Hormone replacement therapy and atherosclerosis in postmenopausal women: does aging limit therapeutic benefits?

Despite the clear-cut epidemiological evidence of protective effects of endogenous estrogens in premenopausal women,1,2 the results of randomized clinical trials using conjugated equine estrogens and medroxyprogesterone acetate instead of natural hormones have led to a paradigm shift in the usefulness of hormone treatment in postmenopausal women.3,4 One of the main criticisms in addition to the types of drugs chosen for treatment was the age of the patients. Indeed, in both WHI trial and HERS study, treatment of patients was initiated in women many years beyond menopause.5 In fact, the number of years since menopause was an independent indicator for nonfatal myocardial infarction or coronary related death.5 In this context, it appears of interest that heart disease may contribute to menopausal age and that menopausal age actually may be an indicator of cardiovascular risk.6,7