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The gonadal hormones include the steroids of the ovary (estrogens and progestins) and testis (chiefly testosterone). Because of their importance as contraceptives, many synthetic estrogens and progestins have been produced. These include synthesis inhibitors, receptor antagonists, and some drugs with mixed effects (ie, agonist effects in some tissues and antagonist effects in other tissues). Mixed agonists with estrogenic effects are called selective estrogen receptor modulators (SERMs). Synthetic androgens, including those with anabolic activity, are also available for clinical use. A diverse group of drugs with antiandrogenic effects is used in the treatment of prostate cancer and benign prostatic hyperplasia in men and hyper-androgenism in women.
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The ovary is the primary source of gonadal hormones in women during the childbearing years (ie, between puberty and menopause). When properly regulated by follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary, each menstrual cycle consists of the following events: A follicle in the ovary matures, secretes increasing amounts of estrogen, releases an ovum, and is transformed into a progesterone-secreting corpus luteum. If the ovum is not fertilized and implanted, the corpus luteum degenerates; the uterine endometrium, which has proliferated under the stimulation of estrogen and progesterone, is shed as part of the menstrual flow, and the cycle repeats. The mechanism of action of both estrogen and progesterone involves entry into cells, binding to cytosolic receptors, and translocation of the receptor–hormone complex into the nucleus, where it modulates gene expression (see Figure 39–1).
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The major ovarian estrogen in women is estradiol. Estradiol has low oral bioavailability but is available in a micronized form for oral use. It can also be administered via transdermal patch, vaginal cream, or intramuscular injection. Long-acting esters of estradiol that are converted in the body to estradiol (eg, estradiol cypionate) can be administered by intramuscular (IM) injection. Mixtures of conjugated estrogens from biologic sources (eg, Premarin) are used orally for hormone replacement therapy (HRT). Synthetic estrogens with high bioavailability (eg, ethinyl estradiol, mestranol) are used in hormonal contraceptives.
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