Male Sexual Dysfunction

Male sexual dysfunction is any disorder that interferes with the male sexual response cycle and includes desire disorders, erectile disorders, and ejaculatory disorders. Sexual dysfunction has a varied etiology and may be due to psychological causes, endocrine diseases, neurogenic dysfunction, chronic medical illness, or medication/substance abuse. These disorders often cause significant distress to the patient and sexual partner. Treatment options include psychotherapy Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. Psychotherapy, physical therapy, and pharmacotherapy based on the causes of dysfunction.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Table of Contents

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Overview

Definition

Male sexual dysfunction is a group of disorders that interfere with any stage of the male’s sexual response cycle and result in disruption of normal sexual function.

Table: Stages of the sexual response cycle
Stage Changes in females Changes in males Changes in both
Desire
  • Motivation or interest in sexual activity
  • Expressed by sexual fantasies
Excitement/arousal
  • Begins with either fantasy or physical contact
  • Vaginal lubrication
  • Clitoral erection
  • Labial swelling
  • Elevation of the uterus in the pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 "hip" bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis (tenting)
  • Begins with either fantasy or physical contact
  • Erections and testicular enlargement
  • Flushing
  • Nipple erection
  • Hemodynamic changes (increased respiration, pulse, and BP)
Orgasm Vaginal and uterine contractions
  • Tightening of the scrotal sac
  • Secretion of a few drops of seminal fluid
  • Ejaculation
  • Facial grimacing
  • Release of tension
  • Slight clouding of consciousness
  • Involuntary anal sphincter contractions
  • Acute increase in BP and pulse
Resolution Women experience little or no refractory period. Men have a refractory period lasting minutes to hours during which they cannot reexperience orgasm.
  • Muscles relax.
  • Cardiovascular state returns to baseline.
  • Sexual organs return to normal baseline.

Epidemiology

  • Decrease in libido: 
    • Affects 5%–15% of men
    • Incidence increases with age.
  • Erectile dysfunction Erectile Dysfunction Erectile dysfunction (ED) is defined as the inability to achieve or maintain a penile erection, resulting in difficulty to perform penetrative sexual intercourse. Local penile factors and systemic diseases, including diabetes, cardiac disease, and neurological disorders, can cause ED. Erectile Dysfunction
    • Affects 18% of men ages 50–59 years
    • Incidence increases with age.
  • Premature ejaculation: 
    • Most common ejaculatory disorder
    • Estimated prevalence 20%–30%

Normal male sexual function

Normal male sexual function is the result of interaction between multiple systems:

  • Vascular
  • Nervous
  • Hormonal
  • Psychological

Vascular

  • Nitric oxide (NO): 
    • Formed by NO synthase via cyclic guanosine monophosphate (cGMP)–mediated reaction
    • Acts as local neurotransmitter in intracavernosal space to facilitate relaxation of intracavernosal trabeculae
    • Blood flow is maximized, leading to penile engorgement.
  • Decreased intracavernosal NO synthase levels found in: 
    • Cigarette smokers
    • Diabetic patients
    • Testosterone-deficient patients
  • Phosphodiesterase 5 (PDE5) inhibitors (e.g., Viagra) act via a cGMP-dependent mechanism to increase intracavernosal NO.
Penile vascular anatomy

Penile vascular anatomy

Image: “Anatomy, descriptive and applied” by Henry Gray. License: Public Domain

Nervous

Autonomic innervation of male sexual response:

  • Erection:
    • Regulated by parasympathetic system
    • Nerves involved: pelvic splanchnic nerves (S2–S4)
  • Emission:
    • Regulated by sympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System
    • Nerve involved: hypogastric nerve (T11–L2)
  • Expulsion:
    • Regulated by visceral and somatic nerves
    • Nerve involved: pudendal nerve

Neural pathways for different types of erections:

