Kerry Hannon

Younger women tormented by hot flashes are coming back for an ultralow dose

For three years, Susan Kirchoff tried all the usual remedies to manage her menopausal hot flashes--exercise, soy foods, herbal supplements. But she still woke up with her nightgown sopping night after night. "My husband thought he was going through it, because I was making him sweat," says the 53-year-old health center director from Portland, Ore. Exhausted and desperate, she talked to her doctor about hormone therapy and her own personal risks: a family history of breast cancer and an elevated platelet blood count, which put her at increased risk of blood clots and stroke. In October, when blood tests revealed a normal platelet count, she decided, "I needed relief." Sure enough, within a few weeks of affixing a dime-size estrogen patch to her abdomen, Kirchoff's hot flashes ceased. She plans to stay on the estrogen for a few years.

Women like Kirchoff have been frightened away from hormone therapy ever since a large clinical trial called the Women's Health Initiative found seven years ago that the treatments raised the risk of breast cancer, heart disease, and strokes. Prescriptions for estrogen and progesterone--the typical combination regimen that protects against uterine cancer, which can result from taking estrogen alone--quickly dropped (breast cancer rates did too, partly because of this). Today, doctors no longer prescribe hormones as they once did to prevent osteoporosis, clogged arteries, and dementia. Many experts, however, contend that the pendulum has swung too far, leaving women without any effective remedy for severe menopausal symptoms. The WHI study, designed to test whether long-term use of hormone therapy could prevent age-related illnesses, "was never meant to test the effectiveness of hormones for symptoms," says Nanette Santoro, director of Montefiore Medical Center's Institute for Reproductive Medicine and Health. The average age of the participants was 63, more than a decade beyond the average age of menopause (and well past the worst of its annoyances).

So now, after trying unhappily to go without, many of the 40 percent of menopausal women who suffer from severe hot flashes and night sweats are turning to a new way of using hormones--an ultralow dose for as short a time aspossible. "The initial drop in hormone prescriptions . . . is now tapering off," says Anne Nedrow, medical director of women's primary care at Oregon Health and Sciences University in Portland, who treated Kirchoff. "We are really filtering out the women that require it for quality-of-life symptom control."

In women just entering menopause, it appears, heart disease risks may be elevated only slightly. One re-evaluation of WHI data found 28 additional cases of heart disease and 28 additional cases of strokes per 10,000 women in their 50s who took the hormone combination for an average of 5» years; for those in their 70s, the numbers were an extra 134 cases of heart disease and 62 strokes. What's more, a study published in the Journal of the American Medical Association in March 2008 indicates that the small increase in the likelihood of having a heart attack, stroke, or dangerous blood clots associated with taking estrogen and progesterone disappears soon after women go off the hormones--though the increased risk of breast cancer persists for more than two years.

Right formula. There are, however, a number of issues women need to consider along with their personal health risks: What formulations of estrogen and progesterone to take, and at what dose? How to get the hormones--pill, patch, gel, or suppository--and how long to take them? How to taper off? For Kirchoff, who had had a hysterectomy, Nedrow recommended just a low dose of estrogen in the form of a skin patch, which she replaces weekly at a cost of $30 per month.

For now, research is lacking to guide women and their doctors to the best of the plethora of hormone choices. Scientists still don't know whether one form of estrogen made from horse urine, called conjugated equine estrogen, poses any greater health risks than estradiol, which comes from plants and is identical in structure to the estrogen made by the body. (For more on bioidentical hormones, go to bioidenticals.) And while some studies suggest that women who use a transdermal delivery method, which bypasses the liver, have lower risks of blood clots and gallstones than those who take pills, no one knows for certain. The ongoing Kronos Early Estrogen Prevention Study, which is randomly assigning patches, pills, and placebos to 720 women ages 42 to 58, is trying to determine if one option is safer and whether estrogen in either form actually protects against coronary artery disease--as well as cognitive decline--if started within three years of menopause. (A handful of previous studies suggest that it might.) "More testing is critical," admits JoAnn Manson, a professor of medicine at Harvard Medical School who is one of the study's principal investigators.

At the moment, doctors are following the recommendations of the Food and Drug Administration: Prescribe the smallest dose that relieves a woman's symptoms, and do it for the shortest period of time. While in the 1990s doctors typically prescribed a 0.625-milligram dose of estrogen and sometimes as much as 5 mg for five to 10 years or more, they now generally start with just 0.3 to 0.5 mg and give it for months or up to a few years. Kirchoff is using a patch that delivers just 0.015 mg of daily estrogen, the lowest dose on the market. Doses of progesterone haven't changed much.

The question of how long a woman can safely be on hormones is a thorny one. There's just no "risk-free interval," says Adriane Fugh-Berman, a professor of family medicine at Georgetown University School of Medicine who serves as a paid expert witness in trials involving the overmarketing of hormone therapy. She says women should be especially wary of hormones if their mothers or sisters had premenopausal breast cancer or if they or close relatives have heart disease or blood clots.

Risk timeline. The increased risk of breast cancer associated with hormone use in the WHI study appears to kick in after five years for those taking estrogen and progesterone and after seven years for those taking estrogen alone. A slightly increased risk of ovarian cancer, however, may occur within four years, regardless of the regimen, according to a study released in July. For every 8,300 women on hormone therapy, one extra case of ovarian cancer would result, a risk that drops back to normal within two years of stopping the treatments.

A good rule of thumb to follow: Stay on hormone therapy for no longer than five years, says Isaac Schiff, chief of obstetrics and gynecology at Massachusetts General Hospital. Taper off earlier if you can. "Some women take it for six months, feel wonderful, and stop," he says. About half of hormone users, though, find they need to taper off gradually to avoid a return of their symptoms. Some can switch to a lower dose, while others may need to alternate between their usual dose and lower-dose pills for three to six months. Those already on very low doses can try skipping days between pills or wearing a patch every other week.

Whether to use a pill, cream, gel, spray, or skin patch depends largely on personal preference and the severity of symptoms. Women with more severe hot flashes may want to opt for a pill if lower-dose patches or creams don't work. Vaginal dryness may be alleviated with a low-dose product delivered through a vaginal ring, cream, or tablet inserted into the vagina to deliver hormones directly to the tissues. Breast cancer patients who simply can't take hormones may find their hot flashes can be relieved by anti-depressants or a pain reliever called gabapentin. (See story below for natural symptom relievers.)

Kirchoff's daily cocktail of estrogen has not been a panacea for all that ails her. "It's definitely not a stress-reducer. I still need to exercise and do all my other healthy living things to combat that," she says emphatically. But she's finally sweating less.