User login
Metformin Gets a Reproductive Reprieve — For Diabetic Moms and Dads Alike
For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.
Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.
The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,
In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.
“On the one hand, metformin can cross the placenta and might directly affect the fetus. On the other hand, poor blood sugar control is a risk factor for birth defects,” she continued. “Insulin in combination with metformin might control blood sugar better than using insulin alone, which may lower the risk of birth defects.”
Switched to insulin monotherapy or prescribed additional insulin within 90 days of their last menstrual period, mothers were assessed for nonchromosomal fetal malformations and nonlive births, spontaneous abortion, and termination. Continuing metformin or adding insulin to metformin in early pregnancy resulted in little to no increased risk for major malformations in infants.
The estimated risk for nonlive birth was 32.7% with insulin monotherapy and 34.3% with insulin plus metformin polytherapy, for a risk ratio (RR) of 1.02 (95% confidence interval (CI), 1.01-1.04).
In addition, the estimated risk for live birth with congenital malformations was 8.0% (5.70-10.2) under insulin monotherapy and 5.7% under insulin plus metformin (95% CI, 4.5-7.3), amounting to a risk ratio of 0.72 (0.51-1.09).
While the results may involve residual confounding by participants’ glycemic control and body mass index, Dr. Chiu said, “Our findings suggest that the current clinical recommendations to switch from metformin to insulin before pregnancy, due to concerns about birth defects, may require reconsideration.”
She noted that previous trials showed adding metformin to insulin in mid-late pregnancy also improved blood sugar control with no increase in risk of birth defects. “However, most of these studies started treatment too late — between 10 and 34 weeks of pregnancy — to determine if metformin could cause birth defects.”
Observational studies found that women with pregestational diabetes who used noninsulin antidiabetics (mainly metformin) in the first trimester had a lower risk of birth defects, compared with those who used insulin, Dr. Chiu added. “However, comparing metformin with insulin may have some biases because women who used metformin generally have less severe diabetes than those who used insulin.”
Aligning with these reassuring findings, a randomized, placebo-controlled trial reported that adding metformin to insulin did not lead to a higher incidence of neonatal morbidity and mortality and was associated with better maternal glycemic control and reduced maternal weight gain. Metformin-exposed offspring, however, had lower birth weights and a higher incidence of being small for gestational age.
Similarly, a recent Nordic register study of more than 3.7 million infants also found no evidence of an increased risk of major defects with the use of metformin vs insulin in the first trimester.
Despite such reassuring findings, however, Dr. Chiu stressed the need to study other pregnancy and infant outcomes as well as the safety of other oral antidiabetics during pregnancy.
Metformin in Fathers
Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.
The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.
“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”
The prevalence of MCMs in the cohort was 4.7% in children of fathers unexposed to diabetes medications (n = 381,041), compared with 6.2% in children of fathers exposed during preconception spermatogenesis to metformin (n = 1730).
By these crude numbers, children with preconception paternal metformin exposure had a nearly 30% increased odds of MCMs. But whereas the crude odds ratio (OR) for MCMs with paternal metformin exposure in all formulations was 1.28 (95% CI, 1.01-1.64), the adjusted OR was 1.00 (95% CI, 0.76 -1.31). Within specific regimens, the adjusted OR was 0.86 (95% CI, 0.60-1.23) for metformin in monotherapy and 1.36 (95% CI, 1.00-1.85) for metformin in polytherapy.
At the outset, Dr. Rotem’s group hypothesized that any crude associations between metformin in polytherapy and birth defects could potentially be explained by poorer underlying parental cardiometabolic risk profiles in those taking multiple diabetes medications. Compared with that of unexposed fathers, the prevalence of cardiometabolic morbidity was indeed substantially higher among both fathers who used metformin during spermatogenesis and their spouses.
In addition, these fathers were more likely to be older, to be smokers, and to have fertility problems. Similarly, mothers were more likely to have cardiovascular comorbidity and to have had fertility problems when the father used metformin.
Moreover, children born to men who used diabetes medications before conception were much more likely to have mothers who also had diabetes and other metabolic conditions, Dr. Rotem noted. “This makes sense since we know that many of these conditions are affected by diet and lifestyle factors that are probably shared across individuals living in the same household.”
Recent research has shown that paternal health and behavior before conception can affect offspring development and long-term health. Characteristics including obesity, diabetes, and metabolic syndrome are seen to affect offspring via complex indirect and direct mechanisms, both genetic and nongenetic.
Doing little to dispel safety concerns, a recent Danish national study reported a link between preconception paternal metformin and major birth defects, particularly genital birth defects in boys. That study, however, lacked data on medication adherence and glycemic control.
“These are well-conducted studies, but it would be useful to see them replicated in different populations, as the sample sizes eligible for analysis are relatively small and some of the confidence intervals are wide,” said Robert W. Platt, PhD, a professor in the departments of Pediatrics and of Epidemiology, Biostatistics, and Occupational Health at McGill University in Montreal, Canada. “However, the results suggest that type 2 diabetics can focus on the most effective treatment pathway for their condition. Metformin does not appear to confer an increased risk of congenital malformations.”
According to an accompanying editorial by Sarah Martins da Silva. MBChB, MD, a reproductive medicine specialist at the University of Dundee in Scotland, the Israeli findings highlight the importance of factoring the sometimes overlooked issue of paternal health into reproductive planning and prenatal care. She stressed that individual risks and benefits should always be carefully considered and results interpreted with caution since such studies lack information on glycemic control. “Nonetheless, these recent analyses suggest that metformin is a safe and effective treatment option for T2D for men and women trying to conceive as well as for managing hyperglycemia in pregnant women in the first trimester,” she wrote and agreed that it may be time to reconsider current prenatal care guidelines that advocate switching to insulin therapy.
The studies by Dr. Chiu and Dr. Rotem were funded by the National Institutes of Health. Dr. Chiu and Dr. Rotem had no competing interests to declare. Dr. Hernandez Diaz, a coauthor on both studies, reported funding from Takeda and consulting for Moderna, Johnson & Johnson, and UCB. Several authors reported support from government and not-for-profit research funding agencies. Dr. Platt disclosed no competing interests. Editorial commentator Dr. Martins da Silva disclosed consulting, speaking, travel, and advisory fees from, variously, Dyneval, Ferring Pharmaceutical, Merck, IBSA, and Gedeon Richer.
For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.
Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.
The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,
In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.
“On the one hand, metformin can cross the placenta and might directly affect the fetus. On the other hand, poor blood sugar control is a risk factor for birth defects,” she continued. “Insulin in combination with metformin might control blood sugar better than using insulin alone, which may lower the risk of birth defects.”
Switched to insulin monotherapy or prescribed additional insulin within 90 days of their last menstrual period, mothers were assessed for nonchromosomal fetal malformations and nonlive births, spontaneous abortion, and termination. Continuing metformin or adding insulin to metformin in early pregnancy resulted in little to no increased risk for major malformations in infants.
The estimated risk for nonlive birth was 32.7% with insulin monotherapy and 34.3% with insulin plus metformin polytherapy, for a risk ratio (RR) of 1.02 (95% confidence interval (CI), 1.01-1.04).
In addition, the estimated risk for live birth with congenital malformations was 8.0% (5.70-10.2) under insulin monotherapy and 5.7% under insulin plus metformin (95% CI, 4.5-7.3), amounting to a risk ratio of 0.72 (0.51-1.09).
While the results may involve residual confounding by participants’ glycemic control and body mass index, Dr. Chiu said, “Our findings suggest that the current clinical recommendations to switch from metformin to insulin before pregnancy, due to concerns about birth defects, may require reconsideration.”
She noted that previous trials showed adding metformin to insulin in mid-late pregnancy also improved blood sugar control with no increase in risk of birth defects. “However, most of these studies started treatment too late — between 10 and 34 weeks of pregnancy — to determine if metformin could cause birth defects.”
Observational studies found that women with pregestational diabetes who used noninsulin antidiabetics (mainly metformin) in the first trimester had a lower risk of birth defects, compared with those who used insulin, Dr. Chiu added. “However, comparing metformin with insulin may have some biases because women who used metformin generally have less severe diabetes than those who used insulin.”
Aligning with these reassuring findings, a randomized, placebo-controlled trial reported that adding metformin to insulin did not lead to a higher incidence of neonatal morbidity and mortality and was associated with better maternal glycemic control and reduced maternal weight gain. Metformin-exposed offspring, however, had lower birth weights and a higher incidence of being small for gestational age.
Similarly, a recent Nordic register study of more than 3.7 million infants also found no evidence of an increased risk of major defects with the use of metformin vs insulin in the first trimester.
Despite such reassuring findings, however, Dr. Chiu stressed the need to study other pregnancy and infant outcomes as well as the safety of other oral antidiabetics during pregnancy.
Metformin in Fathers
Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.
The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.
“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”
The prevalence of MCMs in the cohort was 4.7% in children of fathers unexposed to diabetes medications (n = 381,041), compared with 6.2% in children of fathers exposed during preconception spermatogenesis to metformin (n = 1730).
By these crude numbers, children with preconception paternal metformin exposure had a nearly 30% increased odds of MCMs. But whereas the crude odds ratio (OR) for MCMs with paternal metformin exposure in all formulations was 1.28 (95% CI, 1.01-1.64), the adjusted OR was 1.00 (95% CI, 0.76 -1.31). Within specific regimens, the adjusted OR was 0.86 (95% CI, 0.60-1.23) for metformin in monotherapy and 1.36 (95% CI, 1.00-1.85) for metformin in polytherapy.
At the outset, Dr. Rotem’s group hypothesized that any crude associations between metformin in polytherapy and birth defects could potentially be explained by poorer underlying parental cardiometabolic risk profiles in those taking multiple diabetes medications. Compared with that of unexposed fathers, the prevalence of cardiometabolic morbidity was indeed substantially higher among both fathers who used metformin during spermatogenesis and their spouses.
In addition, these fathers were more likely to be older, to be smokers, and to have fertility problems. Similarly, mothers were more likely to have cardiovascular comorbidity and to have had fertility problems when the father used metformin.
Moreover, children born to men who used diabetes medications before conception were much more likely to have mothers who also had diabetes and other metabolic conditions, Dr. Rotem noted. “This makes sense since we know that many of these conditions are affected by diet and lifestyle factors that are probably shared across individuals living in the same household.”
Recent research has shown that paternal health and behavior before conception can affect offspring development and long-term health. Characteristics including obesity, diabetes, and metabolic syndrome are seen to affect offspring via complex indirect and direct mechanisms, both genetic and nongenetic.
Doing little to dispel safety concerns, a recent Danish national study reported a link between preconception paternal metformin and major birth defects, particularly genital birth defects in boys. That study, however, lacked data on medication adherence and glycemic control.
“These are well-conducted studies, but it would be useful to see them replicated in different populations, as the sample sizes eligible for analysis are relatively small and some of the confidence intervals are wide,” said Robert W. Platt, PhD, a professor in the departments of Pediatrics and of Epidemiology, Biostatistics, and Occupational Health at McGill University in Montreal, Canada. “However, the results suggest that type 2 diabetics can focus on the most effective treatment pathway for their condition. Metformin does not appear to confer an increased risk of congenital malformations.”
According to an accompanying editorial by Sarah Martins da Silva. MBChB, MD, a reproductive medicine specialist at the University of Dundee in Scotland, the Israeli findings highlight the importance of factoring the sometimes overlooked issue of paternal health into reproductive planning and prenatal care. She stressed that individual risks and benefits should always be carefully considered and results interpreted with caution since such studies lack information on glycemic control. “Nonetheless, these recent analyses suggest that metformin is a safe and effective treatment option for T2D for men and women trying to conceive as well as for managing hyperglycemia in pregnant women in the first trimester,” she wrote and agreed that it may be time to reconsider current prenatal care guidelines that advocate switching to insulin therapy.
The studies by Dr. Chiu and Dr. Rotem were funded by the National Institutes of Health. Dr. Chiu and Dr. Rotem had no competing interests to declare. Dr. Hernandez Diaz, a coauthor on both studies, reported funding from Takeda and consulting for Moderna, Johnson & Johnson, and UCB. Several authors reported support from government and not-for-profit research funding agencies. Dr. Platt disclosed no competing interests. Editorial commentator Dr. Martins da Silva disclosed consulting, speaking, travel, and advisory fees from, variously, Dyneval, Ferring Pharmaceutical, Merck, IBSA, and Gedeon Richer.
For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.
Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.
The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,
In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.
“On the one hand, metformin can cross the placenta and might directly affect the fetus. On the other hand, poor blood sugar control is a risk factor for birth defects,” she continued. “Insulin in combination with metformin might control blood sugar better than using insulin alone, which may lower the risk of birth defects.”
Switched to insulin monotherapy or prescribed additional insulin within 90 days of their last menstrual period, mothers were assessed for nonchromosomal fetal malformations and nonlive births, spontaneous abortion, and termination. Continuing metformin or adding insulin to metformin in early pregnancy resulted in little to no increased risk for major malformations in infants.
The estimated risk for nonlive birth was 32.7% with insulin monotherapy and 34.3% with insulin plus metformin polytherapy, for a risk ratio (RR) of 1.02 (95% confidence interval (CI), 1.01-1.04).
In addition, the estimated risk for live birth with congenital malformations was 8.0% (5.70-10.2) under insulin monotherapy and 5.7% under insulin plus metformin (95% CI, 4.5-7.3), amounting to a risk ratio of 0.72 (0.51-1.09).
While the results may involve residual confounding by participants’ glycemic control and body mass index, Dr. Chiu said, “Our findings suggest that the current clinical recommendations to switch from metformin to insulin before pregnancy, due to concerns about birth defects, may require reconsideration.”
She noted that previous trials showed adding metformin to insulin in mid-late pregnancy also improved blood sugar control with no increase in risk of birth defects. “However, most of these studies started treatment too late — between 10 and 34 weeks of pregnancy — to determine if metformin could cause birth defects.”
Observational studies found that women with pregestational diabetes who used noninsulin antidiabetics (mainly metformin) in the first trimester had a lower risk of birth defects, compared with those who used insulin, Dr. Chiu added. “However, comparing metformin with insulin may have some biases because women who used metformin generally have less severe diabetes than those who used insulin.”
Aligning with these reassuring findings, a randomized, placebo-controlled trial reported that adding metformin to insulin did not lead to a higher incidence of neonatal morbidity and mortality and was associated with better maternal glycemic control and reduced maternal weight gain. Metformin-exposed offspring, however, had lower birth weights and a higher incidence of being small for gestational age.
Similarly, a recent Nordic register study of more than 3.7 million infants also found no evidence of an increased risk of major defects with the use of metformin vs insulin in the first trimester.
Despite such reassuring findings, however, Dr. Chiu stressed the need to study other pregnancy and infant outcomes as well as the safety of other oral antidiabetics during pregnancy.
Metformin in Fathers
Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.
The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.
“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”
The prevalence of MCMs in the cohort was 4.7% in children of fathers unexposed to diabetes medications (n = 381,041), compared with 6.2% in children of fathers exposed during preconception spermatogenesis to metformin (n = 1730).
By these crude numbers, children with preconception paternal metformin exposure had a nearly 30% increased odds of MCMs. But whereas the crude odds ratio (OR) for MCMs with paternal metformin exposure in all formulations was 1.28 (95% CI, 1.01-1.64), the adjusted OR was 1.00 (95% CI, 0.76 -1.31). Within specific regimens, the adjusted OR was 0.86 (95% CI, 0.60-1.23) for metformin in monotherapy and 1.36 (95% CI, 1.00-1.85) for metformin in polytherapy.
At the outset, Dr. Rotem’s group hypothesized that any crude associations between metformin in polytherapy and birth defects could potentially be explained by poorer underlying parental cardiometabolic risk profiles in those taking multiple diabetes medications. Compared with that of unexposed fathers, the prevalence of cardiometabolic morbidity was indeed substantially higher among both fathers who used metformin during spermatogenesis and their spouses.
In addition, these fathers were more likely to be older, to be smokers, and to have fertility problems. Similarly, mothers were more likely to have cardiovascular comorbidity and to have had fertility problems when the father used metformin.
Moreover, children born to men who used diabetes medications before conception were much more likely to have mothers who also had diabetes and other metabolic conditions, Dr. Rotem noted. “This makes sense since we know that many of these conditions are affected by diet and lifestyle factors that are probably shared across individuals living in the same household.”
Recent research has shown that paternal health and behavior before conception can affect offspring development and long-term health. Characteristics including obesity, diabetes, and metabolic syndrome are seen to affect offspring via complex indirect and direct mechanisms, both genetic and nongenetic.
Doing little to dispel safety concerns, a recent Danish national study reported a link between preconception paternal metformin and major birth defects, particularly genital birth defects in boys. That study, however, lacked data on medication adherence and glycemic control.
“These are well-conducted studies, but it would be useful to see them replicated in different populations, as the sample sizes eligible for analysis are relatively small and some of the confidence intervals are wide,” said Robert W. Platt, PhD, a professor in the departments of Pediatrics and of Epidemiology, Biostatistics, and Occupational Health at McGill University in Montreal, Canada. “However, the results suggest that type 2 diabetics can focus on the most effective treatment pathway for their condition. Metformin does not appear to confer an increased risk of congenital malformations.”
According to an accompanying editorial by Sarah Martins da Silva. MBChB, MD, a reproductive medicine specialist at the University of Dundee in Scotland, the Israeli findings highlight the importance of factoring the sometimes overlooked issue of paternal health into reproductive planning and prenatal care. She stressed that individual risks and benefits should always be carefully considered and results interpreted with caution since such studies lack information on glycemic control. “Nonetheless, these recent analyses suggest that metformin is a safe and effective treatment option for T2D for men and women trying to conceive as well as for managing hyperglycemia in pregnant women in the first trimester,” she wrote and agreed that it may be time to reconsider current prenatal care guidelines that advocate switching to insulin therapy.
The studies by Dr. Chiu and Dr. Rotem were funded by the National Institutes of Health. Dr. Chiu and Dr. Rotem had no competing interests to declare. Dr. Hernandez Diaz, a coauthor on both studies, reported funding from Takeda and consulting for Moderna, Johnson & Johnson, and UCB. Several authors reported support from government and not-for-profit research funding agencies. Dr. Platt disclosed no competing interests. Editorial commentator Dr. Martins da Silva disclosed consulting, speaking, travel, and advisory fees from, variously, Dyneval, Ferring Pharmaceutical, Merck, IBSA, and Gedeon Richer.
