The management of erectile dysfunction

For a more recent article on this topic, see Erectile dysfunction: causes, assessment and management options.

Introduction
Erectile dysfunction (impotence) is the inability to obtain and sustain an erection adequate for sexual intercourse. This is a common problem and the prevalence increases with age. It is important to distinguish erectile dysfunction from ejaculatory disorders including premature ejaculation and ejaculatory failure. Many men are reluctant to seek help from their doctors as evidenced by the proliferation of franchised, entrepreneurial clinics advertising in the popular press. Basic clinical assessments should be undertaken for all men presenting with erectile dysfunction to identify

– men who have significant underlying medical disease

– those for whom specific medical therapy may be beneficial

– those with a psychogenic cause where psychotherapy as part of the medical management may be important.

Extensive investigations are not usually justified.

History
A careful history, including a drug history, will usually differentiate organic from psychogenic impotence. Drugs that are commonly associated with sexual dysfunction include antihypertensives (including diuretics), cimetidine, major tranquillisers and most antidepressants. Organic impotence generally has a gradual, insidious onset with progressive worsening until no erection is obtained. At first, there may be loss of rigidity and/or difficulty sustaining an erection. Later, there is a complete inability to penetrate. Organic impotence is evident consistently in all situations, whether during attempted intercourse with his regular or another partner, masturbation or in response to erotic stimuli. Nocturnal erections are markedly diminished and this manifests as a loss of erections on waking.

Psychogenic impotence is more likely to have an abrupt onset. This is often related to a distinct precipitating event (e.g. a psychologically traumatic episode of sexual failure). The impotence is often inconsistent, occurring only in certain situations. Nevertheless, organic impotence usually invokes a secondary psychological overlay which may complicate evaluation of the aetiology. This underlines the need for a careful, unhurried approach and empathy during history taking.

Androgen deficiency causes more loss of libido than erectile dysfunction. It is unusual for men complaining of impotence to have androgen deficiency as a cause of their sexual dysfunction. This is in contrast to the low sexual activity of androgen-deficient men which often causes them little concern.

Physical examination
Evidence of possible causative factors (e.g. diabetes, pituitary disease, lipid disorders, vascular or neuropathic disease, androgen deficiency) should be sought systematically. Gonadal status (secondary sexual characteristics, testis size) and visual field defects suggesting pituitary tumour should be assessed. Altered peripheral pulses and neurological reflexes in the legs can be evidence of vascular or neurological disorders.

Investigation
Few investigations of erectile dysfunction lead to specific interventions, so extensive testing cannot be justified in routine practice. Specific correctable underlying causes such as androgen deficiency or pituitary tumour should be sought, even though they are rare. Their treatment may be gratifying and has implications for general health (e.g. general energy and well-being, risk of osteoporosis).

Serum prolactin, testosterone and luteinising hormone (LH) should be measured and repeated if any is abnormal. If consistently abnormal, further investigations are required. Blood glucose and lipids should be measured. Although treatment of diabetes or hyperlipidaemia may not improve erectile function, they should not be overlooked.

Apart from measurement of penile blood pressure which may exclude or confirm a vasculogenic basis, other complex investigations are not usually justified. Surgically correctable vascular lesions are rarely found and, even then, surgical outcomes are functionally very disappointing. Sleep studies with or without determination of nocturnal penile tumescence are not usually justified clinically. They add information which usually does not influence management.

Management
The success of most commonly-used therapies will depend on co-operation of the partner. It is important to determine the partner's attitudes to the problem and involve them in discussions of treatment options. Men who do not have a regular or supportive partner rarely do well with therapies which necessitate treatment at the time of intended intercourse.

Psychotherapy
A psychological reaction to persistent erectile failure is almost inevitable and universal. This complicates the identification of primarily psychogenic impotence so it is essential to have an insightful and empathetic manner to manage erectile dysfunction effectively. Even when erectile dysfunction is primarily organic, appropriate counselling provided by the patient's doctor can be reassuring if adequate time is made available. Psychogenic impotence can be improved with the help of an experienced psychiatrist or psychologist. This psychotherapy requires a supportive and understanding partner willing to participate in couple-oriented behavioural sessions.

In some men with psychogenic impotence, a limited trial of empirical intracavernosal therapy may break the self-reinforcing cycle of performance anxiety and failure. This may restore their confidence in the ability to obtain an adequate erection.

Mechanical devices
Vacuum erection devices
These external devices create a vacuum to induce an erection. This is then maintained by a thick rubber band placed tightly at the root of the penis. They have a modest role in the treatment of men in whom intracavernosal injection therapy is contraindicated (e.g. bleeding diatheses), is unacceptable or fails. These devices have modest efficacy and are suitable mainly for men with psychogenic or partial organic impotence. Their efficacy and acceptability are limited in men with severe neurovascular impotence. Apart from occasional penile bruising, they are generally safe if the duration of each use is limited. Compared with penile implants or long-term intracavernosal injections, their cost is low.

Implants
Surgical penile implants are an expensive last resort when simpler measures (such as psychotherapy, vacuum devices or intracavernosal injections) are ineffective or inappropriate. As most cavernosal tissue is excised, the procedure is functionally irreversible. It is justified only for men with complete organic impotence. Devices vary in complexity from simple semi-rigid rods to fully inflatable with an implanted reservoir. The costs rise accordingly. Satisfaction with the implants is variable, but depends on thorough pre-surgical counselling and close involvement of the partner. Complications include infection, mechanical failure and erosion. These vary with the surgeon's experience.

