The penis is composed of two paired vascular cylinders, the corpora cavernosa, and the corpus spongiosum, which surrounds the urethra and forms the glans penis at its distal extension. Each corpus is encapsulated in a collagenous sheath called the tunica albuginea. Erectile tissue located within each corpus cavernosum is arranged in a honeycomb pattern; interconnected sinusoidal spaces are lined by vascular endothelium and supported by a framework of smooth muscle. Corporal arterial blood flow is derived from terminal branches of the internal pudendal artery, which open directly into the sinusoidal spaces. The cavernous spaces are drained through a set of emissary veins located between the sinusoids and tunica albuginea, which ultimately empty into the deep dorsal vein of the penis.

Penile erection may be elicited by local stimulation of the genitalia, or by central psychogenic stimuli, which activate efferent autonomic nerves. Release of neurotransmitters causes relaxation of arteriolar and sinusoidal smooth muscle, leading to a marked increase in arterial inflow to the penis and expansion of the sinusoidal spaces, resulting in penile tumescence. The blood-filled sinusoidal spaces distend the tunica albuginea, causing mechanical compression of the emissary veins lying under the tunica. Venous drainage is reduced and pressure within the corpora rises above systemic blood pressure. Detumescence may be due to a sympathetic discharge at the time of orgasm, which causes an increase in smooth muscle tone in both the penile vasculature and intracorporal sinusoids. A reduction in arterial inflow occurs causing collapse of the distended sinusoids and an increase in penile venous outflow. Intracorporal pressure falls rapidly and the penis returns to a flaccid or resting state.

Reduced arterial inflow to the penis secondary to atherosclerosis of the internal pudendal artery or its branches is the most common cause of organic impotence. Erectile failure is often seen in men who have conditions associated with an accelerated rate of atherosclerosis such as diabetes, hypertension, hyperlipidaemia, and tobacco use. Some patients have adequate arterial inflow to the penis, but excess venous outflow, so that an erection may be achieved, but not sustained. In these patients a loss of compliance of the elastic framework of the sinusoids prevents their full expansion against the tunica albuginea to occlude the draining emissary veins. Ageing, hypercholesterolaemia, and diabetes may cause alterations in elastic compliance resulting in difficulty maintaining an erection.

Central or peripheral nerve damage may result in failure to initiate the arteriolar and sinusoidal smooth muscle relaxation that facilitates penile erection. Men with multiple sclerosis, spinal cord injury, or diabetic neuropathy may all experience erectile dysfunction. Patients who undergo radical pelvic surgery, such as cystectomy or proctocolectomy are usually impotent because of interruption of the nerve supply to the corpora cavernosa.

Endocrine disorders are the cause of erectile impotence in 25 per cent of affected men: a primary hormone deficiency is present in two-thirds of these patients. Patients with low testosterone levels may have decreased gonadotropin levels secondary to a lesion in the hypothalamus or pituitary. Patients with normal pituitary function may have primary testicular failure, resulting in low testosterone levels and erectile dysfunction. Complications of diabetes, such as autonomic neuropathy, sensory neuropathy, and vascular occlusive disease account from the remaining one-third of impotent patients.

Anxiety and depression are the major causes of psychogenic sexual dysfunction, and may be responsible for diminished libido, erectile failure, or premature ejaculation. Impotence of acute onset, with a history of normal morning erections and erections with masturbation is suggestive of a functional aetiology. These patients should be referred for psychiatric evaluation. Erectile dysfunction which is slowly progressive and which is characterized by change in the quality of all erections is likely to have an organic cause.

Sexual dysfunction may be a side-effect of many commonly used medications. Most drugs prescribed for hypertension have been associated with impotence and/or ejaculatory dysfunction. Patients taking tranquillizers, antidepressants, and antipsychotic drugs may complain of decreased libido and erectile failure. Drugs with antiandrogenic effects, such as digoxin, metoclopramide, and cimetidine, can inhibit the peripheral action of testosterone. Impotence may affect as many as 25 per cent of non-hospital patients receiving medication.

A detailed sexual history is required to document the nature of the sexual dysfunction and features suggesting a psychogenic or organic cause of the impotence. The medical history should include a review of the cardiovascular, neurological, and endocrine systems. Information should be obtained regarding current medications, alcohol and tobacco use, pelvic surgery, or radiation treatment.

