Sexual Dysfunction¶
Chapter 409 | Harrison's 22e · Part 12 – Endocrinology & Metabolism
Detailed clinical reference synthesised from Harrison's Principles of Internal Medicine, 22nd Edition
🔑 Key Clinical Points¶
- See source text for full details
📑 Table of Contents¶
📋 Figures in This Chapter¶
| # | Type | Description |
|---|---|---|
| 1 | 🔀 Flowchart | Algorithm for the evaluation and management of patients with erectile dysfunction |
| 1 | 🖼 Figure | Pathways that control erection and detumescence |
RAW CONTENT¶
[PAGE 3155] 3155 CHAPTER 409 Sexual Dysfunction inhibitors are ineffective, as these drugs facilitate, but do not initiate, 409 Sexual Dysfunction the initial enzyme cascade. In addition to nitric oxide, vasoactive pros- taglandins (PGE, PGF ) are synthesized within the cavernosal tissue 1 2α Kevin T. McVary and increase cyclic AMP levels, also leading to relaxation of cavernosal smooth-muscle cells. Ejaculation is stimulated by the sympathetic nervous system; this results in contraction of the epididymis, vas deferens, seminal vesicles, Male sexual dysfunction affects up to 31% of middle-aged and and prostate, causing seminal fluid to enter the urethra. Seminal fluid elderly men, whereas female sexual dysfunction, although studied less emission is followed by rhythmic contractions of the bulbocavernosus intensely, has a higher prevalence (43%) than male sexual dysfunction. and ischiocavernosus muscles, leading to ejaculation. This is followed Demographic changes, the popularity of newer treatments, and greater by expulsion, characterized by stereotypic rhythmic contractions of the awareness of sexual dysfunction by patients and society have led to striated perineal muscles, leading to forceful expulsion of semen with increased diagnosis and associated health care expenditures for the the bladder neck closed. This emission and expulsion are controlled management of this common disorder. Sexual health and satisfaction by the autonomic (parasympathetic and sympathetic) and somatic with sex life are important aspects of quality of life for many, includ- spinal centers, respectively. The synchronization between autonomic ing those in poor health. Because many patients are reluctant to initi- and somatic spinal centers is orchestrated by interneurons that form a ate discussion of their sex lives, physicians should address this topic spinal ejaculation generator that is present in mammals including man. directly to elicit a history of sexual dysfunction. Specifically addressing Premature ejaculation usually is related to anxiety or a learned sexual health should be a routine part of the clinical encounter, particu- behavior and is amenable to behavioral therapy or treatment with med- larly in those with cardiovascular risk factors. ications such as selective serotonin reuptake inhibitors (SSRIs). Retro- MALE SEXUAL DYSFUNCTION grade ejaculation (RE) results when the internal urethral sphincter does not close; it may occur in men with diabetes or after surgery involving ■ PHYSIOLOGY OF MALE SEXUAL RESPONSE the bladder neck. Anejaculation, the failure of a portion or the whole of An erection is a neurovascular event, and the cardiovascular system the emission process often confused with RE, is commonly the result needs to be intact for sexual stimulation to successfully result in an of selective alpha blockers used in male voiding dysfunction (e.g., tam- erection. Normal male sexual function includes (1) sufficient libido, (2) sulosin, silodosin). the ability to achieve and maintain penile erection, (3) ejaculation, and Detumescence is mediated by norepinephrine from the sympathetic (4) detumescence. Libido refers to sexual desire and is influenced by a nerves, endothelin from the vascular surface, and smooth-muscle con- variety of visual, olfactory, tactile, auditory, imaginative, and hormonal traction induced by postsynaptic α-adrenergic receptors and activation stimuli. Sex steroids, particularly testosterone, act to increase libido. of Rho kinase. These events increase venous outflow and restore the Libido can be diminished by emotional context, systemic illness, hor- flaccid state. Venous leak can cause premature detumescence and is monal disturbances, psychiatric disorders, and medications. caused by insufficient relaxation of the corporal smooth muscle rather Penile tumescence leading to erection depends on an increased flow than a specific anatomic defect. Priapism refers to a persistent and of blood into the lacunar network accompanied by complete relaxation painful erection and may be associated with sickle cell anemia, hyper- of the arteries and corporal smooth muscle. The microarchitecture of coagulable states, spinal cord injury, or injection of vasodilator agents the corpora is composed of a mass of smooth muscle (trabecula) that into the penis. contains a network of endothelial-lined vessels (lacunar