By Marty Makary, commissioner of the U.S. Food and Drug Administration
NOTE: This is such an important topic for the health and wellness of women that The Lab decided to publish it in its entirety, just as it was printed in the Opinion/Commentary section of The Wall Street Journal on November 10, 2025.
Over the past two decades, tens of millions of women have been denied or not offered hormone replacement therapy or have otherwise avoided it because of a medical dogma that it would increase their risk of dying of breast cancer. Clinical trials, however, don’t support that association. It’s time to treat women’s health with rigorous science instead of fear and misinformation.
Today, the U.S. FDA is requesting that drug manufacturers remove black box warnings from these products. These are the strongest drug warning the agency can require, and they have inappropriately scared women off from this life-changing, and sometimes life-saving, treatment.
Hormone replacement therapy (HRT), which consists of estrogen and progesterone (or estrogen alone for women who have had a hysterectomy), is a breakthrough for many women. It alleviates the short-term symptoms of menopause, including hot flashes, night sweats, mood swings and weight gain, and when started within 10 years of menopause it has underappreciated long-term health benefits that even doctors may not be familiar with.
A 1991 review from the University of California San Diego found that HRT may reduce the risk of fatal coronary events by approximately 50%. Several other studies have affirmed this benefit. Heart disease is the No. 1 cause of death in women, claiming more than 300,000 lives annually. HRT’s cardiac benefits may be even more effective than statins at reducing the risk of death from cardiovascular disease.
HRT also has powerful cognitive benefits. A 2005 study from Denmark found that HRT use was associated with a 64% reduction in cognitive decline. And a 1996 study from the University of Southern California found that women using estrogen replacement therapy had a 35% lower risk of Alzheimer’s disease compared with nonusers—a far better outcome than blockbuster Alzheimer’s drugs, which cost tens of thousands of dollars annually for a fraction of the effect.
HRT can also help prevent osteoporosis, a leading cause of disability and death in older women. A 1980 randomized study published in the New England Journal of Medicine found that HRT lowers the risk of suffering a hip or lower forearm fracture by 50% to 60%, reflecting its significant effect on bone strength.
In my professional opinion, the demonization of hormone replacement therapy for perimenopausal women and the underappreciation of its health benefits ranks among the greatest mistakes of modern medicine.
The belief that HRT increases breast cancer mortality can be traced to 2002, when a study called the Women’s Health Initiative found an additional 1 in 1,000 women receiving HRT was later identified to have a nonfatal breast cancer diagnosis compared with a control group. Some experts later recognized that this increased risk could be attributed to the particular hormonal medication used in the study, medroxyprogesterone acetate—a formulation that doctors have since moved away from for hormone replacement therapy.
Even though the 2002 Women’s Health Initiative finding on nonfatal breast cancer wasn’t statistically significant, it triggered a media frenzy and led the public to view HRT as a carcinogen rather than a lifesaving medication. HRT prescriptions fell off a cliff. In 1999, before the study, about 27% of postmenopausal women took HRT. By 2020 it had plummeted to about 5%. Of those who have taken HRT in recent decades, many have been instructed to take as small a dose as possible for the shortest time possible, depriving them of the health benefits of taking HRT over the long term.
The FDA perpetuated the groupthink. In 2003 the agency slapped a black box warning on the entire class of menopausal hormone therapy products, headlining the risks of breast cancer and other complications later recognized to apply only to women initiating HRT after age 60. Many experts point out that the initiation of HRT must be within 10 years of the onset of menopause, because the data clearly demonstrate that the risk-benefit ratio becomes unfavorable when initiated after 60. Unfortunately, this nuance was lost in blanket warnings. The FDA even required these warnings on topical formulations, which are safer than oral ones.
Despite the evidence, many primary-care physicians refuse to prescribe HRT. When asked why, they often cite the widely misinterpreted Women’s Health Initiative study, unaware of studies demonstrating health benefits.
The mischaracterization of HRT has had ripple effects beyond under-prescription. Because the medical establishment didn’t believe there was any acceptable treatment for menopause symptoms, there was little motivation to educate medical students and residents about menopause. According to one 2013 survey, only 20% of OB-GYN residents reported being formally taught about menopause medicine.
As a result, women with mood swings associated with menopause are more likely to be prescribed an antidepressant than estrogen. As a medical student, I witnessed a menopausal woman endure a battery of expensive tests because her medical team failed to recognize classic menopausal symptoms.
Breaking up groupthink is never easy. But the FDA’s removal of the black box warning against HRT is an important step toward treating menopause with the same scientific rigor we use in other areas of medicine.