<!--$RCSfile: InCopy_agile.xsl,v $ $Revision: 1.35 $-->
<!--$RCSfile: drupal.xsl,v $ $Revision: 1.7 $-->
<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>168481</fileName> <TBEID>0C050A5E.SIG</TBEID> <TBUniqueIdentifier>MD_0C050A5E</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240621T113341</QCDate> <firstPublished>20240621T114405</firstPublished> <LastPublished>20240621T114405</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240621T114405</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline>Diana Swift</byline> <bylineText>DIANA SWIFT</bylineText> <bylineFull>DIANA SWIFT</bylineFull> <bylineTitleText>MDedge News</bylineTitleText> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including</metaDescription> <articlePDF/> <teaserImage>301953</teaserImage> <teaser>Physicians can reassure parents with diabetes about the safety of metformin use before conception and in early pregnancy.</teaser> <title>Metformin Gets a Reproductive Reprieve — For Diabetic Moms and Dads Alike</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>endo</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>ob</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term>34</term> <term canonical="true">15</term> <term>21</term> <term>23</term> </publications> <sections> <term canonical="true">27970</term> <term>39313</term> </sections> <topics> <term canonical="true">205</term> <term>206</term> <term>322</term> <term>287</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012a4e.jpg</altRep> <description role="drol:caption">Dr. Yu-Han Chiu</description> <description role="drol:credit"/> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012a4f.jpg</altRep> <description role="drol:caption">Dr. Ran S. Rotem</description> <description role="drol:credit"/> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012a50.jpg</altRep> <description role="drol:caption">Dr. Robert W. Platt</description> <description role="drol:credit"/> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012a51.jpg</altRep> <description role="drol:caption">Dr. Sarah Martins da Silva</description> <description role="drol:credit"/> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Metformin Gets a Reproductive Reprieve — For Diabetic Moms and Dads Alike</title> <deck/> </itemMeta> <itemContent> <p>For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.</p> <p>Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — <span class="Hyperlink"><a href="https://www.acpjournals.org/doi/10.7326/M23-2038">one in mothers</a></span>, the <span class="Hyperlink"><a href="https://www.acpjournals.org/doi/10.7326/M23-1405">other in fathers</a></span> — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in <em>Annals of Internal Medicine</em>.<br/><br/>The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy, <br/><br/>In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.[[{"fid":"301953","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Chiu is an epidemiologist at the Harvard School of Public Health","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Yu-Han Chiu"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]] <br/><br/>“On the one hand, metformin can cross the placenta and might directly affect the fetus. On the other hand, poor blood sugar control is a risk factor for birth defects,” she continued. “Insulin in combination with metformin might control blood sugar better than using insulin alone, which may lower the risk of birth defects.” <br/><br/>Switched to insulin monotherapy or prescribed additional insulin within 90 days of their last menstrual period, mothers were assessed for nonchromosomal fetal malformations and nonlive births, spontaneous abortion, and termination. Continuing metformin or adding insulin to metformin in early pregnancy resulted in little to no increased risk for major malformations in infants.<br/><br/>The estimated risk for nonlive birth was 32.7% with insulin monotherapy and 34.3% with insulin plus metformin polytherapy, for a risk ratio (RR) of 1.02 (95% confidence interval (CI), 1.01-1.04).<br/><br/>In addition, the estimated risk for live birth with congenital malformations was 8.0% (5.70-10.2) under insulin monotherapy and 5.7% under insulin plus metformin (95% CI, 4.5-7.3), amounting to a risk ratio of 0.72 (0.51-1.09).<br/><br/>While the results may involve residual confounding by participants’ glycemic control and body mass index, Dr. Chiu said, “Our findings suggest that the current clinical recommendations to switch from metformin to insulin before pregnancy, due to concerns about birth defects, may require reconsideration.” <br/><br/>She noted that previous trials showed adding metformin to insulin in mid-late pregnancy also improved blood sugar control with no increase in risk of birth defects. “However, most of these studies started treatment too late — between 10 and 34 weeks of pregnancy — to determine if metformin could cause birth defects.”<br/><br/>Observational studies found that women with pregestational diabetes who used noninsulin antidiabetics (mainly metformin) in the first trimester had a lower risk of birth defects, compared with those who used insulin, Dr. Chiu added. “However, comparing metformin with insulin may have some biases because women who used metformin generally have less severe diabetes than those who used insulin.”<br/><br/>Aligning with these reassuring findings, a randomized, <span class="Hyperlink"><a href="https://www.thelancet.com/journals/landia/article/PIIS2213-8587(20)30310-7/abstract">placebo-controlled trial</a></span> reported that adding metformin to insulin did not lead to a higher incidence of neonatal morbidity and mortality and was associated with better maternal glycemic control and reduced maternal weight gain. Metformin-exposed offspring, however, had lower birth weights and a higher incidence of being small for gestational age. <br/><br/>Similarly, a recent Nordic <span class="Hyperlink"><a href="https://diabetesjournals.org/care/article/46/8/1556/151609/Metformin-Versus-Insulin-and-Risk-of-Major">register study</a></span> of more than 3.7 million infants also found no evidence of an increased risk of major defects with the use of metformin vs insulin in the first trimester.<br/><br/>Despite such reassuring findings, however, Dr. Chiu stressed the need to study other pregnancy and infant outcomes as well as the safety of other oral antidiabetics during pregnancy.<br/><br/></p> <h2>Metformin in Fathers</h2> <p>Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe. </p> <p>The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns. <br/><br/>“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”[[{"fid":"301954","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Rotem is a neuroepidemiologist at the Harvard School of Public Health, Boston, Massachusetts","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Ran S. Rotem"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]<br/><br/>The prevalence of MCMs in the cohort was 4.7% in children of fathers unexposed to diabetes medications (n = 381,041), compared with 6.2% in children of fathers exposed during preconception spermatogenesis to metformin (n = 1730).<br/><br/>By these crude numbers, children with preconception paternal metformin exposure had a nearly 30% increased odds of MCMs. But whereas the crude odds ratio (OR) for MCMs with paternal metformin exposure in all formulations was 1.28 (95% CI, 1.01-1.64), the adjusted OR was 1.00 (95% CI, 0.76 -1.31). Within specific regimens, the adjusted OR was 0.86 (95% CI, 0.60-1.23) for metformin in monotherapy and 1.36 (95% CI, 1.00-1.85) for metformin in polytherapy. <br/><br/>At the outset, Dr. Rotem’s group hypothesized that any crude associations between metformin in polytherapy and birth defects could potentially be explained by poorer underlying parental cardiometabolic risk profiles in those taking multiple diabetes medications. Compared with that of unexposed fathers, the prevalence of cardiometabolic morbidity was indeed substantially higher among both fathers who used metformin during spermatogenesis and their spouses.<br/><br/>In addition, these fathers were more likely to be older, to be smokers, and to have fertility problems. Similarly, mothers were more likely to have cardiovascular comorbidity and to have had fertility problems when the father used metformin.<br/><br/>Moreover, children born to men who used diabetes medications before conception were much more likely to have mothers who also had diabetes and other metabolic conditions, Dr. Rotem noted. “This makes sense since we know that many of these conditions are affected by diet and lifestyle factors that are probably shared across individuals living in the same household.”<br/><br/>Recent <span class="Hyperlink"><a href="https://link.springer.com/article/10.1007/s00125-019-4919-9">research</a> </span>has shown that paternal health and behavior before conception can affect offspring development and long-term health. Characteristics including obesity, diabetes, and metabolic syndrome are seen to affect offspring via complex indirect and direct mechanisms, both genetic and nongenetic. <br/><br/>Doing little to dispel safety concerns, a recent <span class="Hyperlink"><a href="https://www.acpjournals.org/doi/10.7326/M21-4389">Danish national study</a> </span>reported a link between preconception paternal metformin and major birth defects, particularly genital birth defects in boys. That study, however, lacked data on medication adherence and glycemic control.<br/><br/>“These are well-conducted studies, but it would be useful to see them replicated in different populations, as the sample sizes eligible for analysis are relatively small and some of the confidence intervals are wide,” said Robert W. Platt, PhD, a professor in the departments of Pediatrics and of Epidemiology, Biostatistics, and Occupational Health at McGill University in Montreal, Canada. “However, the results suggest that type 2 diabetics can focus on the most effective treatment pathway for their condition. Metformin does not appear to confer an increased risk of congenital malformations.”[[{"fid":"301956","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Platt is a professor in the departments of Pediatrics and of Epidemiology, Biostatistics, and Occupational Health at McGill University in Montreal, Canada.","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Robert W. Platt"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]]<br/><br/>According to an <span class="Hyperlink"><a href="https://www.acpjournals.org/doi/10.7326/M24-0883">accompanying editorial</a></span> by Sarah Martins da Silva. MBChB, MD, a reproductive medicine specialist at the University of Dundee in Scotland, the Israeli findings highlight the importance of factoring the sometimes overlooked issue of paternal health into reproductive planning and prenatal care. She stressed that individual risks and benefits should always be carefully considered and results interpreted with caution since such studies lack information on glycemic control. “Nonetheless, these recent analyses suggest that metformin is a safe and effective treatment option for T2D for men and women trying to conceive as well as for managing hyperglycemia in pregnant women in the first trimester,” she wrote and agreed that it may be time to reconsider current prenatal care guidelines that advocate switching to insulin therapy.[[{"fid":"301957","view_mode":"medstat_image_flush_right","fields":{"format":"medstat_image_flush_right","field_file_image_alt_text[und][0][value]":"Dr. Martins da Silva is a reproductive medicine specialist at the University of Dundee in Scotland","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"Dr. Sarah Martins da Silva"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_right"}}]] <br/><br/>The studies by Dr. Chiu and Dr. Rotem were funded by the National Institutes of Health. Dr. Chiu and Dr. Rotem had no competing interests to declare. Dr. Hernandez Diaz, a coauthor on both studies, reported funding from Takeda and consulting for Moderna, Johnson & Johnson, and UCB. Several authors reported support from government and not-for-profit research funding agencies. Dr. Platt disclosed no competing interests. Editorial commentator Dr. Martins da Silva disclosed consulting, speaking, travel, and advisory fees from, variously, Dyneval, Ferring Pharmaceutical, Merck, IBSA, and Gedeon Richer.<span class="end"/></p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
Quitting Anabolic Steroids Can Still Impair Men Afterward
BOSTON — Men who stop using performance-enhancing anabolic-androgenic steroids (AAS) experience significant depression, anxiety, and diminished sexual function within the first year after quitting, new research found.
The data suggest that monitoring these men and, pending clinical trial evidence, intervening to minimize these effects could help prevent recidivism, Bonnie Grant, MBBS, a clinical research fellow at Imperial College London, London, England, told this news organization.
“Nothing has actually been studied in proper randomized controlled trials … but I think there’s going to be a role for medicine alongside psychological treatment … Clinicians often see men who have stopped [taking steroids] who report feeling low in mood … a lot of these men will just restart taking them again,” she said.
Anabolic steroids taken exogenously suppress the hypothalamic-pituitary-gonadal system, thereby suppressing endogenous testosterone secretion. While AAS do enhance muscle-building, they can also lead to enlarged hearts, hypertension, and infertility. Most of these are reversible if the man stops taking the AAS.
However, after stopping, the testosterone levels can take up to a year to return to normal. During that time, the man can experience symptoms including low libido, erectile dysfunction, low mood, and fatigue. This leads to a dependence syndrome in about 30%. About 65% of men who stop taking anabolic steroids will restart taking them within the first year, Dr. Grant said in presenting her findings at the annual meeting of the Endocrine Society.
Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “One question is, if you intervene with an antidepressant, will that prevent the people from relapsing and going back to using? I think that’s certainly something that would need to be explored and tested.”
Dr. Hayes also noted that fertility problems may lead some men to decide to stop using the steroids. “That can be a strong motivator. If you have a motivated patient, then you add in an antidepressant or anxiolytic or link the patients with mental health services. I think that would definitely be beneficial and definitely something we need to address and see if it is worthwhile doing.”
Dr. Grant presented data from her group’s cross-sectional, observational study. Of a total 245 men, 116 were current AAS users, 84 were previous AAS users who had quit within the past year, and 45 had never used them. All completed extensive questionnaires about their substance use, mood, sexual function, and anxiety. They had morning blood tests, and urine samples were taken for toxicology testing.
The three groups didn’t differ by age (most were in their mid-30s) or ethnicity (most were White). However, the proportion who self-reported psychiatric diagnoses (mostly depression or anxiety) was significantly higher among both the current (29%) and past (25%) AAS users than among the never users (6.6%), with P = .0094.
Dr. Hayes commented, “One of the drawbacks of this study was they didn’t have baseline data. But it would make sense, I think, that the incidence of depression and anxiety was higher in the people who went on to use anabolic steroids.”
Use of other illicit drugs — mostly cocaine and cannabis — was also higher among the past (40.5%) and current (47.4%) AAS users than among the nonusers (17.7%), P = .0025.
Not surprisingly, total testosterone levels were much higher in current AAS users (62.8 nmol/L) than in past users (20.1 nmol/L) and nonusers (20.0 nmol/L), P < .001. Levels of luteinizing hormone (LH), follicle-stimulating hormone, and sex hormone-binding globulin were significantly lower in the current AAS users than in the other two groups, while estradiol levels were significantly higher (all P < .001).
There were no differences in total testosterone between the never users and previous users. However, about 25% of the men who stopped continued to have lower-than-normal testosterone levels, Dr. Grant noted.
Depression scores, as assessed by the Beck Depression Inventory-II, were highest in men who stopped using AAS, and lowest in the never users. Moderate to severe depression was present in 20% of the men who stopped using AAS, 6% of current users, and none of the nonusers.
In multivariable analysis, having a prior psychiatric diagnosis increased the risk for current depression on the Beck inventory by twofold in the current AAS users (P = .001) and threefold in the past users (P < .001). “Interestingly, testosterone levels were not associated with depression,” she noted.
Sexual function, as measured by the International Index of Erectile Function (IIEF) 15, was significantly worse among those who had stopped using AAS compared with current users and nonusers (P = .023). At the same time, total testosterone levels were only weakly correlated with IIEF scores.
In multivariate analysis, higher LH levels were associated with worse sexual function (P = .01).
Anxiety, as measured by the General Anxiety Disorder-7 assessment, was higher in previous users than in never users. Overall, 12% of the previous users had moderate or severe anxiety vs just 2% of nonusers.
The next step in the research will be to examine the urine toxicology for AAS and other illicit substances, Dr. Grant said.
“We’re hoping this information will allow for future studies to be developed to design treatments, which will help millions of men worldwide to stop and stay off anabolic steroids,” she concluded.
Dr. Grant and Dr. Hayes had no disclosures.
A version of this article first appeared on Medscape.com.
BOSTON — Men who stop using performance-enhancing anabolic-androgenic steroids (AAS) experience significant depression, anxiety, and diminished sexual function within the first year after quitting, new research found.
The data suggest that monitoring these men and, pending clinical trial evidence, intervening to minimize these effects could help prevent recidivism, Bonnie Grant, MBBS, a clinical research fellow at Imperial College London, London, England, told this news organization.
“Nothing has actually been studied in proper randomized controlled trials … but I think there’s going to be a role for medicine alongside psychological treatment … Clinicians often see men who have stopped [taking steroids] who report feeling low in mood … a lot of these men will just restart taking them again,” she said.
Anabolic steroids taken exogenously suppress the hypothalamic-pituitary-gonadal system, thereby suppressing endogenous testosterone secretion. While AAS do enhance muscle-building, they can also lead to enlarged hearts, hypertension, and infertility. Most of these are reversible if the man stops taking the AAS.
However, after stopping, the testosterone levels can take up to a year to return to normal. During that time, the man can experience symptoms including low libido, erectile dysfunction, low mood, and fatigue. This leads to a dependence syndrome in about 30%. About 65% of men who stop taking anabolic steroids will restart taking them within the first year, Dr. Grant said in presenting her findings at the annual meeting of the Endocrine Society.
Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “One question is, if you intervene with an antidepressant, will that prevent the people from relapsing and going back to using? I think that’s certainly something that would need to be explored and tested.”
Dr. Hayes also noted that fertility problems may lead some men to decide to stop using the steroids. “That can be a strong motivator. If you have a motivated patient, then you add in an antidepressant or anxiolytic or link the patients with mental health services. I think that would definitely be beneficial and definitely something we need to address and see if it is worthwhile doing.”
Dr. Grant presented data from her group’s cross-sectional, observational study. Of a total 245 men, 116 were current AAS users, 84 were previous AAS users who had quit within the past year, and 45 had never used them. All completed extensive questionnaires about their substance use, mood, sexual function, and anxiety. They had morning blood tests, and urine samples were taken for toxicology testing.
The three groups didn’t differ by age (most were in their mid-30s) or ethnicity (most were White). However, the proportion who self-reported psychiatric diagnoses (mostly depression or anxiety) was significantly higher among both the current (29%) and past (25%) AAS users than among the never users (6.6%), with P = .0094.
Dr. Hayes commented, “One of the drawbacks of this study was they didn’t have baseline data. But it would make sense, I think, that the incidence of depression and anxiety was higher in the people who went on to use anabolic steroids.”
Use of other illicit drugs — mostly cocaine and cannabis — was also higher among the past (40.5%) and current (47.4%) AAS users than among the nonusers (17.7%), P = .0025.
Not surprisingly, total testosterone levels were much higher in current AAS users (62.8 nmol/L) than in past users (20.1 nmol/L) and nonusers (20.0 nmol/L), P < .001. Levels of luteinizing hormone (LH), follicle-stimulating hormone, and sex hormone-binding globulin were significantly lower in the current AAS users than in the other two groups, while estradiol levels were significantly higher (all P < .001).
There were no differences in total testosterone between the never users and previous users. However, about 25% of the men who stopped continued to have lower-than-normal testosterone levels, Dr. Grant noted.
Depression scores, as assessed by the Beck Depression Inventory-II, were highest in men who stopped using AAS, and lowest in the never users. Moderate to severe depression was present in 20% of the men who stopped using AAS, 6% of current users, and none of the nonusers.
In multivariable analysis, having a prior psychiatric diagnosis increased the risk for current depression on the Beck inventory by twofold in the current AAS users (P = .001) and threefold in the past users (P < .001). “Interestingly, testosterone levels were not associated with depression,” she noted.
Sexual function, as measured by the International Index of Erectile Function (IIEF) 15, was significantly worse among those who had stopped using AAS compared with current users and nonusers (P = .023). At the same time, total testosterone levels were only weakly correlated with IIEF scores.
In multivariate analysis, higher LH levels were associated with worse sexual function (P = .01).
Anxiety, as measured by the General Anxiety Disorder-7 assessment, was higher in previous users than in never users. Overall, 12% of the previous users had moderate or severe anxiety vs just 2% of nonusers.
The next step in the research will be to examine the urine toxicology for AAS and other illicit substances, Dr. Grant said.
“We’re hoping this information will allow for future studies to be developed to design treatments, which will help millions of men worldwide to stop and stay off anabolic steroids,” she concluded.
Dr. Grant and Dr. Hayes had no disclosures.
A version of this article first appeared on Medscape.com.
BOSTON — Men who stop using performance-enhancing anabolic-androgenic steroids (AAS) experience significant depression, anxiety, and diminished sexual function within the first year after quitting, new research found.
The data suggest that monitoring these men and, pending clinical trial evidence, intervening to minimize these effects could help prevent recidivism, Bonnie Grant, MBBS, a clinical research fellow at Imperial College London, London, England, told this news organization.
“Nothing has actually been studied in proper randomized controlled trials … but I think there’s going to be a role for medicine alongside psychological treatment … Clinicians often see men who have stopped [taking steroids] who report feeling low in mood … a lot of these men will just restart taking them again,” she said.
Anabolic steroids taken exogenously suppress the hypothalamic-pituitary-gonadal system, thereby suppressing endogenous testosterone secretion. While AAS do enhance muscle-building, they can also lead to enlarged hearts, hypertension, and infertility. Most of these are reversible if the man stops taking the AAS.
However, after stopping, the testosterone levels can take up to a year to return to normal. During that time, the man can experience symptoms including low libido, erectile dysfunction, low mood, and fatigue. This leads to a dependence syndrome in about 30%. About 65% of men who stop taking anabolic steroids will restart taking them within the first year, Dr. Grant said in presenting her findings at the annual meeting of the Endocrine Society.
Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “One question is, if you intervene with an antidepressant, will that prevent the people from relapsing and going back to using? I think that’s certainly something that would need to be explored and tested.”
Dr. Hayes also noted that fertility problems may lead some men to decide to stop using the steroids. “That can be a strong motivator. If you have a motivated patient, then you add in an antidepressant or anxiolytic or link the patients with mental health services. I think that would definitely be beneficial and definitely something we need to address and see if it is worthwhile doing.”
Dr. Grant presented data from her group’s cross-sectional, observational study. Of a total 245 men, 116 were current AAS users, 84 were previous AAS users who had quit within the past year, and 45 had never used them. All completed extensive questionnaires about their substance use, mood, sexual function, and anxiety. They had morning blood tests, and urine samples were taken for toxicology testing.
The three groups didn’t differ by age (most were in their mid-30s) or ethnicity (most were White). However, the proportion who self-reported psychiatric diagnoses (mostly depression or anxiety) was significantly higher among both the current (29%) and past (25%) AAS users than among the never users (6.6%), with P = .0094.
Dr. Hayes commented, “One of the drawbacks of this study was they didn’t have baseline data. But it would make sense, I think, that the incidence of depression and anxiety was higher in the people who went on to use anabolic steroids.”
Use of other illicit drugs — mostly cocaine and cannabis — was also higher among the past (40.5%) and current (47.4%) AAS users than among the nonusers (17.7%), P = .0025.
Not surprisingly, total testosterone levels were much higher in current AAS users (62.8 nmol/L) than in past users (20.1 nmol/L) and nonusers (20.0 nmol/L), P < .001. Levels of luteinizing hormone (LH), follicle-stimulating hormone, and sex hormone-binding globulin were significantly lower in the current AAS users than in the other two groups, while estradiol levels were significantly higher (all P < .001).
There were no differences in total testosterone between the never users and previous users. However, about 25% of the men who stopped continued to have lower-than-normal testosterone levels, Dr. Grant noted.
Depression scores, as assessed by the Beck Depression Inventory-II, were highest in men who stopped using AAS, and lowest in the never users. Moderate to severe depression was present in 20% of the men who stopped using AAS, 6% of current users, and none of the nonusers.
In multivariable analysis, having a prior psychiatric diagnosis increased the risk for current depression on the Beck inventory by twofold in the current AAS users (P = .001) and threefold in the past users (P < .001). “Interestingly, testosterone levels were not associated with depression,” she noted.
Sexual function, as measured by the International Index of Erectile Function (IIEF) 15, was significantly worse among those who had stopped using AAS compared with current users and nonusers (P = .023). At the same time, total testosterone levels were only weakly correlated with IIEF scores.
In multivariate analysis, higher LH levels were associated with worse sexual function (P = .01).
Anxiety, as measured by the General Anxiety Disorder-7 assessment, was higher in previous users than in never users. Overall, 12% of the previous users had moderate or severe anxiety vs just 2% of nonusers.
The next step in the research will be to examine the urine toxicology for AAS and other illicit substances, Dr. Grant said.
