A Boost for Hormone Therapy(07.06.21)

Progesterone in tablet form, used in hormone replacement therapy.

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Hormone Therapy Redeemed

After years of studies suggesting estrogen may have health risks for older women, the treatment for menopause is more or less back where it started

The Risks of Combined Hormone Therapy

Taking estrogen plus testosterone, yes testosterone, may be bad for women's hearts

For women trying to keep track of the confusing research on hormone replacement therapy over the past five years, the release of yet another study may not sound like good news. But the latest report, published in the New England Journal of Medicine, helps clarify some of the conflicting results,and offers some reassurance for women wondering whether such hormone therapy is safe.

The New England Journal study is continuation of the landmark Women's Health Initiative (WHI), the largest and longest-running survey of the effects of hormone therapy in post-menopausal women. It was the WHI, back in 2002, that turned everything that doctors and patients had believed about the benefits of hormone therapy on its head. The federally funded trial revealed that estrogen and progestin after menopause did not protect women against heart disease, as doctors had previously thought, but in fact increased their risk of heart attack, stroke and breast cancer. After years of recommending the therapy for women well past menopause, doctors then pulled back, prescribing it only for women having the hardest time with menopausal symptoms of hot flashes and night sweats.

After those surprising results, however, WHI narrowed their focus to study the women most likely to need hormone therapy — those under 60 and just experiencing menopause. And they found that younger post-menopausal women actually enjoyed a lower risk of adverse health effects from hormone therapy than their older counterparts. The new NEJM study specifically reports that women between the ages of 50 and 59, who have had hysterectomies and therefore used estrogen alone (not the estrogen-progestin combination) showed less calcium-based plaque — up to 40% less — in their heart arteries than those on placebo. That's great news for the millions of women struggling with the disruptive symptoms of menopause, but who have been too afraid of the health risks to start hormone therapy. In some cases, even their doctors have been reluctant to prescribe the treatment, after the public lashing the profession received five years ago for "pushing" the therapy so eagerly.

The study is not, however, a free pass for estrogen therapy in all post menopausal women. "These findings provide reassurance to recently menopausal women who are considering estrogen therapy for treatment of menopausal symptoms, that estrogen is not likely to have an adverse effect on the heart," says Dr. JoAnn Manson, chief of preventive medicine at Harvard's Brigham and Women's Hospital and an author of the study. "But it does not mean that women should begin taking estrogen for the express purpose of preventing cardiovascular events because there are other risks of hormone therapy."

Those include the risk of blood clots, stroke and, over a long enough period of time, breast cancer. It's all about balance, and weighing benefits and risks responsibly, says Manson. For women who suffer from the most intense symptoms of menopause, hormone therapy may be worth the slightly increased risk of these conditions, provided that they don't stay on the hormones for more than five years or so. Last April, another study from the WHI supported just this sort of judicious use. That study found that women who began estrogen and progestin, the most commonly prescribed combination (progestinis added to protect against uterine cancer; women with hysterectomies do not need progestin, since they have had their uterus removed), within 10 years of hitting menopause experienced less heart disease than their counterparts who began years after the Change.

 

The reason for that, researchers speculate, could be related to two things. one, it could simply reflect the aging of the arteries; younger women are more likely to have flexible, pliable arteries that respond to estrogen, which tends to discourage plaque formation. Older arteries, on the other hand, are more likely to be stiffer, and already burdened with fatty deposits and plaques; in the presence of these plaques, it turns out, estrogen may even have the reverse effect, causing them to destabilize and rupture, leading to blocked up arteries and a heart attack.

Or, some doctors believe, there may be a window of opportunity where hormone therapy should be started. The whole idea behind estrogen and progestin therapy after menopause is for the supplemental hormones to replace the estrogen that the woman's body is no longer making. If hormone therapy starts while the naturally circulating estrogen is still around, some doctors think that the hormones will continue to exert beneficial effects on the heart. The latest study seems to support this idea.

Still, even if estrogen is linked to less plaque in the arteries, that doesn't mean it outweighs other possible risks of hormone therapy. "People want a simple answer to whether estrogen is bad or good," says Marcia Stefanick, another author of the paper, from Stanford University. "but it's not that simple. We need to ask instead, 'Is it bad or good for what?'"

To get more answers, researchers are taking a closer look at the youngest post-menopausal population — women between 50 and 59 who are most in need of hormone therapy to relieve menopausal symptoms. Already, they are finding that the way estrogen is delivered can make a difference: the patch form of the hormone combination leads to fewer clots than the pill form, since the liver is not engaged as intensely in processing the estrogen when it comes through the mouth, and does not produce as many clotting factors with the skin-based estrogen. "Hormone therapy is an evolving story, and it's a very intriguing mystery that we don't understand yet," says Stefanick. "We don't have all the answers, but we're trying to get those answers now." So stay tuned. There will be more studies on hormone therapy, but at least they're starting to fit together and make sense.