Hormonal treatment
Treatment with testosterone should never be given without clear evidence of androgen deficiency.¹ Once testosterone starts, the endocrine investigations become confusing and it can take many months to clarify the patient's requirement for ongoing therapy. Furthermore, testosterone therapy has a significant placebo effect in eugonadal men with psychogenic impotence. Unlike genuine androgen deficiency, such men generally have an inconsistent and poorly maintained response to testosterone treatment. This further confuses the diagnosis and leads to frustration and disappointment for the patient. A borderline low plasma testosterone is rarely significant in otherwise healthy men presenting with erectile difficulty, particularly if the plasma LH is normal. Patients with hyperprolactinaemia require evaluation for a prolactinoma and their management is dictated by the pituitary tumour. For microprolactinomas, bromocriptine treatment alone can be effective. The more common macroprolactinomas usually require surgery, sometimes with adjuvant radiotherapy.

Intracavernosal therapy
Due to the lack of specific treatments for most causes of erectile dysfunction, intracavernosal injections are in wide use. They represent a major advance in the empirical treatment of erectile dysfunction.

The original drug used for intracavernosal therapy was papaverine, a smooth muscle relaxant, often supplemented with phentolamine, an alpha adrenergic blocker. Neither is registered for treatment of erectile dysfunction in any country. Despite the wide ad hoc usage of these two drugs and their combination, there is little reliable information on their efficacy or safety. Indeed, there is doubt that these combinations are chemically compatible, stable or sterile under the usual circumstances of use. The main reason for the preference for prostaglandin E₁ over the papaverine or papaverine/phentolamine combination is that these older drugs are believed to have a higher incidence of priapism and long-term penile fibrosis. The use of 3 or 4 drug cocktails represents shotgun therapy which is contrary to sound pharmacological principles.

Prostaglandin E₁
Prostaglandin E₁ has the most extensive efficacy and safety record, making it the current drug of choice. It relaxes the smooth muscle of the corpora cavernosa, resulting in a dose-dependent increase in penile blood inflow and tumescence. The magnitude of the blood flow and erectile response varies between individuals and according to the pathology.

The usual starting dose of prostaglandin E₁ is 2.5-5 micrograms. Generally, men with vasculogenic impotence require higher doses than those with neurogenic or psychogenic impotence. The starting doses should be adjusted accordingly. The optimal dose for each patient varies considerably and must be individually titrated by progressively increasing the dose (up to a maximum of 30 micrograms) with successive test injections until an adequate response is achieved. In practical terms, this is defined as an erection firm enough for penetration and lasting from 20-60 minutes. The first injection (at least) should be given under the direct supervision of a doctor and the patient subsequently taught how to self-inject. It is not sufficient just to send the patient home with a prescription and diagram on how to self-inject any more than it is appropriate to ask a diabetic to start insulin self-injection without careful instruction and supervision. Intracavernosal therapy should generally be supervised by a doctor with appropriate experience. Regular monitoring is essential.

If an inadequate response is achieved with maximal prostaglandin E₁ dosage, combination therapy with papaverine alone or with phentolamine has been reported to improve the response. Reliable clinical trials of such add-on therapy are lacking. The risk of adverse effects (priapism, fibrosis, hepatotoxicity, hypotension) is higher with such multi-drug regimens. In addition, the chemical compatibility, stability and sterility of these ad hoc mixtures is not assured.

The most frequent adverse effect of prostaglandin E₁ intracavernosal therapy is penile or perineal pain. Some pain occurs after approximately 20% of injections, but is rarely (<0.4%) severe. Other minor adverse effects include haematoma, oedema or scarring. Fibrosis at the site of repeated injections has been reported in approximately 8% of men and priapism in 1%. These complications may be minimised by not exceeding recommended maximum rates of injection (1 per day, 3 per week). Patients should be carefully instructed to seek medical help if the erection lasts for more than 4 hours (priapism) due to the risk of penile ischaemia with prolonged erection.

Any doctor supervising use of intracavernosal therapy must have reliable referral arrangements in place with a doctor experienced in the management of priapism. Patients should be provided with clear instructions on how to manage excessively prolonged erections. If a full erection persists for more than 2 hours, ice packs, brisk walking and oral pseudoephedrine (120 mg) are usually sufficient to cause detumescence. If these measures are ineffective within 4 hours, patients should contact their doctor and be managed as a medical emergency. Cavernosal aspiration, saline irrigation and sympathomimetic drugs (with blood pressure monitoring) may be required.

Despite initial response rates of about 70% in clinical trials of prostaglandin E₁, many men either decline or fail to continue such therapy. Discontinuation is sometimes due to recovery of sexual function (presumably due to alleviation of psychological factors). More often, it is because of dissatisfaction with therapy, due to inadequate erectile function, adverse effects such as penile pain or poor acceptance of treatment by the patient or his partner.

The presently marketed formulation of prostaglandin E₁ is inconvenient. It needs to be kept frozen due to the lability of the prostaglandin in solution. This makes prostaglandin E₁ awkward to use, especially if the patient must travel. Improved formulations such as a lyophilised powder and a transurethral gel formulation of prostaglandin E₁ as well as an effective oral medication have been developed and should become available in the near future.

Entrepreneurial clinics
Many of these clinics initiate intracavernosal therapy using multi-drug cocktails without establishing a diagnosis or appropriate counselling of the patient or his partner. As a result, while sometimes initially gratifying, such management has poor continuation rates reflecting patient dissatisfaction.