The effect of hormone therapy on the progression of cardiovascular disease in women has been a controversial issue. The Heart and Estrogen/progestin Replacement Study (HERS), a randomized trial involving post-menopausal women with known coronary vascular disease, evaluated the effect of hormones on cardiovascular events. According to the HERS, the risk of cardiovascular events increases significantly during the first year of treatment with an oral conjugated estrogen plus progestin preparation. This risk declines as the study progresses, with a decrease in cardiovascular events occurring in the fourth and fifth years of therapy. Whether these results can be applied to all hormone regimens is uncertain. Grodstein and associates used data from a large observational cohort study, the Nurses' Health Study, to reexamine postmenopausal hormone use and secondary prevention of coronary events.

Questionnaire response data were reviewed for 2,489 female study participants who had reported a history of myocardial infarction or had documented coronary atherosclerosis. Information on the type of hormone replacement, if any, was extracted from the data. Secondary coronary events included nonfatal myocardial infarction and fatal coronary disease.

The relative risk of recurrent major coronary disease was 0.56 in women currently using hormone therapy compared with those who were never treated. Short-term users of hormone therapy (less than one year) showed a higher relative risk (1.25) compared with women who were never treated. Longer-term users of hormone therapy had a decreased risk of a secondary coronary event, demonstrating a highly significant trend of decreasing risk with increasing duration of current hormone use. There was no evidence of risk difference among women taking estrogen alone when compared with women taking estrogen plus progestin.

The authors conclude that this prospective, observational study reveals an increased risk of coronary event recurrence with short-term use of hormone treatment, as did the HERS. Both studies also confirm that this risk decreases with continued use, with long-term use imparting significant reduction of coronary event risk. On the basis of these observations, hormone therapy is not indicated for secondary prevention of major coronary events but may benefit patients after several years of continued use.

editor's note: Herrington and associates (Herrington DM, et al. Effects of estrogen replacement on the progression of coronary-artery atherosclerosis. N Engl J Med August 24, 2000;343:522–9) performed a randomized, controlled study to look at the effect of estrogen replacement on progression of atherosclerotic disease that was confirmed with angiography. The intervention group received 0.625 mg of conjugated estrogen plus 2.5 mg of medroxy-progesterone acetate daily. Patients were followed for a mean 3.2 years and had repeat angiography at the end of follow-up to determine atherosclerotic disease progression. Although the hormone therapy reduced low-density lipoprotein levels and increased high-density lipoprotein levels, there was no detectable difference in atherosclerotic disease progression as determined by coronary artery diameters or in the rate of clinical cardiovascular events. The authors concluded that hormone treatment did not affect coronary atherosclerosis progression in patients with documented disease. This study confirmed the results of the HERS and the data review from the Nurses' Health Study. A newer class of hormone-like compounds called selective estrogen receptor modulators seems to affect tissues differently and may be more useful in reducing postmenopausal cardiovascular risk. Studies are in progress.—r.s.