The SWAN (Study of Women's Health Across the Nation) and KEEPS (Kronos Early Estrogen Prevention Study) trials both investigated menopausal hormone therapy. The KEEPS trial specifically evaluated oral versus transdermal estradiol in women within 3 years of menopause onset. The primary finding regarding cardiovascular risk markers was:
- A Both routes of estradiol increased carotid intima-media thickness (CIMT) versus placebo
- B Neither oral nor transdermal estradiol significantly changed CIMT or coronary artery calcium over 4 years, suggesting a neutral cardiovascular effect within the 'window of opportunity' ✓
- C Oral estradiol significantly increased CIMT while transdermal had no effect
- D Transdermal estradiol reduced coronary artery calcium scores compared to placebo
Explanation
The KEEPS trial (2012) randomized recently menopausal women (< 3 years post-FMP, ages 42–58) to oral conjugated equine estrogen 0.45 mg/day or transdermal estradiol 50 mcg/day vs placebo with cyclic progesterone. The primary endpoints — carotid intima-media thickness (CIMT) and coronary artery calcium (CAC) — showed no significant difference between treatment groups and placebo. This supported the 'timing hypothesis' (critical window) that early initiation of HRT is neither harmful nor beneficial for subclinical atherosclerosis. The ELITE trial (early vs late, 2016) later confirmed that timing of initiation (early vs late post-menopause) affects the cardiovascular effect of HRT.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
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Written and medically reviewed by the StethoPrep medical team.