Perhaps the most talked-about topic in women’s health this summer was hormone replacement therapy (HRT), given the news from the Women’s Health Initiative (WHI) study in early July that taking estrogen and progestin does not protect the heart but in fact slightly increases the risk of heart attack. A month earlier, HRT had been a central topic at this year’s reunion.

Those attending the reunion weekend program heard that research at Yale on the usefulness of HRT in preventing heart disease had also led to unexpected results. Although Yale researcher Teresa L. Caulin-Glaser, M.D., found that hormone replacement provided some beneficial effect for postmenopausal women in her study, the benefit was much less dramatic than had been anticipated from her basic laboratory studies. In her talk, Caulin-Glaser illustrated how results that look robust in the laboratory are not always borne out in clinical trials.

Caulin-Glaser’s presentation was part of a symposium titled “The Growth of Women in Medicine: Progress That Benefits Us All.” Also on the program were Sonja V. Batten, Ph.D., newly arrived associate director of Women’s Health Research at Yale (co-sponsor of the panel with the Office for Women in Medicine). Batten provided an overview of the program, and Susan J. Baserga, M.D. ’88, Ph.D. ’88, detailed the history of the admission of women to the School of Medicine in 1916 (See The Last Barrier, Summer 1998).

Like the researchers in the multisite WHI study, Caulin-Glaser had been intrigued by studies showing that HRT for postmenopausal women might help prevent heart disease. Observational data had suggested—but not proven—that if postmenopausal women with heart disease took hormones, they cut their risk of a cardiac event in half. The promise of significant reductions in vascular inflammation was suggested by Caulin-Glaser’s laboratory studies, in which she treated human endothelial cells in culture with estrogen. But hormones did not prove nearly as effective when she tested them on human subjects.

Caulin-Glaser went on to study the effects of exercise, dietary changes and stress reduction techniques on patients in cardiac rehabilitation. Her findings that exercise and stress management do reduce vascular inflammation suggest that the current failure of HRT to reduce heart disease does not leave physicians empty-handed. “If we can demonstrate the effectiveness of life-style interventions in modulating inflammation, we will have very powerful and safe therapies to offer our patients.” She is frustrated that physicians recommend cardiac rehabilitation for only 30 percent of their patients, for twice as many men as women and for very few minority-group members.

She was not surprised by the recent acknowledgment by the Women’s Health Initiative that HRT is no “magic bullet.” “It is important to appreciate that, although the study has finally given us some solid clinical information to use when treating our patients, many questions still remain,” Caulin-Glaser said in August. “From a research and clinical perspective, it addressed only the use of a combination HRT, estrogen and Provera. Issues not addressed by the study include the effects of estrogen alone, estrogen in combination with less-potent progestins, the use of different delivery routes and determining the safe length of therapy.

“Nature’s way of producing the exact combination of sex hormones may be protective, but the way we are replacing them artificially may be incorrect in dose, combination, delivery route and length of treatment,” she added. “There is much to learn, and that is why the field is so exciting.”