancer Society, and the Kjell and Märta Beijers, the Marcus Borgström, the Åke Wiberg, and the A and M Rudbergs foundations. The authors, Dr. Keating, and Dr. Badalian had no conflicts of interest.
At the same time, oral contraceptive use is associated with a short-term increased risk of breast cancer after discontinuation, although the lifetime risk of breast cancer is not significantly different, the researchers found.
The absolute risk of breast cancer after discontinuation is “extremely small” and should be a limited factor when deciding whether to start oral contraceptive pills (OCPs), a doctor said.
The study was conducted by Torgny Karlsson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala (Sweden) University, and colleagues and published online in Cancer Research.
Reinforcing and extending knowledge
“These findings are generally consistent with what is known, but extend that knowledge, most notably by the longer-term follow-up for the cohort,” commented Nancy L. Keating, MD, MPH, professor of health care policy and medicine at Harvard Medical School and a physician at Brigham and Women’s Hospital, both in Boston. “Other studies have also shown that OCPs lower risk of ovarian and endometrial cancer. This study suggests that this protective benefit extends up to 30-35 years after discontinuing OCPs.”
The results “reinforce the message to patients of the protective effect of OCPs on risk of ovarian and endometrial cancer,” Dr. Keating said. “Women concerned about these cancers can be reassured that this protective effect appears to persist for decades after discontinuing use.”
Prior studies have indicated that oral contraceptives may be associated with an increased risk of breast cancer.
In terms of breast cancer risk, the study “again extends follow-up and shows that risk of breast cancer was higher for current and ever users through age 50,” although the lifetime risk was not elevated, Dr. Keating said.
“The counseling regarding the effect on breast cancer is more complex,” she said. “I tell women about the very small increased risk of breast cancer during and immediately after use. Because cancer is very rare among women at the ages when OCPs are typically prescribed, the absolute risk increase is extremely small. This paper adds reassurance that this small increase in risk does not persist.”
For certain patients, the association may be more relevant.
“For most women, this risk is so small that it should be a limited factor in their decision to start OCPs,” Dr. Keating said. “However, for women with a substantially higher risk of breast cancer, or a family history of breast cancer at a young age, the small increased risk of breast cancer during and immediately after OCP use is more relevant, and counseling should include carefully weighing the benefits and harms of OCPs with other forms of contraception (and no contraception).”
Although the protective effects of oral contraceptives on ovarian and endometrial cancer were well known, the study describes long-term outcomes that can further inform patient counseling, said Samuel S. Badalian, MD, PhD, chief of the department of obstetrics and gynecology at Bassett Medical Center in Cooperstown, N.Y., and clinical professor of obstetrics and gynecology at the State University of New York, Syracuse.
“Women with individual or family risk factors of ovarian or endometrial cancers will need to know about the protective effects of oral contraceptives and long-term benefits related with their use (30-35 years after discontinuation),” Dr. Badalian said. “Women with family history of breast cancer need to know that lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”
Data from the U.K. Biobank
To examine the time-dependent effects between long-term oral contraceptive use and cancer risk, the researchers examined data from 256,661 women from the U.K. Biobank who were born between 1939 and 1970. The researchers identified cancer diagnoses using information from national registers and self-reported data until March 2019.
Of the women included in the study, 82% had used or still were using oral contraceptives, whereas 18% had never used oral contraceptives. Overall, ever users were younger, more frequently smokers, and had a lower body mass index, compared with never users. Most women started using oral contraceptives between 1969 and 1978. Last use of oral contraceptives occurred on average 10.7 years after starting.
The researchers adjusted for covariates and used logistic regression analyses to measure the cumulative risk of cancer. They used Cox regression analysis to examine instantaneous risk, measured using hazard ratios.
In all, there were 17,739 cases of breast cancer (6.9%), 1,966 cases of ovarian cancer (0.76%), and 2,462 cases of endometrial cancer (0.96%).
Among ever users, the likelihood of ovarian cancer (OR, 0.72) and endometrial cancer (OR, 0.68) was lower, compared with never users. “However, we did not see a significant association between oral contraceptive use and breast cancer” for the study period as a whole, the researchers reported. When the researchers limited follow-up to age 50 years, however, the odds ratio for breast cancer was increased (OR, 1.09).
“Surprisingly, we only found a small increased risk of breast cancer among oral contraceptive users, and the increased risk disappeared within a few years after discontinuation,” Åsa Johansson, PhD, a researcher in the department of immunology, genetics, and pathology at Uppsala University and one of the study authors, said in a news release. “Our results suggest that the lifetime risk of breast cancer might not differ between ever and never users, even if there is an increased short-term risk.”
Oral contraceptives today typically use lower doses of estrogen and other types of progesterone, compared with formulas commonly used when participants in the study started taking them, so the results may not directly apply to patients currently taking oral contraceptives, the researchers noted.
The study was supported by the Swedish Research Council, the Swedish Cancer Society, and the Kjell and Märta Beijers, the Marcus Borgström, the Åke Wiberg, and the A and M Rudbergs foundations. The authors, Dr. Keating, and Dr. Badalian had no conflicts of interest.
FROM CANCER RESEARCH
Findings could change breast cancer risk management
The findings come from two large studies, both published on Jan. 20 in the New England Journal of Medicine.
The two articles are “extraordinary” for broadening and validating the genomic panel to help screen women at risk for breast cancer in the future, commented Eric Topol, MD, professor of molecular medicine, Scripps Research, La Jolla, Calif., and Medscape editor in chief.
“Traditionally, genetic testing of inherited breast cancer genes has focused on women at high risk who have a strong family history of breast cancer or those who were diagnosed at an early age, such as under 45 years,” commented the lead investigator of one of the studies, Fergus Couch, PhD, a pathologist at the Mayo Clinic, Rochester, Minn.
“[Although] the risk of developing breast cancer is generally lower for women without a family history of the disease ... when we looked at all women, we found that 30% of breast cancer mutations occurred in women who are not high risk,” he said.
