Hormones Weather 'the Change'

"Little is known about major adverse events that could be associated with three- to five-year exposures to low-dose estrogen and progestins," including breast cancer that occurs five to 10 years after the drugs are taken, the panel said. Its members warned against the overuse of "treatment approaches that are known to carry serious risks."

Feminine Forever

It's been nearly 40 years since New York gynecologist Robert Wilson published "Feminine Forever," a book that fueled the popularity of estrogen and the notion that menopause is a medical problem that needs to be fixed.

Wilson warned that women were doomed to become shriveled, sexless, sickly hags unless they took supplemental estrogen, which could keep them looking and feeling better.

"I vividly remember one ACOG meeting when we were told we should start all our post-menopausal women on estrogen unless they had advanced breast cancer -- it was that good," recalled Bohon of a meeting sponsored by the American College of Obstetricians and Gynecologists.

By the early 1990s, noted Isaac Schiff, chief of obstetrics and gynecology at Massachusetts General Hospital in Boston, "it was almost malpractice not to offer it to women for the prevention of heart disease," although previous studies had linked it to uterine cancer. Schiff chairs ACOG's task force on hormone therapy.

Results from the ongoing Nurses Health Study, a huge study involving 120,000 women begun in 1976, found that women who took hormones had lower rates of heart disease than women who did not, seemed to underscore the benefits of estrogen. Because it was an observational study, however -- one in which an association between the drug and the benefits was found, but no cause-and-effect relationship established -- critics led by the National Women's Health Network said that the benefits could be due to factors other than drugs.

In an attempt to definitively answer the question, NIH funded the landmark WHI, which employed the most rigorous scientific methodology: a randomized, double-blind, placebo-controlled study that involved more than 68,000 women.

The Prempro arm of the study, which involved 16,000 women, was halted in 2002 after researchers decided the risks of continuing were too great. (Two years later, a trial of estrogen-only Premarin involving women who'd had hysterectomies was also stopped early for the same reason.)

For every 10,000 women taking Prempro, there were eight more cases of breast cancer, eight more women had strokes, seven more had a heart attack and 18 more had blood clots, compared with women taking a placebo, researchers found. There was a modest reduction in hip fractures -- five fewer in the Prempro group -- and six fewer colon cancers.

The risk of breast cancer rose significantly after the fourth year, while the risk of cardiovascular problems increased immediately in the hormone group.

"There's really no safe period" of time the drug can be taken without risking side effects, Jacques Roussouw, acting director of the WHI, said at the time.

Serious Symptoms

While most women experience at least some symptoms of menopause, no one knows how many suffer from the most severe, debilitating problems -- drenching night sweats, hot flashes, mood swings and vaginal dryness that makes sex painful -- or how long symptoms typically last. Those are among the questions being examined by a large, long-term NIH-funded study known as SWAN (Study of Women's Health Across the Nation). Mass General's Schiff said that estimates of the most severely affected range from 10 to 25 percent.

"I still prescribe hormones for symptomatic women," Schiff said, "as long as they understand the risks and benefits." Some patients, he said, say they simply cannot function without the drugs; among these patients is a corporate executive whose face repeatedly turned crimson and sweat-drenched during business meetings. Others, he said have told him, "I know I'm going to be the person who gets breast cancer, and I want to stop right now."

Inova's Brown, whose mother has taken hormones for 20 years, said she tries to reassure patients who find they can't go off the drugs without feeling awful.

Brown, who described herself as a "huge hormone fan" before the WHI, said she no longer prescribes the drugs as preventive medicine but tries to reassure jittery younger patients who decide to take hormones that their risk of harm is probably small.

"Who are we to deny them their quality of life?" Brown asked.

One 65-year-old Leesburg woman, who agreed to be interviewed on the condition that her name not be published, decided her quality of life was worth the risk.

Three months after stopping the drugs she had taken for 10 years, "I was miserable, breaking out in hot flashes, sobbing, and my hair was falling out," she said, so she asked her doctor to renew her prescription.

"Most of my friends who took them are still taking them," she said, adding, "Breast cancer is always in the back of my mind. Sometimes I wish I'd never gone on them."

Isidra "Sheila" Munoz, a 57-year-old nurse at Sibley Hospital, said she decided last month to see if she could live without her hormone regimen of 10 years. "I'm fine," said Munoz, who has experienced only minor hot flashes.

Greenberger, head of the Society for Women's Health Research, said she had such severe symptoms when she cut her dose that she doesn't plan to stop taking hormones. Her group receives funding from more than 18 drug companies, including Wyeth, according to its Web site.

She said she hopes future studies will further refine the risk-benefit calculation, and thinks hormones may be beneficial in ways not yet discovered.

"There are still questions that need to be answered and more research that needs to be done," she said. ·

E-mail: boodmans@washpost.com