spaces). Subse- quent compression of the trabecular smooth muscle against the fibro- ■ ERECTILE DYSFUNCTION elastic tunica albuginea causes a passive closure of the emissary veins and accumulation of blood in the corpora. In the presence of a full Epidemiology Erectile dysfunction (ED) is not considered a erection and a competent valve mechanism, the corpora become non- normal part of the aging process. Nonetheless, it is associated with compressible cylinders from which blood does not escape. This cas- certain physiologic and psychological changes related to age. In the cade of relaxation and venous occlusion culminates in a rigid erection. Massachusetts Male Aging Study (MMAS), a community-based survey The central nervous system (CNS) exerts an important influence of men aged 40–70, 52% of responders reported some degree of ED. by either stimulating or antagonizing spinal pathways that mediate Complete ED occurred in 10% of respondents, moderate ED in 25%, erectile function and ejaculation. The erectile response is mediated and minimal ED in 17%. The incidence of moderate or severe ED more by a combination of central (psychogenic) innervation and peripheral than doubled between the ages of 40 and 70. In the National Health (reflexogenic) innervation. Sensory nerves that originate from recep- and Social Life Survey (NHSLS), which included a sample of men and tors in the penile skin and glans converge to form the dorsal nerve of women aged 18–59, 10% of men also reported being unable to main- the penis, which travels to the S2-S4 dorsal root ganglia via the puden- tain an erection. Incidence was highest among men in the age group dal nerve. Parasympathetic nerve fibers to the penis arise from neurons 50–59 (21%) and men who were poor (14%), divorced (14%), and less in the intermediolateral columns of the S2-S4 sacral spinal segments. educated (13%). Sympathetic innervation originates from the T-11 to the L-2 spinal seg- The incidence of ED is also higher among men with certain medical ments and descends through the hypogastric plexus. disorders, such as diabetes mellitus, obesity, lower urinary tract symp- Neural input to smooth-muscle tone is crucial to the initiation toms secondary to benign prostatic hyperplasia (LUTS/BPH), heart and maintenance of an erection. There is also an intricate interaction disease, hypertension, decreased high-density lipoprotein (HDL) lev- between the corporal smooth-muscle cell and its overlying endothelial els, and diseases associated with general systemic inflammation (e.g., cell lining (Fig. 409-1). Nitric oxide, which induces vascular relaxation, rheumatoid arthritis). Cardiovascular disease and ED share etiologies promotes erection and is opposed by endothelin 1 (ET-1) and Rho as well as pathophysiology (e.g., endothelial dysfunction), and the kinase, which mediate vascular contraction. Nitric oxide is synthesized degree of ED appears to correlate with the severity of cardiovascular from L-arginine by nitric oxide synthase (NOS) and is released from disease. Consequently, ED represents a “sentinel symptom” in patients the nonadrenergic, noncholinergic (NANC) autonomic nerve supply with occult cardiovascular and peripheral vascular disease. to act postjunctionally on smooth-muscle cells. Nitric oxide increases Smoking is also a significant risk factor in the development of ED. the production of cyclic 3′,5′-guanosine monophosphate (cyclic GMP), Medications used in treating diabetes or cardiovascular disease are which induces relaxation of smooth muscle (Fig. 409-2). Cyclic GMP additional risk factors (see belo
Flowcharts & Algorithms¶
Reproduced from Harrison's 22nd Edition.
Flowchart 1¶
Caption: FIGURE 409-3 Algorithm for the evaluation and management of patients with erectile dysfunction. PDE, phosphodiesterase.
Figures & Illustrations¶
Reproduced from Harrison's 22nd Edition.
Figure 1¶
Caption: FIGURE 409-1 Pathways that control erection and detumescence. Outflow from the two ways, both of which increase the concentration of nitric oxide (NO) in fibers; second, stimulation of endothelial nitric oxide synthase (eNOS) through then diffuses into the smooth-muscle cells and decreases its intracellular calcium (cGMP), leading to relaxation. A separate mechanism that decreases the intracellular increased cavernosal blood flow, as well as increased levels of vascular endothelial phosphatidylinositol 3 (PI3) kinase pathway. Active treatments (red boxes) include drugs guanylyl cyclase agonists), the cAMP pathway (alprostadil), or both pathways Agents that are being developed include guanylyl cyclase agonists (to bypass the smooth-muscle cells mediated through endothelin). α1, α-adrenergic receptor; GPCR, G NOS, nitric oxide synthase; PGE, prostaglandin E; PGF, prostaglandin F. (Reproduced with 357:2472, 2007.)
Generated from Harrison's Principles of Internal Medicine, 22nd Edition.