Relevant features of the general examination include notation of male body habitus, hair distribution, and penile and testicular development as an assessment of androgen stimulation. Abnormalities in anal sphincter tone, bulbocavenosus reflex, or in perineal sensation may imply a neurological abnormality.

The quality of the femoral and pedal pulses should be ascertained: diminished pulses are suggestive of aortoiliac occlusive disease. Patellar and ankle reflexes should be tested to document integrity of the lumbosacral nervous system.

Fasting blood levels of sugar, cholesterol, triglycerides, testosterone, and prolactin should be measured. A thorough history and physical examination and review of laboratory tests should indicate the aetiology of the erectile dysfunction. In patients in whom the cause is uncertain or perhaps multifactorial (e.g. a diabetic patient taking antihypertensive medication) additional diagnostic testing is required.

Papaverine, a non-specific smooth muscle relaxant, may be injected directly into the corpora cavernosa as a screening test for vasculogenic impotence. Patients with an intact penile arterial and venous circulation will develop a firm erection 2 to 3 min after injection. Failure to achieve an erection implies poor arterial inflow, usually secondary to atherosclerotic occlusive disease. Patients who obtain an initial good erection which is not sustained may have excessive venous drainage or ‘venous leak’. A possible complication of papaverine injection is prolonged penile erection, or priapism.

A positive erectile response to papaverine excludes a vascular aetiology, leaving a psychogenic or neurological process as the possible cause of impotence. Nocturnal penile tumescence monitoring is a non-invasive way to clarify the diagnosis, based on the observation that potent men experience three to five erections at night associated with the rapid eye movement phase of sleep. Patients with psychogenic impotence will have a normal pattern of nocturnal erections, unlike patients with organic impotence. A variety of strain gauge devices are available for at-home testing by the patient.

More specialized studies such as measurement of penile nerve conduction velocity, pudendal arteriography, and cavernosography may be ordered to evaluate specific components of sexual function, especially if reconstructive surgery is planned.

Patients with hypogonadal disorders are treated with parenteral testosterone. Older patients must be screened for prostate cancer, as an occult tumour may be stimulated by exogenous testosterone.

Psychogenic impotence is treated using behaviourally oriented sex therapy. Current psychiatric practice aims at correcting the immediate cause of the sexual dysfunction, rather than treating a remote underlying psychological condition.

Patients with a positive papaverine test may be taught the technique of self-injection into the corpora using an insulin syringe. The erection obtained is suitable for intercourse, usually lasting about 1 h. This treatment option is quite useful in patients with neurological disease, such as spinal cord injury or diabetes.

Rare patients with a discrete blockage in the internal pudendal or penile artery may be candidates for arterial revascularization. Microvascular bypass is performed from the inferior epigastric vein to the dorsal artery of the penis. Reported success rates for arterial surgery vary from 15 to 70 per cent. Surgery for patients with ‘venous leak’ consists of ligation of all abnormal veins draining the corpora in an attempt to decrease excess venous outflow.

The majority of men seeking treatment for impotence have atherosclerotic occlusive disease of the pelvic vessels. These patients are usually not candidates for vascular reconstruction, and have a poor response to papaverine injection. A popular treatment option is placement of an intracorporal penile prosthesis. Prospective implant candidates must understand that the implant will not change libido, sensation, ejaculation, or orgasm.

Diabetics must be aware of the greater risk of infection which may require removal of the device. All prostheses are subject to mechanical failure; the probability of failure is proportional to the complexity of the design.

Silicone semirigid rods are the simplest type of prosthesis. Insertion is readily performed via an infrapubic or penoscrotal approach and malfunction is unusual. However the rods are difficult to conceal and lack flaccidity. Inflatable models provide a natural appearing erect and flaccid state, but are more prone to mechanical breakdown (Fig. 2) 1584. The newer hydraulic penile prosthesis has an advantage in that the penis appearance is more normal, there is a low mechanical failure rate, and erections are satisfactory.

Inability to ejaculate, or delayed ejaculation is thought to have a psychological aetiology; referral should be made for psychiatric evaluation. Premature ejaculation, occurring prior to or upon penetration can be successfully treated with sex therapy.

Any process that affects sympathetic innervation to the seminal vesicles, or that alters the anatomical integrity of the bladder neck can result in retrograde ejaculation or failure of seminal emission.

