Endocrine Abstracts

The Women’s Health Initiative (WHI) placebo-controlled trial of conjugated equine estrogens (CEE) plus medroxyprogesterone (MPA) in 16 608 postmenopausal women, aged 50–79 at randomization, was stopped after an average of 5.6 years of follow-up, due to increased risks, including increased coronary heart disease (CHD), stroke, and pulmonary embolism (PE), compared to health benefits. The WHI trial of CEE only in 10 739 women with prior hysterectomy, also aged 50–79, was also stopped early, after an average of 7.1 years of follow-up, because of excess stroke and no cardiovascular benefit. There was, however, a suggestion of a cardioprotective effect of CEE in women who had been aged 50–59 years at the time of randomization, which had not been seen with CEE+MPA. This prompted a cross-sectional study of coronary artery calcification (CAC) in 1064 CEE trial participants aged 50–59, 1.3 years after stopping study pills, which showed a significantly lower mean CAC score among women who had received CEE for a mean of 7.4 years, compared to placebo. Analyses designed to explore whether the effects of hormone therapy (HT) on risk of cardiovascular disease varied by age or years since menopause, which combined all the data from the two WHI trials, revealed a (non-significant) trend of decreased CHD risk in women who had initiated HT closer to menopause compared to the increase in CHD risk among women more distant from menopause. In contrast, the risk of stroke was elevated regardless of years since menopause. The concept that beneficial cardiovascular effects of HT occur when the therapy is initiated before atherosclerosis develops, referred to as the ‘timing hypothesis’, has been a subject of debate in recent years and will be discussed. Worth noting, follow-up of CEE+MPA trial participants over an average 2.4 year period after women stopped study pills revealed no difference in overall risk of cardiovascular events or CHD by initial treatment.