Detailed definition
The Kronos Early Estrogen Prevention Study (KEEPS) randomized 727 healthy postmenopausal women aged 42–58 within 3 years of menopause to one of three arms: 0.45 mg/day oral CEE, 50 mcg/day transdermal estradiol, or placebo, all with cyclic micronized progesterone. The primary outcome was carotid intima-media thickness progression and coronary artery calcium accrual over 4 years. Neither HRT arm showed significant atherosclerosis progression difference vs. placebo, but secondary outcomes were generally favorable: improvements in vasomotor symptoms, mood, sexual function, hot flashes, sleep, lipid profiles, and bone density. KEEPS-Cog, the cognitive substudy, found no significant differences in cognition between groups but suggested favorable mood effects with transdermal estradiol. KEEPS supports the timing hypothesis: in younger postmenopausal women starting HRT within the window, benefits accrue without the cardiovascular harms seen in older WHI subgroups.
Why it matters in menopause
KEEPS is one of the key randomized trials that grounds the modern reinterpretation of HRT safety in younger women. Together with ELITE and the WHI age-stratified re-analyses, it forms the evidence base for the timing hypothesis.
Related terms
Sources
External references: Wikipedia.