Dr Mike Callander discusses the link between erectile dysfunction and other conditions, and outlines methods for assessment and possible treatment options


Erectile dysfunction (ED) may be defined as the persistent inability to attain and/or maintain an erection sufficient for sexual performance.1 In UK-based studies of men aged 18 to 75 years, 13%–39% reported that they had experienced ED at some time in their life.1–3 Risk factors for ED are similar to those for cardiovascular disease (CVD), and include obesity, metabolic syndrome, hypercholesterolaemia, smoking, and inactivity.1

Although not perceived as a life-threatening condition, ED is closely associated with many important physical conditions, and may affect psychosocial health.1 Self-esteem and relationships are affected,4 with significant impact on the quality of life of patients and their partners.1 In general practice, routine discussion of sexual health needs, incorporated within new patient health checks, may be beneficial.5

Erectile dysfunction in which the man has never been able to attain or sustain an erection, is rare and usually due to anatomical abnormalities or psychological factors, such as guilt or severe anxiety. Erectile dysfunction in which a man who previously could attain and sustain erections and can no longer do so, is the most common type, with most cases having an organic cause such as vascular and neurological disorders. Psychological causes may relate to performance anxiety, stress, or a mood disorder. Erectile dysfunction may also be situational, involving a particular place, time, or partner.

Erectile dysfunction and co-morbidities

Diabetes mellitus
Diabetes mellitus is a major risk factor for the development of ED.6,7 Up to 85% of men with diabetes may have ED,8 and they are likely to present with the condition at an earlier age than those who do not have diabetes.8 The risk of ED increases with duration and poor control of diabetes, with almost 50% of men with diabetes developing ED within 6 years of their diagnosis.7 As such, the current NICE guideline on the management of diabetes recommends:9

  • an annual review of patients for ED
  • assessment and education of men with ED to address contributing factors and treatment options
  • offering phosphodiesterase-5 (PDE5) inhibitors where appropriate, and, if unsuccessful, referral to other services offering other ED treatment modalities.

The response rate of men with ED to oral pharmacotherapy is reported to be lower in men with diabetes than those without the condition. Men with diabetes and ED who fail to respond to PDE5 inhibitors have been shown to have low testosterone levels;10 however, testosterone replacement therapy (TRT) may restore the response.11

Cardiovascular disease
Erectile dysfunction is a cardiovascular risk factor; it is equivalent to a moderate level of smoking and confers a 1.46 increased risk for CVD.1 In addition, ED is a marker of silent coronary artery disease,12 pre-dating established disease in many men by 2 years.13

Depression
Erectile dysfunction and depression share many of the same risk factors, and evidence exists for a causal link between the two conditions.14

Smoking
The risk of ED is almost doubled in smokers compared to non-smokers,15 thus affecting 120,000 young men aged 30–40 years in the UK.16

Assessment of erectile dysfunction

Patients with ED are generally very anxious and need to be put at ease to ensure consultations yield a detailed description of the problem; discussion should include duration of symptoms, precipitants, sexual dysfunction, libido, and partner issues.1 When taking the medical history, the following should be covered:

  • significant medical conditions
  • surgery
  • concurrent medication
  • smoking history
  • alcohol intake
  • history of depression
  • ability to walk a mile in 20 minutes on the flat (which reflects the equivalent metabolic demand on the heart as normal sexual activity).

More specifically, taking a sexual history is important to determine whether the cause of ED is organic, psychological, or mixed. Cases of gradual onset are generally organic in nature, while ED that appears suddenly tends to have a psychological cause. Examinations may be limited to blood pressure, heart sounds, pulse rhythm, peripheral pulses, and genitalia. Digital rectal examination should normally elicit a reflex contraction of the rectal muscle thus confirming that the bulbo-cavernosal reflex is intact.

The following investigations should be performed as recommended by the British Society for Sexual Medicine (BSSM) guideline on erectile dysfunction1 and the World Health Organization:17

  • total testosterone levels between 08:00 and 10:00 when levels are at their highest due to the diurnal variation
  • a fasting full lipid profile
  • a measurement of fasting blood glucose or glycated haemoglobin.

Other tests to be considered if clinically indicated include: prostate specific antigen in men over 50 years of age or those with lower urinary tract symptoms (LUTS); and liver and thyroid function tests. If considering TRT, then a full blood count, and levels of follicle stimulating hormone, luteinising hormone, and prolactin may be prudent.

Use of tools and scores
Penile rigidity is thought to be the most important determinant of the quality of an erection.18 Such information can be gleaned by asking the patient about:

  • his ability to attain and/or maintain an erection
  • premature/retarded ejaculation
  • nocturnal and/or morning erections (absence likely indicates an organic cause)
  • self-stimulation (may indicate a situational cause)
  • libido
  • the last occasion when sexual intercourse was satisfactory (prompting discussion on the man’s relationship with his partner).

