Progestin Use in Postmenopausal Women

ABSTRACT & COMMENTARY

Synopsis: Postmenopausal women with intact uteri do not need to worry that the progestins will nullify the beneficial effects of estrogen replacement.

Source: Grodstein F, et al. N Engl J Med 1996;335:453-461.

Postmenopausal estrogen use is known to have beneficial effects on plasma lipid levels, but in women with intact uteri, progestin is necessary to reduce the risk of endometrial cancer from unopposed estrogen therapy. Since progestins alone tend to raise LDL and lower HDL cholesterol, there has been concern that combination hormone replacement therapy in postmenopausal women will not have the same favorable lipid effects as estrogen alone. This attenuation of estrogens effect was observed in the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial (JAMA 1995; 273:199-208).

Thus, Grodstein and coworkers examined this issue in 59,337 women in the Nurses’ Health Study who were followed for 16 years for cardiovascular disease. They observed a marked decrease in major coronary events (death, infarction, revascularization) among women on combined hormone replacement as compared to women not on hormones (relative risk [RR], 0.4) and women on estrogen alone (RR, 0.6). However, stroke risk was not reduced in the combined group (RR, 1.09) nor in the estrogen group (RR, 1.27) compared to the non-hormone users. They conclude that progestin use does not seem to attenuate the beneficial coronary heart disease effects of estrogen replacement therapy in postmenopausal women.

COMMENT BY MICHAEL H. CRAWFORD, MD

Because this is an uncontrolled observational study and hormone use is self-reported, the issue of whether hormone users are somehow different from non-users in ways that would affect cardiovascular disease risk is of concern. If they are, then the risk attenuation by hormone therapy may be inaccurate, but the relative effect of combined therapy vs. estrogen alone should be valid. Thus, postmenopausal women with intact uteri do not need to worry that the progestins will nullify the beneficial effects of estrogen replacement. (Dr. Crawford is Robert S. Flinn Professor and Chief, Division of Cardiology, University of New Mexico, Albuquerque.)