  • Psychogenic erections:
    • Stimuli: visual or auditory sexual stimuli
    • Stimuli reach brain → released to spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord neural center located at T11–L2 (thoracolumbar erection center)
    • Impulses flow to pelvic vascular bed → blood is redirected into corpora cavernosa/corpus spongiosum 
    • Venous outflow from corpora cavernosa/corpus spongiosum through emissary veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins prevented by mass effect of expanded intracavernosal space → maintains erection
    • Common in younger males
  • Reflex erections:
    • Stimuli: tactile stimulus to penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis or genital area
    • Stimuli activate reflex arc (sacral roots S2–S4, known as sacral erection center).
    • Common at more mature ages
  • Nonsexual nocturnal erections:
    • Occur during REM sleep Sleep Sleep is a reversible phase of diminished responsiveness, motor activity, and metabolism. This process is a complex and dynamic phenomenon, occurring in 4-5 cycles a night, and generally divided into non-rapid eye movement (NREM) sleep and REM sleep stages. Physiology of Sleep (absent in depressed men)
    • Present throughout life

Hormonal

  • Adolescent nocturnal erections: 
    • Gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) → Leydig cell testosterone secretion
  • Testosterone: 
    • Important for libido and NO synthesis
    • Deficiency causes impotence.
    • Sexual potency returns when normalized.
    • Augments psychogenic channels to increase libido
    • Important in maintaining intracavernosal NO synthase levels
  • Hormonal assessment in men with low libido:
    • Testosterone
    • Prolactin
    • Thyroid-stimulating hormone (TSH)
    • Estradiol

Desire Disorder

Features

  • Absence or deficiency of sexual thoughts, desires, or fantasies
  • Duration: ≥ 6 months
  • The disorder causes clinically significant psychological distress.

Risk factors

  • Medications:
    • Selective serotonin reuptake inhibitors Serotonin Reuptake Inhibitors Antidepressants encompass several drug classes and are used to treat individuals with depression, anxiety, and psychiatric conditions, as well as those with chronic pain and symptoms of menopause. Antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and many other drugs in a class of their own. Serotonin Reuptake Inhibitors and Similar Antidepressant Medications (SSRIs)
    • Antiandrogens Antiandrogens Antiandrogenic drugs decrease the effect of androgens. Classes include androgen receptor blockers, 5-alpha-reductase inhibitors, and androgen synthesis inhibitors. Both men and women may use antiandrogens, which treat advanced prostate cancer, benign prostatic hyperplasia (BPH), alopecia, and hirsutism. Androgens and Antiandrogens
    • 5α-reductase inhibitors
    • Opioid analgesics Opioid analgesics Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics
  • Chronic alcoholism
  • Depression
  • Fatigue
  • Recreational drugs
  • Sexual aversion disorder
  • Systemic illness
  • Testosterone deficiency

Management

  • Risk factor modification
  • Treatment options include:
    • Psychotherapy
    • Testosterone replacement

Erectile Disorder

Features

  • Difficulty obtaining or maintaining erection or decrease in erectile rigidity 
  • Duration: ≥ 6 months
  • The disorder causes clinically significant psychological distress.
  • Also known as erectile dysfunction (ED) or impotence

Risk factors

Table: Risk factors for erectile disorder
Medications
  • Antidepressants (SSRIs)
  • Antipsychotics
  • Sympathetic blockers (clonidine, guanethidine, or methyldopa)
  • Thiazide diuretics Thiazide diuretics Thiazide and thiazide-like diuretics make up a group of highly important antihypertensive agents, with some drugs being 1st-line agents. The class includes hydrochlorothiazide, chlorothiazide, chlorthalidone, indapamide, and metolazone. Thiazide Diuretics
  • Antiandrogenic medications or medications with antiandrogenic activity (e.g., spironolactone, ketoconazole)
Chronic medical conditions
  • Cardiovascular diseases
  • CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease
  • Obstructive sleep apnea Obstructive sleep apnea Obstructive sleep apnea (OSA) is a disorder characterized by recurrent obstruction of the upper airway during sleep, causing hypoxia and fragmented sleep. Obstructive sleep apnea is due to a partial or complete collapse of the upper airway and is associated with snoring, restlessness, sleep interruption, and daytime somnolence. Obstructive Sleep Apnea
Neurologic conditions
  • Peripheral (autonomic) neuropathy (e.g., diabetic neuropathy)
  • Multiple sclerosis Multiple Sclerosis Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis
  • Spinal injuries
Psychogenic conditions (psychogenic ED)
  • Stressors
  • Past related traumatic experience
Endocrine conditions
  • Thyroid disorders
  • Hyperprolactinemia Hyperprolactinemia Hyperprolactinemia is defined as a condition of elevated levels of prolactin (PRL) hormone in the blood. The PRL hormone is secreted by the anterior pituitary gland and is responsible for breast development and lactation. The most common cause is PRL-secreting pituitary adenomas (prolactinomas). Hyperprolactinemia
  • Hypogonadism Hypogonadism Hypogonadism is a condition characterized by reduced or no sex hormone production by the testes or ovaries. Hypogonadism can result from primary (hypergonadotropic) or secondary (hypogonadotropic) failure. Symptoms include infertility, increased risk of osteoporosis, erectile dysfunction, decreased libido, and regression (or absence) of secondary sexual characteristics. Hypogonadism
Exercise Extensive bicycling and prolonged pressure on pudendal and cavernosal nerves increase the risk of ED. Regular aerobic exercise not associated with nerve compression decreases the risk of ED.
Penile conditions Peyronie disease

