Implications of recent clinical trials of postmenopausal hormone therapy for management of cardiovascular disease

Estrogen therapy, originally used for the treatment of menopausal vasomotor symptoms, had by 1990 become a mainstay for the prevention of coronary heart disease (CHD) in postmenopausal women. The recommendations for use of estrogen in CHD were based on epidemiologic, animal, and laboratory data. However, a series of clinical trials published from 1998 onward have failed uniformly to confirm a CHD benefit. When the disappointing results of the secondary prevention trials were announced, there was widespread anticipation of more promising results from the primary prevention trials of the Women's Health Initiative (WHI). The WHI trials in generally healthy women also did not provide evidence of benefit, and the use of HT for disease prevention is now discouraged. In response, some commentators have incorrectly stated that the WHI was not a true primary prevention trial. A more appropriate way to frame the question is whether the effects of HT on cardiovascular disease (CVD) differ by age or years since menopause. Some preliminary data suggest that more recently menopausal women starting HT could be at lower risk of CHD (but not stroke) than women more distant from the menopause. However, even if ongoing studies provide evidence that HT can slow the initiation of early atherosclerosis in younger women, this is unlikely to translate into a reconsideration of the use of HT for the prevention of disease, because the long-term effects on cardiovascular events are unknown and unknowable, HT has other adverse effects, and there are more effective and safer ways of preventing cardiovascular disease.