“We’re hoping this information will allow for future studies to be developed to design treatments, which will help millions of men worldwide to stop and stay off anabolic steroids,” she concluded.
Dr. Grant and Dr. Hayes had no disclosures.
A version of this article first appeared on Medscape.com.
<!--$RCSfile: InCopy_agile.xsl,v $ $Revision: 1.35 $-->
<!--$RCSfile: drupal.xsl,v $ $Revision: 1.7 $-->
<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>168384</fileName> <TBEID>0C050840.SIG</TBEID> <TBUniqueIdentifier>MD_0C050840</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240613T111914</QCDate> <firstPublished>20240613T112520</firstPublished> <LastPublished>20240613T112520</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240613T112520</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline>Miriam E. Tucker</byline> <bylineText>MIRIAM E. TUCKER</bylineText> <bylineFull>MIRIAM E. TUCKER</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>BOSTON — Men who stop using performance-enhancing anabolic-androgenic steroids (AAS) experience significant depression, anxiety, and diminished sexual function </metaDescription> <articlePDF/> <teaserImage/> <teaser>Up to a year after quitting, men can experience symptoms including low libido, erectile dysfunction, low mood, and fatigue.</teaser> <title>Quitting Anabolic Steroids Can Still Impair Men Afterward</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>endo</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">34</term> <term>15</term> <term>21</term> </publications> <sections> <term>53</term> <term canonical="true">39313</term> </sections> <topics> <term canonical="true">246</term> <term>206</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Quitting Anabolic Steroids Can Still Impair Men Afterward</title> <deck/> </itemMeta> <itemContent> <p>BOSTON — Men who stop using performance-enhancing anabolic-androgenic steroids (AAS) experience significant <a href="https://emedicine.medscape.com/article/286759-overview">depression</a>, anxiety, and diminished sexual function within the first year after quitting, new research found.</p> <p>The data suggest that monitoring these men and, pending clinical trial evidence, intervening to minimize these effects could help prevent recidivism, Bonnie Grant, MBBS, a clinical research fellow at Imperial College London, London, England, told this news organization.<br/><br/>“Nothing has actually been studied in proper randomized controlled trials … but I think there’s going to be a role for medicine alongside psychological treatment … Clinicians often see men who have stopped [taking steroids] who report feeling low in mood … a lot of these men will just restart taking them again,” she said.<br/><br/>Anabolic steroids taken exogenously suppress the hypothalamic-pituitary-gonadal system, thereby suppressing endogenous <a href="https://reference.medscape.com/drug/depo-testosterone-aveed-342795">testosterone</a> secretion. While AAS do enhance muscle-building, they can also lead to enlarged hearts, <a href="https://emedicine.medscape.com/article/241381-overview">hypertension</a>, and <a href="https://emedicine.medscape.com/article/274143-overview">infertility</a>. Most of these are reversible if the man stops taking the AAS.<br/><br/>However, after stopping, the testosterone levels can take up to a year to return to normal. During that time, the man can experience symptoms including low libido, <a href="https://emedicine.medscape.com/article/444220-overview">erectile dysfunction</a>, low mood, and fatigue. This leads to a dependence syndrome in about 30%. About 65% of men who stop taking anabolic steroids will restart taking them within the first year, Dr. Grant said in presenting her findings at the annual meeting of the Endocrine Society.<br/><br/>Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “One question is, if you intervene with an antidepressant, will that prevent the people from relapsing and going back to using? I think that’s certainly something that would need to be explored and tested.”<br/><br/>Dr. Hayes also noted that fertility problems may lead some men to decide to stop using the steroids. “That can be a strong motivator. If you have a motivated patient, then you add in an antidepressant or anxiolytic or link the patients with mental health services. I think that would definitely be beneficial and definitely something we need to address and see if it is worthwhile doing.”<br/><br/>Dr. Grant presented data from her group’s cross-sectional, observational study. Of a total 245 men, 116 were current AAS users, 84 were previous AAS users who had quit within the past year, and 45 had never used them. All completed extensive questionnaires about their substance use, mood, sexual function, and anxiety. They had morning blood tests, and urine samples were taken for toxicology testing.<br/><br/>The three groups didn’t differ by age (most were in their mid-30s) or ethnicity (most were White). However, the proportion who self-reported psychiatric diagnoses (mostly depression or anxiety) was significantly higher among both the current (29%) and past (25%) AAS users than among the never users (6.6%), with <em>P</em> = .0094.<br/><br/>Dr. Hayes commented, “One of the drawbacks of this study was they didn’t have baseline data. But it would make sense, I think, that the incidence of depression and anxiety was higher in the people who went on to use anabolic steroids.”<br/><br/>Use of other illicit drugs — mostly cocaine and cannabis — was also higher among the past (40.5%) and current (47.4%) AAS users than among the nonusers (17.7%), <em>P</em> = .0025.<br/><br/>Not surprisingly, total testosterone levels were much higher in current AAS users (62.8 nmol/L) than in past users (20.1 nmol/L) and nonusers (20.0 nmol/L), <em>P</em> < .001. Levels of <a href="https://emedicine.medscape.com/article/2089268-overview">luteinizing hormone</a> (LH), <a href="https://emedicine.medscape.com/article/118810-overview">follicle-stimulating hormone</a>, and sex hormone-binding globulin were significantly lower in the current AAS users than in the other two groups, while <a href="https://reference.medscape.com/drug/estrace-vivelle-dot-estradiol-342766">estradiol</a> levels were significantly higher (all <em>P</em> < .001).<br/><br/>There were no differences in total testosterone between the never users and previous users. However, about 25% of the men who stopped continued to have lower-than-normal testosterone levels, Dr. Grant noted.<br/><br/>Depression scores, as assessed by the Beck Depression Inventory-II, were highest in men who stopped using AAS, and lowest in the never users. Moderate to severe depression was present in 20% of the men who stopped using AAS, 6% of current users, and none of the nonusers.<br/><br/>In multivariable analysis, having a prior psychiatric diagnosis increased the risk for current depression on the Beck inventory by twofold in the current AAS users (<em>P</em> = .001) and threefold in the past users (<em>P </em>< .001). “Interestingly, testosterone levels were not associated with depression,” she noted.<br/><br/>Sexual function, as measured by the International Index of Erectile Function (IIEF) 15, was significantly worse among those who had stopped using AAS compared with current users and nonusers (<em>P</em> = .023). At the same time, total testosterone levels were only weakly correlated with IIEF scores.<br/><br/>In multivariate analysis, higher LH levels were associated with worse sexual function (<em>P</em> = .01).<br/><br/>Anxiety, as measured by the General <a href="https://emedicine.medscape.com/article/286227-overview">Anxiety Disorder</a>-7 assessment, was higher in previous users than in never users. Overall, 12% of the previous users had moderate or severe anxiety vs just 2% of nonusers.<br/><br/>The next step in the research will be to examine the urine toxicology for AAS and other illicit substances, Dr. Grant said.<br/><br/>“We’re hoping this information will allow for future studies to be developed to design treatments, which will help millions of men worldwide to stop and stay off anabolic steroids,” she concluded.<br/><br/>Dr. Grant and Dr. Hayes had no disclosures.<span class="end"/></p> <p> <em>A version of this article first appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/quitting-anabolic-steroids-can-still-impair-men-afterward-2024a1000awg">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
Ovarian Cancer Risk Doubled by Estrogen-Only HRT
Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."
Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.
Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)
In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.
Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
Ovarian Cancer Incidence Doubles with Estrogen
At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.
Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).
Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”
Care of Ovarian Cancer Survivors Should Change
The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.
In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.
“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.
“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.
Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.
“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.
Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.
“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”
Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”
These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”
When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”
Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.
Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."
Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.
Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)
In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.
Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
Ovarian Cancer Incidence Doubles with Estrogen
At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.
Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).
Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”
Care of Ovarian Cancer Survivors Should Change
The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.
In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.
“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.
“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.
Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.
“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.
Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.
“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”
Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”
These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”
When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”
Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.
Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."
Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.
Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)
In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.
Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
Ovarian Cancer Incidence Doubles with Estrogen
At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.
Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).
Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”
Care of Ovarian Cancer Survivors Should Change
The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.
In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.
“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.
“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.
Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.
“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.
Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.
“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”
Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”
These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”
When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”
Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.
<!--$RCSfile: InCopy_agile.xsl,v $ $Revision: 1.35 $-->
<!--$RCSfile: drupal.xsl,v $ $Revision: 1.7 $-->
<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>168403</fileName> <TBEID>0C050876.SIG</TBEID> <TBUniqueIdentifier>MD_0C050876</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname>WHI ovarian cancer story</storyname> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240612T152426</QCDate> <firstPublished>20240612T154011</firstPublished> <LastPublished>20240612T154011</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240612T154011</CMSDate> <articleSource>FROM ASCO 2024</articleSource> <facebookInfo/> <meetingNumber>3035-24</meetingNumber> <byline>Jennie Smith</byline> <bylineText>JENNIE SMITH</bylineText> <bylineFull>JENNIE SMITH</bylineFull> <bylineTitleText>MDedge News</bylineTitleText> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer inciden</metaDescription> <articlePDF/> <teaserImage/> <teaser>Long-term follow up in women with hysterectomy included in the WHI reveals significantly more cases of ovarian cancer.</teaser> <title>Ovarian Cancer Risk Doubled by Estrogen-Only HRT</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>oncr</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>ob</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>endo</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">31</term> <term>23</term> <term>15</term> <term>21</term> <term>34</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> <term>27980</term> </sections> <topics> <term canonical="true">217</term> <term>270</term> <term>280</term> <term>192</term> <term>218</term> <term>322</term> <term>263</term> <term>206</term> <term>247</term> <term>210</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Ovarian Cancer Risk Doubled by Estrogen-Only HRT</title> <deck/> </itemMeta> <itemContent> <p>Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is ‘the gift that keeps on giving.’</p> <p><span class="tag metaDescription">Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women.</span> Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. <a href="https://lundquist.org/rowan-t-chlebowski-md-phd">Rowan T. Cheblowski</a>, MD, PhD, of the Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.<br/><br/>Dr. Cheblowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)<br/><br/>In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.<br/><br/>Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.<br/><br/></p> <h2>Ovarian Cancer Incidence Doubles with Estrogen</h2> <p>At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Cheblowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; <em>P</em> = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, <em>P</em> = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group. </p> <p>Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; <em>P</em> = .01).<br/><br/>Conjugated equine estrogen, Dr. Cheblowski, said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”<br/><br/></p> <h2>Care of Ovarian Cancer Survivors Should Change</h2> <p>The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Cheblowski said. </p> <p>In an interview, oncologist <a href="https://doctors.valleyhealth.com/provider/Eleonora+Teplinsky/2527433">Elonora Teplinsky</a>, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today. <br/><br/>“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.<br/><br/>“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.<br/><br/>Oncologist <a href="https://med.stanford.edu/profiles/allison-kurian">Allison Kurian</a>, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance. <br/><br/>“<a href="https://www.whi.org/">WHI</a> is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said. <br/><br/>Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone. <br/><br/>“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.” <br/><br/>Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.” <br/><br/>These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.” <br/><br/>When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”<br/><br/>Dr. Cheblowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.</p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM ASCO 2024
USPSTF Draft Recommendations Support More Options for Osteoporosis Screening, Seek More Research in Men
An influential US panel may largely reaffirm its current recommendation in favor of screening older women to prevent osteoporotic fractures, while also repeating its call for more research to try to determine whether men would benefit from this kind of routine testing.
The US Preventive Services Task Force (USPSTF) on June 11 released a draft update of its recommendations on osteoporosis screening. The task force will accept comments on the draft through July 8. Federal law gives the USPSTF recommendations extra clout, requiring insurers to cover — without co-pay — services that get top marks “A” or “B” from the task force.
The task force intends to maintain a “B” recommendation on screening of older women, indicating that the evidence gathered to date suggests a moderate net benefit. But the draft includes a shift in the approach to this screening.
The USPSTF proposed saying that it recommends screening for osteoporosis in both women aged 65 years and older and postmenopausal women younger than 65 years who are at an increased risk for an osteoporotic fracture. The current recommendation, finalized in 2018, advises “screening for osteoporosis with bone measurement testing [emphasis added]” for these groups.
The proposed change in language — dropping the phrase “with bone measurement testing” — is intended to expand flexibility for clinicians, Esa Davis, MD, MPH, a member of USPSTF and a professor at the University of Maryland School of Medicine, Baltimore, told this news organization.
“It provides them with more options instead of telling them, ‘You have to do it this way,’ ” Dr. Davis said.
The task force’s draft recommendation is not meant to apply to people with secondary osteoporosis due to an underlying medical condition such as cancer, metabolic bone diseases or hyperthyroidism, or chronic use of a medication associated with bone loss.
Rajesh K. Jain, MD, who was not involved with the USPSTF work, read the draft recommendations at the request of this news organization. In an email, he said he generally agreed with the decision to largely stick to the 2018 recommendations for women.
He also noted that there’s still a lack of a clear direction for physicians about assessing osteoporosis risk in men. But multiple randomized control trials of osteoporosis drugs seem to suggest these medicines work for both sexes, said Dr. Jain, who is the endocrinology fellowship program director at University of Chicago Medicine, Chicago.
The USPSTF draft also would reiterate the current “I” grade about screening men for osteoporosis.
An “I” grade means the task force found the current body of available evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis to prevent osteoporotic fractures in men.
“Since there is no recommendation right now, it would have seemed sensible to include a recommendation to screen men with prior fracture or other risk factors for osteoporosis, much like they do for younger women,” Dr. Jain said.
Insufficient Evidence
The USPSTF’s “I” grade is different from a “D” grade, which is what the task force uses to recommend against the use of a service.
A “D” grade means the USPSTF says there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. (The USPSTF makes it easy to search online for grades given to preventive services, including those that got a “D.”)
The USPSTF is calling for more studies on the benefits and harms of screening for osteoporosis to prevent fractures and related morbidity and mortality in men.
“Men do get osteoporosis,” Dr. Davis said. “But unfortunately, the evidence isn’t there” to allow USPSTF to make a recommendation on screening approaches.
“Any man who has concerns about bone health should certainly talk to his clinician and figure out what is the best form of screening” he might want to do, she said.
There’s been a growing interest in the question of whether to screen men for osteoporosis and bone health. For example, Osteoporosis Canada last year updated a guideline to emphasize the need to assess older patients of both sexes for the risk for fractures. But the Canadian Task Force on Preventive Health Care in 2023 came to a conclusion in line with the USPSTF draft.
The Canadian task force recommended against routine screening in men, while adding that clinicians should be alert to changes in health that may indicate the patient has experienced or is at a higher risk for fragility fracture.
Risk Factors, Concerns About Tests
The USPSTF said that risk factors associated with fragility fractures are similar in men and women. These include:
- Increasing age
- Low body mass index
- Excessive alcohol intake
- Current smoking
- Chronic corticosteroid use
- History of prior fractures, falls within the past year, cerebrovascular accident, and diabetes
- Hypogonadism
The process of updating the USPSTF recommendations can serve as a chance to expand public awareness about osteoporosis, as many men may not know to raise the question of their fracture risk during medical appointments, Dr. Davis said.
“Clinicians need to be aware of the risk factors and to be able to have conversations with men,” she said.
Dr. Davis also cautioned about the need to be aware of limitations with clinical risk assessment tools. In the draft recommendation statement, the USPSTF noted that some tools and approaches may be less likely to identify Black, Hispanic, and Asian people as high risk, and subsequently, clinicians may be less likely to offer treatment to them compared with White people of the same age, bone mineral density, and clinical risk profile.
Dr. Davis had no relevant financial relationships. Dr. Jain received research funding from the Amgen Foundation.
A version of this article appeared on Medscape.com.
An influential US panel may largely reaffirm its current recommendation in favor of screening older women to prevent osteoporotic fractures, while also repeating its call for more research to try to determine whether men would benefit from this kind of routine testing.
The US Preventive Services Task Force (USPSTF) on June 11 released a draft update of its recommendations on osteoporosis screening. The task force will accept comments on the draft through July 8. Federal law gives the USPSTF recommendations extra clout, requiring insurers to cover — without co-pay — services that get top marks “A” or “B” from the task force.
The task force intends to maintain a “B” recommendation on screening of older women, indicating that the evidence gathered to date suggests a moderate net benefit. But the draft includes a shift in the approach to this screening.
The USPSTF proposed saying that it recommends screening for osteoporosis in both women aged 65 years and older and postmenopausal women younger than 65 years who are at an increased risk for an osteoporotic fracture. The current recommendation, finalized in 2018, advises “screening for osteoporosis with bone measurement testing [emphasis added]” for these groups.
The proposed change in language — dropping the phrase “with bone measurement testing” — is intended to expand flexibility for clinicians, Esa Davis, MD, MPH, a member of USPSTF and a professor at the University of Maryland School of Medicine, Baltimore, told this news organization.
“It provides them with more options instead of telling them, ‘You have to do it this way,’ ” Dr. Davis said.
The task force’s draft recommendation is not meant to apply to people with secondary osteoporosis due to an underlying medical condition such as cancer, metabolic bone diseases or hyperthyroidism, or chronic use of a medication associated with bone loss.
Rajesh K. Jain, MD, who was not involved with the USPSTF work, read the draft recommendations at the request of this news organization. In an email, he said he generally agreed with the decision to largely stick to the 2018 recommendations for women.
He also noted that there’s still a lack of a clear direction for physicians about assessing osteoporosis risk in men. But multiple randomized control trials of osteoporosis drugs seem to suggest these medicines work for both sexes, said Dr. Jain, who is the endocrinology fellowship program director at University of Chicago Medicine, Chicago.
The USPSTF draft also would reiterate the current “I” grade about screening men for osteoporosis.
An “I” grade means the task force found the current body of available evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis to prevent osteoporotic fractures in men.
“Since there is no recommendation right now, it would have seemed sensible to include a recommendation to screen men with prior fracture or other risk factors for osteoporosis, much like they do for younger women,” Dr. Jain said.
Insufficient Evidence
The USPSTF’s “I” grade is different from a “D” grade, which is what the task force uses to recommend against the use of a service.
A “D” grade means the USPSTF says there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. (The USPSTF makes it easy to search online for grades given to preventive services, including those that got a “D.”)
The USPSTF is calling for more studies on the benefits and harms of screening for osteoporosis to prevent fractures and related morbidity and mortality in men.
“Men do get osteoporosis,” Dr. Davis said. “But unfortunately, the evidence isn’t there” to allow USPSTF to make a recommendation on screening approaches.
“Any man who has concerns about bone health should certainly talk to his clinician and figure out what is the best form of screening” he might want to do, she said.
There’s been a growing interest in the question of whether to screen men for osteoporosis and bone health. For example, Osteoporosis Canada last year updated a guideline to emphasize the need to assess older patients of both sexes for the risk for fractures. But the Canadian Task Force on Preventive Health Care in 2023 came to a conclusion in line with the USPSTF draft.
The Canadian task force recommended against routine screening in men, while adding that clinicians should be alert to changes in health that may indicate the patient has experienced or is at a higher risk for fragility fracture.
Risk Factors, Concerns About Tests
The USPSTF said that risk factors associated with fragility fractures are similar in men and women. These include:
- Increasing age
- Low body mass index
- Excessive alcohol intake
- Current smoking
- Chronic corticosteroid use
- History of prior fractures, falls within the past year, cerebrovascular accident, and diabetes
- Hypogonadism
The process of updating the USPSTF recommendations can serve as a chance to expand public awareness about osteoporosis, as many men may not know to raise the question of their fracture risk during medical appointments, Dr. Davis said.
“Clinicians need to be aware of the risk factors and to be able to have conversations with men,” she said.
Dr. Davis also cautioned about the need to be aware of limitations with clinical risk assessment tools. In the draft recommendation statement, the USPSTF noted that some tools and approaches may be less likely to identify Black, Hispanic, and Asian people as high risk, and subsequently, clinicians may be less likely to offer treatment to them compared with White people of the same age, bone mineral density, and clinical risk profile.
Dr. Davis had no relevant financial relationships. Dr. Jain received research funding from the Amgen Foundation.
A version of this article appeared on Medscape.com.
An influential US panel may largely reaffirm its current recommendation in favor of screening older women to prevent osteoporotic fractures, while also repeating its call for more research to try to determine whether men would benefit from this kind of routine testing.
The US Preventive Services Task Force (USPSTF) on June 11 released a draft update of its recommendations on osteoporosis screening. The task force will accept comments on the draft through July 8. Federal law gives the USPSTF recommendations extra clout, requiring insurers to cover — without co-pay — services that get top marks “A” or “B” from the task force.
The task force intends to maintain a “B” recommendation on screening of older women, indicating that the evidence gathered to date suggests a moderate net benefit. But the draft includes a shift in the approach to this screening.
The USPSTF proposed saying that it recommends screening for osteoporosis in both women aged 65 years and older and postmenopausal women younger than 65 years who are at an increased risk for an osteoporotic fracture. The current recommendation, finalized in 2018, advises “screening for osteoporosis with bone measurement testing [emphasis added]” for these groups.
