Sexual Health

Physiology of erection and ejaculation

Innervation

Autonomic: sympathetic nerves originating from T11-L2 and parasympathetic nerves originating from S2-4 join to form the pelvic plexus. The cavernosal nerves are branches of the pelvic plexus (i.e. parasympathetic) that innervate the penis. Parasympathetic stimulation causes erection; sympathetic activity causes ejaculation and detumescence (loss of erection).

Somatic: somatosensory (afferent) information travels via the dorsal penile and pudendal nerves and enters the spinal cord at S2-4. Onuf’s nucleus (segments S2-4) is the somatic centre for efferent (i.e. somatomotor) innervation of the ischiocavernosus and bulbocavernosus muscles of the penis.

Central: medial preoptic area (MPOA) and paraventricular nucleus (PVN) in the hypothalamus are important centres for sexual function and penile erection.

Mechanism of erection

Neuroendocrine signals from the brain, created by audiovisual or tactile stimuli, activate the autonomic nuclei of the spinal erection centre (T11-L2 and S2-4). Signals are relayed via the cavernosal nerve to the erectile tissue of the corpora cavernosa, activating the veno-occlusive mechanism (Table 13.1). This triggers increased arterial blood flow into sinusoidal spaces (secondary to arterial and arteriolar dilatation), relaxation of cavernosal smooth muscle, and opening of the vascular space. The result is expansion of the sinusoidal spaces against the tunica albuginea which compresses the subtunical venous plexuses, decreasing venous outflow. Maximal stretching of the tunica albuginea, which acts to compress the emissary veins that lie within its inner circular and outer longitudinal layers, reduces venous flow even further. Rising intracavernosal pressure and contraction of the ischiocavernosus muscles produce a rigid erection. Following orgasm and ejaculation, vasoconstriction (due to increased sympathetic activity, endothelin, PGF2, and breakdown of cGMP) produces detumescence. Noradrenaline (NA) released from sympathetic nerve terminals in the corpora acts on smooth muscle cell α₁-adrenoceptors, leading to raised intracellular calcium which helps maintain penile flaccidity (Figs. 13.1 and 13.2).

Ejaculation

Tactile stimulation of the glans penis sends sensory information (via the pudendal nerve) to the lumbar spinal sympathetic nuclei. Sympathetic efferent signals (travelling in the hypogastric nerve) cause contraction of smooth muscle of the epididymis, vas deferens, and secretory glands, propelling spermatozoa and glandular secretions into the prostatic urethra (emission). There is simultaneous closure of the internal urethral sphincter and relaxation of the extrinsic sphincter, directing sperm into the bulbourethra, but preventing sperm from entering the bladder. Rhythmic
contraction of the bulbocavernosus muscle (somatomotor innervation) leads to the pulsatile emission of the ejaculate from the urethra. During ejaculation, the alkaline prostatic secretion is discharged first, followed by spermatozoa and finally, seminal vesicle secretions (ejaculate volume 2-5mL). The seminal vesicles contribute 2mL, prostate 0.5mL, and Cowper’s glands 0.1mL of the ejaculate. There is an additional vasal and testicular contribution (accounting for around 5-10% of the total ejaculate volume).

Table 13.1 Phases of erectile process

Phase	Term	Description
0	Flaccid phase	Cavernosal smooth muscle contracted; sinusoids empty; minimal arterial flow
1	Latent (filling) phase	Increased pudendal artery flow; penile elongation
2	Tumescent phase	Rising intracavernosal pressure; erection forming
3	Full erection phase	Increased cavernosal pressure causes penis to become fully erect
4	Rigid erection phase	Further increases in pressure + ischiocavernosal muscle contraction
5	Detumescence phase (initial, slow and fast phases)	Following ejaculation, sympathetic discharge resumes; there is smooth muscle contraction and vasoconstriction; reduced arterial flow; blood is expelled from sinusoidal spaces

Fig. 13.1 Factors influencing cavernosal smooth muscle.

