A new study compared hormone replacement therapy (HRT) initiated close to the onset of menopause to HRT begun later. The findings were published on March 31 in The New England Journal of Medicine.
The authors note that studies have suggested that HRT is associated with beneficial effects with regard to cardiovascular disease when it is initiated temporally close to menopause but not when it is initiated later. However, the theory that the cardiovascular effects of postmenopausal hormone therapy vary with the timing of therapy initiation (the hormone-timing theory) has not been tested.
The study comprised healthy postmenopausal women who were divided into two groups based on time since menopause (less than 6 years; early postmenopause or 10 or more years; late postmenopause). The subjects were randomly assigned to receive either oral 17β-estradiol (1 mg per day, plus progesterone 45 mg vaginal gel administered once daily for 10 days of each 30-day cycle) or placebo. The primary outcome measurement was the rate of change in carotid-artery intima–media thickness (CIMT), which was measured every 6 months. Secondary outcome measurements included an assessment of coronary atherosclerosis by cardiac computed tomography (CT), which was performed when the women completed the randomly assigned regimen.
The researchers found that, after an average duration of five years, the effect of estradiol, with or without progesterone, on CIMT progression differed between the early and late postmenopause groups. Among women who were less than 6 years past menopause at the study onset, the average CIMT increased by 0.0078 mm per year in the placebo group versus 0.0044 mm per year in the estradiol group. Among women who were 10 or more years past menopause at the study onset, the rates of CIMT progression in the placebo and estradiol groups were similar (HRT: 0.0088; placebo: 0.0100 mm per year). CT measures of coronary-artery calcium, total stenosis (arterial narrowing), and plaque did not differ significantly between the placebo group and the estradiol group in either group.
The authors concluded that oral estradiol therapy was associated with less progression of subclinical atherosclerosis (measured as CIMT) than was placebo when therapy was initiated within six years after menopause but not when it was initiated 10 or more years after menopause. Estradiol had no significant effect on cardiac CT measures of atherosclerosis in either group.