Estrogens, progestins, and coronary heart disease in cynomolgus monkeys

Abstract

Objective: To determine the effects of estrogen deprivation and estrogen replacement on coronary artery atherosclerosis.

Design: Randomized trials using female cynomolgus monkeys as subjects.

Setting: Comparative Medicine Clinical Research Center of an academic medical center.

Patients: Premenopausal and postmenopausal female cynomolgus monkeys fed diets comparable in fat and cholesterol to those consumed by human beings.

Interventions: Menopause was induced by ovariectomy; coronary vasomotion was evaluated during coronary angiography. Treatments involved estrogens and progestins, and coronary artery atherosclerosis was evaluated at necropsy.

Main outcome measure: Coronary artery atherosclerosis extent.

Results: Premenopausal stress induces ovarian dysfunction and exacerbates coronary artery atherosclerosis. Physiologic replacement of ovarian hormones reduces in half the extent of coronary atherosclerosis of surgically menopausal monkeys. Hormone replacement therapy did not enhance regression of established coronary atherosclerosis.

Conclusion: Estrogen deprivation exacerbates and estrogen diminishes coronary artery atherosclerosis of female cynomolgus monkeys fed atherogenic diets.