A 'black box' warning has appeared on hormone replacement therapies in the United States for more than 20 years.Credit: Getty
On Monday, the US Food and Drug Administration announced its intention to eliminate safety warnings for hormone replacement therapy creams, pills and patches used to treat the symptoms of menopause. The move, which the FDA called “a historic action to restore gold-standard science to women’s health”, is drawing both praise and concern from scientists and advocates.
Many argue that the warnings, which have appeared on the products for more than 20 years, have contributed to chronic underuse of menopausal hormone therapy among women who were likely to benefit. Yet some now worry that removing the labels entirely, or making overly broad claims about hormones, health and longevity, might swing the pendulum too far in the opposite direction. “I’m afraid comprehensive discussion about the risks and benefits may not occur in absence of that warning,” says Stephanie Faubion, the director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Florida, and medical director of The Menopause Society a non-profit organization based in Pepper Pike, Ohio, that provides tools and resources to health-care professionals. “We need to end up somewhere in the middle.”
Hormone crash
Hormone therapy was widely prescribed for decades to ease common menopausal symptoms such as hot flushes, night sweats and poor sleep. But prescriptions plunged worldwide in 2002 after an initial report from the Women’s Health Initiative (WHI) — a long-term US study — suggested that postmenopausal participants who were taking oestrogen and progestin (a synthetic form of progesterone) had slightly increased risks of breast cancer, heart attack and stroke1. The findings — widely misinterpreted and overgeneralized — sparked fear among women and clinicians.
In January 2003, the FDA announced that oestrogen-containing menopausal hormone therapy products would require a ‘black box’ safety warning, the agency’s strongest. Regulatory agencies around the world followed the FDA’s lead by changing labels and issuing advisories. Use of these products remained low even though later research hinted at reduced risks of heart disease and death among hormone-therapy users, and lower rates of breast cancer among those taking oestrogen-only therapy.
How menopause reshapes the brain A 2024 review reiterated that the hormone formulations, doses and delivery routes used in the WHI trials differed from those typically used today2. Transdermal patches don’t show the same links to blood clots found with oral hormones, for example. And using lower doses and hormones that are identical to those found in the body might further limit risks. Researchers have also noted that most participants included in the initial, concerning WHI analysis were a decade or more beyond menopause, a stage when the sudden return of oestrogen might pose health problems.
Before the WHI results were reported, about one-quarter of women over the age of 40 used systemic hormone therapy. Now, that figure is about 1.7%, according to The Menopause Society. “I don’t know what percentage should be getting the therapy, but I’d venture to say it is probably more than 1.7%,” says Faubion. “On the other hand, I don’t think we should go back to thinking this is the be-all-end-all longevity drug.”
The balance of risks and benefits depends on a person’s age, years elapsed since menopause, whether the individual has a uterus, existing medical conditions and the therapy’s formulation, route of delivery and dose. “Hormone therapy is not for everyone,” says JoAnn Manson, a women’s health researcher at Harvard Medical School in Boston and a former president of The Menopause Society. Generally, she says, women under the age of 60 and within 10 years of the onset of menopause who are experiencing symptoms might be good candidates.
Manson says she doesn’t think that the message needs to appear in a “frightening black box”. But she says the package inserts should summarize clinical-trial data so that women, together with their clinicians, can make informed and personalized decisions.