Postmenopausal Hormone Therapy and Risk of Cardiovascular Disease by Age and Years Since Menopause

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Abstract
In observational studies of women with and without existing coronary heart disease (CHD), the use of postmenopausal hormone therapy is associated with a reduced risk of CHD events.1 In contrast, clinical trials have shown no benefit and some trials have suggested an increased risk of CHD during the first year after randomization.2,3 The Women's Health Initiative (WHI) reported a hazard ratio (HR) for CHD of 0.95 (95% confidence interval [CI], 0.70-1.16) in the trial of conjugated equine estrogens (CEE) and an HR of 1.24 (95% CI, 1.00-1.54) in the trial of CEE plus medroxyprogesterone acetate (CEE + MPA).3,4 While observational studies have evidently overestimated benefit due to confounding, selection biases, and other limitations,5,6 an additional source of discrepancy may be the timing of initiation of hormone therapy in relation to the underlying state of the vasculature. Some investigators have hypothesized that estrogen may delay the onset of the earliest stages of atherosclerosis, which are more likely to be present in younger women, but it may be ineffective or even trigger events in the presence of existing advanced lesions such as those found in older women.7 The potential existence of a window of opportunity to reduce cardiovascular disease is supported by animal and laboratory studies.6