It's About Time: Hormone Therapy and Subclinical Atherosclerosis

Abundant data support the timing hypothesis, which proposes that hormone therapy (HT) slows atherosclerosis progression in recently menopausal women but has neutral or adverse effects in women who are at least a decade past menopause onset. To directly test this hypothesis, investigators for the ELITE trial randomized healthy women (<6 years or ≥10 years past menopause) without cardiovascular disease (CVD) to oral estradiol (1 mg daily) or placebo. Women with a uterus also received vaginal progesterone or placebo gel. Carotid-artery intima-media thickness (CIMT) was assessed at baseline and every 6 months. Coronary artery atherosclerosis was evaluated at study completion using computed tomography (CT). An earlier report (NEJM JW Womens Health Jul 2015 and Menopause 2015; 22:391) showed that baseline CIMT correlated well with CVD risk factors.

Among 643 participants, median age at enrollment and years since menopause were 55.4 and 3.5, respectively (early-postmenopause group), and 63.0 and 14.1 (late-postmenopause group). After a median 5 years of study medications, among the younger women, the estradiol group had less progression of CIMT than the placebo group (P=0.008). In contrast, in the older women, CIMT progression rates were similar in the HT and placebo groups (P=0.29). The strength of this relation between HT and CIMT progression differed significantly in the younger versus older groups (P=0.007). Coronary artery CT parameters did not differ significantly between the placebo and HT groups regardless of age.