Management

  • Nonpharmaceutical interventions:
    • Risk factor modification
    • Lifestyle changes
    • Psychotherapy (useful in patients with anxiety) 
  • Pharmaceutical interventions:
    • 1st- line: 
      • PDE5 inhibitors (sildenafil, vardenafil, tadalafil, avanafil)
      • Contraindicated in men taking nitrates Nitrates Nitrates are a class of medications that cause systemic vasodilation (veins > arteries) by smooth muscle relaxation. Nitrates are primarily indicated for the treatment of angina, where preferential venodilation causes pooling of blood, decreased preload, and ultimately decreased myocardial O2 demand. Nitrates (causes hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension with antihypertensive medications)
    • 2nd-line:
      • Vacuum devices
      • Penile self-injectable drugs (alprostadil)
      • Intraurethral suppositories
      • Penile prosthesis (surgical)
    • Medical treatment of any underlying medical causes
    • Testosterone replacement not recommended as monotherapy for ED
Table: Medications used for erectile disorder
Medications Mechanism of action Side effects
  • Sildenafil
  • Vardenafil
  • Tadalafil (longest duration of action)
  • Avanafil (fastest onset of action)
PDE5 inhibitors → increase intracavernosal cGMP → increase intracavernosal NO
  • Hypotension (can happen with any antihypertensive medication)
  • Blue vision discoloration
  • Priapism
  • Flushing, headaches, hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss
Alprostadil PGE1 agonist → increase cAMP, decrease Ca2+ → smooth muscle relaxation
  • Injection site reactions or pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
  • Penile discharge
PGE1: prostaglandin E1
Penis enlargement pump

A modern penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis pump utilizing a gaiter system in conjunction with water as a penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis enlarger or penile rigidity device

Image: “A modern penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis pump” by Arctic Sea Limited. License: CC BY 4.0

Ejaculatory Disorders

Features

  • Premature (early) ejaculation: 
    • Ejaculation occurs prior to or within 1 minute after penetration.
    • Inability to delay ejaculation
    • Duration ≥ 6 months
    • Causes clinically significant distress
  • Delayed ejaculation: 
    • Marked delay or absence of ejaculation
    • Duration ≥ 6 months
    • Causes clinically significant distress
  • Retrograde ejaculation:
    • During ejaculation, semen moves in retrograde fashion into bladder rather than exiting urethra.
    • Often occurs following surgery for benign prostatic hyperplasia Benign prostatic hyperplasia Benign prostatic hyperplasia (BPH) is a condition indicating an increase in the number of stromal and epithelial cells within the prostate gland (transition zone). Benign prostatic hyperplasia is common in men > 50 years of age and may greatly affect their quality of life. Benign Prostatic Hyperplasia

Etiology

  • Not well understood
  • Might be related to: 
    • Penile hypersensitivity
    • Genetic predisposing factors
    • Psychogenic factors
    • Medical diseases or surgical complications

Management

  • Psychotherapy
  • Behavioral therapy (stop-and-go technique, squeeze technique)
  • Medications: 
    • SSRIs: 1st-line treatment 
    • Tricyclic antidepressants Tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants (TCAs): 2nd-line treatment
    • Tramadol: 3rd-line treatment 
    • Topical anesthetics (with or without systemic therapy)

