Gonadal Hormones Inhibitors 1 PM 7 41 48

Gonadal Hormones & Inhibitors: 1 PM 7: 41: 48 1/19/2022

• Androgens • Testosterone and related androgens are produced in the testis, the adrenal, and, to a small extent, the ovary. • The hormone is converted in several organs (eg, prostate) to dihydrotestosterone (DHT), which is the active hormone in those tissues. • Because of rapid hepatic metabolism, testosterone given orally has little effect. It may be given by injection in the form of long-acting esters or transdermal PMpatch. 2 7: 41: 56 1/19/2022

• Mechanism of Action • Like other steroid hormones, androgens enter cells and bind to cytosolic receptors. The hormone– receptor complex enters the nucleus and modulates the expression of target genes. 3 PM 7: 41: 56 1/19/2022

• Effects • The major effect of androgenic hormones, in addition to development and maintenance of normal male characteristics, is an anabolic action that involves increased muscle size and strength and increased red blood cell production. Excretion of urea nitrogen is reduced, and nitrogen balance becomes more positive. Testosterone also helps maintain normal bone density. 4 PM 7: 42: 01 1/19/2022

• Clinical Use of the androgens 1. for replacement therapy in hypogonadism 2. Androgens used to stimulate red blood cell production in certain anemias 3. to promote weight gain in patients with wasting syndromes (eg, AIDS patients). 4. The anabolic effects (by athletes) to increase muscle bulk and strength and perhaps enhance athletic performance. 5 PM 7: 42: 01 1/19/2022

• Toxicity • Use of androgens by females causes virilization (hirsutism, enlarged clitoris, deepened voice) and menstrual irregularity. In women who are pregnant with a female fetus, exogenous androgens can cause virilization of the fetus's external genitalia. • Paradoxically, excessive doses in men can result in feminization (gynecomastia, testicular shrinkage, infertility) due to feedback inhibition of the pituitary and conversion of the exogenous androgens to estrogens. • In both sexes, high doses can cause cholestatic jaundice, elevation of liver enzyme levels, and 6 PM 7: 42: 04 1/19/2022 possibly hepatocellular carcinoma.

• Antiandrogens • Reduction of androgen effects is an important mode of therapy for 1. Both benign and malignant prostate disease. 2. Precocious puberty. 3. Hair loss 4. Hirsutism. 7 PM 7: 42: 04 1/19/2022

• A-Receptor Inhibitors • Flutamide and related drugs are nonsteroidal competitive antagonists of androgen receptors. These drugs are used to decrease the action of endogenous androgens in patients with prostate carcinoma. • Spironolactone, a drug used principally as a potassium-sparing diuretic, also inhibits androgen receptors and is used in the treatment of hirsutism in women. 8 PM 7: 42: 05 1/19/2022

• B- 5α-Reductase Inhibitors • Testosterone is converted to DHT( act on prostate cells and hair follicles) by the enzyme 5 α –reductase. This enzyme is inhibited by finasteride, a drug used to treat benign prostatic hyperplasia and, at a lower dose, to prevent hair loss in men. Because the drug does not interfere with the action of testosterone, it is less likely than other antiandrogens to cause impotence, infertility, and loss of libido. • Dutasteride is a newer 5 α -reductase inhibitor with a much longer half-life than that of 9 PM 7: 42: 07 1/19/2022 finasteride.

• C- Gonadotropin-Releasing Hormone Analogs and Antagonists • Suppression of gonadotropin secretion, especially LH, reduces the production of testosterone. This can be effectively accomplished by leuprolide. • It’s used in prostatic carcinoma. During the first week of therapy, an androgen receptor antagonist (eg, flutamide) is added to prevent the tumor flare that can result from the surge in testosterone synthesis caused by the initial agonistic action of the Gn. RH agonist. 10 PM 7: 42: 08 1/19/2022

• D- Combined Hormonal Contraceptives • Used in women with androgen-induced hirsutism. • The estrogen in the contraceptive acts in the liver to increase the production of sex hormone-binding globulin, which in turn reduces the concentration of the free androgen in the blood that is causing the male-pattern hair growth characteristic of hirsutism. 11 PM 7: 42: 08 1/19/2022

• E- Inhibitors of Steroid Synthesis • Ketoconazole, (an antifungal drug), inhibits gonadal and adrenal steroid synthesis. The drug has been used to suppress adrenal steroid synthesis in patients with steroid-responsive metastatic prostate cancer. 12 PM 7: 42: 08 1/19/2022