FDA Panel Challenges Hormone Replacement Therapy Risks

An FDA panel of menopause experts met today to review the current FDA warning labels on hormone therapy for menopausal women. Experts discussed the issues with the labels and the need for education and hormone access. The meeting was organized by FDA Commissioner Marty Makary and moderated by Principal Deputy Commissioner Sara Brenner, M.D., M.P.H. There was not a public comment section at today’s session, but there are plans to open one through the Federal Register as early as next week, Brenner said.

Hormone replacement therapy, which includes systemic and local estrogen, carries a black box label warning stating that the medication causes an increased risk of breast cancer, blood clots and stroke. The warning is the result of a 2002 study done by the Women’s Health Initiative, backed by the U.S. National Institutes of Health.

“The Women's Health Initiative studied conjugated equine estrogen and micro- or medroxyprogesterone acetate, two very explicit and specific drugs that were used in the 1990s in my practice all the time,” Heather Hirsch, M.D., MS, a board-certified internist and founder and CEO of Health By Heather Hirsch MD Collaborative, said. “It's very important to understand that 17 beta estradiol, which is the most potent and naturally occurring form of human estrogen, binds receptors differently than conjugated equine estrogen, and it's scientifically inappropriate to conflate the results in a study that used conjugated equine estrogen to all forms of hormone therapy.”

Hirsch also argued that training gaps in menopause education cause damage and explained clinicians may receive as little as one hour of menopause training. She explained that during med school, it came in the form of a voluntary lunch and learn session on menopause.

Osteoporosis is exacerbated by dropping estrogen levels during menopause. As a result, approximately 70% of hip fractures occur in women, 30% of which will be fatal within one year after surgery.

“According to the NIH consensus statement and the European Foundation for Osteoporosis and Bone Disease, estrogen is the only well-established intervention to reduce the frequency of osteoporosis fracture in postmenopausal women to the tune of 30 to 50%. The WHI itself found a 33% decline in fracture,” Vonda Wright, M.D., MS, an orthopedic surgeon and professor at the University of Central Florida, said.

Despite the FDA approval of estrogen to treat osteoporosis, only 4% of women in the United States currently take it for that purpose, out of fear of the warning label. Wright said

“Estrogen was not the only hormone the panel talked about.” Hirsch said. “Menopausal hormone therapy is the combination of estrogen plus or minus a progestin or a progesterone if a woman has an intact uterus with or without the addition of testosterone.”

Kelly Casperson, M.D., a board-certified urologist, talked about the lack of access women have to testosterone therapy as part of a hormone replacement therapy regimen.

“The FDA is failing women by denying access to a hormone their bodies naturally produce,” Casperson said. “The ovaries and the adrenals make testosterone. The testosterone stereotype is that it's just for libido. It's a half-truth.”

Casperson said that higher testosterone levels in the brain correlated with lower levels of dementia and that testosterone and estrogen may allow women to come off their SSRIs.

“Picture 108 million women energized, focused and ambitious, not in spite of their age, but because they are supported through it. That's the country that we want our children to grow up in, and it's time for the FDA to act,” Casperson said.