Pharmacology of estrogens and estrogen-induced effects on nonreproductive organs and systems

Abstract

The classification of estrogens based on chemical structure and origin is presented. The metabolism of endogenous estrogens and the postulated mechanism of action of steroid hormones are reviewed. Specific effects of estrogen on bone, kidney and coagulation are also discussed.

PIP: This article reviews the effects of estrogens on protein production by the liver, lipid metabolism, bone maturation and structure, and mineral metabolism. Also presented is a comparison of natural steroidal estrogens (estradiol, estrone, conjugated estrogens, and equine estrogens), synthetic steroidal estrogens (esters and 17-alpha-ethinyl estradiol), and nonsteroidal estrogens (diethylstilbestrol, dienestrol, and chlorotrianisene). Delivery of estrogens by different routes produces different effects. However, the metabolic changes that occur from enzyme induction within hepatic tissue are probably related to the type and dosage of estrogen rather than to the route of administration. Preparations containing estrogens that occur naturally in humans have the least exaggerated potency in the hepatic system relative to their estrogenicity, while conjugated estrogens that contain a mixture of equine estrogens are 2-3 times more potent in the hepatic system and ethinyl estradiol and diethylstilbestrol demonstrate a hepatic potency that is 4-18 fold greater than their estrogen potency. Estrogen is believed to induce a hypercoagulation state associated with both oral contraceptive (OC) use and pregnancy, but the clinical significance of increased levels of clotting factors remains undetermined. Estrogen appears to inhibit bone resorption in postmenopausal women and improve calcium balance. Although estrogen receptors are present in the kidney, their physiologic significance remains unknown. Estrogen does cause an increase in levels of plasma renin substrate, plasma renin activity, and angiotensin. Estrogen-induced increases in angiotensin, leading to renal sodium retention, appear to be the mechanism underlying the association of OCs with hypertension.