![if !IE]> <![endif]>
The primary therapeutic use of androgens is as replace-ment therapy in testicular deficiency (Table 63.2), a condition in which induction and maintenance of male secondary sex characteristics are desired. Although replacement therapy is the primary use of androgen ad-ministration, these hormones also are used and abused for their protein anabolic effects.
Testicular failure may occur before puberty and present as delayed puberty and the eunuchoid phenotype, or af-ter puberty, with the development of infertility, impo-tence, or decreased libido in otherwise fully virilized males. The source of hypogonadism can be testicular, as occurs in primary hypogonadism, or it may result from abnormalities of the hypothalamicâ€“pituitary axis, as in secondary hypogonadism.
Prepuberal hypogonadism is often unsuspected until a delay in male sexual development is noticed at the time of puberty.
The eunuchoid phenotype is caused by absent or deficient androgenic induction of the undif-ferentiated embryonic bipotential tissue into fully de-veloped male sex accessory organs. Causes of this con-dition include deficient testicular steroidogenesis (both congenital and acquired), target organ androgen insen-sitivity syndromes (receptor defects, 5 -reductase defi-ciency), deficient pituitary LH and FSH secretion, or deficient hypothalamic GnRH production. Androgen replacement therapy is effective only when the end or-gans are sensitive to androgens, so certain forms of pseudohermaphroditism are unresponsive to androgen replacement.
The compounds most effective in bringing about masculinization are the long-acting enanthate, cypionate, or propionate esters of testosterone; these preparations require intramuscular injection. Recently effective cuta-neous forms of androgens have become available and may be equally effective. Owing to inconsistent drug ab-sorption, oral androgen preparations do not result in full sexual development in prepuberal hypogonado-tropic males.
Postpuberal hypogonadism is also classified as either primary hypogonadism or secondary hypogonadism. Primary hypogonadism occurs after puberty as the re-sult of surgical castration or testicular destruction (e.g., through orchitis, radiation) and is associated with ele-vated levels of LH and FSH. Secondary hypogonadism is usually associated with hypopituitarism from destruc-tion or infiltration of the hypothalamus or pituitary by infarction, tumoral replacement, or surgical removal.
Thus, these individuals have inappropriately low LH and FSH levels that do not respond to GnRH stimula-tion. Androgen replacement in these individuals usually restores secondary male sexual characteristics, such as libido and potency.
Aging in men is associated with decreased testicular function that results in reduced testicular steroidogene-sis, decreased free plasma testosterone levels, decreased 17-ketosteroid excretion, and increased gonadotropin levels. Decreased testicular function has been impli-cated as a cause of reduced libido, muscle mass, muscle strength, and bone density in elderly men. However, these observations are so variable that a causal rela-tionship between lowered androgen levels has not been firmly established. Androgen replacement in elderly men has not been demonstrated to be beneficial unless there is true androgen deficiency. In addition, it is wise to avoid the indiscriminate use of androgens in this age group because of the high incidence of prostate neoplasms (benign and malignant). Androgen administration in re-placement doses has proved to be moderately success-ful in increasing libido and sexual performance in men who have true testicular failure.
Androgens stimulate erythrocytosis and are effective in the treatment of certain anemias that are secondary to endocrine hypofunction or myeloid hypoplasia. In high dosages, these compounds in the past were used in the treatment of several forms of anemia. However recom-binant erythropoietin has replaced the androgens as a more effective treatment of most forms of anemia.
Because of the antagonistic action of androgens in many estrogen-sensitive tissues, it would seem logical that androgens might be effective therapeutic agents in clinical situations of estrogen excess or in the presence of estrogen-dependent neoplasms. However, the viriliz-ing side effects of these compounds have limited their clinical use. Selective protein anabolic forms of andro-gens have been used in certain clinical situations.
Endometriosis is abnormal growth of endometrial tissue in the peritoneal cavity. Women with this disorder have dysmenorrhea, dyspareunia, chronic pelvic pain, and in-fertility. Danazol (Danocrine) is a 2,3-isoxazol deriva-tive of 17 -ethynyl testosterone (ethisterone) that has weak virilizing and protein anabolic properties. It is ef-fective in endometriosis through its negative feedback inhibition of LH and FSH release, which in turn results in decreased ovarian steroidogenesis and regression of endometriomas. Because of the virilizing side effects of danazol, causing acne and hirsutism, its use in en-dometriosis has been largely supplanted by the use of GnRH analogues. Danazol is also approved for use in fi-brocystic breast disease and hereditary angioneurotic edema.
Female hypogonadism, especially prepuberal, may be an indication for androgen therapy. Androgens are nec-essary for normal pubic hair induction and long bone growth in both sexes. In prepuberal females with hy-popituitarism in whom all other hormonal deficiencies (estrogen, progesterone, thyroid, adrenal, and growth hormone) have been corrected, normal sexual develop-ment and long bone growth are not complete without androgen hormone replacement. Estrogen administra-tion during adolescence is necessary for the develop-ment of the breast, the gynecoid pelvis, and other fe-male characteristics. However, maximal long bone growth and development of axillary and pubic hair will not occur without small amounts of androgen replace-ment. The use of methyltestosterone (Android) and di-ethylstilbestrol in combination has been demonstrated to be very effective in inducing complete secondary sex-ual development in these females. Finally, low doses of androgens have been used to facilitate impaired libido in postmenopausal women when combined with estro-gen replacement therapy.
Anabolic activities of testosterone, such as increases in amino acid incorporation into protein and in RNA polymerase activity, have been demonstrated in skeletal muscle. Apart from the direct anabolic effects in specific tissue, androgens antagonize the protein catabolic ac-tion of glucocorticoids. The androgen compounds with the greatest ratio of protein anabolic effects to virilizing effects are the 19-nortestosterone derivatives. Compounds that are used clinically (Table 63.3) include nandrolone phenpropionate (Durabolin), nandrolone decanoate (Deca-Durabolin), methandrostenolone (Dianabol), oxymetholone (Anadrol, Adroyd), stanozolol (Winstrol), and oxandrolone (Anavar).
The protein anabolic compounds are most com-monly used to stimulate appetite and muscle mass in persons with advanced malignancy or other conditions characterized by advanced malnutrition. These com-pounds are also often abused by athletes who are trying to build muscle mass. Athletes often take multiple com-pounds at the same time (stacking) or sequentially to try to maximize their anabolic effects. This type of use is not based on scientific data but rather on hyperbole of-ten spread by individuals with no medical or scientific background. Athletes who use these compounds in this way are unaware of the potential adverse effects or do not care.
Copyright Â© 2018-2023 BrainKart.com; All Rights Reserved. Developed by Therithal info, Chennai.