In both studies, mutations or variants in eight genes – BRCA1, BRCA2, PALB2, BARD1, RAD51C, RAD51D, ATM, and CHEK2 – were found to be significantly associated with breast cancer risk.
However, the distribution of mutations among women with breast cancer differed from the distribution among unaffected women, noted Steven Narod, MD, from the Women’s College Research Institute, Toronto, in an accompanying editorial.
“What this means to clinicians, now that we are expanding the use of gene-panel testing to include unaffected women with a moderate risk of breast cancer in the family history, is that our time will increasingly be spent counseling women with CHEK2 and ATM mutations,” he wrote. Currently, these two are “clumped in with ‘other genes.’ ... Most of the pretest discussion is currently focused on the implications of finding a BRCA1 or BRCA2 mutation.”
The new findings may lead to new risk management strategies, he suggested. “Most breast cancers that occur in women with a mutation in ATM or CHEK2 are estrogen receptor positive, so these women may be candidates for antiestrogen therapies such as tamoxifen, raloxifene, or aromatase inhibitors,” he wrote.
Dr. Narod observed that, for now, the management of most women with either mutation will consist of screening alone, starting with MRI at age 40 years.
The medical community is not ready yet to expand genetic screening to the general population, cautions Walton Taylor, MD, past president of the American Society of Breast Surgeons.
The ASBrS currently recommends that all patients with breast cancer as well as those at high risk for breast cancer be offered genetic testing. “All women at risk should be tested, and all patients with pathogenic variants need to be managed appropriately – it saves lives,” Dr. Taylor emphasized.
However, “unaffected people with no family history do not need genetic testing at this time,” he said in an interview.
As to what physicians might do to better manage patients with mutations that predispose to breast cancer, Dr. Taylor said, “It’s surprisingly easy.”
Every genetic testing company provides genetic counselors to guide patients through next steps, Dr. Taylor pointed out, and most cancer patients have nurse navigators who make sure patients get tested and followed appropriately.
Members of the ASBrS follow the National Comprehensive Cancer Network guidelines when they identify carriers of a pathogenic variant. Dr. Taylor said these are very useful guidelines for virtually all mutations identified thus far.
“This research is not necessarily new, but it is confirmatory for what we are doing, and that helps us make sure we are going down the right pathway,” Dr. Taylor said. “It confirms that what we think is right is right – and that matters,.”
CARRIERS consortium findings
The study led by Dr. Couch was carried out by the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. It involved analyzing data from 17 epidemiology studies that focused on women in the general population who develop breast cancer. For the studies, which were conducted in the United States, pathogenic variants in 28 cancer-predisposition genes were sequenced from 32,247 women with breast cancer (case patients) and 32,544 unaffected women (control persons).
In the overall CARRIERS analysis, the prevalence of pathogenic variants in 12 clinically actionable genes was 5.03% among case patients and 1.63% among control persons. The prevalence was similar in non-Hispanic White women, non-Hispanic Black women, and Hispanic case patients, as well as control persons, they added. The prevalence of pathogenic variants among Asian American case patients was lower, at only 1.64%.
Among patients who had breast cancer, the most common pathogenic variants included BRCA2, which occurred in 1.29% of case patients, followed by CHEK2, at a prevalence of 1.08%, and BRCA1, at a prevalence of 0.85%.
Mutations in BRCA1 increased the risk for breast cancer more than 7.5-fold; mutations in BRCA2 increased that risk more than fivefold, the investigators stated.
Mutations in PALB2 increased the risk of breast cancer approximately fourfold, they added.
Prevalence rates for both BRCA1 and BRCA2 among breast cancer patients declined rapidly after the age of 40. The decline in other variants, including ATM, CHEK2, and PALB2, was limited with increasing age.
Indeed, mutations in all five of these genes were associated with a lifetime absolute risk for breast cancer greater than 20% by the age of 85 years among non-Hispanic Whites.
Pathogenic variants in BRCA1 or BRCA2 yielded a lifetime risk for breast cancer of approximately 50%. Mutations in PALB2 yielded a lifetime breast cancer risk of approximately 32%.
The risk of having a mutation in specific genes varied depending on the type of breast cancer. For example, mutations in BARD1, RAD51C, and RAD51D increased the risk for estrogen receptor (ER)–negative breast cancer as well as triple-negative breast cancer, the authors noted, whereas mutations in ATM, CDH1, and CHEK2 increased the risk for ER-positive breast cancer.
“These refined estimates of the prevalences of pathogenic variants among women with breast cancer in the overall population, as opposed to selected high-risk patients, may inform ongoing discussions regarding testing in patients with breast cancer,” the CARRIERS authors observed.
“The risks of breast cancer associated with pathogenic variants in the genes evaluated in the population-based CARRIERS analysis also provide important information for risk assessment and counseling of women with breast cancer who do not meet high-risk selection criteria,” they suggested.
Similar findings in second study
The second study was conducted by the Breast Cancer Association Consortium under lead author Leila Dorling, PhD, University of Cambridge (England). This group sequenced 34 susceptibility genes from 60,466 women with breast cancer and 53,461 unaffected control persons.
“Protein-truncating variants in five genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a significant risk of breast cancer overall (P < .0001),” the BCAC members reported. “For these genes, odds ratios ranged from 2.10 to 10.57.”
The association between overall breast cancer risk and mutations in seven other genes was more modest, conferring approximately twice the risk for breast cancer overall, although that risk was threefold higher for the TP53 mutation.
For the 12 genes the consortium singled out as being associated with either a significant or a more modest risk for breast cancer, the effect size did not vary significantly between European and Asian women, the authors noted. Again, the risk for ER-positive breast cancer was over two times greater for those who had either the ATM or the CHEK2 mutation. Having mutations in BARD1, BRCA1, BRCA1, PALB2, RAD51C, and RAD51D conferred a higher risk for ER-negative disease than for ER-positive disease.