The close and direct relationship between erection hardness and successful sexual intercourse supports the broader use in clinical practice of the erection hardness score (see Box 1), a simple, valid, reliable, and responsive measure of penal rigidity.18

The association between ED and LUTS may warrant use of the International Prostate Symptom Score. This written screening tool (used to screen for, diagnose, track, and suggest management of the symptoms of benign prostatic hyperplasia) can help determine involvement of the prostate in sexual dysfunction.19

Severe distress
Erectile dysfunction can have a profound effect on the quality of life of affected individuals. Assessment of severe distress requires asking about: significant disruption to normal social and occupational activities; and marked effect on mood, behaviour, social, and environmental awareness, and interpersonal relationships.1 According to the Department of Health guidance published in 1999, pharmacological treatment is available on the NHS where ED is causing severe distress,20 and it may be helpful to compare the patient’s response before and after treatment. However, it is widely accepted amongst expert clinicians working in the field of ED that this guidance is not evidence-based and has never been validated.

Box 1: Erection hardness score18

Erection hardness is scored from 1 to 4, as follows:

  • EHS 1: penis completely hard and fully rigid
  • EHS 2: penis hard enough for penetration but not completely hard
  • EHS 3: penis hard but not hard enough for penetration
  • EHS 4: penis larger but not hard
 
EHS=erection hardness score

Testosterone deficiency

Hypogonadism or testosterone deficiency is a cause of ED that may result in conventional treatments being less effective. Testosterone deficiency syndrome (TDS) is a clinical condition comprising both symptoms and biochemical evidence of testosterone deficiency.21 Symptoms include reduced or loss of libido, reduced strength of erections, fatigue, reduced physical strength, and mood changes. Unless contraindicated, TRT should be considered if biochemical testosterone deficiency is associated with symptoms of testosterone deficiency.21

The Androgen Deficiency in the Ageing Male (ADAM) questionnaire may be useful in diagnosing TDS. While the questionnaire lacks specificity (60%), it is reasonably sensitive (88%) where the patient has a low level of testosterone. Androgen deficiency is suggested where there is a decrease in libido, or in strength of erections, or in any three non-specific questions that include fatigability, decrease in muscle strength, mood changes, and loss of height.22

Treatment of TDS is commonly based on measuring total testosterone levels,23 although bioavailable testosterone24 or free testosterone levels25 may also be used to indicate testosterone deficiency,23 as highlighted in Table 1.

Free testosterone levels are also low in men who are obese and inversely correlate with the degree of obesity.26,27 Increased deposition of abdominal adipose tissue in hypogonadal men who are obese results in a further decrease in testosterone concentrations through the action of aromatase; this enzyme metabolises testosterone to estradiol, leading to further abdominal fat deposition and reduction in testosterone levels.28

There is no evidence that giving testosterone to men with ED and normal testosterone levels improves or restores erectile function.1 Testosterone deficiency is mainly treated with gels, patches, or intramuscular injections. Most men find a long-acting testosterone injection (given every 3 months) or daily application of a transdermal testosterone gel acceptable.1

Table 1: Threshold levels of total, bioavailable, and free testosterone at which treatment of testosterone deficiency syndrome is indicated

Total testosterone
<8 nmol/l Low; treat with exogenous testosterone
8–12 nmol/l
(plus TDS symptoms)
Below normal; treat with TRT
>12 nmol/l Normal; do not treat with exogenous testosterone
Bioavailable testosterone
<2.5 nmol/l Overt deficiency; treat with exogenous testosterone
2.5–4 nmol/l A significant proportion of men with these levels are deficient. If deficient; treat with exogenous testosterone
>4 nmol/l No additional testosterone required; do not treat with exogenous testosterone
Free testosterone
<0.255 nmol/l Low; treat with exogenous testosterone
>0.255 nmol/l No additional testosterone required; do not treat with exogenous testosterone
TDS=testosterone deficiency syndrome; TRT=testosterone replacement therapy

Figure 1: A management algorithm1

figure 1
Grading of risk Cardiovascular status upon presentation ED management recommendations for the primary care physician
Low risk
  • Controlled hypertension
  • Asymptomatic <=3 risk factors for CAD – excluding age and gender
  • Mild valvular disease
  • Minimal/mild stable angina
  • Post successful revascularisation
  • CHF (NYHA class I)
  • Manage within the primary care
    setting
  • Review treatment options with patient and his partner (where possible)
Intermediate risk
  • Recent MI or CVA (i.e. within last 6 weeks)
  • Asymptomatic but >3 risk factors for CAD – excluding age and gender
  • LVD/CHF (NYHA class II)
  • Murmur of unknown cause
  • Moderate stable angina
  • Heart transplant
  • Recurrent TIAs
  • Specialised evaluation recommended (e.g. exercise test for angina, echocardiogram for murmur)
  • Patient to be placed in high-risk or low-risk category, depending upon outcome of testing
High risk
  • Severe or unstable or refractory angina
  • Uncontrolled hypertension
    (SBP >180 mmHg)
  • CHF (NYHA class III, IV)
  • Recent MI or CVA (i.e. within last 14 days)
  • High risk arrhythmias
  • Hypertrophic cardiomyopathy
  • Moderate/severe valve disease
  • Refer for specialised cardiac evaluation and management
  • Treatment for ED to be deferred until cardiac condition established and/or specialist evaluation completed
ED=erectile dysfunction; CHD=coronary heart disease; CAD=coronary artery disease; CHF=congestive heart failure; NYHA=New York Heart Association; MI=myocardial infarction; CVA=cerebral vascular accident; LVD=left ventricular dysfunction; TIA=transient ischaemic attack; SBP=systolic blood pressure

