Erectile dysfunction

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chapter 49 Erectile dysfunction

INTRODUCTION AND OVERVIEW

Erectile dysfunction (ED) was defined by the 1992 National Institutes of Health Consensus Development Panel on Impotence as the persistent inability to achieve and/or maintain an erection sufficient for satisfactory sexual intercourse. It is a symptom that causes significant psychological and relationship stress and is often not investigated or treated, as a significant majority of men do not report it to their doctor.

Until the late 1980s, ED was regarded as mainly psychological in origin. We now understand that ED is a complex process requiring a combination of urological, endocrinological, psychological, vascular and biochemical factors for satisfactory function.

EPIDEMIOLOGY

In recent times there have been many epidemiological studies of erectile dysfunction, the hallmark study being the 1987 Massachusetts Male Aging Study.¹ This study found that ED occurred in 52% of men aged between 40 and 70 years. It confirmed that ED increases in frequency as men grow older, and that age is not a cause but an association of this condition. The study found that the most common pathological factor in ED is vascular disease, found in diabetes, hypertension, obesity and hyperlipidaemia (metabolic syndrome).

Thus the incidence of ED is highly correlated with health conditions such as metabolic syndrome, and with lifestyle factors such as smoking and lack of exercise.

The first Australian-based community study of ED was carried out by Chew and colleagues from the Keogh Institute for Medical Research, Perth, in 1997.² This study found that some degree of ED was present in almost 40% of men aged 18 years or older. Complete ED occurred in 18.6% of men. The prevalence of complete ED increased with age. Despite the frequency of ED, this study found that only 11.6% of men with ED had received treatment.

ANATOMY

The basic anatomy of the penis (Fig 49.1) consists of vascular cavernosal tissue that responds to neurological impulses, resulting in penile rigidity.

FIGURE 49.1 Basic anatomy of the penis

Each corpus cavernosum contains blood-filled compartments called sinusoids or lacunar spaces and is surrounded by a fibrous sheath called the tunica albuginea. The endothelium and integrity of the smooth muscle cells play an important role in the vascular events of erection.

The corpus spongiosum surrounds the urethra and distally forms the glans penis. The arterial inflow arises from the internal pudendal artery, which provides a cavernosal artery for each corpus.

Venous drainage occurs through emissary veins passing through the tunica albuginea. The rigidity during tumescence compresses these veins, causing veno-occlusion. When this mechanism functions poorly, it is often described as venous leakage.

Parasympathetic nerves from the S2 to S4 nerve root control erectile function, and sympathetic nerves from T11 to L2 control detumescence and ejaculation. Penile erection is thus a neurovascular event. Sexual stimulation results in increased parasympathetic activity, leading to release of neurotransmitters from the cavernous nerve terminals and relaxing factors from the endothelial cells in the penis. The neurotransmitters are acetylcholine, vasointestinal peptide and nitric oxide.

PATHOPHYSIOLOGY

Cyclic guanosine monophosphate (cGMP), which arises from the precursor L-arginine by the action of nitric oxide synthase, controls nitric oxide function. Calcium efflux mediated by cGMP leads to smooth muscle cell relaxation in the arteries and arterioles supplying the erectile tissue, increasing blood flow and causing the erection (Fig 49.2). This action is ended by phosphodiesterase type 5 (PDE-5), which leads to detumescence. Additional smooth muscle relaxation via the cyclic adenosine monophosphate (cAMP) pathway is mediated by prostaglandin E₁ and vasointestinal peptide. Availability of nitric oxide in the endothelium decreases with age. Endothelial dysfunction occurs in both coronary artery disease and ED when the action of nitric oxide is affected. Impaired nitric oxide synthesis reduces the capacity of vasodilation and increases the risk of platelet aggregation. Atherosclerosis has a greater effect in ED than the ageing process. Diabetes is associated with both vascular and neurological effects that interfere with the interaction between the endothelium and the smooth muscle cells.

FIGURE 49.2 Biochemical pathway of erection

AETIOLOGICAL FACTORS

As mentioned, the prevalence of ED increases with age; generally 70% of men at the age of 70 years describe a form of erectile dysfunction. Men with sexual dysfunction may have physical and psychological health problems (Box 49.1).

Psychological factors may be the primary cause of the ED or can arise secondary to the distress caused by its presence. Psychological factors include anxiety, stress, depression, relationship issues and other presentations of mental illness.