There was also an association between rare missense variants in six genes – CHEK2, ATM, TP53, BRCA1, CDH1, and RECQL – and overall breast cancer risk, with the clearest evidence being for CHEK2.
“The absolute risk estimates place protein-truncating variants in BRCA1, BRCA2, and PALB2 in the high-risk category and place protein-truncating variants in ATM, BARD1, CHEK2, RAD51CC, and RAD51D in the moderate-risk category,” Dr. Dorling and colleagues reaffirmed.
“These results may guide screening as well as prevention with risk-reducing surgery or medication, in accordance with national guidelines,” the authors suggested.
The CARRIERS study was supported by the National Institutes of Health. The study by Dr. Dorling and colleagues was supported by the European Union Horizon 2020 research and innovation programs, among others. Dr. Narod disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The findings come from two large studies, both published on Jan. 20 in the New England Journal of Medicine.
The two articles are “extraordinary” for broadening and validating the genomic panel to help screen women at risk for breast cancer in the future, commented Eric Topol, MD, professor of molecular medicine, Scripps Research, La Jolla, Calif., and Medscape editor in chief.
“Traditionally, genetic testing of inherited breast cancer genes has focused on women at high risk who have a strong family history of breast cancer or those who were diagnosed at an early age, such as under 45 years,” commented the lead investigator of one of the studies, Fergus Couch, PhD, a pathologist at the Mayo Clinic, Rochester, Minn.
“[Although] the risk of developing breast cancer is generally lower for women without a family history of the disease ... when we looked at all women, we found that 30% of breast cancer mutations occurred in women who are not high risk,” he said.
In both studies, mutations or variants in eight genes – BRCA1, BRCA2, PALB2, BARD1, RAD51C, RAD51D, ATM, and CHEK2 – were found to be significantly associated with breast cancer risk.
However, the distribution of mutations among women with breast cancer differed from the distribution among unaffected women, noted Steven Narod, MD, from the Women’s College Research Institute, Toronto, in an accompanying editorial.
“What this means to clinicians, now that we are expanding the use of gene-panel testing to include unaffected women with a moderate risk of breast cancer in the family history, is that our time will increasingly be spent counseling women with CHEK2 and ATM mutations,” he wrote. Currently, these two are “clumped in with ‘other genes.’ ... Most of the pretest discussion is currently focused on the implications of finding a BRCA1 or BRCA2 mutation.”
The new findings may lead to new risk management strategies, he suggested. “Most breast cancers that occur in women with a mutation in ATM or CHEK2 are estrogen receptor positive, so these women may be candidates for antiestrogen therapies such as tamoxifen, raloxifene, or aromatase inhibitors,” he wrote.
Dr. Narod observed that, for now, the management of most women with either mutation will consist of screening alone, starting with MRI at age 40 years.
The medical community is not ready yet to expand genetic screening to the general population, cautions Walton Taylor, MD, past president of the American Society of Breast Surgeons.
The ASBrS currently recommends that all patients with breast cancer as well as those at high risk for breast cancer be offered genetic testing. “All women at risk should be tested, and all patients with pathogenic variants need to be managed appropriately – it saves lives,” Dr. Taylor emphasized.
However, “unaffected people with no family history do not need genetic testing at this time,” he said in an interview.
As to what physicians might do to better manage patients with mutations that predispose to breast cancer, Dr. Taylor said, “It’s surprisingly easy.”
Every genetic testing company provides genetic counselors to guide patients through next steps, Dr. Taylor pointed out, and most cancer patients have nurse navigators who make sure patients get tested and followed appropriately.
Members of the ASBrS follow the National Comprehensive Cancer Network guidelines when they identify carriers of a pathogenic variant. Dr. Taylor said these are very useful guidelines for virtually all mutations identified thus far.
“This research is not necessarily new, but it is confirmatory for what we are doing, and that helps us make sure we are going down the right pathway,” Dr. Taylor said. “It confirms that what we think is right is right – and that matters,.”
CARRIERS consortium findings
The study led by Dr. Couch was carried out by the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. It involved analyzing data from 17 epidemiology studies that focused on women in the general population who develop breast cancer. For the studies, which were conducted in the United States, pathogenic variants in 28 cancer-predisposition genes were sequenced from 32,247 women with breast cancer (case patients) and 32,544 unaffected women (control persons).
In the overall CARRIERS analysis, the prevalence of pathogenic variants in 12 clinically actionable genes was 5.03% among case patients and 1.63% among control persons. The prevalence was similar in non-Hispanic White women, non-Hispanic Black women, and Hispanic case patients, as well as control persons, they added. The prevalence of pathogenic variants among Asian American case patients was lower, at only 1.64%.
Among patients who had breast cancer, the most common pathogenic variants included BRCA2, which occurred in 1.29% of case patients, followed by CHEK2, at a prevalence of 1.08%, and BRCA1, at a prevalence of 0.85%.
Mutations in BRCA1 increased the risk for breast cancer more than 7.5-fold; mutations in BRCA2 increased that risk more than fivefold, the investigators stated.
Mutations in PALB2 increased the risk of breast cancer approximately fourfold, they added.
Prevalence rates for both BRCA1 and BRCA2 among breast cancer patients declined rapidly after the age of 40. The decline in other variants, including ATM, CHEK2, and PALB2, was limited with increasing age.
Indeed, mutations in all five of these genes were associated with a lifetime absolute risk for breast cancer greater than 20% by the age of 85 years among non-Hispanic Whites.
Pathogenic variants in BRCA1 or BRCA2 yielded a lifetime risk for breast cancer of approximately 50%. Mutations in PALB2 yielded a lifetime breast cancer risk of approximately 32%.
The risk of having a mutation in specific genes varied depending on the type of breast cancer. For example, mutations in BARD1, RAD51C, and RAD51D increased the risk for estrogen receptor (ER)–negative breast cancer as well as triple-negative breast cancer, the authors noted, whereas mutations in ATM, CDH1, and CHEK2 increased the risk for ER-positive breast cancer.
