Androgens side effects

Extracts of corpora lutea were known ia the early tweatieth ceatury to inhibit ovulatioa ia animals. Pure progesterone (3), the active component of the extracts, was isolated ia 1934 and its stmcture reported (15). Several problems limited its use and drove efforts to develop progesterone analogues, ie, it was available only ia small quantities from animal sources, was not orally active, and was discovered to cause androgenic side effects. 

Adverse effects include flushes, weight gain, mood changes, vaginal dryness, decreased libido, breast enlargement and tenderness and in some patients the prolonged time required for the return of normal ovulatory function. Androgen side-effects like acne and hirsutismus can occur with the 19-nortestosterone derivatives. 

The use of the AAS for their anabolic activity or for uses other than androgen replacement has been limited because of their masculinizing actions. This has greatly limited their u.se in women and children. Although anabolic activity is olTen needed clinically, nunc of the products presently available is free of significant androgenic side effects. 

Danazol 600-800 mg orally daily in divided doses Androgenic side effects limit use not preferred in adolescent patients secondary to side-effect profile... 

In AIDS, DHEA supplementation has been shown to increase body weight and CD4 cell count in women but not in men. All patients reported improvement in well being, but no reductions in viral load were detectable. Women with SEE had fewer symptoms or flare-ups of the disease while using DHEA, but problems with androgenic side effects led to a 60% discontinuance rate before a 1-year study could be completed. 

DHEA has some therapeutic value in women with SEE, at least temporarily. Androgenic side effects due to the formation of testosterone, including acne and hirsutism, are predictable when DHEA is used in premenopausal female patients. DHEA may prove to have some value in diabetes mellitus, not diabetes insipidus. It is not known if DHEA has value in postmenopausal osteoporosis. However, postmenopausal women with high levels of DHEA are at greater risk for both cancer and cardiovascular morbidity. The answer is (E). 

Flutamide is an androgen receptor antagonist that achieves peak concentrations approximately 2 to 4 hours after an oral dose. Flutamide is metabolized extensively, with a terminal half-life of about 8 hours. Bicalutamide achieves peak concentrations approximately 6 hours after the dose, with a terminal half-life of 6 to 10 days. Bicalutamide undergoes stereospecihc metabolism, where the S-enantiomer is cleared more rapidly by the liver than the -enantiomer. Nilutamide achieves peak serum concentrations between 1 to 4 hours after an oral dose and has a terminal half-life of 38 to 60 hours. Nilutamide is metabolized extensively, with less than 2% excreted as unchanged drug by the kidney. Side effects common to these agents are hot flashes, gynecomastia, and decreased libido. Flutamide tends to be associated with more diarrhea and requires three-times-daily administration, whereas bicalutamide is dosed once daily. Nilutamide may cause interstitial pneumonia and is associated with the visual disturbance of delayed adaptation to darkness. 

Exemestane is an irreversible aromatase inactivator that binds to the aromatase enzyme to block the production of estrogen from androgens. Exemestane is absorbed rapidly after oral administration, with a terminal half-life of 24 hours. The drug is eliminated primarily by the liver and feces, with less than 1% of the dose excreted unchanged in the urine. Exemestane is indicated for the treatment of advanced breast cancer in postmenopausal women who have had disease progression following tamoxifen therapy. Side effects include hot flashes, fatigue, osteoporosis/bone fractures, and flulike symptoms. 

Letrozole is another selective aromatase that inhibits the conversion of androgens to estrogen. Maximum plasma concentrations occur 1 hour after oral dosing concomitant food has not been shown to have an effect on the extent of absorption of letrazole. The terminal half-life is approximately 2 days. Letrozole is used in the treatment of postmenopausal women with hormone-receptor-positive or unknown advanced breast cancer. Side effects include bone pain, hot flushes, back pain, nausea, arthralgia, osteoporosis/bone fractures, and dyspnea. 

Another therapeutic role for estrogens is in the treatment of cancer. In androgen-dependent prostate carcinoma, estrogens are used therapeutically to suppress androgen formation and thus tumor growth. Estrogens are also used to treat inoperable breast cancer in men and postmenopausal women. However, antiestrogens, such as tamoxifen, have fewer side effects and are usually preferred (see section 5.8.4). 

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