The proposed change in language — dropping the phrase “with bone measurement testing” — is intended to expand flexibility for clinicians, Esa Davis, MD, MPH, a member of USPSTF and a professor at the University of Maryland School of Medicine, Baltimore, told this news organization.
“It provides them with more options instead of telling them, ‘You have to do it this way,’ ” Dr. Davis said.
The task force’s draft recommendation is not meant to apply to people with secondary osteoporosis due to an underlying medical condition such as cancer, metabolic bone diseases or hyperthyroidism, or chronic use of a medication associated with bone loss.
Rajesh K. Jain, MD, who was not involved with the USPSTF work, read the draft recommendations at the request of this news organization. In an email, he said he generally agreed with the decision to largely stick to the 2018 recommendations for women.
He also noted that there’s still a lack of a clear direction for physicians about assessing osteoporosis risk in men. But multiple randomized control trials of osteoporosis drugs seem to suggest these medicines work for both sexes, said Dr. Jain, who is the endocrinology fellowship program director at University of Chicago Medicine, Chicago.
The USPSTF draft also would reiterate the current “I” grade about screening men for osteoporosis.
An “I” grade means the task force found the current body of available evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis to prevent osteoporotic fractures in men.
“Since there is no recommendation right now, it would have seemed sensible to include a recommendation to screen men with prior fracture or other risk factors for osteoporosis, much like they do for younger women,” Dr. Jain said.
Insufficient Evidence
The USPSTF’s “I” grade is different from a “D” grade, which is what the task force uses to recommend against the use of a service.
A “D” grade means the USPSTF says there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. (The USPSTF makes it easy to search online for grades given to preventive services, including those that got a “D.”)
The USPSTF is calling for more studies on the benefits and harms of screening for osteoporosis to prevent fractures and related morbidity and mortality in men.
“Men do get osteoporosis,” Dr. Davis said. “But unfortunately, the evidence isn’t there” to allow USPSTF to make a recommendation on screening approaches.
“Any man who has concerns about bone health should certainly talk to his clinician and figure out what is the best form of screening” he might want to do, she said.
There’s been a growing interest in the question of whether to screen men for osteoporosis and bone health. For example, Osteoporosis Canada last year updated a guideline to emphasize the need to assess older patients of both sexes for the risk for fractures. But the Canadian Task Force on Preventive Health Care in 2023 came to a conclusion in line with the USPSTF draft.
The Canadian task force recommended against routine screening in men, while adding that clinicians should be alert to changes in health that may indicate the patient has experienced or is at a higher risk for fragility fracture.
Risk Factors, Concerns About Tests
The USPSTF said that risk factors associated with fragility fractures are similar in men and women. These include:
- Increasing age
- Low body mass index
- Excessive alcohol intake
- Current smoking
- Chronic corticosteroid use
- History of prior fractures, falls within the past year, cerebrovascular accident, and diabetes
- Hypogonadism
The process of updating the USPSTF recommendations can serve as a chance to expand public awareness about osteoporosis, as many men may not know to raise the question of their fracture risk during medical appointments, Dr. Davis said.
“Clinicians need to be aware of the risk factors and to be able to have conversations with men,” she said.
Dr. Davis also cautioned about the need to be aware of limitations with clinical risk assessment tools. In the draft recommendation statement, the USPSTF noted that some tools and approaches may be less likely to identify Black, Hispanic, and Asian people as high risk, and subsequently, clinicians may be less likely to offer treatment to them compared with White people of the same age, bone mineral density, and clinical risk profile.
Dr. Davis had no relevant financial relationships. Dr. Jain received research funding from the Amgen Foundation.
A version of this article appeared on Medscape.com.
<!--$RCSfile: InCopy_agile.xsl,v $ $Revision: 1.35 $-->
<!--$RCSfile: drupal.xsl,v $ $Revision: 1.7 $-->
<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>168395</fileName> <TBEID>0C050862.SIG</TBEID> <TBUniqueIdentifier>MD_0C050862</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240612T150828</QCDate> <firstPublished>20240612T153039</firstPublished> <LastPublished>20240612T153039</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240612T153039</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline>K. D. Young</byline> <bylineText>KERRY DOOLEY YOUNG</bylineText> <bylineFull>KERRY DOOLEY YOUNG</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>An influential US panel may largely reaffirm its current recommendation in favor of screening older women to prevent osteoporotic fractures, while also repeatin</metaDescription> <articlePDF/> <teaserImage>301910</teaserImage> <teaser>The influential US task force appears likely to largely reiterate recommendations on osteoporosis testing for women, while highlighting the need for more research on this screening for men.</teaser> <title>USPSTF Draft Recommendations Support More Options for Osteoporosis Screening, Seek More Research in Men</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>endo</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>ob</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">34</term> <term>15</term> <term>21</term> <term>23</term> <term>26</term> </publications> <sections> <term canonical="true">75</term> <term>39313</term> </sections> <topics> <term canonical="true">266</term> <term>290</term> <term>206</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012a11.jpg</altRep> <description role="drol:caption">Dr. Esa Davis</description> <description role="drol:credit">USPSTF</description> </link> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/24012a12.jpg</altRep> <description role="drol:caption">Dr. Rajesh K. Jain</description> <description role="drol:credit">University of Chicago Medicine</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>USPSTF Draft Recommendations Support More Options for Osteoporosis Screening, Seek More Research in Men</title> <deck/> </itemMeta> <itemContent> <p>An influential US panel may largely reaffirm its current recommendation in favor of screening older women to prevent osteoporotic fractures, while also repeating its call for more research to try to determine whether men would benefit from this kind of routine testing.</p> <p>The US Preventive Services Task Force (USPSTF) on June 11 released a <span class="Hyperlink"><a href="https://www.uspreventiveservicestaskforce.org/uspstf/draft-recommendation/osteoporosis-screening-prevent-fractures">draft update of its recommendations</a></span> on osteoporosis screening. The task force will accept comments on the <span class="Hyperlink"><a href="https://www.uspreventiveservicestaskforce.org/uspstf/announcements/public-comment-draft-recommendation-statement-and-draft-evidence-review-screening-osteoporosis">draft through July 8</a></span>. Federal law gives the USPSTF recommendations extra clout, requiring insurers to cover — without co-pay — services that get top marks “A” or “B” from the task force.<br/><br/>The task force intends to maintain a “B” recommendation on screening of older women, indicating that the evidence gathered to date suggests a moderate net benefit. But the draft includes a shift in the approach to this screening.<br/><br/>The USPSTF proposed saying that it recommends screening for osteoporosis in both women aged 65 years and older and postmenopausal women younger than 65 years who are at an increased risk for an osteoporotic fracture. The <span class="Hyperlink"><a href="https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/osteoporosis-screening">current recommendation</a></span>, finalized in 2018, advises “screening for osteoporosis <em>with bone measurement testing</em> [emphasis added]” for these groups.<br/><br/>The proposed change in language — dropping the phrase “with bone measurement testing” — is intended to expand flexibility for clinicians, Esa Davis, MD, MPH, a member of USPSTF and a professor at the University of Maryland School of Medicine, Baltimore, told this news organization.[[{"fid":"301910","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Esa Davis, professor at the University of Maryland School of Medicine, Baltimore","field_file_image_credit[und][0][value]":"USPSTF","field_file_image_caption[und][0][value]":"Dr. Esa Davis"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]<br/><br/>“It provides them with more options instead of telling them, ‘You have to do it this way,’ ” Dr. Davis said.<br/><br/>The task force’s draft recommendation is not meant to apply to people with secondary osteoporosis due to an underlying medical condition such as cancer, metabolic bone diseases or hyperthyroidism, or chronic use of a medication associated with bone loss.<br/><br/>Rajesh K. Jain, MD, who was not involved with the USPSTF work, read the draft recommendations at the request of this news organization. In an email, he said he generally agreed with the decision to largely stick to the 2018 recommendations for women.[[{"fid":"301911","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Rajesh K. Jain, the endocrinology fellowship program director at University of Chicago Medicine, Chicago","field_file_image_credit[und][0][value]":"University of Chicago Medicine","field_file_image_caption[und][0][value]":"Dr. Rajesh K. Jain"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]<br/><br/>He also noted that there’s still a lack of a clear direction for physicians about assessing osteoporosis risk in men. But multiple randomized control trials of osteoporosis drugs seem to suggest these medicines work for both sexes, said Dr. Jain, who is the endocrinology fellowship program director at University of Chicago Medicine, Chicago.<br/><br/>The USPSTF draft also would reiterate the current “I” grade about screening men for osteoporosis.<br/><br/>An “I” grade means the task force found the current body of available evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis to prevent osteoporotic fractures in men.<br/><br/>“Since there is no recommendation right now, it would have seemed sensible to include a recommendation to screen men with prior fracture or other risk factors for osteoporosis, much like they do for younger women,” Dr. Jain said.<br/><br/></p> <h2>Insufficient Evidence</h2> <p>The USPSTF’s “I” grade is different from a “D” grade, which is what the task force uses to recommend against the use of a service.</p> <p>A “D” grade means the USPSTF says there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. (The USPSTF makes it easy to search online for grades given to preventive services, including <span class="Hyperlink"><a href="https://www.uspreventiveservicestaskforce.org/uspstf/topic_search_results?topic_status=P&grades%5B%5D=D&searchterm=">those that got a “D.”</a></span>)<br/><br/>The USPSTF is calling for more studies on the benefits and harms of screening for osteoporosis to prevent fractures and related morbidity and mortality in men.<br/><br/>“Men do get osteoporosis,” Dr. Davis said. “But unfortunately, the evidence isn’t there” to allow USPSTF to make a recommendation on screening approaches.<br/><br/>“Any man who has concerns about bone health should certainly talk to his clinician and figure out what is the best form of screening” he might want to do, she said.<br/><br/>There’s been a growing interest in the question of whether to screen men for osteoporosis and bone health. For example, Osteoporosis Canada last year updated a guideline to emphasize the need to <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/997297">assess older patients of both sexes</a></span> for the risk for fractures. But <span class="Hyperlink"><a href="https://www.cmaj.ca/content/195/18/E639">the Canadian Task Force on Preventive Health Care</a></span> in 2023 came to a conclusion in line with the USPSTF draft.<br/><br/>The Canadian task force recommended against routine screening in men, while adding that clinicians should be alert to changes in health that may indicate the patient has experienced or is at a higher risk for fragility fracture.<br/><br/></p> <h2>Risk Factors, Concerns About Tests</h2> <p>The USPSTF said that risk factors associated with fragility fractures are similar in men and women. These include:</p> <ul class="body"> <li>Increasing age</li> <li>Low body mass index</li> <li>Excessive alcohol intake</li> <li>Current smoking</li> <li>Chronic corticosteroid use</li> <li>History of prior fractures, falls within the past year, cerebrovascular accident, and diabetes</li> <li>Hypogonadism</li> </ul> <p>The process of updating the USPSTF recommendations can serve as a chance to expand public awareness about osteoporosis, as many men may not know to raise the question of their fracture risk during medical appointments, Dr. Davis said.<br/><br/>“Clinicians need to be aware of the risk factors and to be able to have conversations with men,” she said.<br/><br/>Dr. Davis also cautioned about the need to be aware of limitations with clinical risk assessment tools. In the draft recommendation statement, the USPSTF noted that some tools and approaches may be less likely to identify Black, Hispanic, and Asian people as high risk, and subsequently, clinicians may be less likely to offer treatment to them compared with White people of the same age, bone mineral density, and clinical risk profile.<br/><br/>Dr. Davis had no relevant financial relationships. Dr. Jain received research funding from the Amgen Foundation.<br/><br/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/uspstf-draft-recommendations-support-some-osteoporosis-2024a1000ays">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
Is Cushing Syndrome More Common in the US Than We Think?
BOSTON — The prevalence of Cushing syndrome (CS) in the United States may be considerably higher than currently appreciated, new data from a single US institution suggest.
In contrast to estimates of 1 to 3 cases per million patient-years from population-based European studies, researchers at the University of Wisconsin, Milwaukee, estimated that the incidence of CS in Wisconsin is a minimum of 7.2 cases per million patient-years. What’s more, contrary to all previous studies, they found that adrenal Cushing syndrome was more common than pituitary adrenocorticotropic hormone (ACTH)–secreting tumors (Cushing disease), and that fewer than half of individuals with adrenal Cushing syndrome had classic physical features of hypercortisolism, such as weight gain, round face, excessive hair growth, and stretch marks.
“Cases are absolutely being missed. ... Clinicians should realize that cortisol excess is not rare. It may not be common, but it needs to be considered in patients with any constellation of features that are seen in cortisol excess,” study investigator Ty B. Carroll, MD, associate professor of medicine, endocrinology and molecular medicine, and the endocrine fellowship program director at Medical College of Wisconsin in Milwaukee, told this news organization.
There are several contributing factors, he noted, “including the obesity and diabetes epidemics which make some clinical features of cortisol excess more common and less notable. Providers get used to seeing patients with some features of cortisol excess and don’t think to screen. The consequence of this is more difficult-to-control diabetes and hypertension, more advance metabolic bone disease, and likely more advanced cardiovascular disease, all resulting from extended exposure to cortisol excess,” he said.
Are Milder Cases the Ones Being Missed?
Asked to comment, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University College of Physicians and Surgeons, New York City, said, “When we talk about Cushing [syndrome], we usually think of pituitary ACTH as more [common], followed by adrenal adenomas, and then ectopic. But they’re seeing more adrenal adenoma ... we are probably diagnosing this a little more now.”
She also suggested that the Wisconsin group may have a lower threshold for diagnosing the milder cortisol elevation seen with adrenal Cushing syndrome. “If you screen for Cushing with a dexamethasone suppression test … [i]f you have autonomous secretion by the adrenal, you don’t suppress as much. ... When you measure 24-hour urinary cortisol, it may be normal. So you’re in this in-between [state]. ... Maybe in Wisconsin they’re diagnosing it more. Or, maybe it’s just being underdiagnosed in other places.”
She also pointed out that “you can’t diagnose it unless you think of it. I’m not so sure that with these mild cases it’s so much that it’s more common, but maybe it’s like thyroid nodules, where we didn’t know about it until everybody started getting all of these CT scans. We’re now seeing all these incidental thyroid nodules ... I don’t think we’re missing florid Cushing.”
However, Dr. Wardlaw said, it’s probably worthwhile to detect even milder hypercortisolism because it could still have long-term damaging effects, including osteoporosis, muscle weakness, glucose intolerance, and frailty. “You could do something about it and normalize it if you found it. I think that would be the reason to do it.”
Is Wisconsin Representative of Cushing Everywhere?
Dr. Carroll presented the findings at the annual meeting of the Endocrine Society. He began by noting that most of the previous CS incidence studies, with estimates of 1.2-3.2 cases per million per year, come from European data published from 1994 to 2019 and collected as far back as 1955. The method of acquisition of patients and the definitions of confirmed cases varied widely in those studies, which reported CS etiologies of ACTH-secreting neoplasms (pituitary or ectopic) in 75%-85% and adrenal-dependent cortisol excess in 15%-20%.
The current study included data from clinic records between May 1, 2017, and December 31, 2022, of Wisconsin residents newly diagnosed with and treated for CS. The CS diagnosis was established with standard guideline-supported biochemical testing and appropriate imaging. Patients with exogenous and non-neoplastic hypercortisolism and those who did not receive therapy for CS were excluded.
A total of 185 patients (73% female, 27% male) were identified from 27 of the total 72 counties in Wisconsin, representing a population of 4.5 million. On the basis of the total 5.9 million population of Wisconsin, the incidence of CS in the state works out to 7.2 cases per million population per year, Dr. Carroll said.
However, data from the Wisconsin Hospital Association show that the University of Wisconsin’s Milwaukee facility treated just about half of patients in the state who are discharged from the hospital with a diagnosis of CS during 2019-2023. “So ... that means that an actual or approximate incidence of 14-15 cases per million per year rather than the 7.2 cases that we produce,” he said.
Etiologies were 60% adrenal (111 patients), 36.8% pituitary (68 patients), and 3.2% ectopic (6 patients). Those proportions were similar between genders.
On biochemical testing, values for late-night salivary cortisol, dexamethasone suppression, and urinary free cortisol were highest for the ectopic group (3.189 µg/dL, 42.5 µg/dL, and 1514.2 µg/24 h, respectively) and lowest for the adrenal group (0.236 µg/dL, 6.5 µg/dL, and 64.2 µg/24 h, respectively). All differences between groups were highly statistically significant, at P < .0001, Dr. Carroll noted.
Classic physical features of CS were present in 91% of people with pituitary CS and 100% of those ectopic CS but just 44% of individuals with adrenal CS. “We found that adrenal-dependent disease was the most common form of Cushing syndrome. It frequently presented without classic physical features that may be due to the milder biochemical presentation,” he concluded.
Dr. Carroll reported consulting and investigator fees from Corcept Therapeutics. Dr. Wardlaw has no disclosures.
A version of this article appeared on Medscape.com.
BOSTON — The prevalence of Cushing syndrome (CS) in the United States may be considerably higher than currently appreciated, new data from a single US institution suggest.
In contrast to estimates of 1 to 3 cases per million patient-years from population-based European studies, researchers at the University of Wisconsin, Milwaukee, estimated that the incidence of CS in Wisconsin is a minimum of 7.2 cases per million patient-years. What’s more, contrary to all previous studies, they found that adrenal Cushing syndrome was more common than pituitary adrenocorticotropic hormone (ACTH)–secreting tumors (Cushing disease), and that fewer than half of individuals with adrenal Cushing syndrome had classic physical features of hypercortisolism, such as weight gain, round face, excessive hair growth, and stretch marks.
“Cases are absolutely being missed. ... Clinicians should realize that cortisol excess is not rare. It may not be common, but it needs to be considered in patients with any constellation of features that are seen in cortisol excess,” study investigator Ty B. Carroll, MD, associate professor of medicine, endocrinology and molecular medicine, and the endocrine fellowship program director at Medical College of Wisconsin in Milwaukee, told this news organization.
There are several contributing factors, he noted, “including the obesity and diabetes epidemics which make some clinical features of cortisol excess more common and less notable. Providers get used to seeing patients with some features of cortisol excess and don’t think to screen. The consequence of this is more difficult-to-control diabetes and hypertension, more advance metabolic bone disease, and likely more advanced cardiovascular disease, all resulting from extended exposure to cortisol excess,” he said.
Are Milder Cases the Ones Being Missed?
Asked to comment, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University College of Physicians and Surgeons, New York City, said, “When we talk about Cushing [syndrome], we usually think of pituitary ACTH as more [common], followed by adrenal adenomas, and then ectopic. But they’re seeing more adrenal adenoma ... we are probably diagnosing this a little more now.”
She also suggested that the Wisconsin group may have a lower threshold for diagnosing the milder cortisol elevation seen with adrenal Cushing syndrome. “If you screen for Cushing with a dexamethasone suppression test … [i]f you have autonomous secretion by the adrenal, you don’t suppress as much. ... When you measure 24-hour urinary cortisol, it may be normal. So you’re in this in-between [state]. ... Maybe in Wisconsin they’re diagnosing it more. Or, maybe it’s just being underdiagnosed in other places.”
She also pointed out that “you can’t diagnose it unless you think of it. I’m not so sure that with these mild cases it’s so much that it’s more common, but maybe it’s like thyroid nodules, where we didn’t know about it until everybody started getting all of these CT scans. We’re now seeing all these incidental thyroid nodules ... I don’t think we’re missing florid Cushing.”
However, Dr. Wardlaw said, it’s probably worthwhile to detect even milder hypercortisolism because it could still have long-term damaging effects, including osteoporosis, muscle weakness, glucose intolerance, and frailty. “You could do something about it and normalize it if you found it. I think that would be the reason to do it.”
Is Wisconsin Representative of Cushing Everywhere?
Dr. Carroll presented the findings at the annual meeting of the Endocrine Society. He began by noting that most of the previous CS incidence studies, with estimates of 1.2-3.2 cases per million per year, come from European data published from 1994 to 2019 and collected as far back as 1955. The method of acquisition of patients and the definitions of confirmed cases varied widely in those studies, which reported CS etiologies of ACTH-secreting neoplasms (pituitary or ectopic) in 75%-85% and adrenal-dependent cortisol excess in 15%-20%.
The current study included data from clinic records between May 1, 2017, and December 31, 2022, of Wisconsin residents newly diagnosed with and treated for CS. The CS diagnosis was established with standard guideline-supported biochemical testing and appropriate imaging. Patients with exogenous and non-neoplastic hypercortisolism and those who did not receive therapy for CS were excluded.
A total of 185 patients (73% female, 27% male) were identified from 27 of the total 72 counties in Wisconsin, representing a population of 4.5 million. On the basis of the total 5.9 million population of Wisconsin, the incidence of CS in the state works out to 7.2 cases per million population per year, Dr. Carroll said.