“These refined estimates of the prevalences of pathogenic variants among women with breast cancer in the overall population, as opposed to selected high-risk patients, may inform ongoing discussions regarding testing in patients with breast cancer,” the CARRIERS authors observed.
“The risks of breast cancer associated with pathogenic variants in the genes evaluated in the population-based CARRIERS analysis also provide important information for risk assessment and counseling of women with breast cancer who do not meet high-risk selection criteria,” they suggested.
Similar findings in second study
The second study was conducted by the Breast Cancer Association Consortium under lead author Leila Dorling, PhD, University of Cambridge (England). This group sequenced 34 susceptibility genes from 60,466 women with breast cancer and 53,461 unaffected control persons.
“Protein-truncating variants in five genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a significant risk of breast cancer overall (P < .0001),” the BCAC members reported. “For these genes, odds ratios ranged from 2.10 to 10.57.”
The association between overall breast cancer risk and mutations in seven other genes was more modest, conferring approximately twice the risk for breast cancer overall, although that risk was threefold higher for the TP53 mutation.
For the 12 genes the consortium singled out as being associated with either a significant or a more modest risk for breast cancer, the effect size did not vary significantly between European and Asian women, the authors noted. Again, the risk for ER-positive breast cancer was over two times greater for those who had either the ATM or the CHEK2 mutation. Having mutations in BARD1, BRCA1, BRCA1, PALB2, RAD51C, and RAD51D conferred a higher risk for ER-negative disease than for ER-positive disease.
There was also an association between rare missense variants in six genes – CHEK2, ATM, TP53, BRCA1, CDH1, and RECQL – and overall breast cancer risk, with the clearest evidence being for CHEK2.
“The absolute risk estimates place protein-truncating variants in BRCA1, BRCA2, and PALB2 in the high-risk category and place protein-truncating variants in ATM, BARD1, CHEK2, RAD51CC, and RAD51D in the moderate-risk category,” Dr. Dorling and colleagues reaffirmed.
“These results may guide screening as well as prevention with risk-reducing surgery or medication, in accordance with national guidelines,” the authors suggested.
The CARRIERS study was supported by the National Institutes of Health. The study by Dr. Dorling and colleagues was supported by the European Union Horizon 2020 research and innovation programs, among others. Dr. Narod disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The findings come from two large studies, both published on Jan. 20 in the New England Journal of Medicine.
The two articles are “extraordinary” for broadening and validating the genomic panel to help screen women at risk for breast cancer in the future, commented Eric Topol, MD, professor of molecular medicine, Scripps Research, La Jolla, Calif., and Medscape editor in chief.
“Traditionally, genetic testing of inherited breast cancer genes has focused on women at high risk who have a strong family history of breast cancer or those who were diagnosed at an early age, such as under 45 years,” commented the lead investigator of one of the studies, Fergus Couch, PhD, a pathologist at the Mayo Clinic, Rochester, Minn.
“[Although] the risk of developing breast cancer is generally lower for women without a family history of the disease ... when we looked at all women, we found that 30% of breast cancer mutations occurred in women who are not high risk,” he said.
In both studies, mutations or variants in eight genes – BRCA1, BRCA2, PALB2, BARD1, RAD51C, RAD51D, ATM, and CHEK2 – were found to be significantly associated with breast cancer risk.
However, the distribution of mutations among women with breast cancer differed from the distribution among unaffected women, noted Steven Narod, MD, from the Women’s College Research Institute, Toronto, in an accompanying editorial.
“What this means to clinicians, now that we are expanding the use of gene-panel testing to include unaffected women with a moderate risk of breast cancer in the family history, is that our time will increasingly be spent counseling women with CHEK2 and ATM mutations,” he wrote. Currently, these two are “clumped in with ‘other genes.’ ... Most of the pretest discussion is currently focused on the implications of finding a BRCA1 or BRCA2 mutation.”
The new findings may lead to new risk management strategies, he suggested. “Most breast cancers that occur in women with a mutation in ATM or CHEK2 are estrogen receptor positive, so these women may be candidates for antiestrogen therapies such as tamoxifen, raloxifene, or aromatase inhibitors,” he wrote.
Dr. Narod observed that, for now, the management of most women with either mutation will consist of screening alone, starting with MRI at age 40 years.
The medical community is not ready yet to expand genetic screening to the general population, cautions Walton Taylor, MD, past president of the American Society of Breast Surgeons.
The ASBrS currently recommends that all patients with breast cancer as well as those at high risk for breast cancer be offered genetic testing. “All women at risk should be tested, and all patients with pathogenic variants need to be managed appropriately – it saves lives,” Dr. Taylor emphasized.
However, “unaffected people with no family history do not need genetic testing at this time,” he said in an interview.
As to what physicians might do to better manage patients with mutations that predispose to breast cancer, Dr. Taylor said, “It’s surprisingly easy.”
Every genetic testing company provides genetic counselors to guide patients through next steps, Dr. Taylor pointed out, and most cancer patients have nurse navigators who make sure patients get tested and followed appropriately.
Members of the ASBrS follow the National Comprehensive Cancer Network guidelines when they identify carriers of a pathogenic variant. Dr. Taylor said these are very useful guidelines for virtually all mutations identified thus far.
“This research is not necessarily new, but it is confirmatory for what we are doing, and that helps us make sure we are going down the right pathway,” Dr. Taylor said. “It confirms that what we think is right is right – and that matters,.”
CARRIERS consortium findings
The study led by Dr. Couch was carried out by the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. It involved analyzing data from 17 epidemiology studies that focused on women in the general population who develop breast cancer. For the studies, which were conducted in the United States, pathogenic variants in 28 cancer-predisposition genes were sequenced from 32,247 women with breast cancer (case patients) and 32,544 unaffected women (control persons).
