Coronary heart disease in postmenopausal recipients of estrogen plus progestin therapy: does the increased risk ever disappear? A randomized trial.
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.


METHODS
Women's Health Initiative randomized, double-blinded, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00000611)


METHODS
40 U.S. clinical centers.


METHODS
16 608 postmenopausal women with an intact uterus at baseline from 1993 to 1998.


METHODS
Conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo.


METHODS
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).


CONCLUSIONS
The analysis may not have fully adjusted for joint determinants of adherence and CHD risk. Sample sizes for some subgroup analyses were small.


CONCLUSIONS
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.


BACKGROUND
National Heart, Lung, and Blood Institute.
Department of Population Medicine, Harvard Medical School/Harvard Pilgrim Health Care Institute, 133 Brookline Avenue, 6th Floor, Boston, MA 02215, USA. darrentoh@post.harvard.edu
Sengwee
S
Toh
Sonia
S
Hernández-Díaz
Roger
R
Logan
Jacques E
JE
Rossouw
Miguel A
MA
Hernán
D000368:Aged; D003327:Coronary Disease / Q000453:epidemiology* / Q000517:prevention & control; D018572:Disease-Free Survival; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects*; D005260:Female; D006801:Humans; D055118:Medication Adherence; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects*; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects*; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors
D004966:Estrogens, Conjugated (USP); D017258:Medroxyprogesterone Acetate