•June 4, 2012, 6:59 p.m. ET
Hormone Use Benefits May Trump Risks; Age Matters

Women who are close to menopause face few dangers from hormone-replacement therapy, and the benefits may outweigh the risks for those who are suffering from severe symptoms.
That’s the consensus of a spate of new analyses clarifying a decade of research since a big government study scared millions of women and their doctors away from using hormone therapy at menopause.

The study—part of the 15-year, $1 billion Women’s Health Initiative—was halted in July, 2002, three years early, when researchers noticed an unexpectedly high rate of breast cancer and heart disease among women taking a popular brand of estrogen and progestin hormones women typically lose in menopause.
The original study wasn’t intended to assess the pros and cons of HT, but to explore whether giving hormones to older women would prevent heart disease, according to WHI researchers. Some 70% of women in the study were over age 60, an average 12 years past menopause. Younger HT users, suffering from hot flashes and other symptoms, were largely excluded.

“My menopausal patients were hysterical. They were calling saying, ‘I’m going to die!’ But this study really didn’t apply to them,” says Mary Jane Minkin, professor of obstetrics and gynecology at the Yale School of Medicine.

Analyses that came out over the past decade showed that women 50 to 59 who started HT near menopause had fewer cardiovascular problems—and fewer deaths from any cause—than those who started years later. Another branch of the study showed that women who took estrogen only also had a lower risk of heart disease and breast cancer.


Percentage of postmenopausal women in the U.S. using hormone therapy in 2002


Percentage using hormone therapy today

Source: North American Menopause Society

Some researchers say the original research deserves credit for alerting doctors to the danger of prescribing HT to older women who were at high risk for heart problems. “Unfortunately, those findings were generalized to all women, including some who suffered needlessly with menopausal symptoms when they would have been candidates for short-term HT,” says Harvard epidemiologist JoAnn Manson, one of the lead WHI investigators. Fears have persisted despite the latest research, she notes. “Even now, I get calls from women who can’t find a doctor or nurse practitioner who is willing to prescribe it.”

Even with the new studies, many aspects of the therapy remain controversial. Last week, the U.S. Preventive Services Task Force issued draft guidelines recommending against women taking hormone therapy to prevent chronic diseases. The North American Menopause Society agreed. “The evidence for long-term use to prevent chronic disease is not there yet, and it’s not clear that it will be,” said NAMS’s executive director Margery Gass, another former Women’s Health Initiative investigator.

Other experts say the preventive-services task force’s analysis ignored evidence that HT reduces the risk of osteoporosis, even in older women. “I don’t think every woman going through menopause should go on HT—far from it,” said Robert Langer, a former Women’s Health Initiative investigator at the University of California, San Diego and now medical director of Jackson Hole Center for Preventive Medicine in Wyoming. “If you start early, it’s an entirely new ballgame than what we tested” in 2002.

Here’s what the latest research says about when women should consider taking hormone therapy.
Hot flashes. Roughly 70% of women going through menopause suffer from hot flashes, night sweats and other symptoms. In 20%, they are severe enough to disrupt sleep and interfere with productivity and quality of life. Estrogen is indisputably the best remedy for such symptoms. Studies also show that it can aid the production of

neurotransmitters that regulate mood, memory, attention, sleep and pain. Women who can’t or don’t want to take hormones can get relief from lifestyle changes, such as avoiding caffeine, alcohol and spicy food that trigger hot flashes. If vaginal dryness is the main symptom, a low-dose of topical estrogen may be all that a woman needs. But, says Elizabeth Lee Vliet, a women’s health physician in Dallas and Tucson, Ariz., “Some women are taking an antidepressant, a sleep aid and an antianxiety medication to do what estrogen alone can, with far less cost and fewer side effects overall.”

Breast cancer. This is the biggest reason some women—and their doctors—fear hormone therapy. In the WHI, women taking estrogen plus progestin had a 20% higher risk of breast cancer than those on the placebo, and they were twice as likely to die from breast cancer, according to a follow-up study in 2010. “Why would anybody want to double their risk of dying from breast cancer?” asks Rowan Chlebowski, a medical oncologist and another WHI investigator. Yet in absolute numbers, the risk remained small: 2.6 breast-cancer deaths per 10,000 women per year in the estrogen-plus-progestin group, compared with 1.6 per 10,000 in placebo group.

Women in the estrogen-only arm of the WHI had a 63% lower risk of dying of breast cancer after 11 years, according to study published last year. The difference has fueled speculation that the progestin used in the WHI, medroxyprogesterone acetate (MPA), plays a role. “We knew by 1960 that MPA could induce breast-cancer cells to grow, whereas estrogen reduced the rate of recurrence,” says Philip Sarrel, an emeritus professor of ob/gyn and psychiatry at Yale School of Medicine.

Heart Disease. Decades of observational studies showed that women who used estrogen had a substantially lower risk of heart disease than those who didn’t, but most of them were younger than 55 and within a few years of menopause when they started. Lab and animal studies have also shown that estrogen staves off hardening of the arteries—but can’t reverse it once it is present. Whether HT truly does protect hearts if it is started early is being tested in another clinical trial known as Keeps, for Kronos Early Estrogen and Progesterone Study.

Stroke and embolism. Both estrogen-plus-progestin and estrogen alone raised the risk of stroke and blood clots in the WHI, and the risks were similar whether the women started sooner or later after menopause. Many experts don’t advise women at high risk for stroke or blood clots to take HT. Other studies have found that the risks of both are reduced when women take transdermal estrogen—in patch, cream or gel form—than in pills as in the WHI.

Osteoporosis. Given that 50% of women over 65 eventually develop osteoporosis, some experts say the bone protection HT gives has been improperly ignored. Others note that women would need to continue taking HT into their 70s and 80s to get the most benefit. “Do you want to be taking hormone therapy for 30 years to prevent a fracture that might not happen in the first place?” asks Dr. Gass. Bisphosphates and other medications can protect bones, but they carry risks of their own.



Taking hormones reduced the diagnoses Type 2 diabetes in the WHI—by 21% in the estrogen-plus-progestin group and 12% in those on estrogen alone.

But the studies did not measure blood glucose. Experts

say more research is needed.

Corrections & Amplifications

Women who have had a hysterectomy can take estrogen alone if they use hormone therapy. Women who still have a uterus need to take progestin along with the estrogen. A graphic that had accompanied an earlier version of this article had the information reversed.

Write to Melinda Beck at HealthJournal@wsj.com

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