Fig. 13.2 Secondary messenger pathways involved in erection (ATP, adenosine triphosphate; Ca²⁺,calcium; cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; GTP, guanosine triphosphate; NA, noradrenaline; NO, nitric oxide; NOS, nitric oxide synthase enzyme; PDE5, phosphodiesterase type 5; PGE1, prostaglandin E1; PGF2, prostaglandin F2; VIP, vasoactive intestinal polypeptide).

Erectile dysfunction: evaluation

Epidemiology

In men aged 40-70y, mild ED is found in 17%, moderate ED in 25%, and complete ED in 10%.2 Incidence increases with age, with complete ED affecting ˜15% of men in their 70’s and 30-40% in their 80’s.

Aetiology

ED is generally divided into psychogenic and organic causes (Table 13.2). It is often multifactorial.

History

Sexual: onset of ED (sudden or gradual); duration of problem; presence of erections (nocturnal, early morning, spontaneous); ability to maintain erections (early collapse, not fully rigid); loss of libido; relationship issues (frequency of intercourse and sexual desire).

Sexual function symptom questionnaires: International Index of Erectile Function (IIEF)—full and short version (IIEF 5) (see

p. 575; Table 13.3); Brief Male Sexual Function Inventory (BMSFI); quality of life questionnaire (QoL-MED).

Medical and surgical: enquire about risk factors, including diabetes mellitus (ED affects 50% overall and 30% of treated diabetics);2 cardiovascular disease; hypertension; peripheral vascular disease; endocrine or neurological disorders; pelvic and penile surgery, radiotherapy, or trauma (which damage innervation and blood supply to the pelvis and penis). Intermediate or high risk cardiovascular disease requires further specialist assessment and treatment prior to ED treatment.

Psychosocial: assess for social stresses, anxiety, depression, coping problems, patient expectations, and relationship details.

Drugs: enquire about current medications and ED treatments already tried and their outcome.

Social: smoking, alcohol consumption.

An organic cause is more likely with gradual onset (unless associated with an obvious cause such as surgery where onset is acute); loss of spontaneous erections; intact libido and ejaculatory function; existing medical risk factors and older age groups.

Investigation

Blood tests: fasting glucose; serum (free) testosterone (taken 8.00-11.00 a.m.); fasting lipid profile are basic work-up tests.3 SHBG; U&E; LH/FSH; prolactin; PSA; thyroid function test should be selected according to patient’s history and risk factor profile.
Nocturnal penile tumescence and rigidity testing: the Rigiscan device contains two rings that are placed around the base and distal penile shaft to measure tumescence and number, duration, and rigidity of nocturnal erections. Useful for diagnosing psychogenic ED and for illustrating this diagnosis to patients.
Penile colour Doppler USS: measures arterial peak systolic and end diastolic velocities,* pre- and post-intracavernosal injection of PGE1.
Cavernosography: imaging and measurement of penile blood flow after intracavernosal injection of contrast and induction of artificial erection, used to identify venous leaks.
Penile arteriography: reserved for trauma-related ED in younger men. Pudendal arteriography is performed before and after drug-induced erection to identify those requiring arterial bypass surgery (although this is less commonly indicated now with the advent of modern penile prostheses).
MRI: useful for assessing penile fibrosis and severe cases of Peyronie’s disease.

Table 13.2 Causes of erectile dysfunction or ‘impotence’