In the overall CARRIERS analysis, the prevalence of pathogenic variants in 12 clinically actionable genes was 5.03% among case patients and 1.63% among control persons. The prevalence was similar in non-Hispanic White women, non-Hispanic Black women, and Hispanic case patients, as well as control persons, they added. The prevalence of pathogenic variants among Asian American case patients was lower, at only 1.64%.
Among patients who had breast cancer, the most common pathogenic variants included BRCA2, which occurred in 1.29% of case patients, followed by CHEK2, at a prevalence of 1.08%, and BRCA1, at a prevalence of 0.85%.
Mutations in BRCA1 increased the risk for breast cancer more than 7.5-fold; mutations in BRCA2 increased that risk more than fivefold, the investigators stated.
Mutations in PALB2 increased the risk of breast cancer approximately fourfold, they added.
Prevalence rates for both BRCA1 and BRCA2 among breast cancer patients declined rapidly after the age of 40. The decline in other variants, including ATM, CHEK2, and PALB2, was limited with increasing age.
Indeed, mutations in all five of these genes were associated with a lifetime absolute risk for breast cancer greater than 20% by the age of 85 years among non-Hispanic Whites.
Pathogenic variants in BRCA1 or BRCA2 yielded a lifetime risk for breast cancer of approximately 50%. Mutations in PALB2 yielded a lifetime breast cancer risk of approximately 32%.
The risk of having a mutation in specific genes varied depending on the type of breast cancer. For example, mutations in BARD1, RAD51C, and RAD51D increased the risk for estrogen receptor (ER)–negative breast cancer as well as triple-negative breast cancer, the authors noted, whereas mutations in ATM, CDH1, and CHEK2 increased the risk for ER-positive breast cancer.
“These refined estimates of the prevalences of pathogenic variants among women with breast cancer in the overall population, as opposed to selected high-risk patients, may inform ongoing discussions regarding testing in patients with breast cancer,” the CARRIERS authors observed.
“The risks of breast cancer associated with pathogenic variants in the genes evaluated in the population-based CARRIERS analysis also provide important information for risk assessment and counseling of women with breast cancer who do not meet high-risk selection criteria,” they suggested.
Similar findings in second study
The second study was conducted by the Breast Cancer Association Consortium under lead author Leila Dorling, PhD, University of Cambridge (England). This group sequenced 34 susceptibility genes from 60,466 women with breast cancer and 53,461 unaffected control persons.
“Protein-truncating variants in five genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a significant risk of breast cancer overall (P < .0001),” the BCAC members reported. “For these genes, odds ratios ranged from 2.10 to 10.57.”
The association between overall breast cancer risk and mutations in seven other genes was more modest, conferring approximately twice the risk for breast cancer overall, although that risk was threefold higher for the TP53 mutation.
For the 12 genes the consortium singled out as being associated with either a significant or a more modest risk for breast cancer, the effect size did not vary significantly between European and Asian women, the authors noted. Again, the risk for ER-positive breast cancer was over two times greater for those who had either the ATM or the CHEK2 mutation. Having mutations in BARD1, BRCA1, BRCA1, PALB2, RAD51C, and RAD51D conferred a higher risk for ER-negative disease than for ER-positive disease.
There was also an association between rare missense variants in six genes – CHEK2, ATM, TP53, BRCA1, CDH1, and RECQL – and overall breast cancer risk, with the clearest evidence being for CHEK2.
“The absolute risk estimates place protein-truncating variants in BRCA1, BRCA2, and PALB2 in the high-risk category and place protein-truncating variants in ATM, BARD1, CHEK2, RAD51CC, and RAD51D in the moderate-risk category,” Dr. Dorling and colleagues reaffirmed.
“These results may guide screening as well as prevention with risk-reducing surgery or medication, in accordance with national guidelines,” the authors suggested.
The CARRIERS study was supported by the National Institutes of Health. The study by Dr. Dorling and colleagues was supported by the European Union Horizon 2020 research and innovation programs, among others. Dr. Narod disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Algorithm trims time to treatment of acute hypertension in pregnancy
Use of a semiautonomous algorithm to initiate treatment for hypertension emergencies in pregnancy significantly increased the number of individuals treated promptly, based on data from 959 obstetric patients.
Data show poor compliance with the current American College of Obstetricians and Gynecologists recommendations for treatment of acute severe hypertension with no more than 30-60 minutes’ delay; low compliance may be caused by “multiple factors including lack of intravenous access, inadequate health care practitioner or nursing availability, and implicit racial biases,” wrote Courtney Martin, DO, of Loma Linda (Calif.) University School of Medicine and colleagues.
Semiautomated treatment algorithms have been used to improve timely treatment of conditions including myocardial infarction, heart failure, acute stroke, and asthma, but their use in obstetrics to date has been limited, the researchers noted.
In a retrospective cohort study published in Obstetrics & Gynecology, the researchers identified pregnant and postpartum women treated for severe hypertension at a single center between January 2017 and March 2020. A semiautonomous treatment algorithm was implemented between May 2018 and March 2019. The algorithm included vital sign monitoring, blood pressure thresholds for diagnosis of severe hypertension, and automated order sets for recommended first-line antihypertensive therapy. The primary outcomes were treatment with antihypertensive therapy within 15, 30, and 60 minutes of diagnosis. “Severe hypertension was defined as systolic blood pressure 160 mm Hg or higher or diastolic blood pressure 110 mm Hg or higher,” the researchers said.
The study population was divided into three groups; a preimplementation group (373 patients) managed between January 2017 and April 2018, a during-implementation group (334 patients) managed between May 2018 and March 2019, and a postimplementation group (252 patients) managed between April 2019 and March 2020. Patient demographics were similar among all three groups.
Timely treatment improves with algorithm
Overall, treatment of severe hypertension within 15 minutes of diagnosis was 36.5% preimplementation, 45.8% during implementation, and 55.6% postimplementation. Severe hypertension treatment within 30 minutes of diagnosis was 65.9% preimplementation, 77.8% during implementation, and 79.0% post implementation. Differences were significant between pre- and post implementation for 15 minutes and 30 minutes, but no significant differences occurred in the patients treated within 60 minutes before and after implementation of the algorithm.
