The “hormone-timing hypothesis” suggests that estrogen-containing postmenopausal treatment is beneficial for newly menopausal women but not for older women. A new study seems to confirm that, at least with regard to vascular effects. In an NIH-sponsored study in California, 643 healthy, postmenopausal women were stratified according to time since menopause (< 6 years [early postmenopause] or ≥ 10 years [late postmenopause]) and were randomized to estradiol 1 mg or placebo. Women with a uterus also received progesterone vaginal gel or placebo gel, respectively. The primary outcome was carotid artery intima-media thickness (CIMT) measured every 6 months. Coronary atherosclerosis was also assessed by cardiac CT at the end of the study. After a median of 5 years, estradiol with or without progesterone resulted in a slower progression of CIMT in younger women who were within 6 years of menopause, but not in older women who were ≥ 10 years past menopause (P = 0.007 for the interaction). There was no difference in CT measures of coronary-artery calcium, total stenosis, or plaque between any of the groups. The authors concluded that oral estradiol therapy was associated with less progression of subclinical atherosclerosis (measured by CIMT) than placebo when therapy was initiated within 6 years of menopause but not after 10 years (NEJM 2016;374:1221-1231). This is more evidence that supports the timing hypothesis (or the critical window-of-opportunity hypothesis) for hormone therapy to slow atherosclerosis progression.