Erectile dysfunction (ED) is a common condition occurring in males over 40 years of age, although it can occur earlier. It is estimated that at least 150 million men globally have ED. It is difficult to obtain accurate values for the true prevalence of erectile dysfunction however, as many patients fail to seek medical attention, and many clinicians are reluctant to ask patients about their sexual health.
We recently spoke to Theresa Lowry Lehnen, RGN, GPN, RNP, BSc, MSc, M. Ed, PhD Clinical Nurse Specialist and Associate Lecturer South East Technological University to understand more about this condition and its impact on males in Ireland.
ED can have a substantial negative impact on a man’s quality of life, Theresa reflects. She says, “Erectile dysfunction is the inability to achieve or maintain an erection for satisfactory sexual performance, and affects a considerable proportion of men at least occasionally. It is often treatable, however, if left untreated, ED can be a source of severe emotional stress for both the man and their partner.”
Theresa notes that erectile dysfunction is often an under recognised, yet important, cardiovascular risk factor. She says, “Owing to its strong association with metabolic syndrome and cardiovascular disease, cardiac assessment is warranted in men with symptoms of ED.”
Aetiology of Erectile Dysfunction
Although most men will experience periodic episodes of erectile dysfunction, it tends to become more frequent with advancing age.
“Many factors can contribute to sexual dysfunction in older men, including physical and psychological conditions, comorbidities and polypharmacy,” she adds. “Aspects of an ageing man’s lifestyle behaviour and androgen deficiency, most often decreasing testosterone levels, can affect sexual function.
“Studies have shown that the percentage of men who engage in some form of sexual activity, decreases from 73% in men aged 57–64 years to 26% for men aged 75–85 years. The aetiology for this decline in male sexual activity is multifactorial, and is in part related to female partners menopause at approximately 52 years of age, leading to a significant decline in female libido and desire to engage in sexual activity.”
While ED is associated with ageing, many studies and largescale surveys have concluded that ED is a major health concern among young men.
Theresa adds, “One study in 2013 reported that 1: 4 men seeking medical help for erectile dysfunction in the real-life setting, is < 40 years of age. Another study in 2016 concluded that 22.1% of men < 40 years of age had low (<21) Sexual Health Inventory for Men (SHIM) scores.
“In the past, erectile dysfunction was almost always considered a psychogenic disorder. However,
evidence now suggests that more than 80% of cases have an organic aetiology. While most patients with ED have organic disease, some do have a primary psychological cause, particularly younger men. Even when ED is organic in nature, there are almost always psychological consequences regarding relationship issues, cultural norms and expectations, loss of self-esteem, shame, and anxiety and depression related to sexual performance.”
Erectile dysfunction is multidimensional in nature, and Theresa says it can be broadly divided into endocrine and nonendocrine causes.
“The condition can be caused by any disease process which affects penile arteries, nerves, hormone levels, smooth muscle tissue, corporal endothelium, or tunica albuginea. It is closely related to cardiovascular disease, diabetes mellitus, hyperlipidaemia, hypertension, and endothelial dysfunction,” she explains.
“Erectile dysfunction and vascular disease are thought to be linked at the level of the endothelium. Endothelial dysfunction, results in the inability of smooth muscle cells lining the arterioles to relax and prevents vasodilatation. The endothelial cell is known to affect vascular tone and impact the process of atherosclerosis and impacting ED, CVD and peripheral vascular disease. Cardiovascular disease and hypertension are very significant risk factors for erectile dysfunction.”
Besides cardiovascular disease, there are strong correlations between ED and hyperlipidaemia, diabetes, hypogonadism, obesity, smoking, alcoholism, benign prostatic hyperplasia (BPH) with lower urinary symptoms (LUTS), depression, and premature ejaculation. Diabetes is a common aetiology of sexual dysfunction, because it can affect both the blood vessels and the nerves that supply the penis. Men with diabetes are four times more likely to experience erectile dysfunction, and on average, experience it 15 years earlier than men without diabetes.