However, data from the Wisconsin Hospital Association show that the University of Wisconsin’s Milwaukee facility treated just about half of patients in the state who are discharged from the hospital with a diagnosis of CS during 2019-2023. “So ... that means that an actual or approximate incidence of 14-15 cases per million per year rather than the 7.2 cases that we produce,” he said.
Etiologies were 60% adrenal (111 patients), 36.8% pituitary (68 patients), and 3.2% ectopic (6 patients). Those proportions were similar between genders.
On biochemical testing, values for late-night salivary cortisol, dexamethasone suppression, and urinary free cortisol were highest for the ectopic group (3.189 µg/dL, 42.5 µg/dL, and 1514.2 µg/24 h, respectively) and lowest for the adrenal group (0.236 µg/dL, 6.5 µg/dL, and 64.2 µg/24 h, respectively). All differences between groups were highly statistically significant, at P < .0001, Dr. Carroll noted.
Classic physical features of CS were present in 91% of people with pituitary CS and 100% of those ectopic CS but just 44% of individuals with adrenal CS. “We found that adrenal-dependent disease was the most common form of Cushing syndrome. It frequently presented without classic physical features that may be due to the milder biochemical presentation,” he concluded.
Dr. Carroll reported consulting and investigator fees from Corcept Therapeutics. Dr. Wardlaw has no disclosures.
A version of this article appeared on Medscape.com.
BOSTON — The prevalence of Cushing syndrome (CS) in the United States may be considerably higher than currently appreciated, new data from a single US institution suggest.
In contrast to estimates of 1 to 3 cases per million patient-years from population-based European studies, researchers at the University of Wisconsin, Milwaukee, estimated that the incidence of CS in Wisconsin is a minimum of 7.2 cases per million patient-years. What’s more, contrary to all previous studies, they found that adrenal Cushing syndrome was more common than pituitary adrenocorticotropic hormone (ACTH)–secreting tumors (Cushing disease), and that fewer than half of individuals with adrenal Cushing syndrome had classic physical features of hypercortisolism, such as weight gain, round face, excessive hair growth, and stretch marks.
“Cases are absolutely being missed. ... Clinicians should realize that cortisol excess is not rare. It may not be common, but it needs to be considered in patients with any constellation of features that are seen in cortisol excess,” study investigator Ty B. Carroll, MD, associate professor of medicine, endocrinology and molecular medicine, and the endocrine fellowship program director at Medical College of Wisconsin in Milwaukee, told this news organization.
There are several contributing factors, he noted, “including the obesity and diabetes epidemics which make some clinical features of cortisol excess more common and less notable. Providers get used to seeing patients with some features of cortisol excess and don’t think to screen. The consequence of this is more difficult-to-control diabetes and hypertension, more advance metabolic bone disease, and likely more advanced cardiovascular disease, all resulting from extended exposure to cortisol excess,” he said.
Are Milder Cases the Ones Being Missed?
Asked to comment, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University College of Physicians and Surgeons, New York City, said, “When we talk about Cushing [syndrome], we usually think of pituitary ACTH as more [common], followed by adrenal adenomas, and then ectopic. But they’re seeing more adrenal adenoma ... we are probably diagnosing this a little more now.”
She also suggested that the Wisconsin group may have a lower threshold for diagnosing the milder cortisol elevation seen with adrenal Cushing syndrome. “If you screen for Cushing with a dexamethasone suppression test … [i]f you have autonomous secretion by the adrenal, you don’t suppress as much. ... When you measure 24-hour urinary cortisol, it may be normal. So you’re in this in-between [state]. ... Maybe in Wisconsin they’re diagnosing it more. Or, maybe it’s just being underdiagnosed in other places.”
She also pointed out that “you can’t diagnose it unless you think of it. I’m not so sure that with these mild cases it’s so much that it’s more common, but maybe it’s like thyroid nodules, where we didn’t know about it until everybody started getting all of these CT scans. We’re now seeing all these incidental thyroid nodules ... I don’t think we’re missing florid Cushing.”
However, Dr. Wardlaw said, it’s probably worthwhile to detect even milder hypercortisolism because it could still have long-term damaging effects, including osteoporosis, muscle weakness, glucose intolerance, and frailty. “You could do something about it and normalize it if you found it. I think that would be the reason to do it.”
Is Wisconsin Representative of Cushing Everywhere?
Dr. Carroll presented the findings at the annual meeting of the Endocrine Society. He began by noting that most of the previous CS incidence studies, with estimates of 1.2-3.2 cases per million per year, come from European data published from 1994 to 2019 and collected as far back as 1955. The method of acquisition of patients and the definitions of confirmed cases varied widely in those studies, which reported CS etiologies of ACTH-secreting neoplasms (pituitary or ectopic) in 75%-85% and adrenal-dependent cortisol excess in 15%-20%.
The current study included data from clinic records between May 1, 2017, and December 31, 2022, of Wisconsin residents newly diagnosed with and treated for CS. The CS diagnosis was established with standard guideline-supported biochemical testing and appropriate imaging. Patients with exogenous and non-neoplastic hypercortisolism and those who did not receive therapy for CS were excluded.
A total of 185 patients (73% female, 27% male) were identified from 27 of the total 72 counties in Wisconsin, representing a population of 4.5 million. On the basis of the total 5.9 million population of Wisconsin, the incidence of CS in the state works out to 7.2 cases per million population per year, Dr. Carroll said.
However, data from the Wisconsin Hospital Association show that the University of Wisconsin’s Milwaukee facility treated just about half of patients in the state who are discharged from the hospital with a diagnosis of CS during 2019-2023. “So ... that means that an actual or approximate incidence of 14-15 cases per million per year rather than the 7.2 cases that we produce,” he said.
Etiologies were 60% adrenal (111 patients), 36.8% pituitary (68 patients), and 3.2% ectopic (6 patients). Those proportions were similar between genders.
On biochemical testing, values for late-night salivary cortisol, dexamethasone suppression, and urinary free cortisol were highest for the ectopic group (3.189 µg/dL, 42.5 µg/dL, and 1514.2 µg/24 h, respectively) and lowest for the adrenal group (0.236 µg/dL, 6.5 µg/dL, and 64.2 µg/24 h, respectively). All differences between groups were highly statistically significant, at P < .0001, Dr. Carroll noted.
Classic physical features of CS were present in 91% of people with pituitary CS and 100% of those ectopic CS but just 44% of individuals with adrenal CS. “We found that adrenal-dependent disease was the most common form of Cushing syndrome. It frequently presented without classic physical features that may be due to the milder biochemical presentation,” he concluded.
Dr. Carroll reported consulting and investigator fees from Corcept Therapeutics. Dr. Wardlaw has no disclosures.
A version of this article appeared on Medscape.com.
<!--$RCSfile: InCopy_agile.xsl,v $ $Revision: 1.35 $-->
<!--$RCSfile: drupal.xsl,v $ $Revision: 1.7 $-->
<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>168339</fileName> <TBEID>0C050753.SIG</TBEID> <TBUniqueIdentifier>MD_0C050753</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240610T143147</QCDate> <firstPublished>20240610T153646</firstPublished> <LastPublished>20240610T153646</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240610T153646</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline>Miriam E. Tucker</byline> <bylineText>MIRIAM E. TUCKER</bylineText> <bylineFull>MIRIAM E. TUCKER</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>BOSTON — The prevalence of Cushing syndrome (CS) in the United States may be considerably higher than currently appreciated, new data from a single US instituti</metaDescription> <articlePDF/> <teaserImage/> <teaser>Providers get used to seeing patients with some features of cortisol excess and don’t think to screen. </teaser> <title>Is Cushing Syndrome More Common in the US Than We Think?</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>endo</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">34</term> <term>15</term> <term>21</term> </publications> <sections> <term>53</term> <term canonical="true">39313</term> </sections> <topics> <term canonical="true">59135</term> <term>206</term> <term>261</term> <term>205</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Is Cushing Syndrome More Common in the US Than We Think?</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">BOSTON</span> — The prevalence of Cushing syndrome (CS) in the United States may be considerably higher than currently appreciated, new data from a single US institution suggest. </p> <p>In contrast to estimates of 1 to 3 cases per million patient-years from population-based European studies, researchers at the University of Wisconsin, Milwaukee, estimated that the incidence of CS in Wisconsin is a minimum of 7.2 cases per million patient-years. What’s more, contrary to all previous studies, they found that adrenal Cushing syndrome was more common than pituitary adrenocorticotropic hormone (ACTH)–secreting tumors (Cushing disease), and that fewer than half of individuals with adrenal Cushing syndrome had classic physical features of <a href="https://emedicine.medscape.com/article/117365-overview">hypercortisolism</a>, such as weight gain, round face, excessive hair growth, and stretch marks.<br/><br/>“Cases are absolutely being missed. ... Clinicians should realize that cortisol excess is not rare. It may not be common, but it needs to be considered in patients with any constellation of features that are seen in cortisol excess,” study investigator Ty B. Carroll, MD, associate professor of medicine, endocrinology and molecular medicine, and the endocrine fellowship program director at Medical College of Wisconsin in Milwaukee, told this news organization. <br/><br/>There are several contributing factors, he noted, “including the obesity and diabetes epidemics which make some clinical features of cortisol excess more common and less notable. Providers get used to seeing patients with some features of cortisol excess and don’t think to screen. The consequence of this is more difficult-to-control diabetes and hypertension, more advance metabolic bone disease, and likely more advanced cardiovascular disease, all resulting from extended exposure to cortisol excess,” he said.<br/><br/> </p> <h2>Are Milder Cases the Ones Being Missed?</h2> <p>Asked to comment, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University College of Physicians and Surgeons, New York City, said, “When we talk about Cushing [syndrome], we usually think of pituitary ACTH as more [common], followed by adrenal adenomas, and then ectopic. But they’re seeing more adrenal adenoma ... we are probably diagnosing this a little more now.”</p> <p>She also suggested that the Wisconsin group may have a lower threshold for diagnosing the milder cortisol elevation seen with adrenal Cushing syndrome. “If you screen for Cushing with a dexamethasone suppression test … [i]f you have autonomous secretion by the adrenal, you don’t suppress as much. ... When you measure 24-hour urinary cortisol, it may be normal. So you’re in this in-between [state]. ... Maybe in Wisconsin they’re diagnosing it more. Or, maybe it’s just being underdiagnosed in other places.” <br/><br/>She also pointed out that “you can’t diagnose it unless you think of it. I’m not so sure that with these mild cases it’s so much that it’s more common, but maybe it’s like thyroid nodules, where we didn’t know about it until everybody started getting all of these CT scans. We’re now seeing all these incidental thyroid nodules ... I don’t think we’re missing florid Cushing.” <br/><br/>However, Dr. Wardlaw said, it’s probably worthwhile to detect even milder hypercortisolism because it could still have long-term damaging effects, including osteoporosis, muscle weakness, glucose intolerance, and frailty. “You could do something about it and normalize it if you found it. I think that would be the reason to do it.”<br/><br/></p> <h2>Is Wisconsin Representative of Cushing Everywhere?</h2> <p>Dr. Carroll presented the findings at the annual meeting of the Endocrine Society. He began by noting that most of the previous CS incidence studies, with estimates of 1.2-3.2 cases per million per year, come from European data published from 1994 to 2019 and collected as far back as 1955. The method of acquisition of patients and the definitions of confirmed cases varied widely in those studies, which reported CS etiologies of ACTH-secreting neoplasms (pituitary or ectopic) in 75%-85% and adrenal-dependent cortisol excess in 15%-20%. </p> <p>The current study included data from clinic records between May 1, 2017, and December 31, 2022, of Wisconsin residents newly diagnosed with and treated for CS. The CS diagnosis was established with standard guideline-supported biochemical testing and appropriate imaging. Patients with exogenous and non-neoplastic hypercortisolism and those who did not receive therapy for CS were excluded. <br/><br/>A total of 185 patients (73% female, 27% male) were identified from 27 of the total 72 counties in Wisconsin, representing a population of 4.5 million. On the basis of the total 5.9 million population of Wisconsin, the incidence of CS in the state works out to 7.2 cases per million population per year, Dr. Carroll said. <br/><br/>However, data from the Wisconsin Hospital Association show that the University of Wisconsin’s Milwaukee facility treated just about half of patients in the state who are discharged from the hospital with a diagnosis of CS during 2019-2023. “So ... that means that an actual or approximate incidence of 14-15 cases per million per year rather than the 7.2 cases that we produce,” he said. <br/><br/>Etiologies were 60% adrenal (111 patients), 36.8% pituitary (68 patients), and 3.2% ectopic (6 patients). Those proportions were similar between genders. <br/><br/>On biochemical testing, values for late-night salivary cortisol, dexamethasone suppression, and urinary free cortisol were highest for the ectopic group (3.189 µg/dL, 42.5 µg/dL, and 1514.2 µg/24 h, respectively) and lowest for the adrenal group (0.236 µg/dL, 6.5 µg/dL, and 64.2 µg/24 h, respectively). All differences between groups were highly statistically significant, at <em>P</em> < .0001, Dr. Carroll noted. <br/><br/>Classic physical features of CS were present in 91% of people with pituitary CS and 100% of those ectopic CS but just 44% of individuals with adrenal CS. “We found that adrenal-dependent disease was the most common form of Cushing syndrome. It frequently presented without classic physical features that may be due to the milder biochemical presentation,” he concluded. <br/><br/>Dr. Carroll reported consulting and investigator fees from Corcept Therapeutics. Dr. Wardlaw has no disclosures. <br/><br/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/cushing-syndrome-more-common-us-than-we-think-2024a1000ar4">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
Losing Weight, Decreasing Alcohol, and Improving Sex Life?
Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail.
When I met him in December 2023, he had hit rock bottom and was willing to try anything.
At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone.
Richard shared some feedback after his first 2 weeks:
The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.
And after 6 weeks:
Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.
And finally, after 8 weeks:
Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you.
Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine.
Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors.
Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone.
At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity.
*Patient’s name has been changed.
Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail.
When I met him in December 2023, he had hit rock bottom and was willing to try anything.
At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone.
Richard shared some feedback after his first 2 weeks:
The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.
And after 6 weeks:
Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.
And finally, after 8 weeks:
Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you.
Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine.
Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors.
Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone.
At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity.
*Patient’s name has been changed.
Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail.
When I met him in December 2023, he had hit rock bottom and was willing to try anything.
At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone.
Richard shared some feedback after his first 2 weeks:
The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.
And after 6 weeks:
Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.
And finally, after 8 weeks:
Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you.
Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine.
Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors.
Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone.
At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity.
*Patient’s name has been changed.
Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
<!--$RCSfile: InCopy_agile.xsl,v $ $Revision: 1.35 $-->
<!--$RCSfile: drupal.xsl,v $ $Revision: 1.7 $-->
<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>168316</fileName> <TBEID>0C0506E8.SIG</TBEID> <TBUniqueIdentifier>MD_0C0506E8</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>353</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240607T115625</QCDate> <firstPublished>20240607T120519</firstPublished> <LastPublished>20240607T120519</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240607T120519</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline>Caroline Messer, MD</byline> <bylineText>CAROLINE MESSER, MD</bylineText> <bylineFull>CAROLINE MESSER, MD</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy Lea</metaDescription> <articlePDF/> <teaserImage/> <teaser>“The vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in <span class="Hyperlink">testosterone.”</span></teaser> <title>Losing Weight, Decreasing Alcohol, and Improving Sex Life?</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>endo</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>cpn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">34</term> <term>9</term> <term>15</term> <term>21</term> </publications> <sections> <term canonical="true">52</term> </sections> <topics> <term canonical="true">246</term> <term>174</term> <term>209</term> <term>296</term> <term>206</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Losing Weight, Decreasing Alcohol, and Improving Sex Life?</title> <deck/> </itemMeta> <itemContent> <p>Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his <span class="Hyperlink">alcohol abuse</span> disorder on multiple occasions: He went to a yearlong class on <span class="Hyperlink">alcoholism</span>, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. </p> <p>When I met him in December 2023, he had hit rock bottom and was willing to try anything.<br/><br/>At our first visit, I prescribed him weekly <span class="Hyperlink">tirzepatide</span> (Zepbound) off label, along with a small dose of <span class="Hyperlink">naltrexone</span>. <br/><br/>Richard shared some feedback after his first 2 weeks:<br/><br/><span class="Emphasis">The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.<br/><br/></span>And after 6 weeks:<br/><br/><span class="Emphasis">Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.<br/><br/></span>And finally, after 8 weeks:<br/><br/><span class="Emphasis">Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. <br/><br/></span>Tirzepatide contains two hormones, <span class="Hyperlink">glucagon</span>-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of <span class="Hyperlink">dopamine</span>. <br/><br/>Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. <br/><br/>Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in <span class="Hyperlink">testosterone</span>, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic <span class="Hyperlink">alcohol use</span> can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. <br/><br/>At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and <span class="Hyperlink">obesity</span>. <br/><br/><span class="Emphasis">*</span><em>Patient’s name has been changed</em><span class="Emphasis">.<br/><br/></span></p> <p> <em>Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.</em> </p> <p> <em> <span class="Emphasis">A version of this article appeared on </span> <span class="Hyperlink"> <a href="https://www.medscape.com/viewarticle/losing-weight-decreasing-alcohol-and-improving-sex-life-2024a1000a7f">Medscape.com</a> </span> <span class="Emphasis">.</span> </em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
Over-the-Counter Arthritis Supplements Pose Adrenal Danger
BOSTON —
Patients who have been taking these supplements for prolonged periods must slowly taper off them with corticosteroid replacement, because abruptly stopping the supplement can precipitate AI, Kevin S. Wei, MD, said in a presentation of 12 cases — the largest such series to date of the phenomenon — at the annual meeting of the Endocrine Society.
The specific supplements used were Artri King in eight of the patients, Ardosons in two, and Ajo Rey in one. In April 2022, the US Food and Drug Administration issued a warning that Artri King contains diclofenac and dexamethasone not listed on the product label. In July 2023, the agency issued an expanded warning about that product and others including Ajo Rey.
The supplements are not believed to be sold in the United States, but they are available in Mexico and can be ordered online, said Dr. Wei, a second-year resident at the Keck School of Medicine at the University of California, Los Angeles.
“We found that quite a lot of patients after they’ve been on the Artri King or some other over the counter arthritis supplement, started developing these cushingoid features seen in the physical exam, such as rounded facial features or stretch marks of their abdomen,” he said.
And “when patients are abruptly taken off those supplements … sometimes this can cause them to go into signs or symptoms of adrenal insufficiency. That can occasionally be life-threatening if it’s not addressed in an inpatient setting,” Dr. Wei said.
In an interview, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University Irving Medical Center, New York, explained that when a person takes these drugs containing hidden glucocorticoids, “they won’t be picked up in a cortisol assay, but they’ll suppress the [adrenocorticotropic hormone] and the person’s own cortisol production. They look like they have Cushing, but when you measure their hormone levels, they’re undetectable. And then people wonder what’s going on. Well, their [hypothalamic-pituitary-adrenal] axis is suppressed.”
But if the product is suddenly stopped without cortisol replacement “If they get an infection they can die because they can’t mount a cortisol response.”
The takeaway message, she said, is “always ask patients to show you their supplements and look at them. In many cases, that’s why they work so well for pain relief because they have ingredients that people shouldn’t be taking.”
Twelve Patients Seen During 2022-2023
The 12 patients were seen during 2022-2023 at an endocrinology consult service in an urban safety net hospital. Their median age was 52 years, and one third were women. All had started using the supplements for joint pain, with a median of about 6 months of use prior to cessation.
Presenting symptoms included nausea/vomiting in 42%, fatigue in 42%, abdominal pain in 33%, and dizziness in 17%. Physical exam findings included moon facies in 66%, central adiposity in 66%, abdominal striae in 50%, dorsocervical fat pad in 33%, and bruising in 33%. Three required intensive care admission.
Cortisol testing was performed in 11 of the patients and was normal (≥ 16 mcg/dL) in just one. AI (≤ 3 mcg/dL) was found in three, while the rest had indeterminate results. Of those seven patients, subsequent cosyntropin-stimulation testing suggested AI (cortisol < 16 mcg/dL at 60 minutes post stimulation) in four patients, while the other two showed reduced but normal responses (cortisol 18.2-18.4 mcg/dL).
Ten of the 12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis, most commonly twice-daily hydrocortisone. Of those ten, eight continued to take the replacement steroids 1-2 years later, Dr. Wei said.
Dr. Wei and Dr. Wardlaw had no disclosures.
A version of this article appeared on Medscape.com.
BOSTON —
Patients who have been taking these supplements for prolonged periods must slowly taper off them with corticosteroid replacement, because abruptly stopping the supplement can precipitate AI, Kevin S. Wei, MD, said in a presentation of 12 cases — the largest such series to date of the phenomenon — at the annual meeting of the Endocrine Society.