Erectile dysfunction may be associated with many medical conditions; it is strongly associated with atherosclerosis, making ED a marker of potential coronary artery disease. Because of the smaller size of the penile arteries compared to the coronary arteries, erectile dysfunction may precede coronary artery disease by 3–5 years. Thus a high level of total cholesterol with a low HDL is an important risk factor for ED causing both arterial and venous dysfunction due to endothelial injury and smooth muscle cell changes.

Smoking has been shown to be an important risk factor for ED. Smoking may result in the arterial inflow problems or faulty veno-occlusive mechanism. Obstructive sleep apnoea has been associated with reduced nocturnal erections.

Diabetes may involve vascular and neurological problems involving vascular insufficiency and sensory and autonomic neuropathy. Men with diabetes experience the onset of ED 10–15 years earlier than those without diabetes. More than 50% of these will have ED at some time, and 39% suffer from the condition all the time. The Massachusetts Male Aging Study showed a 28% probability of complete ED among men with diabetes, compared with a 9% probability in those without diabetes.¹ The risk may depend on the duration of diabetes and the presence of poor glycaemic control.

The neurological causes of ED include multiple sclerosis, temporal lobe epilepsy, Parkinson’s disease, stroke, Alzheimer’s disease and spinal cord injury. Hypoxia associated with respiratory disease may result in the aggravating vascular causes of ED. Renal insufficiency may result in ED in up to 50% of patients due to multiple causes, including vascular, neurological, endocrine and electrolyte and mineral issues.

The medications implicated in ED include blood pressure tablets containing thiazide diuretics and beta-blockers. Antidepressant medication may affect libido and ejaculation more so than erection. Cardiac medication includes digoxin and amiodarone. Many psychotropic medications affect the erection, including the older major tranquillisers and the more modern atypical antipsychotics. An important part of the patient history is to check all prescribed and over-the-counter medications to check for ED as a side effect.

Most of the illicit recreational drugs are associated with erectile dysfunction. Because of its disinhibiting effect, alcohol may occasionally result in enhanced sexual function and is often used by men with premature ejaculation to delay ejaculation.

METABOLIC SYNDROME

The combination of obesity, diabetes, raised lipids and hypertension is known as the metabolic syndrome. This condition is often associated with ED and a low level of testosterone. ED in this situation arises from endothelial dysfunction, which is deterioration of the lining of small blood vessels known as the endothelium. Specific treatment of these four components plus lifestyle modification is an important aspect of the treatment of metabolic syndrome to improve endothelial function. The improvement of weight, blood pressure, lipid levels and glucose control may improve testosterone levels and the symptoms of ED.

Low testosterone, or hypogonadism, remains a controversial topic. Testosterone production falls by 1% per year from the age of 40 years. As men age, high levels of sex hormone binding globulin reduce the amount of a bioavailable testosterone. However, many older men with low-ish testosterone levels remain sexually functional. The role of testosterone in male sexual function was regarded in the past as only essential for libido and general sense of wellbeing, although recently there is evidence that some level of testosterone is required for normal erectile function. Testosterone also plays an important role in the maintenance of bone density, muscle mass, maintenance of male characteristics and a general sense of wellbeing.

LOWER URINARY TRACT SYMPTOMS

Lower urinary tract symptoms are associated with increasing severity of ED, possibly through altered nitric oxide levels in the smooth muscle of the prostate and penis. Radical prostatectomy surgery for prostate cancer (open or robotic) usually results in ED. Even when the neurovascular bundles are saved, and these are the requirement for erectile function, the nerves may take 6–36 months to recover, if ever. Any other form of pelvic injury or surgery has the potential to damage the pelvic nerves and result in ED.

PEYRONIE’S DISEASE

Peyronie’s disease is a fibrotic condition of the corpora cavernosa that results in penile shortening, the presence of a plaque, curvature of erection and occasionally ED. The disease may be self-limiting, taking up to 18 months to resolve. However, sometimes the condition is progressive, resulting in increasing curvature of the erection and requiring surgical straightening. Peyronie’s disease can arise from penile trauma during sexual activity. It can be associated with Dupuytren’s contracture and the HLA-B27 antigen.

DIAGNOSIS

The diagnosis of ED arises from a medical and sexual history and the use of various questionnaires and instruments. An abbreviated version of the international index of erectile function (IIEF) is the five questions of sexual health inventory for men (SHIM). These questions are:

• Do you have the regular confidence that you can get and keep an erection?