The study findings were limited by several factors, including the inability to separate peer-to-peer education and other training from the impact of the algorithm, as well as a lack of data on the effect of the algorithm on maternal or neonatal outcomes, the researchers noted.
However, the results support the potential of a semiautonomous algorithm to significantly improve adherence to the recommended treatment guidelines for severe hypertension in pregnancy and post partum, they said. Given the expected increase in hypertensive disorders in pregnancy because of the trends in older age and higher obesity rates in pregnant women, “Integration of semiautonomous treatment algorithms similar to ours into routine obstetric practices could help reduce the health care burden and improve clinical outcomes, especially in areas with limited health care resources,” they concluded.
Algorithm may reduce disparities
The overall rise in maternal mortality in the United States remains a concern, but “Even more concerning are the disturbing racial disparities that persist across socioeconomic strata,” wrote Alisse Hauspurg, MD, of the University of Pittsburgh in an accompanying editorial. “There is clear evidence that expeditious treatment of obstetric hypertensive emergency reduces the risk of severe morbidities including stroke, eclampsia, and maternal death,” she emphasized, but compliance with the ACOG recommendations to treat severe hypertension within 30-60 minutes of confirmation remains low, she said.
In this study, not only did use of the algorithm reduce time to antihypertensive therapy, but more than 50% of patients were treated for severe hypertension within 15 minutes, and more than 90% within 60 minutes, “which was sustained after the implementation phase,” and aligns with the ACOG recommendations, Dr. Hauspurg said. “Although Martin et al.’s algorithm was limited to the initial management of obstetric hypertensive emergency, it could readily be expanded to follow the full ACOG algorithm for management of hypertension in pregnancy,” she noted.
In addition, Black women are more frequently diagnosed with hypertensive disorders of pregnancy, including severe hypertension, and the algorithm might improve disparities, she said.
“It is plausible that widespread implementation of such a semiautonomous algorithm at hospitals across the country could reduce delays in treatment and prevent hypertension-related morbidities,” said Dr. Hauspurg. “The use of innovative approaches to management of severe hypertension and other obstetric emergencies has the potential to allow provision of more equitable care by overcoming health care practitioner and system biases, which could meaningfully reduce disparities in care and change the trajectory of maternal morbidity and mortality in the United States,” she emphasized.
Need to create culture of safety
“Maternal mortality in the United States is the highest among developed nations, and shocking disparities exist in outcomes for non-Hispanic Black and American Indian/Alaskan Native women,” said Lisa Hollier, MD, of Texas Children’s Health Plan in Bellaire. “In a California review of maternal deaths, the greatest quality improvement opportunities were missed diagnosis and ineffective treatment of preeclampsia and related diseases, which occurred in 65% of the cases where women died of preeclampsia/eclampsia,” she said.
The current study “is very timely as more and more states across the nation are participating in the AIM (Alliance for Innovation on Maternal Health) programs to prevent pregnancy-related mortality,” Dr. Hollier noted.
“This study demonstrated a significant association between implementation of the algorithm and an increased percentage of treatment of severe hypertension within 30 minutes,” Dr. Hollier said. “With the implementation of a comprehensive program that included treatment algorithms, the Illinois Perinatal Quality Collaborative improved timely treatment for women with severe high blood pressure, increasing the percentage of patients treated within 60 minutes from 41% at baseline to 79% in the first year of the project.”
The take-home message is that “implementation of the semiautonomous treatment algorithm can address important clinical variation, including delays in appropriate treatment of severe hypertension,” said Dr. Hollier. However, “One of the potential barriers [to use of an algorithm] is the need for accurate, real-time clinical assessment. Resources must be available to ensure appropriate monitoring,” Dr. Hollier noted. “Collaboration and support of implementation of these treatment algorithms must extend through the nursing staff, the physicians, and advanced-practice providers. Medical staff and administrative leaders are essential in creating a culture of safety and continuous process improvement,” she said.
In addition, “long-term follow-up on the implementation of broader quality improvement programs is essential,” Dr. Hollier said. “While implementation of an algorithm can, and did, result in process improvements, assessment of broader implementation of evidence-based bundles, combined with a systematic approach to redesign of multiple related processes needs to occur and include outcomes of severe maternal morbidity and mortality,” she explained.
The study received no outside funding. The researchers had no financial conflicts to disclose.
Neither Dr. Hauspurg nor Dr. Hollier had financial conflicts to disclose.
Use of a semiautonomous algorithm to initiate treatment for hypertension emergencies in pregnancy significantly increased the number of individuals treated promptly, based on data from 959 obstetric patients.
Data show poor compliance with the current American College of Obstetricians and Gynecologists recommendations for treatment of acute severe hypertension with no more than 30-60 minutes’ delay; low compliance may be caused by “multiple factors including lack of intravenous access, inadequate health care practitioner or nursing availability, and implicit racial biases,” wrote Courtney Martin, DO, of Loma Linda (Calif.) University School of Medicine and colleagues.
Semiautomated treatment algorithms have been used to improve timely treatment of conditions including myocardial infarction, heart failure, acute stroke, and asthma, but their use in obstetrics to date has been limited, the researchers noted.
In a retrospective cohort study published in Obstetrics & Gynecology, the researchers identified pregnant and postpartum women treated for severe hypertension at a single center between January 2017 and March 2020. A semiautonomous treatment algorithm was implemented between May 2018 and March 2019. The algorithm included vital sign monitoring, blood pressure thresholds for diagnosis of severe hypertension, and automated order sets for recommended first-line antihypertensive therapy. The primary outcomes were treatment with antihypertensive therapy within 15, 30, and 60 minutes of diagnosis. “Severe hypertension was defined as systolic blood pressure 160 mm Hg or higher or diastolic blood pressure 110 mm Hg or higher,” the researchers said.
