The Control of Male Sexual Responses

Abstract

Male sexual responses are reflexes mediated by the spinal cord and modulated by neural circuitries involving both the peripheral and central nervous system. While the brain interact with the reflexes to allow perception of sexual sensations and to exert excitatory or inhibitory influences, penile reflexes can occur despite complete transections of the spinal cord, as demonstrated by the reviewed animal studies on spinalization and human studies on spinal cord injury. Neurophysiological and neuropharmacological substrates of the male sexual responses will be discussed in this review, starting with the spinal mediation of erection and its underlying mechanism with nitric oxide (NO), followed by the description of the ejaculation process, its neural mediation and its coordination by the spinal generator of ejaculation (SGE), followed by the occurrence of climax as a multisegmental sympathetic reflex discharge. Brain modulation of these reflexes will be discussed through neurophysiological evidence involving structures such as the medial preoptic area of hypothalamus (MPOA), the paraventricular nucleus (PVN), the periaqueductal gray (PAG), and the nucleus para-gigantocellularis (nPGI), and through neuropharmacological evidence involving neurotransmitters such as serotonin (5-HT), dopamine and oxytocin. The pharmacological developments based on these mechanisms to treat male sexual dysfunctions will complete this review, including phosphodiesterase (PDE-5) inhibitors and intracavernous injections (ICI) for the treatment of erectile dysfunctions (ED), selective serotonin reuptake inhibitor (SSRI) for the treatment of premature ejaculation, and cholinesterase inhibitors as well as alpha adrenergic drugs for the treatment of anejaculation and retrograde ejaculation. Evidence from spinal cord injured studies will be highlighted upon each step.

Neural Control and Physiology of Sexual Function: Effect of Spinal Cord Injury

“…NO, the primary neurotransmitter responsible for penile erection and clitoral engorgement, is released at nerve endings during sexual arousal and sexual stimulation (neuronal NO or nNO) and is also made in the endothelium itself (endothelial NO or eNO). 3 With the release of nNO at the nerve endings of the genital nerve fibers during sexual arousal, smooth muscle relaxation is initiated. The health of the endothelium will determine the contribution of eNO to the erectile process.…”

“…9 Through fMRI studies, some authors have concluded that the vagus nerve can convey sensory information from cervical stimulation in women with complete SCI, 10 but this has been relatively unexplored. 3 Reflexogenic genital arousal is produced by tactile stimulation to the genitals resulting in afferent stimuli to the spinal cord (afferent input), with some signals following an ascending tract (sensory perception) and others activating the autonomic nuclei S2-S4 resulting in cavernosal nerve activation, smooth muscle relaxation, and tumescence (efferent output). 7 In complete spinal cord lesions above the T10, impulses fail to reach the psychogenic arousal center of T11-L2 and cannot ascend the spinal cord to add to sensory perception.…”

Premature ejaculation associated with lumbosacral lesions

“…Lost climactic sensation during ejaculation might also be explained by the fact that these men with lumbosacral lesions cannot experience even mild autonomic hyperreflexia which has been associated with climactic responses in men with SCI. 12,13,18 Yet, the premature nature of ejaculation following lower SCI remains a mystery.…”

“…These patients also suffer from severe erectile dysfunction, which is seldom treated successfully with phosphodiesterase inhibitors (sidelnafil, tadalafil, vardenafil), and which usually requires intracavernous injections (papaverine, prostaglandins or trimix) or a combination of treatments. Their PEs may be treated with antidepressive drugs such as selective serotonin reuptake inhibitors (for example, sertraline, fluoxetine, paroxetine), 13 which are known for their side effects on ejaculation, but follow ups would be required to explore the patients' satisfaction with these treatments (for example, the treatments may not help for the already poor sensations felt during ejaculation). Upon satisfaction with selective serotonine reuptake inhibitors (SSRIs), the new Dapoxetine treatment (a short acting SSRI) would be promising, although the drug is not universally available (in particular in North America where it has not received Food and Drug Administation approval).…”

“…3,6 This phenomenon is in marked contrast with the reflex expulsive ejaculations that are observed in men with higher spinal lesions (for example, cervical or thoracic lesions). [10][11][12][13][14] This study was designed to analyze the retrospective data from patients with lower lumbosacral lesions who have consulted our sexual dysfunction clinic in rehabilitation over the past 20 years. The goal was to explore to what extent these PEs are systematic in men with lower lumbosacral lesions (that is, L5 and below), and if so which specific type of lumbosacral lesions (that is, conus terminalis, epiconus, cauda equina) appear to be associated with this phenomenon.…”