• When you have erections with sexual stimulation, are the erections enough for penetration?

• During sexual intercourse, how often are you able to maintain an erection after you have penetrated your partner?

• During sexual intercourse, how difficult is it to maintain your erection to completion of intercourse?

• When you attempt sexual intercourse, how often is it satisfactory for you?

It is important to take a general history and a sexual history. Taking a general history may provide clues to the presence of risk factors that can be revealed by the patient’s medical history. Other important factors are the use of medications, tobacco, alcohol and other recreational drugs, and psychological and relationship issues.

The sexual history should establish the exact nature of the problem, whether it is one of erectile dysfunction, libido or ejaculation. It is important to ask:

• how long the problem has been present

• whether the change was sudden or gradual

• whether the problem occurs in all situations or varies

• whether nocturnal and morning erections occur

• whether the problem is the same with masturbation

• whether penile curvature has developed

• whether the problem has ever been present before

• about details of the current relationship.

NORMAL CHANGES OF AGEING

It is important to differentiate the normal changes of ageing that occur with men and provide reassurance that these do not necessarily require treatment. Ageing men require reassurance that change in erectile function is a natural process. Older men require more stimulation to achieve an erection, they experience a less intense orgasm, reduced ejaculatory volume and a longer refractory period (the time it takes to repeat sexual activity). Older men may therefore have difficulty using condoms, as their erections are not as robust.

EXAMINATION

The examination of men with ED should be general as well as paying specific attention to the genitals, secondary sexual characteristics, peripheral pulses and prostate.

Examination of the penis may reveal Peyronie’s disease. Examination of the testis may indicate hypogonadism or the presence of Klinefelter’s syndrome. The character of limb pulses indicates peripheral vascular status. Digital rectal examination reveals the presence of anal tone, the bulbocavernosus reflex and the state of the prostate.

Ideally, the partner of the man with ED should be present, as the partner often reveals information that is relevant to the potential cause, such as the state of the relationship, and the man’s and the partner’s expectations.

INVESTIGATIONS

Investigations include routine blood testing for fasting lipids and glucose, liver function, creatinine, morning total testosterone and a PSA prostate blood test if indicated. Some centres perform more sophisticated testing, which includes an office prostaglandin E₁ (PGE₁) injection test, a duplex Doppler ultrasound scan of the penile blood flow and, when indicated, overnight erection testing with a Rigiscan monitor. For men who may be considered for vascular surgery, investigations such as cavernosometry and selective pudendal arteriography may reveal vascular lesions, especially in the case of trauma.

TREATMENT

FIRST-LINE THERAPY

Psychological and relationship factors should always be included in the initial assessment, as well as lifestyle issues, with particular emphasis on diet, weight loss and exercise. Men are often reluctant to undergo psychological and lifestyle counselling, as they generally seek a quick fix. However, when psychological issues predominate as the cause of ED, a medical treatment may not be overly effective.

Yoga and meditation can reduce the effects of stress and relieve anxiety about the condition. Exercising the pelvic floor muscles may result in improved quality of erection and ejaculation.

Oral PDE5 inhibitors (sildenafil, tadalafil, vardenafil) are effective in up to 70–80% of men with ED. Side effects may include flushing of the face, headache, blocked nose, gastric reflux and some muscle and lower back pain. These medications enhance penile blood flow via the cGMP cycle, prolonging smooth muscle cell relaxation by inhibiting the PDE5 action.

PDE5 inhibitors may not be effective in the presence of low testosterone, and so replacement of testosterone may result in an improved response. PDE5 inhibitors are generally taken orally one hour before planned sexual activity on an as-required basis. These medications are effective with the treatment of vascular causes of ED, and are being assessed for their effectiveness in recovery of erectile function following treatment for prostate cancer with daily dosing of the lowest dose of a PDE5 inhibitor.

Non-arteritic anterior ischaemic optic nerve neuropathy (NAION) is a condition resulting in visual loss often seen in older men in the age group of those who take PDE5 inhibitors. No direct cause or link has been found. These men have the vascular risk factors for NAION in that they are older men, with a history of hypertension, diabetes and smoking.