Retrograde ejaculation is common after prostatectomy and in patients with diabetic neuropathy. Patients who have undergone a retroperitoneal lymph node dissection or bilateral sympathectomies also experience retrograde ejaculation. Viable sperm may be recovered from bladder urine after ejaculation and can be used for intrauterine insemination. Antegrade ejaculation may occur in some patients if imipramine or ephedrine is taken several hours prior to intercourse.

Elucidation of the physiology of penile erection and ejaculation has been a major advance in the understanding of male sexual dysfunction. The widespread demand for treatment of ejaculatory and erectile disorders will continue to promote scientific investigation in this field and encourage the rapid evolution of treatment options.

Infertility, defined as the inability to conceive after 1 year of unprotected intercourse, affects nearly 15 per cent of married couples. The male is partly or entirely responsible in 30 to 50 per cent of these cases.

The reproductive history is the starting point in the evaluation of the infertile couple. Have there been previous pregnancies with the present spouse or another partner? Are the husband and wife aware of the appropriate timing of intercourse to maximize the chance of conception?

A medical history is obtained with emphasis on specific conditions which may affect spermatogenesis, such as testicular maldescent or torsion, and mumps orchitis. Use of alcohol, tobacco, marijuana, and anabolic steroids is associated with impaired sperm production. Radiation, chemotherapy, and industrial exposure to pesticides may irreversibly damage germ cells and cause infertility.

A history of inguinal or scrotal surgery may be relevant because of potential iatrogenic injury to the vas or testicular artery. Retroperitoneal surgery such as lymphadenectomy for testicular cancer may alter seminal emission and ejaculation. Diabetic patients with autonomic neuropathy may have scant ejaculate volume secondary to retrograde ejaculation of semen into the bladder.

The body habitus, distribution of hair, and the presence of gynaecomastia should be noted, as should the size and position of the testes, and any asymmetry. The presence of bilateral vas deferens should be ascertained. Tenderness or induration of the epididymis may be due to previous infection with resultant scarring and obstruction to sperm passage.

About 40 per cent of men who present for an infertility evaluation have a varicocele, or dilatation of the veins of the pampiniform plexus within the spermatic cord, usually on the left side. Examination of the spermatic cords should be carried out in both the supine and standing positions in conjunction with a Valsalva manoeuvre to detect reflux of venous blood and distension of the cord. Finally, rectal examination is required to evaluate the prostate and seminal vesicles. Infection of the prostate, manifested by white blood cells in the semen (pyospermia) may be a cause of impaired sperm function.

The specimen should be collected by masturbation after 48 h of sexual abstinence. Minimal standards of adequacy for the semen analysis have been established (Table 1) 465. A sperm density of at least 20 × 10&sup6; per ml is required for normal fertility. Sixty per cent of the sperm should demonstrate normal morphology and at least 60 per cent should show good motility with forward progression. Sperm agglutination, suggesting the presence of antisperm antibodies, should be absent, as should pyospermia. A viral infection, febrile illness, drug exposure, or unusual stress in the preceding 3 months may adversely affect the semen quality. It is important to obtain additional specimens about 120 days later, to allow time for a new cycle of spermatogenesis.

Routine endocrinological assessment of the infertile male is performed by determining the levels of follicle stimulating hormone, luteinizing hormone, and testosterone.

A pretesticular cause of male infertility is one in which there is inadequate hormonal stimulation of the testes. Congenital or acquired abnormalities of the hypothalamus or pituitary may result in low levels of follicle stimulating hormone and luteinizing hormone, and impaired spermatogenesis. These men may appear inadequately virilized as evidence by eunuchoid proportions, decreased body hair, and gynaecomastia. Hypogonadotrophic hypogonadism is rare, but is potentially treatable with appropriate hormone replacement therapy.

In these patients, impaired spermatogenesis is secondary to primary testicular dysfunction, which may be reflected in elevated gonadotropin levels. Conditions such as cryptorchidism and germ cell aplasia are associated with an increased level of follicle stimulating hormone, reflecting damage to the germinal epithelium. In patients with Klinefelter's syndrome, or a varicocele, the level of follicle stimulating hormone may be normal, but production of sperm by the testis is abnormal.

