Doctors respond to ‘data-free’ decision over menopause hormone therapy: ‘It’s not true’

Estrogen-related medications for menopause will no longer carry broad black-box warnings, Marty Makary, commissioner of the US Food and Drug Administration (FDA), announced last week, bypassing the regulatory agency’s typical process and, according to experts, overstating the science behind the medications – with troubling implications for future drug decisions. The decision to remove an ominous warning from 2003 about the risks of cardiovascular disease, breast cancer and dementia makes sense for local vaginal estrogen products, but systemic estrogen is more complicated, menopause experts said – and more than these nuances, they worried about the scientific process, or lack thereof, in making the decision. Hormone therapy can ease symptoms of menopause, including hot flashes, insomnia and joint pain. But health officials took claims of the benefits a major step forward, indicating the therapy can also prevent heart disease, osteoporosis, Alzheimer’s disease and death. “There may be no other medication in the modern era that can improve the health outcomes of women on a population level than hormone replacement therapy,” Makary said, calling it a “life-changing, even life-saving treatment” and positioning the announcement as a “medical breakthrough”. Other officials at the press conference offered similarly rosy perspectives. Hormone therapy is “extending the lives for as much as 10 years”, said Robert F Kennedy Jr, secretary of the US Department of Health and Human Services (HHS). “Today, we have the opportunity to add up to a decade of healthy years to the life of every woman that you love,” said Alicia Jackson, head of the Advanced Research Projects Agency for Health and founder of Evernow, a startup that provides virtual menopause care. “Estrogen is one of the most effective longevity interventions for women.” Yet there is no evidence that hormone therapy has benefits among the wider population of menopausal women beyond those who have symptoms, researchers said. “To make that blanket statement that every woman should take this to prevent heart disease – it’s not true,” said Lauren Streicher, clinical professor of obstetrics and gynecology and founding medical director of the Center for Sexual Medicine and Menopause at the Northwestern University school of medicine. The “data-free” decision sends a “harmful” and confusing message, said Pauline Maki, professor of psychiatry, psychology and obstetrics and gynecology at the University of Illinois college of medicine. “Women are trying desperately to get the truth, and they’re having a really difficult time,” she said. When it comes to using menopause hormone therapy for dementia, her area of expertise, “the harm is maybe real, but certainly it’s not showing benefit”. An HHS spokesperson said that “randomized studies show that women who initiate HRT within 10 years of the onset of menopause (generally before age 60) have a reduction in all-cause mortality and fractures”. The HHS did not respond to questions about officials’ statements on purported protection against dementia and other issues or the evidence for using the medications widely. This is the first time the FDA has relied on a roundtable panel, which was not open to public comments in advance, to inform their regulatory decision-making, according to Pink Sheet. Streicher, who has long advocated for changes to the black-box warning, was going to be on the panel in July, but after a few preliminary meetings, she dropped out. “It became very clear to me that this was not going to be a scientific panel. This isn’t the scientific approach,” she said. “I said: ‘I’m out. I don’t want any part of this.’” Streicher attended the press conference earlier this month. “They were trying to get people to pack the room,” she said. The organizers urged attendees to wear their white coats to give the event the imprimatur of expertise, Streicher said. She didn’t. She says she’s worried about the precedent set by the decision. The agency is also re-examining medications like mifepristone, which is a safe and effective medication for abortion. “It was very clear that Makary already had an agenda, that he was going to want to remove these labels, and was just kind of doing this public discourse of passionate people saying: ‘This is why it should happen,’” she said. “They handpick the people who they know are going to say what they want them to say.” Makary’s most recent book has a chapter on hormone replacement therapy, titled OMG HRT, arguing that hormone therapy has been shown to “increase a woman’s longevity by three years”. The more accepted medical term for the treatment for women over 40 is menopause hormone therapy (MHT). The July panel included researchers who have published on menopause as well as doctors with large social media followings; no oncologists participated. The process involved letting panelists “express their opinions”, Makary said, followed by a literature review at FDA and the recommendation to “remove certain blackbox warnings”, which Makary himself signed. Typically, expert advisory committees hold public discussions on the evidence and then make recommendations to the FDA, which subject-matter experts at the agency – rarely the commissioner – may or may not accept. The FDA opted for the panel because advisory committee meetings are “bureaucratic, long, often conflicted and very expensive”, Makary said in response to a question about the process. More panels with guests who “​​speak [their] mind passionately” will happen in the future, he added. The evidence itself on the medications is nuanced. Streicher notes “there’s really two very separate issues, and they muddy those”. Local vaginal estrogen, which is usually a cream, tablet, insert, suppository or vaginal ring, treats symptoms like dryness and irritation as well as recurrent urinary tract infections and urgency. “Those products are really totally safe,” Streicher said, adding that they never should have had the warning applied to them. Systemic estrogen is more complicated. There are many preparations, applications and ways it’s metabolized. Some specific medications do have risks – oral estrogen, for example, increases the risk of getting a blood clot, while a transdermal patch doesn’t. These labels need to be modified in a thoughtful, product-specific way, Streicher said. There’s also a small increased risk of breast cancer with synthetic progesterone. The medications are not suitable for everyone, especially people with a history of breast or uterine cancer. Maki, a leading researcher on menopause and dementia, once believed memory issues could be linked to the loss of estrogen that occurs during menopause. Research indicated that women who used hormone therapy to treat menopause symptoms saw improvements to their memory. Maki conducted a large randomized study among a bigger group of menopausal women, not just those with symptoms. “Far from showing benefit, it actually showed a trend toward harm,” Maki said. Three other large randomized trials had similar results. Symptoms like hot flashes can be incredibly disruptive, with three-quarters of sufferers saying they have trouble sleeping – which can contribute to memory issues, especially over the course of seven or eight years. Maki now believes that treating those symptoms – whether with hormone therapy or other medications – is key to improving memory, as demonstrated in another study of hers with a non-hormonal treatment. To use hormone therapy for dementia prevention more widely is “just not based in science”, Maki said. Related: CDC website altered to reflect RFK Jr’s belief in link between vaccines and autism Yet in a “stunning” move, Maki said, health officials cherry-picked data from a small study in one community while ignoring larger randomized trials. Officials positioned the decision as a move against “medical group think” and “medical dogma”, as Makary put it. “For the first time in a generation, the FDA is standing with science and standing with women,” said Kennedy. “Today, we are restoring integrity to medicine, restoring faith in public health.” The American medical establishment turned its back on women, said Kennedy, who recently sought to link women’s use of Tylenol in pregnancy to autism. “The label was designed to frighten women and to silence doctors,” Kennedy said, decrying “a culture of fear”. Makary said the decision was “challenging the paternalism of medicine”, but then said hormone therapy “​​has saved marriages”, indicating that one of the key outcomes of the medication is marital satisfaction. “It was not only scientifically wrong, but it was offensive,” Streicher said. Hormone therapy is safe and effective for those with menopause symptoms, she said: “But do I tell every single woman who goes through menopause that she needs to be on hormone therapy? Absolutely not.”