Androgens and Antiandrogens

Androgens and Antiandrogens

Androgens and Antiandrogens

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Testosterone is the principal androgen in males. Secreted by cells in the testes in response to luteinizing hormone released from the pituitary gland, testosterone can directly bind to androgen receptors and is converted in some tissues to dihydrotestosterone, which also binds to androgen receptors. Activation of androgen receptors results in differentiation of the external genitalia, increased hair growth during puberty, and stimulation of the prostate gland.

Testosterone also contributes to the mass and strength of skeletal muscle, which explains the abuse of androgen analogs (steroids) by some athletes. Testosterone is also converted to estrogen, which then binds to estrogen receptors and mediates closure of the epiphyses in the bone. The major condition for which testosterone is used therapeutically is male hypogonadism. Because it is metabolized completely in the liver, testosterone is usually administered transdermally.

A number of drugs have antiandrogenic effects. Some were designed for this purpose, but others were developed for some other therapeutic goal. For example, ketoconazole, an antifungal drug, blocks the synthesis of steroids, including testosterone and cortisol. Spironolactone, a diuretic, is also a weak inhibitor of the androgen receptor and a weak inhibitor of testosterone synthesis. Androgen-receptor antagonists can be used in combination with a gonadotropin-releasing hormone (GnRH) analog in the treatment of metastatic prostate cancer.

In some tissue, testosterone is converted to dihydrotestosterone by an enzyme called 5-alpha-reductase. An inhibitor of this enzyme, finasteride, was designed as a treatment for benign prostatic hypertrophy. When it is administered to men with moderately severe symptoms, urine flow increases and prostatic volume decreases. Impotence is an infrequent side effect of the use of finasteride, which is also approved for the topical treatment of male pattern baldness.

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