Hormone Therapy Risks Linger On

Researchers with the Women's Health Initiative (WHI) are adding yet another chapter to the continuing (and confusing) story of hormone therapy (HT) taken during and after menopause. In the latest report, appearing in the Journal of the American Medical Association (JAMA), the study doctors report that the health risks of taking the combined hormones estrogen and progestin can linger for up to three years after women stop taking them.

Most of the 16,600 women participating in the WHI at centers across the country stopped taking their supplemental hormone therapy after 2002, when the study found that the treatment increased a woman's risk of breast cancer, and did not protect women from heart disease, as doctors had previously thought. But the WHI continued to follow these subjects for heart disease, various cancers, stroke, fractures and other causes of death. They found, to their surprise, that the women who had taken HT for three to eight years had a 12% greater risk of overall death than women who had been assigned a placebo pill.

Most of that increased risk was due to the greater danger of breast and other cancers among these women. "We had all hoped to see the breast cancer risk diminish rapidly [after hormone therapy was stopped]," says Dr. Gerardo Heiss, the lead author of the JAMA study and an epidemiologist at the University of North Carolina's School of Public Health. "But that was not the case with women in the WHI."

The good news is that many of the other health risks associated with hormone therapy —heart disease and blood clotting, for example — did diminish rapidly once the hormones were stopped. Less welcome is the fact that any benefits derived from estrogen and progestin in keeping bones strong also dissipated soon after the women terminated their hormone therapy.

While the fact that HT's risks may last longer than any woman would like, doctors stress that this risk is still very small. The overall risk of cancer, for instance, among women taking estrogen and progestin, comes to three extra cases per 1000 women per year. For breast cancer, the study found one extra case per 1000 women per year. "It's helpful to translate the findings into absolute cases," notes Dr. JoAnn Manson, chief of preventive medicine at Harvard's Brigham and Women's Hospital. "So for women who are having distressing menopausal symptoms, who are not sleeping, they are going to get quality of life benefits and it's important for them to understand what the absolute risks are."

Manson also notes that at the time the study was being conducted, between 1993 and 1998, the estrogen and progestin preparations were not available in the lower doses that are used today, and that most women had been taking the hormones for longer than the one to two years that current guidelines recommend. (Researchers are planning to study the long-term risk-benefit profile of lower dose formulations and shorter exposure periods.)

In the meantime, what does this study say about the safety of hormone therapy? The results are in line with previous findings, which exposed the breast cancer risk associated with the hormones and the lack of heart benefit from the therapy. What this study does is define how long those risks can last. "The results should not be cause for alarm or panic among women," says Manson. "The findings do underscore the point that HT should not be used for chronic disease prevention, but remains a viable option for short-term treatment of menopausal symptoms. When used for the short-term treatment of distressing symptoms, it's likely that the benefits outweigh the risks." As confusing as they seem, taken together, every analysis from the WHI actually does paint a clearer picture of how estrogen and progestin can affect a woman's body during and after menopause, and doctors are learning more about the safest way to provide women with the advantages of these hormones in relieving menopausal symptoms. It's just that the story has many chapters yet to come.