The study population was divided into three groups; a preimplementation group (373 patients) managed between January 2017 and April 2018, a during-implementation group (334 patients) managed between May 2018 and March 2019, and a postimplementation group (252 patients) managed between April 2019 and March 2020. Patient demographics were similar among all three groups.
Timely treatment improves with algorithm
Overall, treatment of severe hypertension within 15 minutes of diagnosis was 36.5% preimplementation, 45.8% during implementation, and 55.6% postimplementation. Severe hypertension treatment within 30 minutes of diagnosis was 65.9% preimplementation, 77.8% during implementation, and 79.0% post implementation. Differences were significant between pre- and post implementation for 15 minutes and 30 minutes, but no significant differences occurred in the patients treated within 60 minutes before and after implementation of the algorithm.
The study findings were limited by several factors, including the inability to separate peer-to-peer education and other training from the impact of the algorithm, as well as a lack of data on the effect of the algorithm on maternal or neonatal outcomes, the researchers noted.
However, the results support the potential of a semiautonomous algorithm to significantly improve adherence to the recommended treatment guidelines for severe hypertension in pregnancy and post partum, they said. Given the expected increase in hypertensive disorders in pregnancy because of the trends in older age and higher obesity rates in pregnant women, “Integration of semiautonomous treatment algorithms similar to ours into routine obstetric practices could help reduce the health care burden and improve clinical outcomes, especially in areas with limited health care resources,” they concluded.
Algorithm may reduce disparities
The overall rise in maternal mortality in the United States remains a concern, but “Even more concerning are the disturbing racial disparities that persist across socioeconomic strata,” wrote Alisse Hauspurg, MD, of the University of Pittsburgh in an accompanying editorial. “There is clear evidence that expeditious treatment of obstetric hypertensive emergency reduces the risk of severe morbidities including stroke, eclampsia, and maternal death,” she emphasized, but compliance with the ACOG recommendations to treat severe hypertension within 30-60 minutes of confirmation remains low, she said.
In this study, not only did use of the algorithm reduce time to antihypertensive therapy, but more than 50% of patients were treated for severe hypertension within 15 minutes, and more than 90% within 60 minutes, “which was sustained after the implementation phase,” and aligns with the ACOG recommendations, Dr. Hauspurg said. “Although Martin et al.’s algorithm was limited to the initial management of obstetric hypertensive emergency, it could readily be expanded to follow the full ACOG algorithm for management of hypertension in pregnancy,” she noted.
In addition, Black women are more frequently diagnosed with hypertensive disorders of pregnancy, including severe hypertension, and the algorithm might improve disparities, she said.
“It is plausible that widespread implementation of such a semiautonomous algorithm at hospitals across the country could reduce delays in treatment and prevent hypertension-related morbidities,” said Dr. Hauspurg. “The use of innovative approaches to management of severe hypertension and other obstetric emergencies has the potential to allow provision of more equitable care by overcoming health care practitioner and system biases, which could meaningfully reduce disparities in care and change the trajectory of maternal morbidity and mortality in the United States,” she emphasized.
Need to create culture of safety
“Maternal mortality in the United States is the highest among developed nations, and shocking disparities exist in outcomes for non-Hispanic Black and American Indian/Alaskan Native women,” said Lisa Hollier, MD, of Texas Children’s Health Plan in Bellaire. “In a California review of maternal deaths, the greatest quality improvement opportunities were missed diagnosis and ineffective treatment of preeclampsia and related diseases, which occurred in 65% of the cases where women died of preeclampsia/eclampsia,” she said.
The current study “is very timely as more and more states across the nation are participating in the AIM (Alliance for Innovation on Maternal Health) programs to prevent pregnancy-related mortality,” Dr. Hollier noted.
“This study demonstrated a significant association between implementation of the algorithm and an increased percentage of treatment of severe hypertension within 30 minutes,” Dr. Hollier said. “With the implementation of a comprehensive program that included treatment algorithms, the Illinois Perinatal Quality Collaborative improved timely treatment for women with severe high blood pressure, increasing the percentage of patients treated within 60 minutes from 41% at baseline to 79% in the first year of the project.”
The take-home message is that “implementation of the semiautonomous treatment algorithm can address important clinical variation, including delays in appropriate treatment of severe hypertension,” said Dr. Hollier. However, “One of the potential barriers [to use of an algorithm] is the need for accurate, real-time clinical assessment. Resources must be available to ensure appropriate monitoring,” Dr. Hollier noted. “Collaboration and support of implementation of these treatment algorithms must extend through the nursing staff, the physicians, and advanced-practice providers. Medical staff and administrative leaders are essential in creating a culture of safety and continuous process improvement,” she said.
In addition, “long-term follow-up on the implementation of broader quality improvement programs is essential,” Dr. Hollier said. “While implementation of an algorithm can, and did, result in process improvements, assessment of broader implementation of evidence-based bundles, combined with a systematic approach to redesign of multiple related processes needs to occur and include outcomes of severe maternal morbidity and mortality,” she explained.
The study received no outside funding. The researchers had no financial conflicts to disclose.
Neither Dr. Hauspurg nor Dr. Hollier had financial conflicts to disclose.
Use of a semiautonomous algorithm to initiate treatment for hypertension emergencies in pregnancy significantly increased the number of individuals treated promptly, based on data from 959 obstetric patients.
Data show poor compliance with the current American College of Obstetricians and Gynecologists recommendations for treatment of acute severe hypertension with no more than 30-60 minutes’ delay; low compliance may be caused by “multiple factors including lack of intravenous access, inadequate health care practitioner or nursing availability, and implicit racial biases,” wrote Courtney Martin, DO, of Loma Linda (Calif.) University School of Medicine and colleagues.
Semiautomated treatment algorithms have been used to improve timely treatment of conditions including myocardial infarction, heart failure, acute stroke, and asthma, but their use in obstetrics to date has been limited, the researchers noted.
