Hormone replacement therapy: benefits outweigh risks for some women

It’s been a decade since postmenopausal women were warned off hormone replacement therapy after a large randomized trial called the Women’s Health Initiative found that the combination of synthetic estrogen and progesterone caused more heart attacks and strokes than it prevented — in addition to raising breast cancer risks. But follow-up studies conducted by some of the WHI’s leading investigators have since indicated that the benefits of hormone pills outweigh the risks, at least for healthy women in their 50s who are suffering from menopausal hot flashes and night sweats.

A series of research reviews published this week in the journal Climacteric questions the wisdom of abandoning HRT altogether. As the journal’s editors in chief wrote, “an entire generation of younger doctors has never prescribed HRT’’ even to those who have dozens of hot flashes a day, drenched sleepless nights, and mood changes that often accompany these symptoms. What doctors should be doing, the editors wrote, is balancing the small risks of hormone use against the improved quality of life that a few years of hormone therapy might provide.


Several years ago, my former colleague, Dr. Bernadine Healy — who initiated the WHI trial when she was head of the National Institutes of Health — complained to me that the pendulum had swung too hard away from hormone use after the negative research findings.

The WHI study, she told me, was designed to look at whether hormone replacement therapy could prevent strokes, fractures, dementia, and heart disease in older women a decade or two past menopause since doctors had been routinely telling women that menopause was a disease that needed to be treated with hormones. It didn’t include many women who had recently gone through menopause or who needed the treatment to ease their symptoms. Regardless, many women experiencing debilitating hot flashes in the years after the WHI results were released were left to tough it out by their doctors who were unwilling to prescribe risky hormones for symptom relief.

Since then, studies examining the effects of hormone replacement therapy in women in the throes of menopause have had largely reassuring results, showing that the risks, such as increased breast cancer and blood clots, are pretty low for those in their 50s. For example, those taking a combination of estrogen and progesterone for five years have a 26 percent greater risk of getting breast cancer during that period of time, but since breast cancer rates are very low for women in their 50s, the absolute increase in risk was only 4 cases in 1,000 women.


(Breast cancer risks have been shown to reverse within a few years of stopping hormone therapy.)

“I do think the pendulum is finally coming to rest in a more appropriate spot,’’ said Brigham and Women’s Hospital’s Dr. JoAnn Manson, one of the WHI principal investigators who co-authored a paper in the Climacteric journal. “The one size fits all approach to decision making — either HRT for everyone or no one — is inappropriate. We have a clearer and more nuanced understanding of which women are appropriate candidates.’’

Taking a combination of estrogen and progesterone for a maximum of five years, said Manson, is considered to be relatively safe and low risk for healthy women suffering from hot flashes and night sweats. Most women can wean themselves off hormones after that period of time without returning to the severe hot flashes of their early menopausal days.

Researchers still don’t know whether so-called bioidentical forms of the hormones — which have the same molecular structure as hormones naturally made by a woman’s ovaries — are any safer than synthetic forms manufactured in laboratories; that’s a question an ongoing trial is attempting to address. Studies are also still trying to determine whether hormone therapy confers heart protective effects — as opposed to heart risks — on women who begin taking it right at the onset of menopause.

Certain women, however, should avoid hormone therapy altogether if they’re at higher risk of suffering harmful effects associated with hormone use. These include women who have a history of blood clots, breast cancer, heart disease, or stroke, or those who are obese or have diabetes, which puts them at higher risk of heart disease.


For some high-risk women, using an estrogen cream or gel applied topically might be a safe option because it doesn’t appear to pose the same blood clot risk, Manson said. But, she added, women can also turn to lifestyle approaches to control hot flashes, including exercise, weight loss, and avoiding triggers such as hot drinks and spicy foods. Antidepressants such as selective serotonin reuptake inhibitors (Prozac, Paxil, Celexa) and the anti-seizure drug gabapentin can also provide some symptom relief, Manson said, but they’re not approved for the treatment of hot flashes.

If vaginal dryness and painful intercourse are the only menopausal symptoms a woman experiences, she might want to use a topical estrogen cream or vaginal ring, said Manson, to avoid any systemic risks caused by pills that deliver hormones throughout the bloodstream.

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