Inflammatory	Prostatitis
Mechanical	Peyronie’s disease
Psychological	Depression; anxiety; relationship difficulties; lack of attraction; stress
Occlusive vascular factors	*Arteriogenic:* hypertension; smoking; hyperlipidaemia; diabetes mellitus; peripheral vascular disease
Occlusive vascular factors	*Venogenic:* impairment of veno-occlusive mechanism (due to anatomical or degenerative changes)
Trauma	Pelvic fracture; spinal cord injury; penile fracture/trauma
Extra factors	*Iatrogenic:* pelvic surgery; prostatectomy^*
Extra factors	*Other:* increasing age (secondary to atherosclerosis in penile arteries, leading to corporeal ischaemia and fibrosis); chronic renal failure; cirrhosis, low flow priapism (i.e. corporeal fibrosis); smoking
Neurogenic	*CNS :* multiple sclerosis (MS ); Parkinson’s disease; multisystem atrophy; tumour
	*Spinal cord:* spina bifida; MS ; spinal cord injury; tumour
	*PNS:* pelvic surgery or radiotherapy; peripheral neuropathy (diabetes, alcohol-related)
Chemical	Antihypertensives (β -blockers, thiazides, ACE inhibitors) Antiarrhythmics (amiodarone) Antidepressants (tricyclics, MAOIs, SSRIs) Anxiolytics (benzodiazepine) Antiandrogens (finasteride, cyproterone acetate) GNRH analogues Anticonvulsants (phenytoin, carbamazepine) Anti-Parkinson drugs (levodopa) Statins (atorvastatin) Alcohol (Refer to BNF)
Endocrine	Diabetes mellitus^;** hypogonadism; hyperprolactinaemia; hypo and hyperthyroidism
^Of note, nerve sparing techniques for radical prostatectomy have improved post-operative potency rates to around 50-70%.4 ^*Note that this list of causes is not in the order of frequency, i.e. diabetes mellitus is one of the most important causes. MAOIs = monoamine oxidase inhibitors; SSRIs = serotonin reuptake inhibitors; BNF = British National Formulary (bnf.org).

Table 13.3 International Index of Erectile Function short form (IIEF 5). Also known as the Sexual Health Inventory for Men (SHIM)

1. How do you rate your confidence that you could get and keep an erection?		Very low 1	Low 2	Moderate 3	High 4	Very high 5
2. When you had erections with sexual stimulation, how often were your erections hard enough for penetration?	No sexual activity 0	Almost never or never 1	A few times 2	Sometimes 2	Most times 4	Almost always or always 5
3. During sexual intercourse, how often were your erections hard enough for penetration?	Did not attempt intercourse 0	Almost never or never 1	A few times 2	Sometimes 2	Most times 4	Almost always or always 5
4. during sexual intercourse, how difficult was it to maintain your erection to completion of intercourse?	Did not attempt intercourse 0	Extremely difficult 1	Very difficult 2	Difficult 3	Slightly difficult 4	Not difficult 5
5. When you attempted sexual intercourse, how often was it satisfactory to you?	Did not attempt intercourse 0	Almost never or never 1	A few times 2	Sometimes 2	Most times 4	Almost always or always 5
IIEF 5 is scored from 1-25. Scores 1-7 = severe ED ; 8-11 = moderate ED ; 12-16 = mild to moderate ED ; 17-21 = mild ED ; 22-25 = no ED .

* Normal values: peak systolic velocity >35cm/s; end diastolic velocity <5cm/s.

1 Montorsi F, AdaikanG, Becher E, et al. (2010) Summary of the recommendations on sexual dysfunction in men. J Sex Med 7:3572-88.

2 Feldman HA, Goldstein I, Hatzichristou D, et al. (1994) Impotence and its medical and psychological correlates: results of the Massachusetts Male Aging Study. J Urol 151:54-61.

3 Hackett G, Kell P, Ralph D, et al. (2008) British Society for Sexual Medicine guidelines on the management of sexual dysfunction. J Sex Med 5:1841-65.

4 Catalona WJ, Carvalhal GF, Mager DE, et al. (1999) Potency, continence and complication rates in 1,870 consecutive radical retropubic prostatectomies. J Urol 162:433-8.

Erectile dysfunction: treatment

Correct any reversible causes (i.e. alter lifestyle, stop smoking, change medication, etc.) (Table 13.2).

Psychosexual therapy

Aims to understand and address underlying psychological issues and provides information and treatment in the form of sex education, psychosexual counselling, instruction on improving partner communication skills, cognitive therapy, and behavioural therapy (programmed relearning of couple’s sexual relationship). Pharmacotherapy may be a useful adjuvant.

