Estrogen-plus-progestin therapy increases the risk of coronary heart disease (CHD) in postmenopausal women. However, this increased risk might be limited to the first years of use and to women who start therapy late in menopause.
To estimate the effect of continuous estrogen-plus-progestin therapy on CHD risk over time and stratified by years since menopause, i.e., to estimate an adherence-adjusted effect.
The Women's Health Initiative randomized, double-blinded, placebo-controlled trial.
40 US clinical centers.
16,608 postmenopausal women with an intact uterus at baseline in 1993-1998
Conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d or placebo.
Adherence-adjusted hazard ratios (HRs) estimated via inverse probability weighting and CHD-free survival curves.
Compared with no use of hormone therapy, the HR (95% confidence interval [CI]) for continuous use of estrogen-plus-progestin was 2.36 (1.55-3.62) for the first 2 years and 1.69 (0.98-2.89) for the first 8 years. For women within 10 years after menopause, the HRs (95% CI) were 1.29 (0.52-3.18) for the first 2 years and 0.64 (0.21-1.99) for the first 8 years, and the CHD-free survival curves for continuous use and no use of estrogen-plus-progestin crossed at about 6 (95% CI: 2-10) years.
The analysis may have not fully adjusted for joint determinants of adherence and CHD risk. Sample sizes for some subgroup analyses were small.
There was no suggestion of a decreased risk of CHD from estrogen-plus-progestin within the first 2 years after randomization, including women who initiated therapy within 10 years after menopause, and a cardioprotective effect became apparent only after 6 years of use.