Between 5 and 15 per cent of infertile men have antisperm antibodies in their semen, detectable by immunobead testing. Antisperm antibody tests should be performed in men in whom agglutinated sperm or low sperm motility is noted on the semen analysis, and in couples with an abnormal postcoital test.

Spermatozoa may be motile, but not functional. A cross-species sperm penetration assay is available to measure the ability of human sperm to penetrate zona-free hamster ova. The assay is currently used to evaluate men with normal semen analyses, and ‘unexplained infertility’, and as a screening test for patients who may be candidates for in-vitro fertilization.

By combining the results of endocrinological testing, semen analysis, and relevant features of the patient history and physical examination, a comprehensive plan for patient treatment can be devised.

No sperm are seen on at least two semen analyses. Retrograde ejaculation of semen should be investigated by examination of a centrifuged specimen of post-ejaculation urine. Serum gonadotropin levels have important prognostic value in the evaluation of the patient with azoospermia: if levels of follicle stimulating hormone are more than three times normal, an intrinsic testicular abnormality with irreversible germ cell dysfunction is present. This is considered untreatable.

In azoospermic patients with normal follicle stimulating hormone levels and normal size testes, a testis biopsy must be performed to distinguish between obstruction and primary testicular failure of spermatogenesis. Bilateral testis biopsy is performed under general anaesthesia. Transverse scrotal incisions are made, exposing the tunica albuginea of the testis, which is incised. A small quantity of seminiferous tubules is extruded and sharply excised for histological analysis.

If the testis biopsy shows active spermatogenesis and the patient is azoospermic, he must have obstruction of the excurrent duct system, probably at the level of the epididymis or vas deferens. An intraoperative vasogram will determine the site of obstruction. Repair of epididymal obstruction is performed with microsurgical technique. The epididymis is sectioned serially until sperm are recovered from a dilated tubule. Continuity of the ductal system is restored by direct anastomosis of the inner lumen of the vas to the single epididymal tubule using sutures of 10–0 nylon (Fig. 5) 1587. Obstruction within the vas may be treated by performing a two-layer end-to-end vasovasostomy using the operating microscope.

If the testis biopsy shows absent or incomplete spermatogenesis the couple are advised to pursue other options, such as donor insemination or adoption.

The most common abnormalities seen on semen analysis are decreased motility of the sperm, often associated with abnormal morphology, and decreased sperm number. These patients should be examined carefully for varicocele, which is the only surgically correctable cause of poor sperm motility. Varicocele repair is most commonly performed at the level of the internal ring through a standard inguinal incision. The spermatic cord is mobilized and the dilated veins (usually 2–4) are identified and ligated (Fig. 6) 1588. After varicocele ligation the semen quality improves in 50 to 80 per cent of men, with an associated pregnancy rate of 30 to 45 per cent.

In the absence of a varicocele there are limited treatment options available to men with abnormal semen parameters. Empirical medical therapy using clomiphene citrate or human gonadotropins may be tried, but with a low probability of success.

Intrauterine insemination and in-vitro fertilization have become used increasingly to treat men with poor quality sperm. The semen is washed and a ‘swim-up’ technique is used to concentrate the most motile sperm, which are then used for fertilization.

At present the pathophysiology of testicular dysfunction is poorly understood, and there are few treatment options for men with impaired spermatogenesis. Recent experience with assisted reproductive technologies and sperm penetration assays should give new insight into male reproductive physiology and uncover causes of male infertility not diagnosable by current methods.

Cockett ATK, Takihara H, Cosentino MJ. The varicocele. Fertil Steril 1984; 41: 5–11.

Heiman JR, LoPiccolo J. Clinical outcome of sex therapy. Arch Gen Psychiatry 1983; 40: 443–9.

Kerin JFP, et al. Improved conception rate after intrauterine insemination of washed spermatozoa from men with poor quality semen. Lancet 1984; i: 533–36.

Krane RJ, Goldstein IG, Saenz De Tejada I. Impotence. N Engl J Med 1989; 321: 1648–59.

Sherins R. J. Hypogonadotropic hypogonadism. In: Garcia CR, et al, eds. Current Therapy of Infertility, 2nd edn. St. Louis: CV Mosby Co, 1984: 147–52.

Thiagarajah S, Vaughan, ED, Kitchin, JD. Retrograde ejaculation: successful pregnancy following combined sympathomimetic medication and insemination. Fertil Steril 1978; 30: 96–100.