Porth's Essentials of Pathophysiology, 4e

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Disorders of the Male Genitourinary System

C h a p t e r 3 9

level, location, and extent of the lesion. Somatosensory innervation of the genitalia is essential to the reflex mechanisms involved in erection; this becomes impor- tant with aging and conditions such as diabetes that impair peripheral nerve function. Extensive pelvis sur- gery, especially radical prostatectomy (even so-called “nerve-sparing” procedures), are common causes of erectile dysfunction (ED) due to both direct and indirect nerve damage. Hormonal causes of ED include a decrease in andro- gen levels because of both primary and secondary hypo- gonadism. Androgen levels may be decreased because of aging (andropause). Hyperprolactinemia from any cause interferes with both reproduction and erectile function. This is because prolactin acts centrally to inhibit the release of the hypothalamic GnRH that controls the release of the pituitary gonadotropic hormones, LH and FSH. Elevated prolactin levels may also interfere with normal functioning at the level of the gonad. Common risk factors for generalized penile arte- rial insufficiency include hypertension, hyperlipidemia, cigarette smoking, diabetes mellitus, and pelvic irra- diation. 8 In hypertension, erectile function is impaired not so much by the increased blood pressure as by the associated stenotic arterial lesions. Focal stenosis of the common penile artery most often occurs in men who sustained blunt pelvic or perineal trauma (e.g., from bicycling accidents). Failure of the veins to close com- pletely during an erection (veno-occlusive dysfunction) may occur in men with large venous channels that drain the corpora cavernosa. Other disorders that impair venous occlusion are degenerative changes involving the tunica albuginea, as in Peyronie disease. Many drugs are reported to cause ED, including anti- depressant, antipsychotic, antiandrogen, and antihyper- tensive medications. 5,6,8 Cigarette smoking can induce vasoconstriction and penile venous leakage because of its effects on cavernous smooth muscle and can dou- ble the risk of erectile dysfunction. 8 Alcohol in small amounts may increase libido and improve erection; however, in large amounts it can cause central sedation, decreased libido, and transient ED. Aging is known to increase the risk of ED. 9 After 50 years of age, the overall prevalence of ED is reported to be greater than 50%. 10 Many of the pathologic pro- cesses that contribute to ED are more common in older men, including diabetes, hyperlipidemia, vascular dis- ease, and the long-term effects of cigarette smoking. Age-related declines in testosterone may also play a role (andropause). Psychosocial problems such as depres- sion, esteem issues, partner relationships, history of substance abuse, and anxiety and fear of performance failure also may contribute to ED in older men. 10 A diagnosis of ED requires careful history (medical, sexual, and psychosocial), physical examination, and laboratory tests aimed at determining what other tests are needed to rule out organic causes of the disorder. Because many medications, including prescribed, over- the-counter, and illicit drugs, can cause ED, a careful drug history is indicated. Erectile dysfunction is now recognized as a marker for cardiovascular disease, and is now considered a

component of the metabolic syndrome (a collection of cardiovascular risk factors; see Chapter 33). 5,6,11,12 The presence of ED can be an early warning sign of under- lying vascular disease (coronary, cerebrovascular, and peripheral) which can be asymptomatic especially in patients with type 2 diabetes. It has been proposed that men with smaller penile arteries (diameter 1–2 mm) suf- fer obstruction from artherosclerotic plaque burden ear- lier than those with larger coronary (3–4 mm), carotid (5–7 mm), or ileofemoral (6–8 mm) arteries, hence ED may be symptomatic before a coronary event. In addi- tion, the association between ED and the metabolic syndrome may be related to the underlying endothelial dysfunction seen in both conditions (see Chapter 18). Men with ED should be evaluated for coexisting vas- cular disease and cardiovascular risk factors should be modified or treated (e.g., smoking, diabetes, hyperten- sion, and hyperlipidemia). 5,6,11 Treatment methods include psychosexual counsel- ing, androgen replacement therapy (when androgen deficiency is confirmed), oral and intracavernous drug therapy, vacuum constriction devices, and surgical treat- ment (prosthesis and vascular surgery). 5,6,8 Among the commonly prescribed drugs used for the treatment of ED are the selective inhibitors of phosphodiesterase type 5 (PDE-5), the enzyme that inactivates cGMP (sildenafil, vardenafil, and tadalafil). These drugs act by facilitating corporeal smooth muscle relaxation in response to sex- ual stimulation. The concomitant use of PDE-5 inhibi- tors and nitrates (used, for example, in ischemic heart disease) is absolutely contraindicated because of the risk of profound hypotension. 11 The PDE-5 inhibitors are taken orally. Alprostadil, a prostaglandin E 1 ana- log, acts by producing relaxation of cavernous smooth muscle. It is either injected directly into the cavernosa (with diffusion into the opposite cavernosa) or placed in the urethra as a minisuppository. Phentolamine ( α 2 - adrenergic receptor antagonist) and papaverine (smooth muscle relaxant) are also administered by intracavern- ous injection. ■■ The male genitourinary system, which consists of the genital ducts, accessory genital organs, and penis, functions in both urine elimination and reproduction.The testes or male gonads function in both production of male germ cells (spermatogenesis) and the secretion of the male sex hormone, testosterone. ■■ Testosterone is essential for differentiation of the internal and external genitalia in the male embryo, descent of the testes in the fetus, development of primary and secondary male sex characteristics during puberty, and maintenance of these characteristics during adult life. SUMMARY CONCEPTS

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