Reproduced with kind permission from the British Society for Sexual Medicine

Treatment

Primary care physicians in the UK are required to follow authoritative endorsed guidelines on the management of ED as part of their terms of service. The major influence has been the Department of Health’s guidance on good practice; these are non-evidence based documents defining patients who qualify for treatment on the NHS.20,29 The BSSM has produced a comprehensive evidence-based guideline that is relevant for primary and secondary care professionals.1

Phosphodiesterase-5 inhibitors

Efficacy
Phosphodiesterase-5 inhibitors were the first effective oral therapy available for ED and remain the first-line treatment.1 They act by inhibiting the breakdown of cyclic guanosine monophosphate by PDE5 in the smooth muscle cells lining the blood vessels, thus increasing blood flow to the penis during sexual stimulation.30 This action is substantiated by improvement in scores measuring erection hardness, together with the increased likelihood of successful intercourse and a completely hard erection.31

Studies have shown that efficacy is similar for all three drugs approved by the European Medicines Agency (sildenafil, vardenafil, and tadalafil),32 with 75% of all sexual attempts resulting in successful intercourse.1 For example, a review of clinical trials of PDE5 inhibitors reported that sildenafil improved erections by 77% and 84% for men taking 50 and 100 mg, respectively, at 24 weeks; and was effective in men with ED associated with diabetes and prostate cancer, and in psychogenic ED.32 Studies assessing patient preference have indicated that tadalafil is preferred to sildenafil and vardenafil, possibly because of its longer duration of action.33,34

Safety

Phosphodiesterase-5 inhibitors are generally well tolerated, and do not significantly increase the rate of myocardial infarction.1

Concomitant antihypertensive medication

Reports suggest that around 68% of men with hypertension have some degree of ED, and men with ED are also more likely to have hypertension.35 The addition of PDE5 inhibitors to antihypertensive medicines (such as diuretics and beta blockers) usually results in either no or small reductions in blood pressure, and no increase in serious adverse events. However, some PDE5 inhibitors (e.g. tadalafil) should be used with caution in patients taking alpha blockers, as some patients may develop orthostatic hypotension. Organic nitrates are an absolute contraindication for use with PDE5 inhibitors owing to a synergistic drop in blood pressure in some patients.35

Commissioning services

The purpose of the 2007 Primary care services framework: management of sexual health in primary care36 was to equip commissioners, providers, and practitioners with the necessary background knowledge, service, and implementation details to deliver a high-quality, patient-focused, integrated sexual-health service in primary care. The document thus advised:

  • that there is a need for sexual health services in primary care
  • commissioners and providers should agree funding that reflects services delivered locally.

A holistic approach to managing ED may enable demands on other services to be reduced, for example, pre-diabetes, early heart disease, depression, and relationship problems.

Conclusion

Erectile dysfunction is associated with many physical conditions and may affect the psychosocial health of men, impacting on both them and their partners. Treatment of ED has been found to have a positive influence on the overall health and quality of life of men with erection problems; improvements in well being,37 mental health,37 and partner relationships,38,39 have been reported along with a reduction in depression.38,40 Phosphodiesterase-5 inhibitors improve erectile function in a large percentage of men with ED and remain the mainstay of pharmacotherapy for this condition.

Primary care is the ideal setting for the management of ED particularly in the context of specialist community based clinics. These can offer men and their partners a holistic approach to this common problem and are able to treat most patients successfully. The 10-minute consultation is suited to managing ED. Three appointments at weekly intervals will successfully treat the majority of men. The available guidelines referred to in this article are simple to interpret and easy to implement.

  • ED represents a likely early manifestation of CVD and should prompt a full CVD risk assessment
  • ED often precedes frank coronary disease by 2 years
  • A full CVD risk assessment plus preventative therapy could reduce later costs of treating manifest CVD
  • Most cases of ED can be managed in primary care without referral by using the management algorithm
  • Commissioners should consider developing community specialist services for ED to avoid paying full tariff charge at hospitals
  • Tariff prices: urology outpatient = £132 (new), £69 (follow-up)a
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