Key takeaways:
- The FDA convened an knowledgeable panel to debate the protection and efficacy of menopausal HT.
- Some panel members said the boxed warning for HT must be modified to raised replicate revealed proof.
Editor’s observe: This can be a creating information story. Please verify again quickly for updates.
Members of an FDA knowledgeable panel mentioned reassessing boxed warnings for menopausal HT and how you can higher educate sufferers and well being care professionals.
Issues about menopausal HT stem again to the publication of findings from the Girls’s Well being Initiative in JAMA in 2002. As Healio beforehand reported, the examine discovered girls receiving estrogen plus progestin had considerably elevated danger for whole CVD, stroke and pulmonary embolism, and a nominally elevated danger for breast most cancers. The trial was stopped early on account of “well being dangers that exceeded well being advantages over a mean follow-up of 5.2 years.” The outcomes of the trial led to a big lower in using HT amongst girls.
Throughout the knowledgeable panel, members introduced knowledge displaying no elevated dangers for quite a few antagonistic well being outcomes for girls who used menopausal HT. Howard N. Hodis, MD, the Harry J. Bauer and Dorothy Bauer Rawlins Professor of Cardiology at College of Southern California Keck Faculty of Drugs, mentioned there are points with each trial, together with the WHI, and emphasised that the medical neighborhood ought to observe all the information when weighing advantages and dangers with menopausal HT.
Howard N. Hodis
“We’ve 50 years of knowledge,” Hodis mentioned through the panel. “These knowledge must be adopted. Not simply the information that provides us these specific outcomes that we need to imagine however have a look at all the knowledge.”
Security for vaginal HT
One of many subjects mentioned was variations in security outcomes between vaginal and systemic HT. Whereas the boxed warning for the 2 kinds of HT is identical on account of laws on class labeling, security between them differs, panel members mentioned.
James Simon, MD, CCD, NCMP, IF, medical professor at George Washington College and founder and medical director of IntimMedicine Specialists, mentioned the label for 4 µg Imvexxy (Mayne Pharma), a vaginal comfortable gel estradiol, and all estrogen merchandise embrace warnings about elevated danger for stroke, dementia, myocardial infarction, breast most cancers, pulmonary embolism and endometrial most cancers. Simon, nonetheless, mentioned vaginal estrogens, by the use of their supply, must be unable to have an effect on different organs. Simon added that 4 µg Imvexxy delivers comparable estradiol ranges to girls as prasterone (Intrarosa, AMAG Prescribed drugs), which doesn’t embrace most of the similar label warnings as Imvexxy.
“The FDA has a really difficult, oftentimes troublesome balancing act in developing a label that’s comprehensible, that’s easy and that fastidiously and accurately balances dangers and the advantages of a given product,” Simon mentioned through the panel. “I imagine that when it comes to the low-dose vaginal estrogen label, they’ve failed.”
JoAnn Pinkerton, MD, FACOG, MSCP, professor of obstetrics and gynecology at College of Virginia Well being System, introduced knowledge from a scientific overview and meta-analysis revealed within the American Journal of Obstetrics and Gynecology in 2025 displaying that girls who had breast most cancers utilizing vaginal HT had no elevated danger for most cancers recurrence in contrast with controls. Pinkerton mentioned the label for vaginal HT must be modified primarily based on the proof.
JoAnn Pinkerton
“The boxed warning will not be supported by science,” Pinkerton mentioned through the panel. “It harms girls. It displays a category labeling which was extrapolated from [the WHI trial]. It overstates danger. There’s an absence of a randomized medical trial or constant observational proof linking vaginal estrogen for [genitourinary syndrome of menopause] to most cancers, coronary heart illness, dementia, blood clots or stroke.”
Stephanie S. Faubion, MD, MBA, FACP, MSCP, IF, professor and chair within the division of medication and the Penny and Invoice George Director of the Mayo Clinic Middle for Girls’s Well being, and Medical Director of The Menopause Society, informed Healio that she agreed boxed warning adjustments for systemic HT are wanted.
Stephanie S. Faubion
“It’s problematic and is a deterrent for a lot of girls who’re good candidates for using systemic HT,” Faubion informed Healio. “[The boxed warning] shouldn’t be on low-dose vaginal merchandise, because the dangers aren’t the identical.”
Deeper dive into WHI knowledge
A number of panel members introduced knowledge on menopausal HT security, together with knowledge on the WHI. Pinkerton introduced knowledge revealed from the WHI that confirmed amongst girls aged 50 to 59 years, girls receiving estrogen alone had extra favorable outcomes than girls receiving estrogen plus progestin. Moreover, estrogen alone was linked with a big discount in breast most cancers incidence and mortality over long-term follow-up. Pinkerton mentioned girls aged 50 to 59 years within the examine had low absolute dangers of lower than 1 per 1,000 girls per 12 months for coronary coronary heart illness, stroke, pulmonary embolism, colorectal most cancers, hip fracture and all-cause mortality.