Drug therapy

Phosphodiesterase type-5 (PDE5) inhibitors: first-line therapies which include sildenafil (Viagra^®), tadalafil (Cialis^®), vardenafil (Levitra^®) (Table 13.4). PDE5 inhibitors enhance cavernosal smooth muscle relaxation and erection by blocking the breakdown of cGMP by phosphodiesterase. Sexual stimulus is still required to initiate events. Success is reported in up to 80%. Early use of PDE5 inhibitors following radical prostatectomy can help optimize the return of spontaneous erections (penile rehabilitation).

Contraindications: patients taking nitrates, recent myocardial infarction, recent stroke, hypotension, unstable angina, non-arteritic anterior ischaemic optic nerve neuropathy (NAION). Cautions: intermediate and high risk cardiovascular disease requires cardiac review prior to treatment, use with α-blockers, groups with predisposition to priapism.

Dopamine receptor agonist: apomorphine (Uprima^®), taken sublingually, acts centrally on dopaminergic receptors in the paraventricular nucleus of the hypothalamus to enhance and coordinate the effect of sexual stimuli. Side effects: nausea, headache, dizziness. Not commonly used.

Intraurethral therapy: second-line therapy when oral therapies have been ineffective. A synthetic prostaglandin E1 (PGE1) pellet (alprostadil) is placed into the urethra via a specialized applicator (Medicated Urethral System for Erection (MUSE)^TM device). Once inserted, the penis is gently rolled to encourage the pellet to dissolve into the urethral mucosa from where it enters the corpora. PGE1 acts to increase cAMP within the corporal smooth muscle, resulting in muscle relaxation. Side effects: penile and urethral pain, priapism, local reactions.

Intracavernosal injection therapy

Alprostadil (Caverjet^TM).
Papaverine (PDE inhibitor). Usually given in combination with either phentolamine (α-adrenoceptor antagonist) or PGE1 in patients who have failed oral or single-agent injectable therapies.

Training of technique and first dose is given by a health professional. Needle is inserted at right angles into the corpus cavernosum on the lateral aspects of mid-penile shaft. Discontinuation rates from penile injection techniques are high. Contraindications: sickle cell disease or high-risk candidate for priapism. Adverse effects: pain, priapism, haematoma.

Vacuum erection device

Used when pharmacotherapies have failed. It contains three components: a vacuum chamber, pump, and constriction band. The penis is placed in the chamber and the vacuum created by the pump increases blood flow to the corpora cavernosa to induce an erection. The constriction band is placed onto the base of the penis to retain blood in the corpora and maintain rigidity. Relative contraindication: anticoagulation therapy. Side effects: penile coldness, bruising.

Microvascular arterial bypass and venous ligation surgery

Used in: specialist centres where there is a clear-cut diagnosis of a vascular disorder. Acts to increase arterial inflow and decrease venous outflow. Rarely used now as it is uncommon for success rates to exceed 50%.

Penile prosthesis

Semi-rigid, malleable, and inflatable penile prostheses are available when other therapies have failed or are unsuitable. Also indicated for Peyronie’s disease, trauma, and penile fibrosis (i.e. secondary to priapism). The device is surgically implanted into the corpora to provide penile rigidity and generally has high satisfaction rates, up to 90% (Fig. 13.3). Side effects: infection, erosion, mechanical failure, penile shortening, glans may not fully engorge.

Testosterone replacement therapy

Indicated for hypogonadism and is available in oral, buccal, intramuscular, pellet, transdermal patch, and gel forms. Most guidelines recommend PSA, Hb, and LFT checks before and after starting treatment (see

pp. 596-7). It can improve the results of PDE5 inhibitors in hypogonadal men.

Table 13.4 A comparison of PDE5 inhibitors

PDE5I	Doses (mg )	Half-life	Effective within	Duration of action	Common side effects
Sildenafil (Viagra)	25/50/100	3.7h	30-60min	Up to 4-5h	Headache, dizzy, GI upset, flushing, nasal congestion, blurred vision
Vardenafil (Levitra)	5/10/20	3.9h	25-60min	Up to 4-5h	As above
Tadalafil (Cialis)	2.5/5/10/20	17.5h	30min to 2h	Up to 36h	As above