The American College of Physicians developed this guideline to present the available evidence on hormonal testing in and pharmacologic management of erectile dysfunction. Current pharmacologic therapies include phosphodiesterase-5 (PDE-5) inhibitors, such as sildenafil, vardenafil, tadalafil, mirodenafil, and udenafil, and hormonal treatment.
Published literature on this topic was identified by using MEDLINE (1966 to May 2007), EMBASE (1980 to week 22 of 2007), Cochrane Central Register of Controlled Trials (second quarter of 2007), PsycINFO (1985 to June 2007), AMED (1985 to June 2007), and SCOPUS (2006). The literature search was updated by searching for articles in MEDLINE and EMBASE published between May 2007 and April 2009. Searches were limited to English-language publications. This guideline grades the evidence and recommendations by using the American College of Physicians' clinical practice guidelines grading system.
The American College of Physicians recommends that clinicians initiate therapy with a PDE-5 inhibitor in men who seek treatment for erectile dysfunction and who do not have a contraindication to PDE-5 inhibitor use (Grade: strong recommendation; high-quality evidence).
The American College of Physicians recommends that clinicians base the choice of a specific PDE-5 inhibitor on the individual preferences of men with erectile dysfunction, including ease of use, cost of medication, and adverse effects profile (Grade: weak recommendation; low-quality evidence).
The American College of Physicians does not recommend for or against routine use of hormonal blood tests or hormonal treatment in the management of patients with erectile dysfunction (Grade: insufficient evidence to determine net benefits and harms).
Erectile dysfunction (ED) is a common male sexual disorder. The relative benefits and harms of pharmacologic therapies for ED, as well as the value of hormonal testing in men with ED, are uncertain.
To evaluate the efficacy and harms of oral phosphodiesterase-5 (PDE-5) inhibitors and hormonal treatments for ED and assess the effect of measuring serum hormone levels on treatment outcomes for ED.
English-language studies from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, AMED, and SCOPUS through April 2009. Trial reference lists also were scanned.
Randomized, controlled trials (RCTs) of oral PDE-5 inhibitors and hormonal treatment for ED, and observational studies reporting measurement of serum hormone levels, prevalence of hormonal abnormalities, or both in men with ED.
Two independent reviewers abstracted data on study, participant, and treatment characteristics; efficacy and harms outcomes; and prevalence of hormonal abnormalities.
Data, primarily from short-term trials (≤12 weeks), indicate that PDE-5 inhibitors were more effective than placebo in improving sexual intercourse success (69.0% vs. 35.0%). The proportion of men with improved erections was significantly greater among those treated with PDE-5 inhibitors (range, 67.0% to 89.0%) than with placebo (range, 27.0% to 35.0%). The PDE-5 inhibitors were associated with increased risk for any adverse events compared with placebo (for example, relative risk with sildenafil, 1.72 [95% CI, 1.53 to 1.93]). In 4 head-to-head RCTs comparing sildenafil, vardenafil, and tadalafil, improvement of ED and adverse events did not differ among treatments. Results from 15 RCTs evaluating hormonal treatment of ED were inconsistent on whether treatment improved outcomes. Evidence was insufficient regarding whether men with ED had a higher prevalence of hypogonadism than men without ED.
Many RCTs were of low methodological and reporting quality, particularly those involving hormonal treatments or directly comparing different PDE-5 inhibitors. Most RCTs provided only short-term efficacy and harms data.
Oral PDE-5 inhibitors improved erectile functioning and had similar efficacy and safety profiles. Results on the efficacy of hormonal treatments and the value of hormone testing in men with ED were inconclusive.
Agency for Healthcare Research and Quality.
Methods: Systematic reviews were conducted of literature since 1996 on 9 proposed nontraditional markers of CHD risk: high-sensitivity C-reactive protein, ankle–brachial index, leukocyte count, fasting blood glucose, periodontal disease, carotid intima–media thickness, coronary artery calcification score on electron-beam computed tomography, homocysteine, and lipoprotein(a). The reviews followed a hierarchical approach aimed at determining which factors could practically and definitively reassign persons assessed as intermediate-risk according to their Framingham score to either a high-risk or low-risk strata, and thereby improve outcomes by means of aggressive risk-factor modification in those newly assigned to the high-risk stratum.
Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of using the nontraditional risk factors studied to screen asymptomatic men and women with no history of CHD to prevent CHD events. (I statement).
]]>Purpose: To assist the U.S. Preventive Services Task Force (USPSTF) in determining whether CRP should be incorporated into guidelines for CHD risk assessment.
Data Sources: MEDLINE search of English-language articles (1966 to November 2007), supplemented by reference lists of reviews, pertinent studies, editorials, and Web sites and by expert suggestions.
Study Selection: Prospective cohort, case–cohort, and nested case–control studies relevant to the independent predictive ability of CRP when used in intermediate-risk persons.
Data Extraction: Included studies were reviewed according to predefined criteria, and the quality of each study was rated.
Data Synthesis: The validity of the body of evidence and the net benefit or harm of using CRP for CHD risk assessment were evaluated. The combined magnitude of effect was determined by meta-analysis. The body of evidence is of good quality, consistency, and applicability. For good studies that adjusted for all Framingham risk variables, the summary estimate of relative risk for incident CHD was 1.58 (95% CI, 1.37 to 1.83) for CRP levels greater than 3.0 mg/L compared with levels less than 1.0 mg/L. Analyses from 4 large cohorts were consistent in finding evidence that including CRP improves risk stratification among initially intermediate-risk persons. C-reactive protein has desirable test characteristics, and good data exist on the prevalence of elevated CRP levels in intermediate-risk persons. Limited evidence links changes in CRP level to primary prevention of CHD events.
Limitations: Study methods for measuring Framingham risk variables and other covariates varied. Ethnic and racial minority populations were poorly represented in most studies, limiting generalizability. Few studies directly assessed the effect of CRP on risk reclassification in intermediate-risk persons.
Conclusion: Strong evidence indicates that CRP is associated with CHD events. Moderate, consistent evidence suggests that adding CRP to risk prediction models among initially intermediate-risk persons improves risk stratification. However, sufficient evidence that reducing CRP levels prevents CHD events is lacking.
]]>Purpose: To summarize the results of 9 systematic reviews of novel risk factors to help the U.S. Preventive Services Task Force (USPSTF) evaluate the factors' clinical usefulness.
Data Sources: Results from a MEDLINE search for English-language articles published from 1966 to September 2008, using the Medical Subject Heading terms cohort studies and cardiovascular diseases in combination with terms for each risk factor.
Study Selection: Studies were included if the participants had no baseline cardiovascular disease and the investigators adjusted for at least 6 Framingham risk factors.
Data Extraction: Study quality was evaluated by using USPSTF criteria and overall quality of evidence for each risk factor by using a modified version of the Grading of Recommendations, Assessment, Development, and Evaluation framework. Each factor's potential clinical value was evaluated by using a set of criteria that emphasized the importance of the effect of that factor on the reclassification of intermediate-risk persons.
Data Synthesis: 9 systematic reviews were conducted. C-reactive protein (CRP) was the best candidate for use in screening and the most rigorously studied, but evidence that changes in CRP level lead to primary prevention of CHD events is inconclusive. The other evaluated risk factors were coronary artery calcium score as measured by electron-beam computed tomography, lipoprotein(a) level, homocysteine level, leukocyte count, fasting blood glucose, periodontal disease, ankle–brachial index, and carotid intima–media thickness. The availability and validity of the evidence varied considerably across the risk factors in terms of aggregate quality, consistency of findings, and applicability to intermediate-risk persons in the general population. For most risk factors, no studies assessed their usefulness for reclassifying intermediate-risk persons.
Limitations: Because of lack of access to original data, no firm conclusions could be drawn about differences in risk prediction among racial and ethnic groups. The review did not emphasize within-cohort comparisons of multiple risk factors.
Conclusion: The current evidence does not support the routine use of any of the 9 risk factors for further risk stratification of intermediate-risk persons.
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