Inhibition of coronary artery atherosclerosis by 17-beta estradiol in ovariectomized monkeys. Lack of an effect of added progesterone.

TLDR

Estrogen replacement therapy is generally linked to lower coronary heart disease risk, yet the mechanisms and the effect of adding progesterone remain uncertain. The study examined whether sex hormone replacement influences diet‑induced coronary artery atherosclerosis in ovariectomized adult female cynomolgus monkeys. Monkeys were randomly assigned to no hormone, continuous 17‑beta estradiol plus cyclic progesterone, or continuous estradiol alone, with hormones delivered via sustained‑release subcutaneous implants over 30 months. Both hormone regimens reduced atherosclerosis by about half, independently of lipid changes, showing that physiologic estradiol, with or without progesterone, inhibits plaque progression and may explain estrogen therapy’s cardioprotective effect.

Abstract

Although controversy continues, the preponderance of evidence indicates that estrogen replacement therapy favorably influences the risk of coronary heart disease in postmenopausal women. It remains uncertain how this effect is mediated and whether the cyclic addition of a progestin may influence adversely an estrogen-related cardioprotective effect. We investigated the influence of sex hormone replacement therapy on diet-induced coronary artery atherosclerosis in estrogen-deficient (ovariectomized) adult female cynomolgus monkeys. Monkeys were assigned randomly to one of three treatment groups: 1) no hormone replacement (n = 17), 2) continuously administered 17-beta estradiol plus cyclically administered progesterone (n = 20), and 3) continuously administered 17-beta estradiol (n = 18). The physiologic patterns of plasma estradiol and progesterone concentrations were maintained by administering the hormones in sustained-release subcutaneous Silastic implants. The experiment lasted 30 months. At necropsy, coronary artery atherosclerosis was inhibited similarly (reduced by approximately one-half) in animals in both hormone replacement groups (p less than or equal to 0.05). Antiatherogenic effects of hormone replacement were independent of variation in total plasma cholesterol, lipoprotein cholesterol, apoprotein A-1 and B concentrations, high density lipoprotein subfraction heterogeneity, and low density lipoprotein molecular weight. We conclude that physiologic estrogen replacement therapy with or without added progesterone inhibits atherosclerosis progression in ovariectomized monkeys. This may explain why estrogen replacement therapy results in reduced risk of coronary heart disease in postmenopausal women.