The Biochemistry of Oral Contraceptive Steroids

Abstract

As a prelude to an explanation of the mode of action of modern oral contraceptives a review of the structure biologic activity receptor binding pharmacokinetics and biologic effects of estrogens and progestogens in oral contraceptives is presented. Biologic activity of sex steroids is defined by results of bioassays and the efficacy potency and toxicity may vary between different species and when combined with other agents. Steroids act by binding to specific target cell receptors that also possess specific binding sites for specific regions of the cell DNA. Bioavailability of the steroids is largely determined by plasma concentrations. The chemical structure of the steroids influences both receptor binding and bioavailability profoundly. Estrogens include natural steroids certain nonsteroid plant isoflavones totally unrelated synthetic estrogens and synthetic steroid esters. Progestins used pharmacologically may be structurally related to testosterone (norgestrel norethindrone) or progesterone (megestrol acetate). In combined oral contraceptives the estrogen works by inhibiting tonic gonadotropin secretion (FSH) in the beginning of the cycle so that no dominant follicle matures. Without a follicle to secrete estradiol no LH surge occurs to stimulate release of an oocyte. Progestins also act to inhibit LH. Pills counter other processes to decrease the chance of pregnancy such as maturation of the endometrium. The synthetic anti-progestin RU-486 also inhibits development of follicles in women when endogenous progesterone levels are low an example of agonist-antagonist activity.