SECOND-LINE THERAPY

Before the discovery of PDE5 inhibitors, intracavernosal self-injection was the main medical treatment for ED. In the 1980s, papaverine was used until the discovery of prostaglandin E₁ (PGE₁, or alprostadil). Penile injection therapy works through the cAMP cycle and is effective in more serious cases of ED and in men with neurogenic ED. PGE₁ can be mixed with papaverine and phentolamine to form a preparation known as TriMix when PGE₁ on its own is ineffective in severe cases of ED. PGE₁ can produce some delayed pain in some men, but generally it is well tolerated. Overdosing with PGE₁ may result in a prolonged erection known as priapism. This requires emergency treatment, for detumescence of the penis. Regular use of penile injection therapy may result in penile fibrosis, which may result in similar symptoms to those of Peyronie’s disease, such as curvature of the erection.

An intraurethral therapy with PGE₁ was briefly available in Australia, with a product called medicated urethral system for erection (MUSE). This has not been found to be an overly effective medication. Another second-line treatment is the use of a vacuum erection device, a non-invasive treatment that is a useful alternative for those who do not wish to or are unable to take oral or injectable medication. The vacuum device applies a negative pressure to the penis, drawing venous blood into the penis, which is then retained by the application of an elastic constriction band to the base of the penis.

THIRD-LINE THERAPY

Surgical implantation of a penile prosthesis or implant is considered when other treatments have failed. The three-piece penile prosthesis is a highly engineered product, is well concealed and has a low rate of mechanical failure.

Vascular surgery consists of venous ligation or dorsal vein arterialisation. Because of its poor long-term prognosis, this type of surgery is now mainly relegated to younger men with traumatic arterial lesions with no evidence of atherosclerosis.

TESTOSTERONE

Should the man with ED be shown to be deficient in testosterone, consideration is given to testosterone supplementation. Testosterone may improve libido and play some role in improving erectile function. Caution should be exercised with testosterone therapy in the presence of an enlarged prostate and when there is a risk of prostate cancer. Testosterone replacement therapy is available as oral capsules, skin patches, skin gel, injection therapy and skin implants. There is much controversy over the level of testosterone that is regarded as being low for both sexual and general health matters. A level of total testosterone ≤ 8 nmol/L has always been regarded as the point where testosterone treatment is commenced. A ‘grey area’ of testosterone level between 8 and 12 nmol/L is now under research for consideration of treatment of sexual and general health problems.

NON-PRESCRIPTION TREATMENTS

The most effective treatments remain the prescription oral and injectable medications. Their use has been undermined by massive internet promotions to obtain similar products without prescription or assessment. Often these products are counterfeit.

Some men prefer treatment for ED to be complementary based, but no studies have yet shown any to be as effective as the prescription medications. However, a practitioner prescribing safe complementary medications for ED may be of much benefit through counselling skills and a genuine interest in helping the patient.

Traditional Chinese medicine

Erectile dysfunction belongs to ‘Yang Wei’ in traditional Chinese medicine (TCM). In TCM normal sexual functioning depends on the health of the kidney and the liver. Kidney yang controls the functional aspect of an erection and kidney jing the ability to reproduce, while the liver channel passes through the external genitals. Weakness of the kidney reduces the physiological ‘Fire of desire’, while stagnation of liver qi reduces the physical ability.

In general, TCM treatment for this condition is to strengthen the kidney and liver, and the treatment should be combined with psychological treatment.

SUMMARY

Erectile dysfunction may be a presenting sign of undiagnosed vascular disease elsewhere in the body. Even when vascular causes of ED predominate, the psychological issues that are inevitably present should also be addressed. Low testosterone level may be a cause of ED, although it is usually associated with low libido. Low libido can be also a presenting sign of depression and relationship issues.

The increasing incidence of ED together with the ageing population will result in increasing requests for treatment because of people’s expectations of maintaining good quality of life in their senior years. The man must be fit enough to engage in sexual intercourse to be considered suitable for any ED treatment. Patients often have misguided fears of the risks of oral ED medication. Counselling can be an effective treatment on its own and can improve the effectiveness of medical treatment. Involvement of the partner improves the outcome of the combined counselling and medical treatment.

Men should be encouraged to have an annual health check, particularly in the middle years when there is a family history of diabetes, hypertension, hyperlipidaemia and bowel and prostate cancer. These check-ups allow men to be assessed for metabolic syndrome, physical fitness, mental health and sexual function. They may also encourage men to be more aware of their general health and the benefits of a healthy lifestyle, and prevent ill health at an earlier stage. Regular checks may allow interventions to be more effective for smoking, excessive alcohol intake, illicit drug use and weight and exercise issues.

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