The specific supplements used were Artri King in eight of the patients, Ardosons in two, and Ajo Rey in one. In April 2022, the US Food and Drug Administration issued a warning that Artri King contains diclofenac and dexamethasone not listed on the product label. In July 2023, the agency issued an expanded warning about that product and others including Ajo Rey.
The supplements are not believed to be sold in the United States, but they are available in Mexico and can be ordered online, said Dr. Wei, a second-year resident at the Keck School of Medicine at the University of California, Los Angeles.
“We found that quite a lot of patients after they’ve been on the Artri King or some other over the counter arthritis supplement, started developing these cushingoid features seen in the physical exam, such as rounded facial features or stretch marks of their abdomen,” he said.
And “when patients are abruptly taken off those supplements … sometimes this can cause them to go into signs or symptoms of adrenal insufficiency. That can occasionally be life-threatening if it’s not addressed in an inpatient setting,” Dr. Wei said.
In an interview, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University Irving Medical Center, New York, explained that when a person takes these drugs containing hidden glucocorticoids, “they won’t be picked up in a cortisol assay, but they’ll suppress the [adrenocorticotropic hormone] and the person’s own cortisol production. They look like they have Cushing, but when you measure their hormone levels, they’re undetectable. And then people wonder what’s going on. Well, their [hypothalamic-pituitary-adrenal] axis is suppressed.”
But if the product is suddenly stopped without cortisol replacement “If they get an infection they can die because they can’t mount a cortisol response.”
The takeaway message, she said, is “always ask patients to show you their supplements and look at them. In many cases, that’s why they work so well for pain relief because they have ingredients that people shouldn’t be taking.”
Twelve Patients Seen During 2022-2023
The 12 patients were seen during 2022-2023 at an endocrinology consult service in an urban safety net hospital. Their median age was 52 years, and one third were women. All had started using the supplements for joint pain, with a median of about 6 months of use prior to cessation.
Presenting symptoms included nausea/vomiting in 42%, fatigue in 42%, abdominal pain in 33%, and dizziness in 17%. Physical exam findings included moon facies in 66%, central adiposity in 66%, abdominal striae in 50%, dorsocervical fat pad in 33%, and bruising in 33%. Three required intensive care admission.
Cortisol testing was performed in 11 of the patients and was normal (≥ 16 mcg/dL) in just one. AI (≤ 3 mcg/dL) was found in three, while the rest had indeterminate results. Of those seven patients, subsequent cosyntropin-stimulation testing suggested AI (cortisol < 16 mcg/dL at 60 minutes post stimulation) in four patients, while the other two showed reduced but normal responses (cortisol 18.2-18.4 mcg/dL).
Ten of the 12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis, most commonly twice-daily hydrocortisone. Of those ten, eight continued to take the replacement steroids 1-2 years later, Dr. Wei said.
Dr. Wei and Dr. Wardlaw had no disclosures.
A version of this article appeared on Medscape.com.
BOSTON —
Patients who have been taking these supplements for prolonged periods must slowly taper off them with corticosteroid replacement, because abruptly stopping the supplement can precipitate AI, Kevin S. Wei, MD, said in a presentation of 12 cases — the largest such series to date of the phenomenon — at the annual meeting of the Endocrine Society.
The specific supplements used were Artri King in eight of the patients, Ardosons in two, and Ajo Rey in one. In April 2022, the US Food and Drug Administration issued a warning that Artri King contains diclofenac and dexamethasone not listed on the product label. In July 2023, the agency issued an expanded warning about that product and others including Ajo Rey.
The supplements are not believed to be sold in the United States, but they are available in Mexico and can be ordered online, said Dr. Wei, a second-year resident at the Keck School of Medicine at the University of California, Los Angeles.
“We found that quite a lot of patients after they’ve been on the Artri King or some other over the counter arthritis supplement, started developing these cushingoid features seen in the physical exam, such as rounded facial features or stretch marks of their abdomen,” he said.
And “when patients are abruptly taken off those supplements … sometimes this can cause them to go into signs or symptoms of adrenal insufficiency. That can occasionally be life-threatening if it’s not addressed in an inpatient setting,” Dr. Wei said.
In an interview, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University Irving Medical Center, New York, explained that when a person takes these drugs containing hidden glucocorticoids, “they won’t be picked up in a cortisol assay, but they’ll suppress the [adrenocorticotropic hormone] and the person’s own cortisol production. They look like they have Cushing, but when you measure their hormone levels, they’re undetectable. And then people wonder what’s going on. Well, their [hypothalamic-pituitary-adrenal] axis is suppressed.”
But if the product is suddenly stopped without cortisol replacement “If they get an infection they can die because they can’t mount a cortisol response.”
The takeaway message, she said, is “always ask patients to show you their supplements and look at them. In many cases, that’s why they work so well for pain relief because they have ingredients that people shouldn’t be taking.”
Twelve Patients Seen During 2022-2023
The 12 patients were seen during 2022-2023 at an endocrinology consult service in an urban safety net hospital. Their median age was 52 years, and one third were women. All had started using the supplements for joint pain, with a median of about 6 months of use prior to cessation.
Presenting symptoms included nausea/vomiting in 42%, fatigue in 42%, abdominal pain in 33%, and dizziness in 17%. Physical exam findings included moon facies in 66%, central adiposity in 66%, abdominal striae in 50%, dorsocervical fat pad in 33%, and bruising in 33%. Three required intensive care admission.
Cortisol testing was performed in 11 of the patients and was normal (≥ 16 mcg/dL) in just one. AI (≤ 3 mcg/dL) was found in three, while the rest had indeterminate results. Of those seven patients, subsequent cosyntropin-stimulation testing suggested AI (cortisol < 16 mcg/dL at 60 minutes post stimulation) in four patients, while the other two showed reduced but normal responses (cortisol 18.2-18.4 mcg/dL).
Ten of the 12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis, most commonly twice-daily hydrocortisone. Of those ten, eight continued to take the replacement steroids 1-2 years later, Dr. Wei said.
Dr. Wei and Dr. Wardlaw had no disclosures.
A version of this article appeared on Medscape.com.
<!--$RCSfile: InCopy_agile.xsl,v $ $Revision: 1.35 $-->
<!--$RCSfile: drupal.xsl,v $ $Revision: 1.7 $-->
<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>168319</fileName> <TBEID>0C0506EB.SIG</TBEID> <TBUniqueIdentifier>MD_0C0506EB</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240606T125036</QCDate> <firstPublished>20240606T125637</firstPublished> <LastPublished>20240606T125637</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240606T125637</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline>Miriam E. Tucker</byline> <bylineText>MIRIAM E. TUCKER</bylineText> <bylineFull>MIRIAM E. TUCKER</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Use of over-the-counter arthritis supplements containing undisclosed glucocorticoids can lead to iatrogenic adrenal dysfunction, Cushing syndrome, and/or adrena</metaDescription> <articlePDF/> <teaserImage/> <teaser>Patients taking OTC arthritis supplements may need to taper use to avoid adrenal insufficiency, dysfunction, says presenter.</teaser> <title>Over-the-Counter Arthritis Supplements Pose Adrenal Danger</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>endo</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">34</term> <term>15</term> <term>21</term> </publications> <sections> <term canonical="true">39313</term> </sections> <topics> <term canonical="true">277</term> <term>266</term> <term>206</term> <term>265</term> <term>252</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Over-the-Counter Arthritis Supplements Pose Adrenal Danger</title> <deck/> </itemMeta> <itemContent> <p>BOSTON — <span class="tag metaDescription">Use of over-the-counter arthritis supplements containing undisclosed glucocorticoids can lead to iatrogenic adrenal dysfunction, Cushing syndrome, and/or adrenal insufficiency (AI).</span> </p> <p>Patients who have been taking these supplements for prolonged periods must slowly taper off them with corticosteroid replacement, because abruptly stopping the supplement can precipitate AI, Kevin S. Wei, MD, said in a presentation of 12 cases — the largest such series to date of the phenomenon — at the annual meeting of the Endocrine Society.<br/><br/>The specific supplements used were Artri King in eight of the patients, Ardosons in two, and Ajo Rey in one. In April 2022, the US Food and Drug Administration issued a warning that Artri King contains <a href="https://www.fda.gov/drugs/medication-health-fraud/public-notification-artri-king-contains-hidden-drug-ingredients">diclofenac and dexamethasone</a> not listed on the product label. In July 2023, the agency issued an <a href="https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-consumers-not-purchase-or-use-artri-and-ortiga-products-which-may-contain-hidden-drug">expanded warning</a> about that product and others including Ajo Rey.<br/><br/>The supplements are not believed to be sold in the United States, but they are available in Mexico and can be ordered online, said Dr. Wei, a second-year resident at the Keck School of Medicine at the University of California, Los Angeles.<br/><br/>“We found that quite a lot of patients after they’ve been on the Artri King or some other over the counter arthritis supplement, started developing these cushingoid features seen in the physical exam, such as rounded facial features or stretch marks of their abdomen,” he said.<br/><br/>And “when patients are abruptly taken off those supplements … sometimes this can cause them to go into signs or symptoms of adrenal insufficiency. That can occasionally be life-threatening if it’s not addressed in an inpatient setting,” Dr. Wei said.<br/><br/>In an interview, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University Irving Medical Center, New York, explained that when a person takes these drugs containing hidden glucocorticoids, “they won’t be picked up in a cortisol assay, but they’ll suppress the [adrenocorticotropic hormone] and the person’s own cortisol production. They look like they have Cushing, but when you measure their hormone levels, they’re undetectable. And then people wonder what’s going on. Well, their [hypothalamic-pituitary-adrenal] axis is suppressed.”<br/><br/>But if the product is suddenly stopped without cortisol replacement “If they get an infection they can die because they can’t mount a cortisol response.”<br/><br/>The takeaway message, she said, is “always ask patients to show you their supplements and look at them. In many cases, that’s why they work so well for pain relief because they have ingredients that people shouldn’t be taking.”</p> <h2>Twelve Patients Seen During 2022-2023</h2> <p>The 12 patients were seen during 2022-2023 at an endocrinology consult service in an urban safety net hospital. Their median age was 52 years, and one third were women. All had started using the supplements for joint pain, with a median of about 6 months of use prior to cessation.</p> <p>Presenting symptoms included nausea/vomiting in 42%, fatigue in 42%, abdominal pain in 33%, and dizziness in 17%. Physical exam findings included moon facies in 66%, central adiposity in 66%, abdominal striae in 50%, dorsocervical fat pad in 33%, and bruising in 33%. Three required intensive care admission.<br/><br/>Cortisol testing was performed in 11 of the patients and was normal (≥ 16 mcg/dL) in just one. AI (≤ 3 mcg/dL) was found in three, while the rest had indeterminate results. Of those seven patients, subsequent cosyntropin-stimulation testing suggested AI (cortisol < 16 mcg/dL at 60 minutes post stimulation) in four patients, while the other two showed reduced but normal responses (cortisol 18.2-18.4 mcg/dL).<br/><br/>Ten of the 12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis, most commonly twice-daily hydrocortisone. Of those ten, eight continued to take the replacement steroids 1-2 years later, Dr. Wei said.<br/><br/>Dr. Wei and Dr. Wardlaw had no disclosures.<span class="end"/></p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/over-counter-arthritis-supplements-pose-adrenal-danger-2024a1000amy">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
No Increased Risk for Fractures Seen With Frequent Steroid Injections for Musculoskeletal Conditions
TOPLINE:
The cumulative effect of frequent corticosteroid injections (CSIs), a common treatment for musculoskeletal pain, does not appear to increase the risk for fractures.
METHODOLOGY:
- Researchers utilized an institutional electronic health record database to identify adults in Olmsted County, Minnesota, receiving corticosteroid injections from May 1, 2018, to July 1, 2022.
- Corticosteroid equivalents were calculated for medications injected, including methylprednisolone, triamcinolone, betamethasone, and dexamethasone.
- Patients were excluded if they had a prescription for oral prednisone equivalents greater than 2.5 mg/day for more than 30 days.
- Fracture events were identified using ICD-9 and ICD-10 codes and were included only if they occurred after the first corticosteroid injection.
TAKEAWAY:
- A total of 7197 patients were analyzed, with a mean age of 64.4 years, and of these patients, 346 (4.8%) had a new fracture in a mean time of 329 days from the first corticosteroid injection, including 149 (43.1%) in classic osteoporotic locations.
- The study reported no increased fracture risk associated with corticosteroid injections and no significant difference in fracture rates across cumulative corticosteroid injection dose quartiles, regardless of osteoporosis status.
- Factors such as previous fractures, age, and Charlson Comorbidity Index were associated with a higher risk for fractures, not corticosteroid injections.
IN PRACTICE:
“Clinicians should be reassured that frequent CSI is not associated with higher fracture risk and should not withhold these important pain treatments owing to concern for fracture,” wrote the authors of the study.
SOURCE:
The study was led by Terin T. Sytsma, MD, Division of Community Internal Medicine, Geriatrics, and Palliative Care, Mayo Clinic, Rochester, Minnesota. It was published online in JAMA Network Open.
LIMITATIONS:
The study’s retrospective cohort design and its focus on a predominantly White population in a single community may limit the generalizability of the findings. Confounding variables such as smoking status, alcohol intake, and physical activity were acknowledged as potential contributors to fracture risk. Only clinically apparent fractures were considered, excluding silent vertebral fractures, and differences in corticosteroid formulation were not delineated.
DISCLOSURES:
The study was supported by a Mayo Clinic Catalyst Award to Dr. Sytsma. The authors had no conflicts of interest to report.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
TOPLINE:
The cumulative effect of frequent corticosteroid injections (CSIs), a common treatment for musculoskeletal pain, does not appear to increase the risk for fractures.
METHODOLOGY:
- Researchers utilized an institutional electronic health record database to identify adults in Olmsted County, Minnesota, receiving corticosteroid injections from May 1, 2018, to July 1, 2022.
- Corticosteroid equivalents were calculated for medications injected, including methylprednisolone, triamcinolone, betamethasone, and dexamethasone.
- Patients were excluded if they had a prescription for oral prednisone equivalents greater than 2.5 mg/day for more than 30 days.
- Fracture events were identified using ICD-9 and ICD-10 codes and were included only if they occurred after the first corticosteroid injection.
TAKEAWAY:
- A total of 7197 patients were analyzed, with a mean age of 64.4 years, and of these patients, 346 (4.8%) had a new fracture in a mean time of 329 days from the first corticosteroid injection, including 149 (43.1%) in classic osteoporotic locations.
- The study reported no increased fracture risk associated with corticosteroid injections and no significant difference in fracture rates across cumulative corticosteroid injection dose quartiles, regardless of osteoporosis status.
- Factors such as previous fractures, age, and Charlson Comorbidity Index were associated with a higher risk for fractures, not corticosteroid injections.
IN PRACTICE:
“Clinicians should be reassured that frequent CSI is not associated with higher fracture risk and should not withhold these important pain treatments owing to concern for fracture,” wrote the authors of the study.
SOURCE:
The study was led by Terin T. Sytsma, MD, Division of Community Internal Medicine, Geriatrics, and Palliative Care, Mayo Clinic, Rochester, Minnesota. It was published online in JAMA Network Open.
LIMITATIONS:
The study’s retrospective cohort design and its focus on a predominantly White population in a single community may limit the generalizability of the findings. Confounding variables such as smoking status, alcohol intake, and physical activity were acknowledged as potential contributors to fracture risk. Only clinically apparent fractures were considered, excluding silent vertebral fractures, and differences in corticosteroid formulation were not delineated.
DISCLOSURES:
The study was supported by a Mayo Clinic Catalyst Award to Dr. Sytsma. The authors had no conflicts of interest to report.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
TOPLINE:
The cumulative effect of frequent corticosteroid injections (CSIs), a common treatment for musculoskeletal pain, does not appear to increase the risk for fractures.
METHODOLOGY:
- Researchers utilized an institutional electronic health record database to identify adults in Olmsted County, Minnesota, receiving corticosteroid injections from May 1, 2018, to July 1, 2022.
- Corticosteroid equivalents were calculated for medications injected, including methylprednisolone, triamcinolone, betamethasone, and dexamethasone.
- Patients were excluded if they had a prescription for oral prednisone equivalents greater than 2.5 mg/day for more than 30 days.
- Fracture events were identified using ICD-9 and ICD-10 codes and were included only if they occurred after the first corticosteroid injection.
TAKEAWAY:
- A total of 7197 patients were analyzed, with a mean age of 64.4 years, and of these patients, 346 (4.8%) had a new fracture in a mean time of 329 days from the first corticosteroid injection, including 149 (43.1%) in classic osteoporotic locations.
- The study reported no increased fracture risk associated with corticosteroid injections and no significant difference in fracture rates across cumulative corticosteroid injection dose quartiles, regardless of osteoporosis status.
- Factors such as previous fractures, age, and Charlson Comorbidity Index were associated with a higher risk for fractures, not corticosteroid injections.
IN PRACTICE:
“Clinicians should be reassured that frequent CSI is not associated with higher fracture risk and should not withhold these important pain treatments owing to concern for fracture,” wrote the authors of the study.
SOURCE:
The study was led by Terin T. Sytsma, MD, Division of Community Internal Medicine, Geriatrics, and Palliative Care, Mayo Clinic, Rochester, Minnesota. It was published online in JAMA Network Open.
LIMITATIONS:
The study’s retrospective cohort design and its focus on a predominantly White population in a single community may limit the generalizability of the findings. Confounding variables such as smoking status, alcohol intake, and physical activity were acknowledged as potential contributors to fracture risk. Only clinically apparent fractures were considered, excluding silent vertebral fractures, and differences in corticosteroid formulation were not delineated.
DISCLOSURES:
The study was supported by a Mayo Clinic Catalyst Award to Dr. Sytsma. The authors had no conflicts of interest to report.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
<!--$RCSfile: InCopy_agile.xsl,v $ $Revision: 1.35 $-->
<!--$RCSfile: drupal.xsl,v $ $Revision: 1.7 $-->
<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>168298</fileName> <TBEID>0C05067E.SIG</TBEID> <TBUniqueIdentifier>MD_0C05067E</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240604T130227</QCDate> <firstPublished>20240604T131116</firstPublished> <LastPublished>20240604T131116</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240604T131116</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline>Jeff Evans</byline> <bylineText>EDITED JEFF EVANS</bylineText> <bylineFull>EDITED JEFF EVANS</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>The cumulative effect of frequent corticosteroid injections (CSIs), a common treatment for musculoskeletal pain, does not appear to increase the risk for fractu</metaDescription> <articlePDF/> <teaserImage/> <teaser>Fracture risk was not associated with the cumulative dose of injected corticosteroids in patients receiving the shots for musculoskeletal pain, regardless of osteoporosis status.</teaser> <title>No Increased Risk for Fractures Seen With Frequent Steroid Injections for Musculoskeletal Conditions</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>rn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>endo</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">26</term> <term>21</term> <term>15</term> <term>34</term> </publications> <sections> <term canonical="true">27970</term> <term>39313</term> </sections> <topics> <term canonical="true">265</term> <term>289</term> <term>290</term> <term>268</term> <term>206</term> <term>266</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>No Increased Risk for Fractures Seen With Frequent Steroid Injections for Musculoskeletal Conditions</title> <deck/> </itemMeta> <itemContent> <h2>TOPLINE:</h2> <p>The cumulative effect of frequent corticosteroid injections (CSIs), a common treatment for musculoskeletal pain, does not appear to increase the risk for fractures.</p> <h2>METHODOLOGY:</h2> <ul class="body"> <li>Researchers utilized an institutional electronic health record database to identify adults in Olmsted County, Minnesota, receiving corticosteroid injections from May 1, 2018, to July 1, 2022.</li> <li>Corticosteroid equivalents were calculated for medications injected, including methylprednisolone, triamcinolone, betamethasone, and dexamethasone.</li> <li>Patients were excluded if they had a prescription for oral prednisone equivalents greater than 2.5 mg/day for more than 30 days.</li> <li>Fracture events were identified using ICD-9 and ICD-10 codes and were included only if they occurred after the first corticosteroid injection.</li> </ul> <h2>TAKEAWAY:</h2> <ul class="body"> <li>A total of 7197 patients were analyzed, with a mean age of 64.4 years, and of these patients, 346 (4.8%) had a new fracture in a mean time of 329 days from the first corticosteroid injection, including 149 (43.1%) in classic osteoporotic locations.</li> <li>The study reported no increased fracture risk associated with corticosteroid injections and no significant difference in fracture rates across cumulative corticosteroid injection dose quartiles, regardless of osteoporosis status.</li> <li>Factors such as previous fractures, age, and Charlson Comorbidity Index were associated with a higher risk for fractures, not corticosteroid injections.</li> </ul> <h2>IN PRACTICE:</h2> <p>“Clinicians should be reassured that frequent CSI is not associated with higher fracture risk and should not withhold these important pain treatments owing to concern for fracture,” wrote the authors of the study.</p> <h2>SOURCE:</h2> <p>The study was led by Terin T. Sytsma, MD, Division of Community Internal Medicine, Geriatrics, and Palliative Care, Mayo Clinic, Rochester, Minnesota. It was <a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2024.14316?guestAccessKey=0a17f92b-55e9-4f3d-a099-936934961dfa">published online</a> in <em>JAMA Network Open</em>.</p> <h2>LIMITATIONS:</h2> <p>The study’s retrospective cohort design and its focus on a predominantly White population in a single community may limit the generalizability of the findings. Confounding variables such as smoking status, alcohol intake, and physical activity were acknowledged as potential contributors to fracture risk. Only clinically apparent fractures were considered, excluding silent vertebral fractures, and differences in corticosteroid formulation were not delineated.</p> <h2>DISCLOSURES:</h2> <p>The study was supported by a Mayo Clinic Catalyst Award to Dr. Sytsma. The authors had no conflicts of interest to report.<span class="end"/></p> <p> <em>This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.<br/><br/>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/frequent-corticosteroid-injections-show-no-increased-risk-2024a1000ac0">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
Calcium and CV Risk: Are Supplements and Vitamin D to Blame?
