Hormone replacement therapy should start early

Don’t categorically reject hormone replacement therapy (HRT) just yet: When women begin HRT before age 60, their risk of death is 39 percent less than women not on hormones, according to a new survey.

The findings are based on a Cornell University-Stanford University meta-analysis (a study of other previously published studies), which pooled the results of 30 clinical trials of HRT with almost 27,000 women.

“The results of our analysis indicate that the benefits of HRT outweigh the risks in women who have recently entered menopause,” says Edwin E. Salpeter, who did the statistical analyses for the study. Salpeter is a professor of physics emeritus at Cornell and the 1997 Crafoord Prize laureate who has turned his interest to medical issues in recent years.

The first author of the study, which is published in the July issue of the Journal of General Internal Medicine (Vol. 19:7, 2004), is his daughter, Shelley R. Salpeter, M.D., a clinical professor of medicine at Stanford University School of Medicine and a physician at Santa Clara Valley Medical Center in San Jose, Calif.

The new findings appear contrary to two large, well-publicized studies, the Heart and Estrogen/Progestin Replacement Study and the Women’s Health Initiative, which found no difference in mortality rates for those taking HRT or a placebo. Women taking HRT, these two studies found, had increases in breast cancer, stroke, heart attacks and pulmonary embolism and decreases in colon cancer, hip fractures and diabetes mellitus. The conclusion from these trials was that the risks of HRT outweighed the benefits in these patients. However, these findings were based on samples of women whose mean age was 65 years at the start of the trial.

However, an earlier survey, the Nurses’ Health Study, says Shelley Salpeter, “was a large prospective study that found that women who started treatment within two years of menopause had a total mortality risk of 0.63 that of nonusers. Our findings are consistent with this result and suggest that HRT may help prevent and perhaps even halt the progression of cardiovascular disease when started in women in early postmenopause.”

She notes, however, that the accumulated evidence suggests that once heart disease has already developed, HRT has no effect in reversing the process. In fact, heart attacks could even be increased in this older age group due to an increased risk for blood clots.

“The beneficial effects of HRT in younger postmenopausal women appear to be due to HRT’s ability to increase high-density lipoproteins (“good” fats) and reduce low-density lipoproteins (“bad” fats), glucose, weight, insulin levels, the incidence of new-onset diabetes and a handful of other risk factors for heart diseases,” says Shelley Salpeter.

The Salpeters point out that the meta-analysis found no change in breast cancer deaths or total cancer deaths in women of all ages on HRT compared with those not on it, and it also showed a significant decrease in the risk of deaths from causes other than cancer or cardiovascular events, perhaps due to HRT’s other benefits. These other benefits include a 35 percent reduction in hip fracture and new-onset diabetes mellitus and a 60 percent reduction in recurrent urinary tract infections (which can lead to fatal sepsis). The authors conclude that each woman should make the decision regarding hormone replacement on an individual basis, taking into consideration her age, the degree of bothersome postmenopausal symptoms and her underlying health-risk factors.

The other co-authors of the study are Judith M.E. Walsh, M.D., of the University of California-San Francisco; and Elizabeth Greyber, M.D., and Thomas M. Ormiston, M.D., both of the Santa Clara Valley Medical Center. The study was funded, in part, by the Santa Clara Valley Medical Center and the University of California-San Francisco.