Combination hormones for menopause don't reduce CHD risk

Estrogen plus progestin therapy does not reduce coronary heart disease risk during the first three to six years of use in women who started therapy close to menopause, researchers said.

Combination hormone replacement therapy increases the risk for coronary heart disease (CHD) in postmenopausal women, but this effect might be limited to the first years of use and to women who start therapy late in menopause. To examine these variables, researchers stratified the risks over time and reported their results in the Feb. 15 Annals of Internal Medicine.

Researchers used data from 16,608 postmenopausal women in the Women's Health Initiative estrogen plus progestin trial. The women had been treated with conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or with placebo. CHD was defined as acute myocardial infarction requiring overnight hospitalization, silent myocardial infarction identified through serial electrocardiography, or death due to CHD.

Among women within 10 years of menopause at randomization, 2,782 were randomized to hormone therapy and 2,712 were randomized to placebo. Thirty-one CHD cases (14 in the first two years) occurred among those in the hormone group compared with 34 cases (12 in the first two years) in the placebo group.

During follow-up, 188 CHD cases (80 in the first two years) occurred in the 8,506 women assigned to hormone therapy compared with 147 cases (51 in the first two years) in the 8,102 women assigned to placebo. Compared with no use of hormone therapy, the hazard ratio for continuous use of estrogen plus progestin therapy was 2.36 (95% CI, 1.55 to 3.62) for the first two years and 1.69 (CI, 0.98 to 2.89) for the first eight years. For women within 10 years after menopause, the hazard ratios were 1.29 (CI, 0.52 to 3.18) for the first two years and 0.64 (CI, 0.21 to 1.99) for the first eight years.

The CHD-free survival curves for continuous use and no use of combination therapy crossed at about six years (CI, two years to 10 years), the point at which researchers described a possible cardioprotective effect in women who began therapy closer to menopause.

Limitations include that the analysis may not have fully adjusted for adherence and CHD risk. Also, sample sizes for some subgroup analyses were below the typical level of statistical significance. Further, the study did not address clinical and public health issues of hormone therapy or risk-benefit considerations, but instead focused on the effect of one common formulation of estrogen plus progestin therapy on CHD.