Medical brain notes 47

  CLINICAL USES   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.   Hypogonadism   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 hypothalamic–pituitary axis, as in  secondary hypogonadism.   Prepuberal Hypogonadism   Prepuberal hypogonadism is often unsuspected until a delay in male sexual development is noticed at the time  of pub...

  ADVERSE EFFECTS   As a class, the androgens are relatively safe and non-toxic. However, in inappropriate doses or for inappro-priate reasons, their use can result in significant toxicity.   Toxicity in Men   The administration of androgens to sexually mature hy-pogonadal men is associated with few untoward effects. However, prepuberal or hypogonadal males never ex-posed to testosterone show enhanced sensitivity to ad-ministered androgens, and many do not like the effects. Testosterone administration can cause irritability, agita-tion, or aggressive behavior. Androgen administration to normal males inhibits the release of the pituitary go-nadotropins FSH, LH, and as a consequence, endoge-nous testicular production of testosterone is reduced. Spermatogenesis is also reduced, and if administration is continued, azoospermia and infertility may result. Peripheral aromatization of androgens to estrogens can cause gynecomastia. Cessation of exogenous androgen treatment in...

  ANTIANDROGENS   By definition, antiandrogens are substances that pre-vent or depress the action of male hormones in their target organs. Potential sites of action include go-nadotropin suppression, inhibition of androgen synthe-sis, and androgen receptor blockade. Compounds that affect each of these sites are available. Potential clinical uses of antiandrogens include suppression of androgen excess and treatment of androgen-dependent tumors. Extreme clinical examples of androgen excess include central precocious puberty, the adrenogenital syn-dromes, and androgen-secreting adrenal, ovarian, or testicular tumors. Less severe problems include idio-pathic hirsutism, premenstrual syndrome, and severe cystic acne.     Inhibitors of Androgen Biosynthesis   Ketoconazole ( Nizoral ) is a broad-spectrum antifungal agent  that in very high doses inhibits several steps in the biosynthesis of both adrenal and gonadal steroids. While the normal antifungal dose is 200 ...

  Drugs Used in the Treatment  of Erectile Dysfunction The term impotence has been used to indicate the inability of the male to attain and maintain erection of the penis sufficient to permit satisfactory sexual inter-course. Erectile dysfunction (ED) is the preferred term. ED is a common problem, especially among older men. Perhaps a more precise term for ED is that used to sig-nify inability of the man to achieve an erect penis as part of the multifaceted process of male sexual func-tion. Overall, the process encompasses a variety of physical aspects with significant psychological and be-havioral components.   In the United States approximately 10 million men have ED. While erectile function may not be the most important indicator of sexual satisfaction, ED may con-tribute to mental stress that affects interactions with family and associates. While many advances have oc-curred in the diagnosis and treatment of ED, other aspects remain poorly understood by the general po...

  PHYSIOLOGY OF PENILE ERECTION   The physiology of penile erection involves an interplay of anatomical, hemodynamic, neurophysiological, and sex hormone interaction. Penile erection is the result of a complex interaction between the central nervous sys-tem and other local factors. This physical event also can be influenced by psychological factors.   The penis is mainly supplied by the internal puden-dal artery, and three major sets of veins, superficial, in-termediate, and deep veins, drain it. Drug-induced changes in neurotransmitter action can affect local blood flow. Vascular supply, intrinsic smooth muscles of the penis, and adjacent striated muscles are controlled by nerves arising from the thoracolumbar sympathetic, the lumbosacral parasympathetic, and the lumbosacral somatic systems. The pudendal nerve is the major so-matic pathway innervating the male genitalia.   In addition to the integrated participation of the pe-ripheral nerves, central neural pathways...

  INDIVIDUAL AGENTS   The pharmacological agents useful in this disorder may be grouped under five broad categories of treatment (Table 64.2). Such a classification system takes into ac-count the mode of drug action, the route of administra-tion, and the means by which target organ selectivity is achieved.   Oral medication for treatment of ED is relatively new. Earlier measures often employed the intracaver nosal injection of a vasoactive agent or a systemic mode of drug administration.   Local injections or dermal ap-plications were frequently required for satisfactory pharmacological actions upon the vascular smooth mus-cles of the penis. Compounds with relatively short dura-tion of action were found to be less than satisfactory in maintaining penile erections.   Combinations of drugs have sometimes been used to take advantage of the differing onset and duration of action of the individual compounds. A rapid onset of ac-tion and a sufficient duration are impo...