In recently postmenopausal women, HRT reduced a composite of death, MI, or heart failure at 10 years

Randomized controlled trial (RCT) (Danish Osteoporosis Prevention Study [DOPS]). ClinicalTrials.gov NCT00252408.

Unclear allocation concealment.*

Blinded* (outcome assessors).

10 years of therapy and 16 years follow-up (registry data). Trial was stopped early after a mean 10 years of therapy due to safety concerns based on other studies.

Denmark.

1006 healthy, white, recently postmenopausal women 45 to 58 years of age (mean age 50 y, mean time since menopause 0.6 y), with last menstrual bleeding 3 to 24 months before study entry, or perimenopausal symptoms (including irregular menstruation) and postmenopausal serum follicle-stimulating hormone (FSH) > 2 SDs greater than the premenopausal mean. Women 45 to 52 years of age who had had a hysterectomy were included if they had increased serum FSH. Exclusion criteria included history of bone disease, cancer, or thromboembolic disease; glucocorticoid therapy for > 6 months; HRT in the past 3 months; or alcohol or drug dependency.

HRT (n = 502) or no HRT (n = 504). Women with an intact uterus received synthetic 17-β-estradiol, 2 mg, for 12 days; 17-β-estradiol, 2 mg, plus norethisterone acetate, 1 mg, for 10 days; and 17-β-estradiol, 1 mg, for 6 days; women who had had a hysterectomy received 17-β-estradiol, 2 mg/d.

Primary outcome was a composite of death, myocardial infarction (MI), or heart failure (HF). Secondary outcomes included death, MI, HF, stroke, venous thromboembolism (VTE), and cancer.

100% (intention-to-treat analysis).