Normal Sexual Function

The brain exerts an important modulatory influence over spinal reflex pathways that control penile function (Giuliano and Rampin, 2000). A variety of visual, auditory, olfactory, and imaginative stimuli elicit erectile responses that involve cortical, thalamic, rhinencephalic, and limbic input to the medial preoptic-anterior hypothalamic area, which acts as an integrating center. Other areas of the brain, such as the amygdaloid complex, may inhibit sexual function. 

Erection occurs when adrenergic-induced sinusoid tone is antagonized by sacral parasympathetic stimulation that produces sinusoidal relaxation primarily by synthesis and release of the nonadrenergic-noncholinergic (NANC) neurotransmitter nitric oxide (NO). The contribution of acetylcholine-dependent release of NO from the vascular endothelium is uncertain. In vitro electrical stimulation of isolated corpus cavemosum strips (with or without endothelium) produces sinusoidal relaxation by release of neurotransmitters within nerve terminals that is resistant to adrenergic and cholinergic blockers. Inhibitors of the synthesis of NO or of guanosine monophosphate (GMP), 

FIGURE 60.1 Mechanism of action of sildenafil in corpus cavernosal smooth muscle cells. NANC Non-adrenergic, noncholinergic NO nitric oxide PDE5 Phosphodiesterase Type 5. 

Seminal emission and ejaculation are under control of the sympathetic nervous system. Emission results from a-adrenergic-mediated contraction of the epididymis, vas deferens, seminal vesicles, and prostate, which causes seminal fluid to enter the prostatic urethra. Concomitant closure of the bladder neck prevents retrograde flow of semen into the bladder, and antegrade ejaculation results from contraction of the muscles of the pelvic floor including the bulbocavemosus and ischiocavernosus muscles. 

Orgasm is a psychosensory phenomenon in which the rhythmic contraction of the pelvic muscles is perceived as pleasurable. Orgasm can occur without either erection or ejaculation or in the presence of retrograde ejaculation (Gingell and Lockyer, 1999). 

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FSH and hCG also find application in the treatment of male subfertility or related conditions. Both are administered to males exhibiting hypogonadotrophic hypogonadism to stimulate sperm synthesis and normal sexual function. hCG has found limited application in the treatment of prepubertal cryptorchidism (a condition characterized by failure of the testes to descend fully into the scrotum from the abdomen). The ability of this hormone to stimulate testosterone production also caught the attention of some athletes, and, as a result, the International Olympic Committee has banned its use. 

Levodopa (L-dopa) is a natural intermediate in the biosynthesis of catecholamines in the brain and peripheral adrenergic nerve terminals. In the biologic sequence of events it is converted to dopamine, which in turn serves as a substrate of the neurotransmitter norepinephrine. Levodopa is used successfully in the treatment of Parkinson s syndrome, a disease characterized by dopamine deficiency. When levodopa is administered to an individual with this syndrome, the symptoms of Parkinson s disease are ameliorated, presumably because the drug is converted to dopamine and thereby counteracts the deficiency. Individuals treated with levodopa, especially older men, have been observed to experience a sexual rejuvenation. This effect has led to the belief that levodopa stimulates sexual powers. Consequently, studies with younger men complaining of decreased erectile ability have shown that levodopa increases libido and the incidence of penile erections. Overall, however, these effects are short lived and do not reflect continued satisfactory sexual function and potency. Thus, levodopa is not a true aphrodisiac. The increased sexual activity experienced by parkinsonian patients treated with levodopa may reflect improved well-being and partial recovery of normal sexual functions that were impaired by Parkinson s disease. 

A 49-year-old man with bipolar disorder had erectile dysfunction shortly after starting to take haloperidol 50 mg/day and lithium 1500 mg/day (38). Before this he had had normal sexual function. After 2 months, the dosage of haloperidol was reduced to 20 mg/day, but... 

A 17-year-old man who had been abusing amfetamine and cannabis for 2 years took amfetamine 1 g orally over the course of an evening and suddenly felt an uncomfortable sensation in his groin and thought that his penis was being sucked into his abdomen. Physical examination was normal. The serum prolactin and bilirubin concentrations were raised. He had normal sexual function, and was able to attain and sustain an erection. He described the phenomenon of penile shrinkage as Whizz-Dick and stated that all the amfetamine users with whom he was in contact were... 

When libido is decreased, a patient may not develop erections. The relationship between erectile dysfunction and serum testosterone levels is a complicated one. Patients with normal serum testosterone levels may have erectile dysfunction, and patients with subnormal serum testosterone levels may have normal sexual function. ... 

The goal of treatment is an improvement in the quantity and quality of penile erections suitable for intercourse. Simple as this may sound, health care providers need to ensure that patients have reasonable expectations for any therapies that are initiated. Furthermore, only patients with erectile dysfunction should be treated. Patients who have normal sexual function should not seek—or be encouraged to seek—treatment in an effort to enhance sexual function or enable increased activity. 

A 59-year-old man developed a perineal mass 2 hours after taking a second dose of tamsulosin for lower urinary tract symptoms. The proximal part of the penis shaft was stiff, consistent with partial priapism. Ultrasound examination showed no flow in the cavernosal artery and MR imaging showed edema towards the base of the penis. Surgical exploration allowed blood to be aspirated from the thrombotic segment and a shunt to be inserted in the corpus cavemosum spongiosum. Postoperatively normal sexual function was restored within 3 months. 