Clinical Relevance

  • Hypogonadism Hypogonadism Hypogonadism is a condition characterized by reduced or no sex hormone production by the testes or ovaries. Hypogonadism can result from primary (hypergonadotropic) or secondary (hypogonadotropic) failure. Symptoms include infertility, increased risk of osteoporosis, erectile dysfunction, decreased libido, and regression (or absence) of secondary sexual characteristics. Hypogonadism: medical condition characterized by little or no spontaneous sex hormone production. Hypogonadism Hypogonadism Hypogonadism is a condition characterized by reduced or no sex hormone production by the testes or ovaries. Hypogonadism can result from primary (hypergonadotropic) or secondary (hypogonadotropic) failure. Symptoms include infertility, increased risk of osteoporosis, erectile dysfunction, decreased libido, and regression (or absence) of secondary sexual characteristics. Hypogonadism may be due to primary causes (e.g., testicular disease) or secondary causes (e.g., pituitary or hypothalamic diseases). This condition is associated with decreased libido, gynecomastia Gynecomastia Gynecomastia is a benign proliferation of male breast glandular ductal tissue, usually bilateral, caused by increased estrogen activity, decreased testosterone activity, or medications. The condition is common and physiological in neonates, adolescent boys, and elderly men. Gynecomastia, and testicular atrophy. Diagnosis requires careful assessment and measurement of prolactin level, and MRI might be considered in secondary causes.
  • Peyronie disease: penile condition that presents with palpable plaque and abnormally increased curvature of penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis when erect. Peyronie disease is associated with painful erections and/or ED. This disease has a genetic predisposition and might occur because of penile trauma. Treatment includes medical options (vitamin E supplementation, colchicine, tamoxifen, acetyl-L-carnitine, calcium channel blockers Calcium Channel Blockers Calcium channel blockers (CCBs) are a class of medications that inhibit voltage-dependent L-type calcium channels of cardiac and vascular smooth muscle cells. The inhibition of these channels produces vasodilation and myocardial depression. There are 2 major classes of CCBs: dihydropyridines and non-dihydropyridines. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers)) and surgical repair.
  • Sexual physiology Sexual physiology Sexual physiology and development begin in early childhood and represent a complex process of events that lead to the final development of sexual orientation and behavior. Sexual behavior and interactions include several changes that are quite different between males and females. Sexual Physiology: sexual physiology and development begins from early childhood, representing a complex process of events that lead to final development of sexual orientation and behavior. Sexual behavior and interactions include several changes that differ greatly between males and females.
  • Female sexual dysfunction Female sexual dysfunction Female sexual dysfunction represents a variety of disorders in any part of the sexual response cycle, including desire disorders, arousal disorders, orgasmic disorders, and pain disorders. The condition may result from stresses and interpersonal conflicts as well as physical illness or medication/substance use. Female Sexual Dysfunction: sexual dysfunction in any part of the sexual response cycle seen in women. Female sexual dysfunction Female sexual dysfunction Female sexual dysfunction represents a variety of disorders in any part of the sexual response cycle, including desire disorders, arousal disorders, orgasmic disorders, and pain disorders. The condition may result from stresses and interpersonal conflicts as well as physical illness or medication/substance use. Female Sexual Dysfunction includes desire disorders, arousal disorders, orgasmic disorders, and pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain disorders. These disorders may arise from stress and interpersonal conflicts, as well as from physical illness or medication/substance use and can cause significant distress.

References

  1. Ganti L, et al. (2016). Sexual dysfunctions and paraphilic disorders. Chapter 16 of First Aid for the Psychiatry Clerkship, 4th ed., pp. 173–176. McGraw Hill Education.
  2. Wittmann D, Khera M, Trost L, Mulhall J. (2020). Contemporary considerations in the pathophysiology of low sex drive in men. J Sex Med. https://pubmed.ncbi.nlm.nih.gov/32115396/ 
  3. Tsertsvadze A, Fink HA, Yazdi F, et al. (2009). Oral phosphodiesterase-5 inhibitors and hormonal treatments for erectile dysfunction: a systematic review and meta-analysis. Ann Intern Med. https://pubmed.ncbi.nlm.nih.gov/19884626/

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