Management of Erectile Dysfunction Reviewed CME
News Author: Laurie Barclay, MD
CME Author: Charles P. Vega, MD

CME Released: 02/09/2010

February 9, 2010 — The best practices to manage erectile dysfunction (ED) in the family practice setting are reviewed in an article published in the February 1 issue of American Family Physician.

"...ED is defined by the National Institutes of Health as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance," writes Joel J. Heidelbaugh, MD, from the University of Michigan in Ann Arbor. "ED is the most common sexual problem in men; it often causes serious distress, prompting men to seek medical attention they may not otherwise seek. It often has a profound effect on intimate relationships, quality of life, and overall self-esteem [and] may also be the presenting symptom or harbinger of undetected cardiovascular disease."

ED may result from organic causes related to vascular, neurogenic, hormonal, anatomic, or drug-induced conditions; psychological causes; or a combination of both. ED will affect up to one third of men during their lifetime, and it increases in incidence with age. Predictive factors associated with a greatly increased risk for ED are obesity, sedentary lifestyle, and smoking.

In most cases, history and physical examination are sufficient to diagnose ED. Medical history should determine the presence of diabetes or other comorbid conditions that can increase the risk for ED, medication history may reveal use of medications with sexual adverse effects, and sexual history should assess libido and ability to reach orgasm and to ejaculate. Physical examination should include cardiovascular and neurologic assessment, genital inspection, and digital rectal examination.

Although there is no preferred first-line diagnostic test, initial diagnostic evaluation should usually consist only of a fasting serum glucose level and lipid panel, thyroid-stimulating hormone test, and morning total testosterone level. Optional laboratory tests may include complete blood count; free testosterone, luteinizing hormone, and prolactin levels; sex hormone–binding globulin test; and/or urinalysis.

Evaluations that may be considered in selected patients with ED include psychological or psychiatric consultation, in-depth psychosexual and relationship evaluation, neurophysiologic penile and sphincter testing, nocturnal penile tumescence and rigidity assessment, specialized endocrinologic testing, and/or vascular diagnostics.

First-line treatment of ED consists of lifestyle interventions (weight loss, increased exercise, and smoking cessation), discontinuation or changing of medications that may cause ED, and pharmacotherapy with phosphodiesterase type 5 (PDE5) inhibitors.

The most effective orally administered drugs for treatment of ED are the PDE5 inhibitors, which have been shown to be effective for ED associated with diabetes mellitus, spinal cord injury, and antidepressant use.

"The three PDE5 inhibitors are considered to be relatively similar in effectiveness, but there are differences in dosing, onset of action, and duration of therapeutic effect," Dr. Heidelbaugh writes. "An open-label trial found that patients preferred tadalafil and vardenafil over sildenafil, yet most evidence supports equal effectiveness between sildenafil and vardenafil. PDE5 inhibitors are generally well tolerated, with mild transient adverse effects of headache, flushing, dyspepsia, rhinitis, and abnormal vision."

When PDE5 inhibitors are ineffective, alternative therapeutic options may include intraurethral and intracavernosal injections of alprostadil, vacuum pump devices, and surgically implanted penile prostheses.

For men with hypogonadism, testosterone supplementation generally improves ED and libido but is associated with a higher risk for prostate adenocarcinoma. Interval monitoring of hemoglobin, serum transaminase, and prostate-specific antigen levels is therefore required.

Cognitive behavioral therapy and therapy aiming to improve the quality of relationships may be helpful for couples affected by ED.

Risk for coronary, cerebrovascular, and peripheral vascular diseases is increased in men with ED. Because symptoms of ED may occur 3 years earlier, on average, than symptoms of coronary artery disease, screening for cardiovascular risk factors should be considered in men with ED.

Key clinical recommendations for practice, and their accompanying level of evidence rating, are as follows:

Diagnostic workup for ED should usually be limited to a fasting serum glucose level and lipid panel, thyroid-stimulating hormone test, and a morning total testosterone level (level of evidence, C).
Oral PDE5 inhibitors should be first-line treatment of ED (level of evidence, A).
PDE5 inhibitors are most effective in treating ED associated with diabetes mellitus and spinal cord injury, and sexual dysfunction associated with antidepressants (level of evidence, A).
Psychosocial therapy may be a useful adjunctive treatment of ED, as well as testosterone supplementation in men with hypogonadism (level of evidence, B).
Testosterone supplementation improves ED and libido in men with hypogonadism (level of evidence, B).
Screening for cardiovascular risk factors should be considered in men with ED (level of evidence, C).
"The economic impact of ED is multifactorial, with direct costs that include physician evaluation, pharmacotherapy, and diagnostic testing, and indirect costs that include lost time at work, lost productivity, and effects on the man's partner, family, and co-workers," Dr. Heidelbaugh concludes. "The Prostate Cancer Prevention Trial determined that men with ED have a significantly greater likelihood of having angina, myocardial infarction, stroke, transient ischemic attack, congestive heart failure, or cardiac arrhythmia compared with men without ED. Because most men are asymptomatic before an acute coronary syndrome, ED may serve as a sentinel marker for prompting discussions centered on promotion of cardiovascular risk stratification and modification."

