ACP Issues Guidelines for Treatment of Erectile Dysfunction

Laurie Barclay, MD

October 19, 2009

October 19, 2009 — The American College of Physicians (ACP) has issued recommendations for the treatment of erectile dysfunction (ED), defined as the persistent inability to achieve or maintain penile erection sufficient for satisfactory sexual performance. Evaluation and consideration of treatment are indicated when ED persists for at least 3 months.

The new clinical practice guidelines, which are published early release in the October 20 issue of the Annals of Internal Medicine, strongly urge physicians to begin therapy with an oral phosphodiesterase type 5 (PDE-5) inhibitor in men who seek treatment of ED, unless they are receiving nitrate therapy or have another contraindication to use of PDE-5 inhibitors.

"The evidence is insufficient to compare the effectiveness or adverse effects of different PDE-5 inhibitors for the treatment of ED because there were only a few head-to-head trials," lead author Amir Qaseem, MD, PhD, MHA, FACP, senior medical associate at the ACP, said in a news release.

Therefore, the guideline recommends that physicians decide on a specific PDE-5 inhibitor to prescribe based on individual patient preferences, taking into account convenience and ease of use, medication costs, and safety and adverse effects profile. Available PDE-5 inhibitors include sildenafil, vardenafil, tadalafil, mirodenafil, and udenafil.

Because available evidence is inconclusive about the efficacy of hormonal therapy for ED in patients with low testosterone levels, the ACP does not recommend for or against routine hormonal blood tests or treatment in patients with ED. Measurement of hormone levels may be appropriate in specific patients.

Clinicians should consider the presence or absence of symptoms of hormonal dysfunction, such as decreased libido, premature ejaculation, or fatigue, and of physical findings such as testicular or muscle atrophy, when considering whether to measure hormone levels in individual patients.

Risk factors for ED include advanced age, diabetes, vascular diseases, psychiatric disorders, and possibly hypogonadism. Worldwide prevalence of ED exceeded 152 million in 1995, and with the graying of the population, it is estimated that it will be approximately 322 million by the year 2025.

The accompanying review of evidence included an analysis of information from 130 randomized controlled trials of oral PDE-5 inhibitors used for ED as monotherapy or in combination. The study authors identified these trials by searching English-language publications in MEDLINE (from 1966 - May 2007), EMBASE (from 1980 - week 22 of 2007), the Cochrane Central Register of Controlled Trials (second quarter of 2007), PsycINFO (from 1985 - June 2007), AMED (from 1985 - June 2007), and SCOPUS (in 2006). The investigators further updated this search by searching for articles in MEDLINE and EMBASE published between May 2007 and April 2009.

Regardless of the specific cause of ED, such as diabetes, depression, or prostate cancer, or baseline severity, treatment with a PDE-5 inhibitor was associated with statistically significant and clinically meaningful improvements in sexual intercourse and in erectile function. For sildenafil and vardenafil, improvement in erectile functioning was related to higher doses, but this was not true for tadalafil. Higher doses were also linked to a higher risk for adverse effects.

The evidence review also showed a relatively good tolerability profile of PDE-5 inhibitors. Adverse effects were mostly mild or moderate, including headaches, flushing, dyspepsia, and rhinorrhea. Less common adverse effects were visual disturbances, myalgia, nausea, diarrhea, vomiting, dizziness, and chest pain.

Although trials reviewed as part of the evidence base for this guideline did not report priapism, this adverse effect was reported infrequently during postmarketing surveillance.

Various PDE-5 inhibitors did not differ significantly in the incidence of adverse events. There was high-quality evidence that men treated with a PDE-5 inhibitor are more likely to have at least 1 adverse event vs placebo. The incidence for more serious adverse events was less than 2%, and incidence did not differ between PDE-5 inhibitors and placebo.

Available testosterone formulations include oral, injection, gel, patch, and cream. Evidence regarding the efficacy of hormonal therapy for ED was inconclusive because trials comparing testosterone vs placebo in hypogonadal men with ED were small, of low quality, or showed inconsistent effects on erectile function.

"The evidence regarding the incidence of adverse events was limited and inconclusive, and more high-quality head-to-head trials are needed to explore differences in adverse events, especially severe adverse events," the guidelines authors write. "The evidence regarding the utility of routine hormonal blood tests was inconclusive given the limited number of studies and various methodological issues and needs to be further developed."

Specific recommendations in this clinical practice guideline, and their accompanying level of evidence rating, are as follows:

  1. The ACP recommends that clinicians begin treatment with a PDE-5 inhibitor in men who seek treatment of ED and who have no contraindication to use of PDE-5 inhibitors (grade: strong recommendation; high-quality evidence).

  2. The ACP recommends that clinicians choose a specific PDE-5 inhibitor based on the individual preferences of men with ED, considering ease of use, cost of medication, and adverse effects profile (grade: weak recommendation; low-quality evidence).

  3. The ACP does not recommend for or against routine use of hormonal blood tests or hormonal therapy for patients with ED (grade: insufficient evidence to determine net benefits and harms).

Financial support for the development of this guideline was provided exclusively from the ACP operating budget. The recommendations are not intended to represent an official position of the Agency for Healthcare Research and Quality or the US Department of Health and Human Services. Some of the guidelines authors have disclosed various financial relationships with Bristol-Myers Squibb, the Centers for Disease Control and Prevention, Novo Nordisk, Merck Vaccines, Boehringer Ingelheim, Wyeth, Sanofi Pasteur, Pfizer, and/or Up-to-Date.

Ann Intern Med. Published online October 20, 2009.