This transcript has been edited for clarity.
Tricia Ward: Hi. I’m Tricia Ward, from theheart.org/Medscape Cardiology. I’m joined today by Dr Matthew Budoff. He is professor of medicine at UCLA and the endowed chair of preventive cardiology at the Lundquist Institute. Welcome, Dr Budoff.
Matthew J. Budoff, MD: Thank you.
Dietary Calcium vs Coronary Calcium
Ms. Ward: The reason I wanted to talk to you today is because there have been some recent studies linking calcium supplements to an increased risk for cardiovascular disease. I’m old enough to remember when we used to tell people that dietary calcium and coronary calcium weren’t connected and weren’t the same. Were we wrong?
Dr. Budoff: I think there’s a large amount of mixed data out there still. The US Preventive Services Task Force looked into this a number of years ago and said there’s no association between calcium supplementation and increased risk for cardiovascular disease.
As you mentioned, there are a couple of newer studies that point us toward a relationship. I think that we still have a little bit of a mixed bag, but we need to dive a little deeper into that to figure out what’s going on.
Ms. Ward: Does it appear to be connected to calcium in the form of supplements vs calcium from foods?
Dr. Budoff: We looked very carefully at dietary calcium in the MESA study, the multiethnic study of atherosclerosis. There is no relationship between dietary calcium intake and coronary calcium or cardiovascular events. We’re talking mostly about supplements now when we talk about this increased risk that we’re seeing.
Does Vitamin D Exacerbate Risk?
Ms. Ward: Because it’s seen with supplements, is that likely because that’s a much higher concentration of calcium coming in or do you think it’s something inherent in its being in the form of a supplement?
Dr. Budoff: I think there are two things. One, it’s definitely a higher concentration all at once. You get many more milligrams at a time when you take a supplement than if you had a high-calcium food or drink.
Also, most supplements have vitamin D as well. I think vitamin D and calcium work synergistically. When you give them both together simultaneously, I think that may have more of a potentiating effect that might exacerbate any potential risk.
Ms. Ward: Is there any reason to think there might be a difference in type of calcium supplement? I always think of the chalky tablet form vs calcium chews.
Dr. Budoff: I’m not aware of a difference in the supplement type. I think the vitamin D issue is a big problem because we all have patients who take thousands of units of vitamin D — just crazy numbers. People advocate really high numbers and that stays in the system.
Personally, I think part of the explanation is that with very high levels of vitamin D on top of calcium supplementation, you now absorb it better. You now get it into the bone, but maybe also into the coronary arteries. If you’re very high in vitamin D and then are taking a large calcium supplement, it might be the calcium/vitamin D combination that’s giving us some trouble. I think people on vitamin D supplements really need to watch their levels and not get supratherapeutic.
Ms. Ward: With the vitamin D?
Dr. Budoff: With the vitamin D.
Diabetes and Renal Function
Ms. Ward: In some of the studies, there seems to be a higher risk in patients with diabetes. Is there any reason why that would be?
Dr. Budoff: I can’t think of a reason exactly why with diabetes per se, except for renal disease. Patients with diabetes have more intrinsic renal disease, proteinuria, and even a reduced eGFR. We’ve seen that the kidney is very strongly tied to this. We have a very strong relationship, in work I’ve done a decade ago now, showing that calcium supplementation (in the form of phosphate binders) in patients on dialysis or with advanced renal disease is linked to much higher coronary calcium progression.
We did prospective, randomized trials showing that calcium intake as binders to reduce phosphorus led to more coronary calcium. We always thought that was just relegated to the renal population, and there might be an overlap here with the diabetes and more renal disease. I have a feeling that it has to do with more of that. It might be regulation of parathyroid hormone as well, which might be more abnormal in patients with diabetes.
Avoid Supratherapeutic Vitamin D Levels
Ms. Ward:: What are you telling your patients?
Dr. Budoff: I tell patients with normal kidney function that the bone will modulate 99.9% of the calcium uptake. If they have osteopenia or osteoporosis, regardless of their calcium score, I’m very comfortable putting them on supplements.
I’m a little more cautious with the vitamin D levels, and I keep an eye on that and regulate how much vitamin D they get based on their levels. I get them into the normal range, but I don’t want them supratherapeutic. You can even follow their calcium score. Again, we’ve shown that if you’re taking too much calcium, your calcium score will go up. I can just check it again in a couple of years to make sure that it’s safe.
Ms. Ward:: In terms of vitamin D levels, when you’re saying “supratherapeutic,” what levels do you consider a safe amount to take?
Dr. Budoff: I’d like them under 100 ng/mL as far as their upper level. Normal is around 70 ng/mL at most labs. I try to keep them in the normal range. I don’t even want them to be high-normal if I’m going to be concomitantly giving them calcium supplements. Of course, if they have renal insufficiency, then I’m much more cautious. We’ve even seen calcium supplements raise the serum calcium, which you never see with dietary calcium. That’s another potential proof that it might be too much too fast.
For renal patients, even in mild renal insufficiency, maybe even in diabetes where we’ve seen a signal, maybe aim lower in the amount of calcium supplementation if diet is insufficient, and aim a little lower in vitamin D targets, and I think you’ll be in a safer place.
Ms. Ward: Is there anything else you want to add?
Dr. Budoff: The evidence is still evolving. I’d say that it’s interesting and maybe a little frustrating that we don’t have a final answer on all of this. I would stay tuned for more data because we’re looking at many of the epidemiologic studies to try to see what happens in the real world, with both dietary intake of calcium and calcium supplementation.
Ms. Ward: Thank you very much for joining me today.
Dr. Budoff: It’s a pleasure. Thanks for having me.
Dr. Budoff disclosed being a speaker for Amarin Pharma.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Tricia Ward: Hi. I’m Tricia Ward, from theheart.org/Medscape Cardiology. I’m joined today by Dr Matthew Budoff. He is professor of medicine at UCLA and the endowed chair of preventive cardiology at the Lundquist Institute. Welcome, Dr Budoff.
Matthew J. Budoff, MD: Thank you.
Dietary Calcium vs Coronary Calcium
Ms. Ward: The reason I wanted to talk to you today is because there have been some recent studies linking calcium supplements to an increased risk for cardiovascular disease. I’m old enough to remember when we used to tell people that dietary calcium and coronary calcium weren’t connected and weren’t the same. Were we wrong?
Dr. Budoff: I think there’s a large amount of mixed data out there still. The US Preventive Services Task Force looked into this a number of years ago and said there’s no association between calcium supplementation and increased risk for cardiovascular disease.
As you mentioned, there are a couple of newer studies that point us toward a relationship. I think that we still have a little bit of a mixed bag, but we need to dive a little deeper into that to figure out what’s going on.
Ms. Ward: Does it appear to be connected to calcium in the form of supplements vs calcium from foods?
Dr. Budoff: We looked very carefully at dietary calcium in the MESA study, the multiethnic study of atherosclerosis. There is no relationship between dietary calcium intake and coronary calcium or cardiovascular events. We’re talking mostly about supplements now when we talk about this increased risk that we’re seeing.
Does Vitamin D Exacerbate Risk?
Ms. Ward: Because it’s seen with supplements, is that likely because that’s a much higher concentration of calcium coming in or do you think it’s something inherent in its being in the form of a supplement?
Dr. Budoff: I think there are two things. One, it’s definitely a higher concentration all at once. You get many more milligrams at a time when you take a supplement than if you had a high-calcium food or drink.
Also, most supplements have vitamin D as well. I think vitamin D and calcium work synergistically. When you give them both together simultaneously, I think that may have more of a potentiating effect that might exacerbate any potential risk.
Ms. Ward: Is there any reason to think there might be a difference in type of calcium supplement? I always think of the chalky tablet form vs calcium chews.
Dr. Budoff: I’m not aware of a difference in the supplement type. I think the vitamin D issue is a big problem because we all have patients who take thousands of units of vitamin D — just crazy numbers. People advocate really high numbers and that stays in the system.
Personally, I think part of the explanation is that with very high levels of vitamin D on top of calcium supplementation, you now absorb it better. You now get it into the bone, but maybe also into the coronary arteries. If you’re very high in vitamin D and then are taking a large calcium supplement, it might be the calcium/vitamin D combination that’s giving us some trouble. I think people on vitamin D supplements really need to watch their levels and not get supratherapeutic.
Ms. Ward: With the vitamin D?
Dr. Budoff: With the vitamin D.
Diabetes and Renal Function
Ms. Ward: In some of the studies, there seems to be a higher risk in patients with diabetes. Is there any reason why that would be?
Dr. Budoff: I can’t think of a reason exactly why with diabetes per se, except for renal disease. Patients with diabetes have more intrinsic renal disease, proteinuria, and even a reduced eGFR. We’ve seen that the kidney is very strongly tied to this. We have a very strong relationship, in work I’ve done a decade ago now, showing that calcium supplementation (in the form of phosphate binders) in patients on dialysis or with advanced renal disease is linked to much higher coronary calcium progression.
We did prospective, randomized trials showing that calcium intake as binders to reduce phosphorus led to more coronary calcium. We always thought that was just relegated to the renal population, and there might be an overlap here with the diabetes and more renal disease. I have a feeling that it has to do with more of that. It might be regulation of parathyroid hormone as well, which might be more abnormal in patients with diabetes.
Avoid Supratherapeutic Vitamin D Levels
Ms. Ward:: What are you telling your patients?
Dr. Budoff: I tell patients with normal kidney function that the bone will modulate 99.9% of the calcium uptake. If they have osteopenia or osteoporosis, regardless of their calcium score, I’m very comfortable putting them on supplements.
I’m a little more cautious with the vitamin D levels, and I keep an eye on that and regulate how much vitamin D they get based on their levels. I get them into the normal range, but I don’t want them supratherapeutic. You can even follow their calcium score. Again, we’ve shown that if you’re taking too much calcium, your calcium score will go up. I can just check it again in a couple of years to make sure that it’s safe.
Ms. Ward:: In terms of vitamin D levels, when you’re saying “supratherapeutic,” what levels do you consider a safe amount to take?
Dr. Budoff: I’d like them under 100 ng/mL as far as their upper level. Normal is around 70 ng/mL at most labs. I try to keep them in the normal range. I don’t even want them to be high-normal if I’m going to be concomitantly giving them calcium supplements. Of course, if they have renal insufficiency, then I’m much more cautious. We’ve even seen calcium supplements raise the serum calcium, which you never see with dietary calcium. That’s another potential proof that it might be too much too fast.
For renal patients, even in mild renal insufficiency, maybe even in diabetes where we’ve seen a signal, maybe aim lower in the amount of calcium supplementation if diet is insufficient, and aim a little lower in vitamin D targets, and I think you’ll be in a safer place.
Ms. Ward: Is there anything else you want to add?
Dr. Budoff: The evidence is still evolving. I’d say that it’s interesting and maybe a little frustrating that we don’t have a final answer on all of this. I would stay tuned for more data because we’re looking at many of the epidemiologic studies to try to see what happens in the real world, with both dietary intake of calcium and calcium supplementation.
Ms. Ward: Thank you very much for joining me today.
Dr. Budoff: It’s a pleasure. Thanks for having me.
Dr. Budoff disclosed being a speaker for Amarin Pharma.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Tricia Ward: Hi. I’m Tricia Ward, from theheart.org/Medscape Cardiology. I’m joined today by Dr Matthew Budoff. He is professor of medicine at UCLA and the endowed chair of preventive cardiology at the Lundquist Institute. Welcome, Dr Budoff.
Matthew J. Budoff, MD: Thank you.
Dietary Calcium vs Coronary Calcium
Ms. Ward: The reason I wanted to talk to you today is because there have been some recent studies linking calcium supplements to an increased risk for cardiovascular disease. I’m old enough to remember when we used to tell people that dietary calcium and coronary calcium weren’t connected and weren’t the same. Were we wrong?
Dr. Budoff: I think there’s a large amount of mixed data out there still. The US Preventive Services Task Force looked into this a number of years ago and said there’s no association between calcium supplementation and increased risk for cardiovascular disease.
As you mentioned, there are a couple of newer studies that point us toward a relationship. I think that we still have a little bit of a mixed bag, but we need to dive a little deeper into that to figure out what’s going on.
Ms. Ward: Does it appear to be connected to calcium in the form of supplements vs calcium from foods?
Dr. Budoff: We looked very carefully at dietary calcium in the MESA study, the multiethnic study of atherosclerosis. There is no relationship between dietary calcium intake and coronary calcium or cardiovascular events. We’re talking mostly about supplements now when we talk about this increased risk that we’re seeing.
Does Vitamin D Exacerbate Risk?
Ms. Ward: Because it’s seen with supplements, is that likely because that’s a much higher concentration of calcium coming in or do you think it’s something inherent in its being in the form of a supplement?
Dr. Budoff: I think there are two things. One, it’s definitely a higher concentration all at once. You get many more milligrams at a time when you take a supplement than if you had a high-calcium food or drink.
Also, most supplements have vitamin D as well. I think vitamin D and calcium work synergistically. When you give them both together simultaneously, I think that may have more of a potentiating effect that might exacerbate any potential risk.
Ms. Ward: Is there any reason to think there might be a difference in type of calcium supplement? I always think of the chalky tablet form vs calcium chews.
Dr. Budoff: I’m not aware of a difference in the supplement type. I think the vitamin D issue is a big problem because we all have patients who take thousands of units of vitamin D — just crazy numbers. People advocate really high numbers and that stays in the system.
Personally, I think part of the explanation is that with very high levels of vitamin D on top of calcium supplementation, you now absorb it better. You now get it into the bone, but maybe also into the coronary arteries. If you’re very high in vitamin D and then are taking a large calcium supplement, it might be the calcium/vitamin D combination that’s giving us some trouble. I think people on vitamin D supplements really need to watch their levels and not get supratherapeutic.
Ms. Ward: With the vitamin D?
Dr. Budoff: With the vitamin D.
Diabetes and Renal Function
Ms. Ward: In some of the studies, there seems to be a higher risk in patients with diabetes. Is there any reason why that would be?
Dr. Budoff: I can’t think of a reason exactly why with diabetes per se, except for renal disease. Patients with diabetes have more intrinsic renal disease, proteinuria, and even a reduced eGFR. We’ve seen that the kidney is very strongly tied to this. We have a very strong relationship, in work I’ve done a decade ago now, showing that calcium supplementation (in the form of phosphate binders) in patients on dialysis or with advanced renal disease is linked to much higher coronary calcium progression.
We did prospective, randomized trials showing that calcium intake as binders to reduce phosphorus led to more coronary calcium. We always thought that was just relegated to the renal population, and there might be an overlap here with the diabetes and more renal disease. I have a feeling that it has to do with more of that. It might be regulation of parathyroid hormone as well, which might be more abnormal in patients with diabetes.
Avoid Supratherapeutic Vitamin D Levels
Ms. Ward:: What are you telling your patients?
Dr. Budoff: I tell patients with normal kidney function that the bone will modulate 99.9% of the calcium uptake. If they have osteopenia or osteoporosis, regardless of their calcium score, I’m very comfortable putting them on supplements.
I’m a little more cautious with the vitamin D levels, and I keep an eye on that and regulate how much vitamin D they get based on their levels. I get them into the normal range, but I don’t want them supratherapeutic. You can even follow their calcium score. Again, we’ve shown that if you’re taking too much calcium, your calcium score will go up. I can just check it again in a couple of years to make sure that it’s safe.
Ms. Ward:: In terms of vitamin D levels, when you’re saying “supratherapeutic,” what levels do you consider a safe amount to take?
Dr. Budoff: I’d like them under 100 ng/mL as far as their upper level. Normal is around 70 ng/mL at most labs. I try to keep them in the normal range. I don’t even want them to be high-normal if I’m going to be concomitantly giving them calcium supplements. Of course, if they have renal insufficiency, then I’m much more cautious. We’ve even seen calcium supplements raise the serum calcium, which you never see with dietary calcium. That’s another potential proof that it might be too much too fast.
For renal patients, even in mild renal insufficiency, maybe even in diabetes where we’ve seen a signal, maybe aim lower in the amount of calcium supplementation if diet is insufficient, and aim a little lower in vitamin D targets, and I think you’ll be in a safer place.
Ms. Ward: Is there anything else you want to add?
Dr. Budoff: The evidence is still evolving. I’d say that it’s interesting and maybe a little frustrating that we don’t have a final answer on all of this. I would stay tuned for more data because we’re looking at many of the epidemiologic studies to try to see what happens in the real world, with both dietary intake of calcium and calcium supplementation.
Ms. Ward: Thank you very much for joining me today.
Dr. Budoff: It’s a pleasure. Thanks for having me.
Dr. Budoff disclosed being a speaker for Amarin Pharma.
A version of this article appeared on Medscape.com.
