BACKGROUND
Estrogen plus progestin therapy increases the risk for 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.
OBJECTIVE
To estimate the effect of continuous estrogen plus progestin therapy on CHD risk over time and stratified by years since menopause.
DESIGN
Women's Health Initiative randomized, double-blinded, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00000611)
SETTING
40 U.S. clinical centers.
PATIENTS
16 608 postmenopausal women with an intact uterus at baseline from 1993 to 1998.
INTERVENTION
Conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo.
MEASUREMENTS
Adherence-adjusted hazard ratios and CHD-free survival curves estimated through inverse probability weighting.
RESULTS
Compared with no use of hormone therapy, the hazard ratio for continuous use of estrogen plus progestin therapy was 2.36 (95% CI, 1.55 to 3.62) for the first 2 years and 1.69 (CI, 0.98 to 2.89) for the first 8 years. For women within 10 years after menopause, the hazard ratios were 1.29 (CI, 0.52 to 3.18) for the first 2 years and 0.64 (CI, 0.21 to 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 years (CI, 2 years to 10 years).
LIMITATION
The analysis may not have fully adjusted for joint determinants of adherence and CHD risk. Sample sizes for some subgroup analyses were small.
CONCLUSION
No suggestion of a decreased risk for CHD was found within the first 2 years of estrogen plus progestin use, including in women who initiated therapy within 10 years after menopause. A possible cardioprotective effect in these women who initiated therapy closer to menopause became apparent only after 6 years of use.
PRIMARY FUNDING SOURCE
National Heart, Lung, and Blood Institute.