Male sexual function
Many drugs affect sexual function in the male by interfering with the mechanisms responsible for erection or ejaculation. These drugs may act centrally to inhibit cerebral control or they may exert specific influence on either the blood supply or the innervation of the penis or accessory glands.
Erection – Anatomy of the penis
The erectile tissue of the human penis is composed of three muscle bundles, two corpora cavernosa situated dorsally and the corpus spongiosum, which surrounds the urethra. Within each muscle bundle lie many cavernous spaces separated by trabeculae, which contain smooth muscle. The control of blood flow into and out of these cavernous spaces is responsible for erection and detumescence.
Vascular supply to the penis
The internal pudendal arteries provide the blood supply to the penis. Each internal pudendal artery gives off a bulbar branch and a urethral artery that supply the corpus spongiosum. The internal pudendal artery then divides into the deep and dorsal arteries of the penis. The deep artery runs through each corpus cavernosum, giving off helical arteries that subdivide into end arteries. These end arteries provide blood flow directly into the cavernous spaces. The dorsal artery remains external. There are many anastomotic connections between all the arteries. Venous drainage parallels the arterial blood supply.
Innervation of the penis
The penis is innervated by both the autonomic (parasympathetic and sympathetic) and somatic systems. These supply the smooth muscle of the corpora as well as the blood vessels. The autonomic supply arises from the pelvic plexus, which receives both parasympathetic and sympathetic systems. The sympathetic supply originates between TIO and L2 and the parasympathetic from S2 to S4. The parasympathetic fibres condense into the pelvic nerve. The sensory supply from the penis runs in the pudendal nerve, which also arises in the S2 to S4 region of the spinal cord.
The classical neurotransmitters are catecholamines produced by adrenergic (sympathetic) nerves and acetylcholine produced by cholinergic (parasympathetic) fibres. However, pharmacological experiments have shown that neither system is adequate to explain erectile mechanisms completely. Other neurotransmitters have also been implicated, including vasoactive intestinal peptide (VIP). Current evidence indicates that several neurotransmitters previously postulated as active, including prostaglandins, histamine and amino acids, are probably not involved in the production of erection in humans.
Endocrinology of testicular and sexual function
Gonadotrophin-releasing hormone (GnRH) is produced in pulsatile fashion by the hypothalamus. This stimulates release of FSH and LH from the anterior pituitary. These hormones are synergistically involved in the production of testosterone and in spermatogenesis. The endocrine control of testicular function is complex but relevant, as drugs can interfere at several points along the endocrine pathway. LH stimulates the production of testosterone by the Leydig cells.
Testosterone as well as FSH from the anterior pituitary are the main hormones regulating the seminiferous pithelium. They mediate this regulation by acting on the Sertoli cell. Both FSH and testosterone are involved in the regulation of the formation and secretion of ABP. As already described, the level of ABP in the lumen of the seminiferous epithelium will control the concentration of free testosterone and dihydrotestosterone in the microenvironment around the developing sperm cells. Prolactin metabolism is also indirectly involved in male reproductive function. Some drugs that produce hyperprolactinaemia are associated with sexual dysfunction. Prolactin appears to reduce end-organ response to LH and interferes with the conversion of testosterone to the biologically active form, dihydrotestosterone.
Drug-induced changes in FSH and LH metabolism can, therefore, affect testosterone levels, leading to sexual dysfunction and/or disorders of spermatogenesis. In the clincial setting, low testosterone levels tend to be associated with reduced libido rather than erectile dysfunction.