<!--$RCSfile: InCopy_agile.xsl,v $ $Revision: 1.35 $-->
<!--$RCSfile: drupal.xsl,v $ $Revision: 1.7 $-->
<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>168248</fileName> <TBEID>0C0505A2.SIG</TBEID> <TBUniqueIdentifier>MD_0C0505A2</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>353</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240604T114806</QCDate> <firstPublished>20240604T120152</firstPublished> <LastPublished>20240604T120153</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240604T120152</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline>Ward and Budoff</byline> <bylineText>INTERVIEWER: TRICIA WARD; INTERVIEWEE: MATTHEW J. BUDOFF, MD</bylineText> <bylineFull>INTERVIEWER: TRICIA WARD; INTERVIEWEE: MATTHEW J. BUDOFF, MD</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType>Opinion</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>This transcript has been edited for clarity. Tricia Ward: Hi. I’m Tricia Ward, from theheart.org/Medscape Cardiology. I’m joined today by Dr Matthew Budoff. He </metaDescription> <articlePDF/> <teaserImage/> <teaser>Tricia Ward interviews Dr. Matthew Budoff about the link between calcium intake and higher risk for CV events. Is it the link seen for dietary intake vs supplements, and could vitamin D be the modifier?</teaser> <title>Calcium and CV Risk: Are Supplements and Vitamin D to Blame?</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>card</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>endo</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>chph</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">5</term> <term>34</term> <term>15</term> <term>21</term> <term>6</term> </publications> <sections> <term canonical="true">52</term> <term>39313</term> <term>41022</term> </sections> <topics> <term canonical="true">193</term> <term>194</term> <term>206</term> <term>205</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Calcium and CV Risk: Are Supplements and Vitamin D to Blame?</title> <deck/> </itemMeta> <itemContent> <p><em>This transcript has been edited for clarity</em>. <br/><br/><strong>Tricia Ward:</strong> Hi. I’m Tricia Ward, from theheart.org/Medscape Cardiology. I’m joined today by Dr Matthew Budoff. He is professor of medicine at UCLA and the endowed chair of preventive cardiology at the Lundquist Institute. Welcome, Dr Budoff. <br/><br/><strong>Matthew J. Budoff, MD:</strong> Thank you. </p> <h2>Dietary Calcium vs Coronary Calcium</h2> <p><strong>Ms. Ward:</strong> The reason I wanted to talk to you today is because there have been some <span class="Hyperlink"><a href="https://doi.org/10.7326/M23-2598">recent studies</a></span> linking calcium supplements to an <span class="Hyperlink"><a href="https://doi.org/10.1136/heartjnl-2021-320215">increased risk</a></span> for cardiovascular disease. I’m old enough to remember when we used to tell people that dietary calcium and coronary calcium weren’t connected and weren’t the same. Were we wrong?<br/><br/><strong>Dr. Budoff:</strong> I think there’s a large amount of mixed data out there still. The US Preventive Services Task Force <span class="Hyperlink"><a href="https://doi.org/10.1001/jama.2017.21640">looked into this</a></span> a number of years ago and said there’s no association between calcium supplementation and increased risk for cardiovascular disease. <br/><br/>As you mentioned, there are a couple of newer studies that point us toward a relationship. I think that we still have a little bit of a mixed bag, but we need to dive a little deeper into that to figure out what’s going on. <br/><br/><strong>Ms. Ward:</strong> Does it appear to be connected to calcium in the <span class="Hyperlink"><a href="https://doi.org/10.1136/heartjnl-2011-301345">form of supplements vs calcium from foods</a></span>? <br/><br/><strong>Dr. Budoff:</strong> We looked very carefully at dietary calcium in <span class="Hyperlink"><a href="https://doi.org/10.1161/JAHA.116.003815">the MESA study</a></span>, the multiethnic study of <span class="Hyperlink">atherosclerosis</span>. There is no relationship between dietary calcium intake and coronary calcium or cardiovascular events. We’re talking mostly about supplements now when we talk about this increased risk that we’re seeing.<br/><br/></p> <h2>Does Vitamin D Exacerbate Risk? </h2> <p><strong>Ms. Ward:</strong> Because it’s seen with supplements, is that likely because that’s a much higher concentration of calcium coming in or do you think it’s something inherent in its being in the form of a supplement?<strong><br/><br/>Dr. Budoff:</strong> I think there are two things. One, it’s definitely a higher concentration all at once. You get many more milligrams at a time when you take a supplement than if you had a high-calcium food or drink.<br/><br/>Also, most supplements have vitamin D as well. I think vitamin D and calcium work synergistically. When you give them both together simultaneously, I think that may have more of a potentiating effect that might exacerbate any potential risk. <br/><br/><strong>Ms. Ward:</strong> Is there any reason to think there might be a difference in type of calcium supplement? I always think of the chalky tablet form vs calcium chews. <br/><br/><strong>Dr. Budoff:</strong> I’m not aware of a difference in the supplement type. I think the vitamin D issue is a big problem because we all have patients who take thousands of units of vitamin D — just crazy numbers. People advocate really high numbers and that stays in the system. <br/><br/>Personally, I think part of the explanation is that with very high levels of vitamin D on top of calcium supplementation, you now absorb it better. You now get it into the bone, but <span class="Hyperlink"><a href="https://doi.org/10.1016/j.jcmg.2020.06.030">maybe also into the coronary arteries</a></span>. If you’re very high in vitamin D and then are taking a large calcium supplement, it might be the <span class="Hyperlink">calcium/vitamin D</span> combination that’s giving us some trouble. I think people on vitamin D supplements really need to watch their levels and not get supratherapeutic. <br/><br/><strong>Ms. Ward:</strong> With the vitamin D? <br/><br/><strong>Dr. Budoff:</strong> With the vitamin D.<br/><br/></p> <h2>Diabetes and Renal Function</h2> <p><strong>Ms. Ward:</strong> In some of the studies, there seems to be <span class="Hyperlink"><a href="https://doi.org/10.2337/dc23-0109">a higher risk in patients with diabetes</a></span>. Is there any reason why that would be?<br/><br/><strong>Dr. Budoff:</strong> I can’t think of a reason exactly why with diabetes per se, except for renal disease. Patients with diabetes have more intrinsic renal disease, <span class="Hyperlink">proteinuria</span>, and even a reduced eGFR. We’ve seen that the kidney is very strongly tied to this. We have a very strong relationship, in work I’ve done a decade ago now, showing that <span class="Hyperlink"><a href="https://doi.org/10.5414/cnp74012">calcium supplementation (in the form of phosphate binders) </a></span>in patients on dialysis or with advanced renal disease is linked to much higher coronary calcium progression. <br/><br/>We did <span class="Hyperlink"><a href="https://doi.org/10.1046/j.1523-1755.2002.00434.x">prospective, randomized trials </a></span>showing that calcium intake as binders to reduce phosphorus led to more coronary calcium. We always thought that was just relegated to the renal population, and there might be an overlap here with the diabetes and more renal disease. I have a feeling that it has to do with more of that. It might be regulation of <span class="Hyperlink">parathyroid hormone</span> as well, which might be more abnormal in patients with diabetes. <br/><br/></p> <h2>Avoid Supratherapeutic Vitamin D Levels</h2> <p><strong>Ms. Ward:</strong>: What are you telling your patients? <br/><br/><strong>Dr. Budoff:</strong> I tell patients with normal kidney function that the bone will modulate 99.9% of the calcium uptake. If they have osteopenia or <span class="Hyperlink">osteoporosis</span>, regardless of their calcium score, I’m very comfortable putting them on supplements. <br/><br/>I’m a little more cautious with the vitamin D levels, and I keep an eye on that and regulate how much vitamin D they get based on their levels. I get them into the normal range, but I don’t want them supratherapeutic. You can even follow their calcium score. Again, we’ve shown that if you’re taking too much calcium, your calcium score will go up. I can just check it again in a couple of years to make sure that it’s safe. <br/><br/><strong>Ms. Ward:</strong>: In terms of vitamin D levels, when you’re saying “supratherapeutic,” what levels do you consider a safe amount to take?<br/><br/><strong>Dr. Budoff:</strong> I’d like them under 100 ng/mL as far as their upper level. Normal is around 70 ng/mL at most labs. I try to keep them in the normal range. I don’t even want them to be high-normal if I’m going to be concomitantly giving them calcium supplements. Of course, if they have renal insufficiency, then I’m much more cautious. We’ve even seen calcium supplements <span class="Hyperlink"><a href="https://doi.org/10.3390%2Fjcm4030414">raise the serum calcium</a></span>, which you never see with dietary calcium. That’s another potential proof that it might be too much too fast. <br/><br/>For renal patients, even in mild renal insufficiency, maybe even in diabetes where we’ve seen a signal, maybe aim lower in the amount of calcium supplementation if diet is insufficient, and aim a little lower in vitamin D targets, and I think you’ll be in a safer place. <br/><br/><strong>Ms. Ward:</strong> Is there anything else you want to add? <br/><br/><strong>Dr. Budoff:</strong> The evidence is still evolving. I’d say that it’s interesting and maybe a little frustrating that we don’t have a final answer on all of this. I would stay tuned for more data because we’re looking at many of the epidemiologic studies to try to see what happens in the real world, with both dietary intake of calcium and calcium supplementation. <br/><br/><strong>Ms. Ward:</strong> Thank you very much for joining me today. <br/><br/><strong>Dr. Budoff:</strong> It’s a pleasure. Thanks for having me. <br/><br/>Dr. Budoff disclosed being a speaker for Amarin Pharma.</p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/calcium-and-cv-risk-are-supplements-and-vitamin-d-blame-2024a10009av">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
Investigational Male Contraceptive Suppresses Sperm Rapidly
BOSTON — An investigational male contraceptive gel suppresses sperm more rapidly than previous products in development, new data suggested.
The product, 8 mg segesterone acetate (Nestorone) combined with 74 mg testosterone (“NesT”) is a gel that a man applies daily to both shoulders. The progesterone blocks spermatogenesis, and the testosterone restores blood levels to maintain sexual function. It is under development by the National Institute of Child Health and Human Development (NICHD) in collaboration with the Population Council, the Los Angeles Biomedical Research Institute, and the University of Washington School of Medicine.
Currently, the only available male contraceptives are vasectomy, which isn’t easily reversible, and condoms, which have a high failure rate. Previous attempts to develop a “male pill” have been unsuccessful for a variety of reasons, but so far, this product appears effective and safe, Diana Blithe, PhD, chief of the Contraceptive Development Program at NICHD, said at a press briefing held on June 2, 2024, during the annual meeting of the Endocrine Society.
“It’s been a long time coming. … Men need and want more contraceptive options such as an effective reversible method,” she told this news organization.
New phase 2b data show that among 222 couples in which the man initially had normal (> 15 million/mL) sperm counts, the median time to suppression (< 1 million/mL) was less than 8 weeks with NesT compared with 9-15 weeks seen in previous trials of injected male hormonal contraceptives. Nearly all (86%) had achieved suppression by 15 weeks.
After two consecutive counts of < 1 million/mL, the couples entered the trial’s ongoing 2-year efficacy phase. There have been no major safety concerns thus far, but “we need more data,” Dr. Blithe noted.
Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “certainly, I think it’s a big advance on what we have so far. … I think it’s showing great promise.”
Dr. Hayes did caution, though, that “with real-world use, daily application of a gel might be a bit more challenging than taking an injection…an injection is more consistent. With a gel, patients might forget or shower it off. But I don’t think 1 day of interruption would be a significant thing.”
Transference of the topical to a partner or a child is another potential concern, Dr. Hayes noted, although this is true of current testosterone gel products as well. During the briefing, Dr. Blithe said that this issue is why the product is recommended to be placed on the upper arms rather than the abdomen or another spot more likely to come into contact with another person. Also, in the trial, men were instructed to wear shirts during intercourse.
Regarding the rapidity of sperm suppression, Dr. Hayes said, “It’s surprising. It looks great as a reversible contraceptive. … Normally, you think of the life cycle of the sperm being about 72 days. So to see 50% suppression by 8 weeks, and then 85%-90% by 15 weeks, that’s very rapid. It may be that the progesterone that they’re using is very potent. Progestins can have some negative effects on lipids and mood. We didn’t really see the safety data in this presentation. So that will be interesting to see.”
During the briefing, Dr. Blithe said that the phase 2b trial is expected to finish by the end of this year, and in the meantime, the researchers are communicating with the US Food and Drug Administration about the design of a phase 3 trial because this is an unprecedented area. “They don’t have guidelines yet. They’ll need to develop them first.”
Dr. Blithe has been the NICHD principal investigator on cooperative research and development agreements with HRA Pharma and Daré Bioscience. Dr. Hayes had no disclosures.
A version of this article appeared on Medscape.com .
BOSTON — An investigational male contraceptive gel suppresses sperm more rapidly than previous products in development, new data suggested.
The product, 8 mg segesterone acetate (Nestorone) combined with 74 mg testosterone (“NesT”) is a gel that a man applies daily to both shoulders. The progesterone blocks spermatogenesis, and the testosterone restores blood levels to maintain sexual function. It is under development by the National Institute of Child Health and Human Development (NICHD) in collaboration with the Population Council, the Los Angeles Biomedical Research Institute, and the University of Washington School of Medicine.
Currently, the only available male contraceptives are vasectomy, which isn’t easily reversible, and condoms, which have a high failure rate. Previous attempts to develop a “male pill” have been unsuccessful for a variety of reasons, but so far, this product appears effective and safe, Diana Blithe, PhD, chief of the Contraceptive Development Program at NICHD, said at a press briefing held on June 2, 2024, during the annual meeting of the Endocrine Society.
“It’s been a long time coming. … Men need and want more contraceptive options such as an effective reversible method,” she told this news organization.
New phase 2b data show that among 222 couples in which the man initially had normal (> 15 million/mL) sperm counts, the median time to suppression (< 1 million/mL) was less than 8 weeks with NesT compared with 9-15 weeks seen in previous trials of injected male hormonal contraceptives. Nearly all (86%) had achieved suppression by 15 weeks.
After two consecutive counts of < 1 million/mL, the couples entered the trial’s ongoing 2-year efficacy phase. There have been no major safety concerns thus far, but “we need more data,” Dr. Blithe noted.
Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “certainly, I think it’s a big advance on what we have so far. … I think it’s showing great promise.”
Dr. Hayes did caution, though, that “with real-world use, daily application of a gel might be a bit more challenging than taking an injection…an injection is more consistent. With a gel, patients might forget or shower it off. But I don’t think 1 day of interruption would be a significant thing.”
Transference of the topical to a partner or a child is another potential concern, Dr. Hayes noted, although this is true of current testosterone gel products as well. During the briefing, Dr. Blithe said that this issue is why the product is recommended to be placed on the upper arms rather than the abdomen or another spot more likely to come into contact with another person. Also, in the trial, men were instructed to wear shirts during intercourse.
Regarding the rapidity of sperm suppression, Dr. Hayes said, “It’s surprising. It looks great as a reversible contraceptive. … Normally, you think of the life cycle of the sperm being about 72 days. So to see 50% suppression by 8 weeks, and then 85%-90% by 15 weeks, that’s very rapid. It may be that the progesterone that they’re using is very potent. Progestins can have some negative effects on lipids and mood. We didn’t really see the safety data in this presentation. So that will be interesting to see.”
During the briefing, Dr. Blithe said that the phase 2b trial is expected to finish by the end of this year, and in the meantime, the researchers are communicating with the US Food and Drug Administration about the design of a phase 3 trial because this is an unprecedented area. “They don’t have guidelines yet. They’ll need to develop them first.”
Dr. Blithe has been the NICHD principal investigator on cooperative research and development agreements with HRA Pharma and Daré Bioscience. Dr. Hayes had no disclosures.
A version of this article appeared on Medscape.com .
BOSTON — An investigational male contraceptive gel suppresses sperm more rapidly than previous products in development, new data suggested.
The product, 8 mg segesterone acetate (Nestorone) combined with 74 mg testosterone (“NesT”) is a gel that a man applies daily to both shoulders. The progesterone blocks spermatogenesis, and the testosterone restores blood levels to maintain sexual function. It is under development by the National Institute of Child Health and Human Development (NICHD) in collaboration with the Population Council, the Los Angeles Biomedical Research Institute, and the University of Washington School of Medicine.
Currently, the only available male contraceptives are vasectomy, which isn’t easily reversible, and condoms, which have a high failure rate. Previous attempts to develop a “male pill” have been unsuccessful for a variety of reasons, but so far, this product appears effective and safe, Diana Blithe, PhD, chief of the Contraceptive Development Program at NICHD, said at a press briefing held on June 2, 2024, during the annual meeting of the Endocrine Society.
“It’s been a long time coming. … Men need and want more contraceptive options such as an effective reversible method,” she told this news organization.
New phase 2b data show that among 222 couples in which the man initially had normal (> 15 million/mL) sperm counts, the median time to suppression (< 1 million/mL) was less than 8 weeks with NesT compared with 9-15 weeks seen in previous trials of injected male hormonal contraceptives. Nearly all (86%) had achieved suppression by 15 weeks.
After two consecutive counts of < 1 million/mL, the couples entered the trial’s ongoing 2-year efficacy phase. There have been no major safety concerns thus far, but “we need more data,” Dr. Blithe noted.
Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “certainly, I think it’s a big advance on what we have so far. … I think it’s showing great promise.”
Dr. Hayes did caution, though, that “with real-world use, daily application of a gel might be a bit more challenging than taking an injection…an injection is more consistent. With a gel, patients might forget or shower it off. But I don’t think 1 day of interruption would be a significant thing.”
Transference of the topical to a partner or a child is another potential concern, Dr. Hayes noted, although this is true of current testosterone gel products as well. During the briefing, Dr. Blithe said that this issue is why the product is recommended to be placed on the upper arms rather than the abdomen or another spot more likely to come into contact with another person. Also, in the trial, men were instructed to wear shirts during intercourse.
Regarding the rapidity of sperm suppression, Dr. Hayes said, “It’s surprising. It looks great as a reversible contraceptive. … Normally, you think of the life cycle of the sperm being about 72 days. So to see 50% suppression by 8 weeks, and then 85%-90% by 15 weeks, that’s very rapid. It may be that the progesterone that they’re using is very potent. Progestins can have some negative effects on lipids and mood. We didn’t really see the safety data in this presentation. So that will be interesting to see.”
During the briefing, Dr. Blithe said that the phase 2b trial is expected to finish by the end of this year, and in the meantime, the researchers are communicating with the US Food and Drug Administration about the design of a phase 3 trial because this is an unprecedented area. “They don’t have guidelines yet. They’ll need to develop them first.”
Dr. Blithe has been the NICHD principal investigator on cooperative research and development agreements with HRA Pharma and Daré Bioscience. Dr. Hayes had no disclosures.
A version of this article appeared on Medscape.com .
<!--$RCSfile: InCopy_agile.xsl,v $ $Revision: 1.35 $-->
<!--$RCSfile: drupal.xsl,v $ $Revision: 1.7 $-->
<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>168276</fileName> <TBEID>0C050624.SIG</TBEID> <TBUniqueIdentifier>MD_0C050624</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname/> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240603T123332</QCDate> <firstPublished>20240603T124307</firstPublished> <LastPublished>20240603T124307</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240603T124307</CMSDate> <articleSource>FROM ENDO 2024</articleSource> <facebookInfo/> <meetingNumber/> <byline>Miriam E. Tucker</byline> <bylineText>MIRIAM E. TUCKER</bylineText> <bylineFull>MIRIAM E. TUCKER</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>BOSTON — An investigational male contraceptive gel suppresses sperm more rapidly than previous products in development, new data suggested.</metaDescription> <articlePDF/> <teaserImage/> <teaser>The topical gel is applied to the shoulders daily. </teaser> <title>Investigational Male Contraceptive Suppresses Sperm Rapidly</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>endo</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>ob</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term canonical="true">34</term> <term>15</term> <term>21</term> <term>23</term> </publications> <sections> <term>53</term> <term canonical="true">39313</term> </sections> <topics> <term>200</term> <term>206</term> <term>246</term> <term canonical="true">287</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Investigational Male Contraceptive Suppresses Sperm Rapidly</title> <deck/> </itemMeta> <itemContent> <p>BOSTON — An investigational male contraceptive gel suppresses sperm more rapidly than previous products in development, new data suggested.</p> <p>The product, 8 mg segesterone acetate (Nestorone) combined with 74 mg testosterone (“NesT”) is a gel that a man applies daily to both shoulders. The progesterone blocks spermatogenesis, and the testosterone restores blood levels to maintain sexual function. It is under development by the National Institute of Child Health and Human Development (NICHD) in collaboration with the Population Council, the Los Angeles Biomedical Research Institute, and the University of Washington School of Medicine.<br/><br/>Currently, the only available male contraceptives are vasectomy, which isn’t easily reversible, and condoms, which have a high failure rate. Previous attempts to develop a “male pill” have been unsuccessful for a variety of reasons, but so far, this product appears effective and safe, Diana Blithe, PhD, chief of the Contraceptive Development Program at NICHD, said at a press briefing held on June 2, 2024, during the <span class="Hyperlink"><a href="https://www.medscape.com/viewcollection/37492">annual meeting of the Endocrine Society</a></span>.<br/><br/>“It’s been a long time coming. … Men need and want more contraceptive options such as an effective reversible method,” she told this news organization.<br/><br/>New phase 2b data show that among 222 couples in which the man initially had normal (> 15 million/mL) sperm counts, the median time to suppression (< 1 million/mL) was less than 8 weeks with NesT compared with 9-15 weeks seen in previous trials of injected male hormonal contraceptives. Nearly all (86%) had achieved suppression by 15 weeks.<br/><br/>After two consecutive counts of < 1 million/mL, the couples entered the trial’s ongoing 2-year efficacy phase. There have been no major safety concerns thus far, but “we need more data,” Dr. Blithe noted.<br/><br/>Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “certainly, I think it’s a big advance on what we have so far. … I think it’s showing great promise.”<br/><br/>Dr. Hayes did caution, though, that “with real-world use, daily application of a gel might be a bit more challenging than taking an injection…an injection is more consistent. With a gel, patients might forget or shower it off. But I don’t think 1 day of interruption would be a significant thing.”<br/><br/>Transference of the topical to a partner or a child is another potential concern, Dr. Hayes noted, although this is true of current testosterone gel products as well. During the briefing, Dr. Blithe said that this issue is why the product is recommended to be placed on the upper arms rather than the abdomen or another spot more likely to come into contact with another person. Also, in the trial, men were instructed to wear shirts during intercourse.<br/><br/>Regarding the rapidity of sperm suppression, Dr. Hayes said, “It’s surprising. It looks great as a reversible contraceptive. … Normally, you think of the life cycle of the sperm being about 72 days. So to see 50% suppression by 8 weeks, and then 85%-90% by 15 weeks, that’s very rapid. It may be that the progesterone that they’re using is very potent. Progestins can have some negative effects on lipids and mood. We didn’t really see the safety data in this presentation. So that will be interesting to see.”<br/><br/>During the briefing, Dr. Blithe said that the phase 2b trial is expected to finish by the end of this year, and in the meantime, the researchers are communicating with the US Food and Drug Administration about the design of a phase 3 trial because this is an unprecedented area. “They don’t have guidelines yet. They’ll need to develop them first.”<br/><br/>Dr. Blithe has been the NICHD principal investigator on cooperative research and development agreements with HRA Pharma and Daré Bioscience. Dr. Hayes had no disclosures.</p> <p> <em> <span class="Emphasis">A version of this article appeared on </span> <span class="Hyperlink"> <a href="https://www.medscape.com/viewarticle/investigational-male-contraceptive-suppresses-sperm-rapidly-2024a1000acp">Medscape.com</a> </span> <span class="Emphasis">.</span> </em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM ENDO 2024