Hodis additionally introduced knowledge from WHI and said the one antagonistic consequence with an absolute danger of 10 occasions per 10,000 girls per 12 months was deep vein thrombosis amongst girls receiving estrogen plus progestin. He added all-cause mortality was considerably decrease with each estrogen and estrogen plus progestin in contrast with placebo. Alzheimer’s illness was additionally considerably decrease amongst girls receiving estrogen alone vs. placebo, Hodis mentioned.
Hodis added that whereas the unique WHI paper confirmed elevated danger for “nominal statistical significance” for breast most cancers with estrogen plus progestin, additional changes for a number of statistical testing, sequential monitoring and confounding bias confirmed the affiliation was not vital.
“It’s previous time to cease overstating dangers, and selling concern and confusion about HT, which has been proven to soundly provide life-enhancing and lifesaving advantages for numerous menopausal girls,” Hodis mentioned through the panel.
Extra training wanted
Mary Jane Minkin, MD, medical professor within the division of obstetrics, gynecology and reproductive sciences at Yale College Faculty of Drugs, mentioned one of many greatest points surrounding menopausal HT is a scarcity of training amongst well being care professionals. She mentioned knowledge revealed in Menopause in 2023 which discovered 31.3% of residency applications within the U.S. had a standardized menopause program and 29.3% had time devoted to a menopause clinic.
Mary Jane Minkin
“We have to begin to coaching individuals,” Minkin mentioned through the panel. “We have to do what we will, whether or not it’s attain out via movies or [other methods]. The opposite factor that’s essential is we now have to coach different practitioners. We have to practice nurse practitioners, we have to practice our [physician assistants], and lots of of them are tremendously concerned about menopause care.”
Heather Hirsch, MD, MS, NCMP, a board-certified internist and founder and CEO of Well being by Heather Hirsch MD Collaborative, mentioned a better emphasis must be positioned on coaching well being care professionals throughout all specialties about menopause.
Heather Hirsch
“I do suppose that the American School of Graduate Medical Schooling should place extra emphasis on instructing all clinicians and well being care professionals beginning in medical college, via their residency coaching,” Hirsch mentioned through the panel. “Even when a clinician will not be going to be the prescriber per se, if there’s a clear consensus for who ought to or may have a session for HT, I do suppose that’s actually necessary.”
Shifting ahead
Most members of the panel mentioned they favor labeling adjustments for menopausal HT. When requested what the most important knowledge gaps have been on menopausal HT, Simon said he desires to see the FDA observe the information which have already been revealed.
Barbara Levy, MD, FACOG, FACS, MSCP, medical professor of obstetrics and gynecology at George Washington College Faculty of Drugs and Well being Science,; voluntary medical professor within the division of obstetrics, gynecology & reproductive sciences at College of California, San Diego Well being Sciences, and Chief Medical Officer at Visana Well being, mentioned one other randomized medical trial is unlikely to be funded, so researchers want to seek out different methods to assemble knowledge.
“What we now have to do is get greater pondering and mix knowledge from [randomized controlled trials] from Cochrane with real-world knowledge,” Levy mentioned through the panel. “There’s a whole lot of real-world knowledge on the market.”
vHirsch mentioned the members of the panel didn’t imagine HT was “applicable” for all girls, however many ladies who may benefit from remedy don’t obtain it on account of well being care professionals not being educated about it. Faubion informed Healio that well being care professionals should take a number of elements under consideration when assessing whether or not a affected person would profit from menopausal HT.
“Calculating a person lady’s risk-benefit ratio for using HT includes quite a few elements, together with her age, time since menopause onset, estrogen plus progesterone or estrogen alone (eg, presence or absence of a uterus), heart problems and breast most cancers danger elements in addition to private preferences,” Faubion mentioned.
For extra info:
Stephanie S. Faubion, MD, MBA, FACP, MSCP, IF may be reached at editor@healio.com.
References:
Allen JT, et al. Menopause. 2023;doi:10.1097/GME.0000000000002234.
Beste ME, et al. Am J Obstet Gynecol. 2025;doi:10.1016/j.ajog.2024.10.054.
Rossouw JE, et al. JAMA. 2002;doi:10.1001/jama.288.3.321.
Sources/Disclosures
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Disclosures:
Simon reviews receiving analysis assist from AbbVie, Bayer Healthcare, Mylan/Viatris and Myovant Sciences; consulting or advising for Ascend Therapeutics, Bayer HealthCare Prescribed drugs, Besins Healthcare, Biote Medical LLC, Cosette Prescribed drugs, Femasys, Mayne Pharma, Pfizer and Vella Biosciences; talking for Ascend Therapeutics, Lawley Prescribed drugs, Mayne Pharma, Myovant Sciences and Pharmavite LLC; and holding inventory in Sermonix Prescribed drugs. Faubion and Hirsch report no related monetary disclosures. Healio couldn’t affirm related monetary disclosures for Hodis, Levy, Minkin and Pinkerton previous to publication.
