Estrogen-related menopause drugs will no longer carry broad “black box” warnings, Marty Macari, Commissioner of the US Food and Drug Administration (FDA) announced last week, bypassing the typical regulatory agency process and, according to experts, exaggerating the science behind these drugs, with troubling implications. for future medication decisions.
The decision to remove a dire 2003 warning about the risks of heart disease, breast cancer and dementia makes sense for topical vaginal estrogen products, but with systemic estrogen the situation is more complicated, menopause experts say—and what worries them more than those nuances is the scientific process, or lack thereof, in making the decision.
Hormone therapy can relieve menopausal symptoms, including hot flashes, insomnia, and joint pain. But health officials hailed the benefit claims as a big step forward, pointing out that the therapy could also prevent heart disease, osteoporosis, Alzheimer's disease and death.
“In the modern era, there may be no other drug that can improve women's health at the population level other than hormone replacement therapy,” Makary said, calling it a “life-changing and even life-saving treatment” and touting the announcement as a “medical breakthrough.”
Other officials at the news conference offered a similarly rosy outlook.
Hormone therapy 'extends life by as much as 10 years', claims Robert F. Kennedy Jr.Secretary of the US Department of Health and Human Services (HHS).
“Today we have the opportunity to add up to ten healthy years to the life of every woman you love,” said Alicia Jackson, head of the US Advanced Research Projects Agency. Health and founder of Evernow, a startup providing virtual menopause care. “Estrogen is one of the most effective tools for prolonging women’s lives.”
However, there is no evidence that hormone therapy benefits the broader population of menopausal women beyond those who have symptoms, the researchers say.
“The blanket statement that every woman should take this medication to prevent cardiovascular disease is not true,” said Lauren Streicher, clinical professor of obstetrics and gynecology and founding medical director of the Center for Sexual Medicine and Sexual Medicine. Menopause at Northwestern University School of Medicine.
The “no data” decision sends a “harmful” and confusing message, said Pauline Mackie, a professor of psychiatry, psychology, and obstetrics and gynecology at the University of Illinois College of Medicine.
“Women are desperate to find out the truth and it's very difficult for them,” she said. When it comes to the use of menopausal hormone therapy for dementia (her area of expertise), “the harm may be real, but it certainly doesn't do any good.”
An HHS spokesperson said that “randomized studies show that women who start HRT within 10 years of menopause (typically before age 60) experience reductions in all-cause mortality and fractures.”
HHS did not respond to questions about officials' claims about purported protection against dementia and other problems, or about evidence of the drugs' widespread use.
This is the first time the FDA has used a roundtable that was not open to public comment in advance to inform its regulatory decisions. according to to the Pink Leaf. Streicher, who has long advocated changing the black box warning, was set to join the commission in July, but after several preliminary meetings she withdrew.
“It became very clear to me that this would not be a scientific commission. This is not a scientific approach,” she said. “I said, ‘I’m coming out. I don't want to be a part of this.”
Streicher attended the press conference earlier this month. “They were trying to get people to fill the room,” she said. Streicher said organizers encouraged participants to wear white coats to add an expert touch to the event. She didn't.
She says she is concerned about the precedent the decision sets. The agency is also reviewing drugs such as mifepristone, which is a safe and effective abortion treatment.
“It was very clear that Macarius already had an agenda, that he was going to remove these labels and was just having a public discourse where passionate people were saying, 'This is why this needs to happen,'” she said. “They handpick people who they know are going to say what they want them to say.”
Macari's latest book has a chapter on hormone replacement therapy called OMG HRT, which claims that hormone therapy “increases a woman's life expectancy by three years.” The more common medical term for treating women over 40 is menopausal hormone therapy (MHT). July panel included researchers who have published articles on menopause, as well as doctors with large social media followings; oncologists did not participate.
According to Makary, the process included giving panel members the opportunity to “express their opinions,” followed by a literature review to the FDA and a recommendation to “remove certain black box warnings,” which Makary himself signed.
Typically, expert advisory committees hold public discussions of the evidence and then make recommendations to the FDA, which the agency's subject matter experts—rarely the commissioner—may or may not accept.
The FDA chose the panel because advisory committee meetings are “bureaucratic, lengthy, often controversial and very expensive,” Makary said in response to a question about the process. More panels with guests “speaking” [their] mind passionately” will happen in the future, he added.
The evidence on drugs itself is nuanced. Streicher notes that “there are actually two completely different problems, and they are confusing them.”
Topical vaginal estrogen, which usually comes in the form of a cream, tablet, insert, suppository, or vaginal ring, treats symptoms such as dryness and irritation, as well as recurrent urinary tract infections and urgency. “These products really are completely safe,” Streicher said, adding that the warning should never have been applied to them.
With systemic estrogen the situation is more complicated. There are many drugs, uses, and ways to metabolize it. Some specific medications do have risks: for example, oral estrogen increases the risk of a blood clot, but the transdermal patch does not. According to Streicher, these labels need to be modified thoughtfully and based on the specific product. There is also a small increased risk of breast cancer when taking synthetic progesterone. Medicines are not suitable for everyone, especially people who have had breast or uterine cancer.
Mackie, a leading researcher into menopause and dementia, once believed that memory problems could be linked to the loss of estrogen that occurs during menopause. Research has shown that women who used hormone therapy to treat menopausal symptoms noticed an improvement in their memory. Maki conducted a large randomized trial study among a larger group of menopausal women, not just those with symptoms.
“Not only did it show a benefit, it also showed a trend toward harm,” Mackie said. Three other large randomized trials yielded similar results.
Symptoms such as hot flashes can be incredibly disruptive, with three quarters of sufferers saying they have trouble sleeping, which can contribute to memory problems, especially over seven or eight years.
Mackie now believes that treating these symptoms—whether with hormone therapy or other medications—is the key to improving memory, as demonstrated by her other research using non-hormonal treatments. The increased use of hormone therapy to prevent dementia is “simply not based on science,” Mackie said.
However, Mackie said health officials took a “stunning” step: They cherry-picked data from a small study conducted in one community while ignoring larger randomized trials. Officials positioned the decision as a move against “medical group thinking” and “medical dogma,” as Macarius put it.
“For the first time in a generation, the FDA is supporting science and women,” Kennedy said. “Today we are restoring the integrity of medicine, restoring faith in public health.”
The American medical establishment has turned its back on women, said Kennedy, who recently tried to link women's use of Tylenol during pregnancy to autism. “The label was designed to scare women and silence doctors,” Kennedy said, denouncing the “culture of fear.”
Makary said the decision “challenges the paternalism of medicine,” but then said hormone therapy has “saved marriages,” pointing out that one of the key treatment outcomes is marital satisfaction.
“Not only was it scientifically incorrect, it was offensive,” Streicher said.
Hormone therapy is safe and effective for people with menopausal symptoms, she said: “But do I tell every woman going through menopause that she needs to have hormone therapy? Absolutely not.”
