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HRT and CHD, Revisited

Hormone replacement therapy’s effects on cardiovascular disease may depend on the timing of initiation.

In 2002, Women’s Health Initiative (WHI) investigators found combination hormone replacement therapy (HRT; estrogen plus progesterone) to be associated with increased risk for coronary heart disease (JW Cardiology Aug 23 2002). Now, researchers have conducted a secondary analysis of the WHI trials, combined, to determine whether HRT’s cardiovascular effects vary according to the timing of HRT initiation. The trials involved 27,347 postmenopausal women ages 50 to 79: 10,739 who had undergone a hysterectomy and had been randomized to receive estrogen or placebo, and 16,608 without hysterectomy who had been randomized to estrogen/progesterone or placebo.

Risks for CHD and for all-cause mortality were decreased, albeit nonsignificantly, in patients taking HRT within 10 years after menopause; these risks rose as time since menopause increased. Risk for stroke, however, was increased across all subgroups, irrespective of time since menopause. In an age-stratified analysis, incidence of index events (including CHD, stroke, pulmonary embolism, and death from any cause) increased with age but was not affected by HRT use.

Comment: These findings support the notion that HRT should not be used to reduce cardiovascular disease risk, particularly in older women. The data do, however, add to the growing body of evidence that HRT-associated CHD risk is time-dependent, increasing with distance from menopause. This fact should be reassuring to younger women using HRT for symptomatic relief. Still, in this analysis, HRT — irrespective of time of initiation — was associated with a significantly increased risk for stroke. Ongoing studies such as KEEPS will address HRT’s effects on cardiovascular disease in recently menopausal women.

— JoAnne M. Foody, MD

Published in Journal Watch Cardiology April 18, 2007

Citation(s):

Rossouw JE et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007 Apr 4; 297:1465-77.

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