“Obesity is also correlated to the development of several types of dysfunction, including a decrease in sex drive and an increase in episodes of ED,” she continues. “Neurogenic erectile dysfunction is caused by a deficit in nerve signalling to the corpora cavernosa. Such deficits can be secondary to spinal cord injury, multiple sclerosis, Parkinson disease, lumbar disc disease, traumatic brain injury, radical pelvic surgery and diabetes. Men being treated for prostate cancer with treatments such as radical prostatectomy, radiation therapy or the use of lutenising hormonereleasing hormone (LHRH) agonists and antagonists often experience ED.”
Numerous medications are listed with erectile dysfunction and/ or a decreased libido as a side effect. Drugs that can cause ED include hydrochlorothiazide’s and beta-blocking agents. Medications used to treat depression, particularly the SSRIs such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, can also contribute to ED. The severity of erectile dysfunction is often described as mild, moderate or severe according to the five-item International Index of Erectile Function (IIEF-5) questionnaire, with a score of 1–7 indicating severe, 8–11 moderate, 12–16 mild–moderate, 17–21 mild and 22–25 no erectile dysfunction.
The International Index of Erectile Function (IIEF-5) Questionnaire
The IIEF is a multidimensional validated questionnaire with 15 questions in the five domains of sexual function (erectile and orgasmic functions, sexual desire, satisfaction with intercourse and overall sexual satisfaction), and there is also an abbreviated format of five questions in the Sexual Health Inventory for Men (SHIM).
Investigations and Diagnosis
Theresa continues, “A thorough medical history, detailed sexual history, and physical examination are required before commencing treatment or further investigations. It is important to distinguish between psychological and organic causes of ED, as well as to ensure that the patient has erectile dysfunction and not another disorder. History that points towards a psychological aetiology include, sudden onset of erectile dysfunction especially if it is related to a new partner or a major life-changing event, situational ED, normal erections with masturbation or a different partner, presence of morning erections and high daily variability in erectile rigidity.
“The main differential diagnosis for erectile dysfunction is hypogonadism, loss of libido, depression with low mood, and other psychological conditions. It may also be the first manifestation of diabetes or cardiovascular disease as well as depression. It is important to differentiate between true erectile dysfunction and other sexual disorders such as premature ejaculation, and this is usually assessed by obtaining a good sexual history.
“A complete medication list including supplements should be checked with the patient. ED can be a result of prescription or other medications. Prescription drugs that can cause ED include, antidepressants especially SSRIs, cimetidine, ketoconazole, spironolactone, sympathetic blockers, thiazide diuretics, and other antihypertensives. ACE inhibitors and calcium channel blockers are the least likely to cause ED. Beta-blockers are only a minor contributor, while alpha-blockers can improve erectile function.”
Vascular risk factors such as hypertension and diabetes and lifestyle factors such as smoking, activity level, alcohol intake, and the use of any recreational drugs should be assessed, Theresa adds. A full general and cardiovascular examination should be undertaken, as erectile dysfunction can be the first symptom of underlying vascular disease. Peripheral pulses should be checked and blood pressure measured. The genitalia should be carefully inspected for hypogonadism, signs of infection, the presence of penile fibrosis or plaques, and phimosis.
Theresa continues, “The role of testosterone replacement therapy (TRT) as a potential to improve erectile function in ED remains an issue for clinicians who are comfortable treating androgen deficiency. Androgens are known to have a significant impact on the function of the smooth musculature within the corpus spongiosum.
“Testosterone supplementation is more effective as a treatment for low libido than for ED. For most men with both ED and hypogonadism, oral PDE5 inhibitors alone are recommended as the initial therapy. Testosterone supplementation is reasonable in men with proven hypogonadism and ED who have already failed PDE5 inhibitor therapy or who also have low libido. Hypogonadal patients with borderline erectile rigidity are most likely to benefit from testosterone supplementation.
“Testosterone replacement therapy may cause increased levels of haemoglobin or haematocrit which is associated with an increased risk of heart attack, stroke and blood clots. Testosterone treatment can also cause an enlarged prostate or other prostate disorders. During TRT treatment, the prostate specific antigen (PSA) will be measured to monitor for any changes and this is particularly important in men over 45 years of age.