In a retrospective cohort study published in Obstetrics & Gynecology, the researchers identified pregnant and postpartum women treated for severe hypertension at a single center between January 2017 and March 2020. A semiautonomous treatment algorithm was implemented between May 2018 and March 2019. The algorithm included vital sign monitoring, blood pressure thresholds for diagnosis of severe hypertension, and automated order sets for recommended first-line antihypertensive therapy. The primary outcomes were treatment with antihypertensive therapy within 15, 30, and 60 minutes of diagnosis. “Severe hypertension was defined as systolic blood pressure 160 mm Hg or higher or diastolic blood pressure 110 mm Hg or higher,” the researchers said.
The study population was divided into three groups; a preimplementation group (373 patients) managed between January 2017 and April 2018, a during-implementation group (334 patients) managed between May 2018 and March 2019, and a postimplementation group (252 patients) managed between April 2019 and March 2020. Patient demographics were similar among all three groups.
Timely treatment improves with algorithm
Overall, treatment of severe hypertension within 15 minutes of diagnosis was 36.5% preimplementation, 45.8% during implementation, and 55.6% postimplementation. Severe hypertension treatment within 30 minutes of diagnosis was 65.9% preimplementation, 77.8% during implementation, and 79.0% post implementation. Differences were significant between pre- and post implementation for 15 minutes and 30 minutes, but no significant differences occurred in the patients treated within 60 minutes before and after implementation of the algorithm.
The study findings were limited by several factors, including the inability to separate peer-to-peer education and other training from the impact of the algorithm, as well as a lack of data on the effect of the algorithm on maternal or neonatal outcomes, the researchers noted.
However, the results support the potential of a semiautonomous algorithm to significantly improve adherence to the recommended treatment guidelines for severe hypertension in pregnancy and post partum, they said. Given the expected increase in hypertensive disorders in pregnancy because of the trends in older age and higher obesity rates in pregnant women, “Integration of semiautonomous treatment algorithms similar to ours into routine obstetric practices could help reduce the health care burden and improve clinical outcomes, especially in areas with limited health care resources,” they concluded.
Algorithm may reduce disparities
The overall rise in maternal mortality in the United States remains a concern, but “Even more concerning are the disturbing racial disparities that persist across socioeconomic strata,” wrote Alisse Hauspurg, MD, of the University of Pittsburgh in an accompanying editorial. “There is clear evidence that expeditious treatment of obstetric hypertensive emergency reduces the risk of severe morbidities including stroke, eclampsia, and maternal death,” she emphasized, but compliance with the ACOG recommendations to treat severe hypertension within 30-60 minutes of confirmation remains low, she said.
In this study, not only did use of the algorithm reduce time to antihypertensive therapy, but more than 50% of patients were treated for severe hypertension within 15 minutes, and more than 90% within 60 minutes, “which was sustained after the implementation phase,” and aligns with the ACOG recommendations, Dr. Hauspurg said. “Although Martin et al.’s algorithm was limited to the initial management of obstetric hypertensive emergency, it could readily be expanded to follow the full ACOG algorithm for management of hypertension in pregnancy,” she noted.
In addition, Black women are more frequently diagnosed with hypertensive disorders of pregnancy, including severe hypertension, and the algorithm might improve disparities, she said.
“It is plausible that widespread implementation of such a semiautonomous algorithm at hospitals across the country could reduce delays in treatment and prevent hypertension-related morbidities,” said Dr. Hauspurg. “The use of innovative approaches to management of severe hypertension and other obstetric emergencies has the potential to allow provision of more equitable care by overcoming health care practitioner and system biases, which could meaningfully reduce disparities in care and change the trajectory of maternal morbidity and mortality in the United States,” she emphasized.
Need to create culture of safety
“Maternal mortality in the United States is the highest among developed nations, and shocking disparities exist in outcomes for non-Hispanic Black and American Indian/Alaskan Native women,” said Lisa Hollier, MD, of Texas Children’s Health Plan in Bellaire. “In a California review of maternal deaths, the greatest quality improvement opportunities were missed diagnosis and ineffective treatment of preeclampsia and related diseases, which occurred in 65% of the cases where women died of preeclampsia/eclampsia,” she said.
The current study “is very timely as more and more states across the nation are participating in the AIM (Alliance for Innovation on Maternal Health) programs to prevent pregnancy-related mortality,” Dr. Hollier noted.
“This study demonstrated a significant association between implementation of the algorithm and an increased percentage of treatment of severe hypertension within 30 minutes,” Dr. Hollier said. “With the implementation of a comprehensive program that included treatment algorithms, the Illinois Perinatal Quality Collaborative improved timely treatment for women with severe high blood pressure, increasing the percentage of patients treated within 60 minutes from 41% at baseline to 79% in the first year of the project.”
The take-home message is that “implementation of the semiautonomous treatment algorithm can address important clinical variation, including delays in appropriate treatment of severe hypertension,” said Dr. Hollier. However, “One of the potential barriers [to use of an algorithm] is the need for accurate, real-time clinical assessment. Resources must be available to ensure appropriate monitoring,” Dr. Hollier noted. “Collaboration and support of implementation of these treatment algorithms must extend through the nursing staff, the physicians, and advanced-practice providers. Medical staff and administrative leaders are essential in creating a culture of safety and continuous process improvement,” she said.
In addition, “long-term follow-up on the implementation of broader quality improvement programs is essential,” Dr. Hollier said. “While implementation of an algorithm can, and did, result in process improvements, assessment of broader implementation of evidence-based bundles, combined with a systematic approach to redesign of multiple related processes needs to occur and include outcomes of severe maternal morbidity and mortality,” she explained.
The study received no outside funding. The researchers had no financial conflicts to disclose.
Neither Dr. Hauspurg nor Dr. Hollier had financial conflicts to disclose.
FROM OBSTETRICS & GYNECOLOGY