Follicle stimulating hormone is responsible for the growth of testes. It promotes spermatogenesis. Along with LH, FSH plays an essential role in maintaining the normal testicular functions such as development of male sex organs e.g. penis, scrotum development of secondary sexual characters e.g. growth of facial. 

Genitourinary smooth muscle is partially dependent on autonomic innervation for normal function. Therefore, ganglionic blockade causes hesitancy in urination and may precipitate urinary retention in men with prostatic hyperplasia. Sexual function is impaired in that both erection and ejaculation may be prevented by moderate doses. 

The corpus luteum arises from the ruptured follicle and secretes progesterone, which has an important role in the estrous or menstrual cycle. Luteal progesterone is also required to maintain early pregnancy in most mammalian species, including humans (Csapo Pulkkinen, 1978). Therefore, establishment and maintenance of normal corpora luteaare essential for normal reproductive function. However, with the exception of evaluations to establish their presence or absence, these structures are not evaluated in routine testing. Increased rates of follicular atresia and oocyte toxicity may lead to premature menopause in humans. Altered follicular development, failure to ovulate or altered corpus luteum formation and function can disrupt cyclicity, reduce fertility and interfere with normal sexual behaviour. Therefore, significant increases in the rate of follicular atresia, evidence of oocyte toxicity, interference with ovulation or altered corpus luteum formation or function should be considered adverse effects. 

Altered sexual function and fertility. Toxicity may be expressed as alterations to the female or male reproductive organs, the related endocrine system or pregnancy outcomes. The manifestations of such toxicity may include, but not be limited to, adverse effects on onset of puberty, gamete production and transport, reproductive cycle normality, sexual behaviour, fertility, gestation, parturition, lactation, pregnancy outcomes, premature reproductive senescence or modifications in other functions that are dependent on the integrity of the reproductive systems. 

Steidle C, Schwartz S, Jacoby K, Sebree T, Smith T, Bachand R. AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J Clin Endocrinol Metab 2003 88 2673-8. 

In the normal daily dose of 1 mg, which is sufficient to treat male pattern hair loss, finasteride is well tolerated over long periods. There is a very slightly higher incidence of impaired sexual function in users compared with placebo (17). In women too, low doses of finasteride (2.5 mg/day) are well tolerated when used to treat hirsutism (18). However, many of the problems seen... 

The effect of adding finasteride 5 mg/day to high-dose bicalutamide 150 mg/ day has been studied in 41 men with advanced prostate cancer treated over a mean of 3.9 years (21). The serum prostate-specific antigen (PSA) concentration was measured every 2 weeks until disease progression. At the first nadir of PSA, the median fall from baseline was 96.5% a second nadir occurred in 30 of 41 patients, with a median fall of 98.5% from baseline. The median times to each nadir were 3.7 and 5.8 weeks respectively. The median time to treatment failure was 21 months. Adverse effects were minor, including gynecomastia. Sex drive was normal in 17 of 29 men at baseline and in 12 of 24 men at the second PSA nadir, but one-third of the men had spontaneous erections at both times. The authors concluded that finasteride provided additional intracellular androgen blockade when added to bicalutamide. The duration of control was comparable to that achieved with castration, with preserved sexual function in some patients. 

A variety of endocrine, vascular, neurological, and psychiatric diseases disrupt normal sexual and reproductive function in men. Furthermore, sexual dysfunction may be the presenting symptom of systemic disease. 

In a comparison of carvedilol with valsartan in 160 patients with hypertension (mean age 46 years) each treatment was continued for 16 weeks, with crossover after 4 weeks of placebo (9). Blood pressure was significantly lowered by both drugs (48% normalization with valsartan and 45% with carvedilol). In the first month of treatment, sexual activity (assessed as the number of episodes of sexual intercourse per month) fell with both treatments compared with baseline, although the change was statistically significant only with carvedilol. After the first month of treatment, sexual activity further worsened with carvedilol, but it improved or recovered fully with valsartan. The results were confirmed by the crossover. This confirms that beta-blockers can cause chronic worsening of sexual function. 

There is some evidence that male sexual dysfunction occurs less often with alpha-blockers than with other types of anti-hjrpertensive drugs (2). For example, in a comparison of the effects of prazosin and hydrochlorothiazide on sexual function in 12 hjrpertensive men, plethysmographic measurements and subjective assessments showed less dysfunction with prazosin than with hydrochlorothiazide (3). There is no evidence that this effect can be used therapeutically, but cases of priapism have been reported for example, a 55-year-old man presented with priapism having taken prazosin 7.5 mg tds for 4 months. After a further 3 months, prazosin was discontinued and erectile function became normal (4). 

Developed in the late 1930s, anabolic steroids were primarily used to treat hypogonadism, a condition in which the testes do not produce sufficient testosterone for normal growth, development, and sexual functioning. These compounds are used medically to treat delayed puberty, some types of impotence, and wasting of the body caused by HIV infection or other diseases. Some of the commonly used/abused anabolic steroids are Anadrol (ox-ymetholone), Oxandrin (oxandrolone), Dianabol (methandrostenolone), Deco-Durabolin (nandrolone decanoate), and Depa-Testosterone (testosterone cypionate). 

Clinical studies have reported very few adverse effects that are of a mild nature (usually gastric distress or headache) following saw palmetto administration at normal doses. One randomized, double-blind study of finasteride, tamsulosin, and saw palmetto for 3 months observed no differences among the three treatments in terms of the effectiveness measures and no change in sexual function in those individuals receiving saw palmetto, though ejaculation disorders were noted as the most common side effect in those individuals receiving either tamsulosin or finasteride (26). 

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