Opinion | Hormonal menopause therapy hurt by misinterpreted study

Abundant research has since debunked those initial findings. But the damage was done: For a long time, medical schools taught that hormone treatments did more harm than good. Many physicians stopped prescribing it, even when the evidence changed and major medical societies altered their guidelines.

The mistaken belief that hormone therapy should be avoided led to a huge treatment vacuum in menopause care. One study found that only 4 percent of women 50 and older in 2018 and 2019 were receiving hormone therapy, down from more than 22 percent in 1999 and 2000.

I was in my second year of medical school when news of that flawed study, conducted by the Women’s Health Initiative (WHI), came out. I remember learning that the outcomes were so negative that the National Institutes of Health, which funded the research, decided to end the study three years early. Participants assigned to receive hormones were told to stop because they were too dangerous.

I thought that was the end of the story — until I started doing research for this series on menopause. In fact, dozens of papers, including some authored by WHI investigators, have since shown that the initial results were badly misinterpreted.

Much of the error stems from the assumption that the WHI student examined the safety and effectiveness of hormone therapy among menopausal women. It did not. As two of the WHI investigators wrote in a 2016 New England Journal of Medicine article, the goal of the study was to examine whether hormone therapy could be used to prevent long-term chronic diseases in postmenopausal women. The average age of menopausal women in the United States is 51. In the WHI study, the average age of participants was 63.

The correct conclusion from the original study should have been that the risks of hormone therapy outweigh its benefits if used in postmenopausal women for the purpose of preventing chronic diseases. What was reported in 2002, though, was that younger women shouldn’t be taking hormones, even though it was the most effective treatment for menopausal symptoms such as hot flashes, night sweats, painful sex and urine leakage. In younger women, hormones also had the added benefit of reducing bone loss and improving heart health.

Earlier this month, WHI researchers published an updated analysis of their results. As JoAnn E. Manson, the paper’s lead investigator and professor at Harvard Medical School, told me in an interview, the bottom line is that hormone therapy is appropriate for the management of menopausal symptoms when initiated before the age of 60. “The WHI findings should not be used as a reason to deny hormone therapy to these women,” she said.

Manson is quick to clarify that women who are not experiencing menopausal symptoms should not be using hormone therapy to prevent chronic diseases. That’s because the bar is set much higher when used solely for prevention rather than for treatment.

In addition, the WHI findings show that the risk of oral hormone therapy increases substantially when started many years after a woman’s last period. But older women are not without options, Manson told me. For example, low-dose vaginal estrogen can alleviate symptoms such as vaginal dryness and discomfort during sex, since such non-oral therapy is not absorbed as much through the bloodstream — and is therefore less risky.

There are also some women who should not take hormone therapy, such as those with a history of prior estrogen-sensitive cancer, blood clots or heart attacks. Others might have a personal preference for non-hormonal therapies, including some antidepressants and fezolinetant, a drug approved in 2023 to treat hot flashes.

“It’s important that clinicians be able to discuss these options fully with patients,” Manson said. But she is aware that many patients cannot find a clinician to even discuss treatment possibilities. She finds it troubling that physicians continue to lack training to manage a condition that 100 percent of middle-aged women will go through.

This must change. Clinicians and patients should learn about how a misinterpreted study led to substandard care for millions of women. They need to spread the word that hormone therapy for menopausal women does not deserve its bad reputation. It never did.

Thanks to readers who sent in questions, some of which I addressed in last week’s edition of The Checkup newsletter. I’ll be answering more in future pieces. I’d love to hear from you. What topics around menopause and perimenopause should I cover next?