“As a result of using testosterone replacement, natural production of testosterone may be reduced. This may lead to a reduction in sperm production and fertility. Other side effects of TRT include: weight gain, increased appetite, hot flushes, acne, depression, restlessness, irritability, aggression, tiredness, general weakness and excessive sweating. Lifestyle modifications are considered first-line therapy for ED, and men should be encouraged to make the necessary changes to benefit both their sexual function and their overall health.
“PDE5 inhibitors are highly effective and have an overall success rate of up to 76%. PDE5 inhibitors are contraindicated in patients taking nitrates, but otherwise are safe and effective. When PDE5 inhibitors are co-administered with nitrates, pronounced systemic vasodilation and severe hypotension can occur.
“PDE5 inhibitors and α-adrenergic receptor blockers, often used for treatment of BPH, need to be taken at least 4 hours apart. Among second-line therapies, external vacuum devices (VCDs) are a good, non-surgical option for patients with ED. VCDs are clear plastic chambers placed over the penis, tightened against the lower abdomen with a mechanism to create a vacuum inside the chamber. This directs blood into the penis. If an adequate erection occurs inside the chamber, the patient slips a small constriction band off the end of the VCD and onto the base of the penis. An erection beyond 30 minutes is not recommended. While cumbersome, these devices are considered safe.
“Other second-line therapy includes the use of either intracavernosal injection (ICI) or intraurethral suppositories (IUS). A small needle is used to inject the ICI medication into the lateral aspect of the penis through a small-gauge needle. These vasoactive agents include prostaglandin E1, papaverine and phentolamine and sometimes atropine, which work alone or in combination to elicit an erection. Response is dose related, usually occurs within 10– 15 minutes, and does not require stimulation. A concern with ICI use is priapism, and if this occurs the patient will need to seek urgent medical attention. Bruising can also occur, due to it being an injected medication. The intraurethral suppository consists of a tiny pellet of prostaglandin E1 inserted into the urethral meatus. Response is dose related, and onset usually occurs within 10–15 minutes. Patients need to be trained on the technique of the IUS before use, and should be advised that pain or burning may occur with this medication.
“In men who fail to respond to first or second-line therapy, or who are not interested in conservative therapies, penile prosthesis implantation is available. Penile implants include malleable and inflatable devices, although most implants used are of the inflatable variety. Adverse effects including malfunction and infection are rare, and patient satisfaction is high.”
Outlook
Theresa told us that future Therapies for ED Clinical studies in gene therapy are looking towards replacing proteins that may not be functioning properly in the penile tissue of men with erectile dysfunction.
She says, “Replacement of these proteins may result in improvement in ED. Experimental animal models have demonstrated improvement in erectile function with gene therapy. Human studies may demonstrate success with this therapy in the future, however, gene therapy in humans is controversial, and can take a long time for regulatory approval and public acceptance.
“Stem cell studies may also provide advancements in the treatment of ED in the future. The mechanism of action of stem cells is to generate angiogenesis with subsequent increase in cavernosal smooth muscle cells within the corporal bodies.
“The clinical studies published to date provide encouraging results, with improvement of sexual function reported with no side effects. Although pioneering, stem cell studies to date are small scale, with a short follow up period, various aetiologies of ED and without a control group. Melanocortin activators are drugs that act through the central nervous system, and have been shown in animal studies to produce an erection. Initial studies in humans suggest that the drug (PT-141) can be effective if given intranasally in men with psychological rather than physical causes, and mild to moderate ED.
“Larger studies are necessary, however, to demonstrate the safety and overall effectiveness of these drugs. Another potential new treatment for ED, is penile low intensity shock wave lithotripsy. This consists of 1500 shocks twice a week for 3–6 weeks. The purpose is to stimulate neovascularisation to the corporal bodies with improvement in penile blood flow and endothelial function. The use of low-intensity shock wave lithotripsy may convert PDE5 inhibitor non-responders to responders.”
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