Coping With the Change

Since clinical trials indicated that hormone replacement therapy carries significant risks, women have been confused about how best to manage their transition through menopause. Now a federal panel of experts provides some answers.

Over the next two decades, about 40 million American women will enter menopause. Many of them will have to deal with a range of discomforts, from mood swings and decreased sexual desire to hot flashes and night sweats. To relieve these ailments, doctors have for many years offered hormone replacement therapy (HRT), a treatment that replenishes some of the hormones whose concentrations wane in the post-reproductive years.

But in 2002, use of HRT dropped dramatically when clinical trials run by the Women's Health Initiative (WHI) revealed that the medication increased women's risk of heart disease, breast cancer, and dangerous blood clots (see "Hot Flash!"). Although those studies were designed to test whether HRT could prevent chronic diseases and not whether they would alleviate menopausal symptoms, the results left women wondering what to do about their hot flashes and night sweats. To help address this question, the National Institutes of Health (NIH) convened a panel of experts in March to review published data on the biology of menopause, the types of conditions women experience, and strategies used to relieve them.

The group's first order of business was teasing out which symptoms are due to the ovaries shutting down and which are simply the result of aging, according to physician Carol Mangione of the David Geffen School of Medicine at the University of California, Los Angeles, who chaired the NIH panel. The researchers concluded that hot flashes, night sweats, vaginal dryness, and possibly problems sleeping are tied to the menopausal transition. But the same cannot be said for other conditions that some women in their 40s or 50s experience, including mood swings, depression, difficulty in thinking and remembering, back pain, fatigue, and urinary incontinence. Losing interest in sex lies somewhere in between: Vaginal dryness could reduce a woman's enthusiasm for intercourse, but loss of libido might be more related to aging. Thus, lumping the ailments together and treating them with the same medication is inappropriate, according to the panel's report (see NIH State-of-the-Science Conference on Management of Menopause-Related Symptoms).

According to the panel, most women don't require drugs at all. "Menopause is something all women go through and does not necessarily require medical treatment," says Mangione. "Few women will have severe and disabling symptoms. ... The majority will have some symptoms, but they will be mild and will subside [without chemical intervention]." Several studies support this assertion, and show that up to one-third of menopausal women who received a placebo instead of medication saw their symptoms disappear. According to the experts, this "placebo effect" is larger than that seen in most medical studies. "We don't really understand why the effect is so large, but it might suggest that there is a big segment of the population that is going to feel better without any [hormone] treatments," says Mangione.

For the minority of women who do suffer from severe hot flashes and night sweats--particularly those who undergo menopause more abruptly and earlier in life because they had their ovaries removed or received chemotherapy--HRT is the most effective treatment, according to the panel. In such cases, women and their doctors will face the difficult decision of balancing potential benefits against the potential risks of hormone regimens.

The WHI trials that were halted three years ago were designed to test whether long-term use of HRT could prevent chronic diseases, such as heart attacks and dementia, in postmenopausal women. No comparable trial to date has assessed the use of hormones to relieve the bothersome manifestations of menopause. The NIH panel calls for such a study. The experts recommend a trial of a form of HRT that they dub "menopausal hormone therapy" to reflect a shift of focus from the "replacement" of lost hormones to the use of hormones to alleviate moderate to severe symptoms for a relatively short period of time. The study should determine the minimum amount of hormone needed, the most appropriate duration, methods for tapering off the medicine, and the long-term effects of the regimen.

Despite agreement about the importance of such a trial, the panel's conclusions were not entirely without controversy. Not everyone at the conference agreed, for example, on which conditions belong on the list of symptoms that are directly tied to hormone depletion. "I would say that the evidence for a link between mood symptoms and menopause is split," says Peter J. Schmidt, chief of reproductive endocrine studies at the National Institute of Mental Health in Bethesda, Maryland. "Ten studies say 'No way' and another ten say 'Yes.' And then there are several studies that can go either way depending on how you interpret the data." In his presentation to the panel, Schmidt indicated that although most menopausal women do not develop depression, a small subgroup might be at risk of the disease during perimenopause--the four to ten years time span before a woman's final menstrual period when hormones start to go haywire.

Some of the discrepancies in interpretation stem from the fact that different women grapple with different manifestations of menopause. Furthermore, most analyses trying to assess women's experiences are fraught with methodological problems. For example, scientists often ask study participants about current symptoms, thereby missing those that occur between interviews. In addition, few experiments attempt to measure severity and frequency of symptoms.

The panel also found that much published work on alternative remedies had serious limitations and called for additional research in this area. Similarly, the report revealed a dearth of studies on racially diverse groups of women with menopause symptoms. One of the only investigations to fit the bill, the Study of Women's Health Across the Nation, has found that significantly more African-American and Hispanic women, with a few Asian-American women, report hot flashes and night sweats in comparison to Caucasian women. Attitudes toward menopause also differ among racial groups. African-American women are more likely to view the absence of menstrual periods and freedom from birth control as a welcome change. And if the panel is correct in suggesting that few menopausal women experience symptoms severe enough to require medical treatment, those who accept menopause as a normal rite of passage might have the right idea.

Laura Bonetta is a freelance science writer in the Washington, D.C., area who had been looking forward to blaming hormones for her difficulties thinking and remembering.