Estrogen Plus Progestin And The Risk Of Coronary Heart Disease

Two recent studies were reported in the same issue of the New England Journal of Medicine (8/7/03) looking at the relationship between hormone therapy (HT) and cardiovascular disease in menopausal women.  The first study provided the final results of the National Institutes of Health (NIH) Women's Health Initiative (WHI) trial comparing estrogen plus progestin versus placebo in healthy postmenopausal women. This study concluded that there was no protective effect of combined HT against coronary heart disease over a five-year period.  In fact, the study suggested that there was a greater possibility of an adverse effect, especially during the first year of combination therapy. As a result of these data, combination HT cannot be recommended for the purpose of preventing coronary heart disease in menopausal women.  These data should have no impact, however, on the decision to treat disruptive menopausal symptoms with combination HT in otherwise healthy women for 5 years or less.  It is also important to note that this study did not report the results of the group taking estrogen therapy alone, without concomitant progesterone. 

The WHI is the largest study ever conducted in women.  It included a randomized primary-prevention trial of estrogen plus progestin in 16,608 postmenopausal women who were 50 to 79 years old at the beginning of the study.  Study participants were randomly assigned to receive a placebo or the formulation in the drug Prempro™:  conjugated equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg per day).

After an average follow-up of 5.2 years, the study data and safety monitoring board recommended stopping the combination HT trial early because the overall risks exceeded the benefits to the women in the trial. Contrary to predictions of a risk reduction benefit for coronary heart disease, the combined HT group actually experienced an elevated risk, especially in the first year of therapy.  Although higher base-line levels of low-density lipoprotein cholesterol were associated with an excess risk of CHD among women who received HT, higher baseline levels of C-reactive protein, other biomarkers, and other clinical characteristics did not significantly modify the treatment-related risk of CHD.

Tomorrow we will discuss the results of the second related study.

Created: 9/8/2003  -  Donnica Moore, M.D.