Dr. Heidelbaugh has disclosed no relevant financial relationships.

Am Fam Physician. 2010;81:305-312. Abstract

Clinical Context

Sexual function in men requires a complex combination of sensory and psychological input and depends on a mix of neurotransmitters from both sympathetic and parasympathetic nerve terminals. Finally, as nitric oxide performs a critical role in erections, vascular health is also critical for good sexual function.

The complexity of male sexual function means that there is much that can go wrong, and it often does. Up to one third of men experience ED at some point in their lives, and the risk for ED increases with age. The current review describes the appropriate workup and treatment of ED.

Study Highlights

There is no preferred, first-line diagnostic test for ED. Men with ED should have a thorough medical history to investigate possible comorbid conditions, such as diabetes or obesity, that can promote ED. Physicians should also complete a sexual history on these patients, including an evaluation of libido and orgasm/ejaculatory function, as well as review medications that might inhibit erections.
The physical examination should include a cardiovascular, neurologic, and genital examination along with a digital rectal examination.
Given the common association of ED with some chronic illnesses, men with ED should be evaluated with a fasting serum glucose level, lipid panel, thyroid-stimulating hormone test, and morning total testosterone level.
Primary treatment of patients with ED should include lifestyle modifications focusing on weight loss in overweight or obese men and smoking cessation for smokers. Weight loss has been associated with improvements in ED.
PDE5 inhibitors are also considered first-line therapy for ED. Although these medications have been demonstrated to improve erections among men with different chronic conditions promoting ED, approximately one third of men do not respond to PDE5 inhibitors. In addition, these medications do not improve libido.
There are limited data to suggest that one PDE5 inhibitor is superior to another. Headache is the most common adverse effect of PDE5 inhibitors, occurring in approximately 10% of patients.
Hypogonadism is estimated to be present in 5% to 10% of men with ED, and treatment with testosterone supplementation can improve both erections and libido in these men. Response rates to testosterone treatment are higher in primary vs secondary testicular failure and with transdermal vs oral or intramuscular testosterone.
Testosterone therapy is associated with a higher risk for erythrocytosis, elevated serum transaminase levels, benign prostatic hypertrophy, and adenocarcinoma of the prostate. Men receiving treatment with testosterone should be monitored accordingly.
Alprostadil is a second-line agent for ED and can be applied directly as an injection into the corpus cavernosum or through the urethra. The intracavernosal route of administration is more effective and better tolerated than the intraurethral route.
Vacuum pump devices can also be effective for ED, but they are contraindicated among men with sickle cell disease or who are receiving long-term anticoagulant therapy.
Behavioral therapy can be effective for ED, especially in cases when the patient can have normal erections during masturbation or sex with another partner.
Men with ED are at higher risk for cardiovascular disease, and the diagnosis of ED should prompt consideration of cardiovascular risk screening.

Clinical Implications

Men presenting with ED should have a thorough sexual history and a digital rectal examination. The laboratory workup of ED may be limited to a fasting serum glucose level, lipid panel, thyroid-stimulating hormone test, and morning total testosterone level.
PDE5 inhibitors are a first-line treatment of ED, but no one PDE5 inhibitor has proven itself superior to others. Testosterone therapy can improve both libido and erections among men with ED. Vacuum pump devices should be avoided among men receiving anticoagulants, and injected alprostadil is more effective than the intraurethral route of administration.

CME Test

Questions answered incorrectly will be highlighted.

All of the following tests should be part of the routine evaluation of men with ED except:

Digital rectal examination
Serum 17-OH progesterone
Serum lipid panel
Total morning testosterone levels

Which of the following statements regarding the management of ED is most accurate?

Tadalafil has been proven to offer superior efficacy vs sildenafil or vardenafil
The vacuum pump is ideal for men receiving anticoagulant medications
Testosterone therapy can improve both libido and erections among men with hypogonadism
Intraurethral alprostadil is more effective vs intracavernosal alprostadil injections