Adding Testosterone to Sildenafil Offers No Benefit

Ricki Lewis, PhD

November 19, 2012

Testosterone added to sildenafil (Viagra, Pfizer) is no better than placebo in improving erectile dysfunction (ED) or sexual satisfaction, according to a study published online November 19 in the Annals of Internal Medicine.

Many men with ED also have low testosterone. Because in animal models testosterone regulates corporeal venous occlusion, penile blood flow, corpus cavernosum smooth muscle mass, and regulates penile nitric oxide synthase, Matthew Spitzer, MD, from the Boston University School of Medicine in Massachusetts and colleagues hypothesized that adding testosterone to phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, could increase the effect of the drug. Association of the hormone in humans with sexual desire and response supports the hypothesis.

Although many physicians already test testosterone levels and supplement deficits when prescribing a PDE5 inhibitor, the American College of Physicians determined that evidence is insufficient to support this practice. In a parallel, randomized, placebo-controlled, double-blinded trial, the current study compared testosterone plus sildenafil to placebo plus sildenafil in middle-aged to older men with low testosterone levels and ED.

Primary outcome was improved erectile response. Secondary outcomes were other aspects of the sexual response, including sexual desire, ejaculation, and orgasm; frequency, quality, and satisfaction with intercourse; quality-of-life assessment; well-being; mood; and intimacy with a partner.

The investigation, performed from September 2004 until May 2010, had screening, drug-dose optimization, and intervention phases. Participants were between the ages of 40 and 70 years, scored less than 25 points on the erectile function domain (EFD) of the International Index of Erectile Function, and had total testosterone levels lower than 11.45 nmol/L or free testosterone levels lower than 173.35 pmol/L.

Half of the 140 participants received sildenafil plus daily 1% transdermal gel containing 10 g testosterone for 14 weeks, and the other half received the drug plus placebo gel. Ten men in the testosterone group and 12 men in the placebo group did not complete the protocol.

Candidates were excluded if they did not have sexual partners or had prostate or breast cancer, penile abnormalities, untreated sleep apnea, major psychiatric diseases, recent myocardial infarction or stroke, or elevated hematocrit, creatinine, prostate-specific antigen, hemoglobin A1c, or blood pressure levels.

The researchers optimized sildenafil dose during a 3- to 7-week period. Each participant applied 3 tubes of gel daily, with varying contents. After 2 weeks, an unblinded physician adjusted each man's dose to achieve the desired testosterone level.

The investigators used several rating scales to assess participants' perceptions of their sexual activity during the trial period. Liquid chromatography-tandem mass spectrometry assayed total testosterone levels from morning blood samples.

The researchers predicted that the sample sizes were sufficient to show that adding placebo gel to sildenafil would add 2 points to the EFD score, and adding testosterone gel would add 6 or more points. However, the anticipated boost with testosterone did not happen.

"The primary analysis indicated that 14-week change in EFD score after randomization...did not differ significantly between the testosterone and placebo groups (difference between mean changes, 2.2 [(confidence interval), −0.8 to 5.1]; P = 0.150)," the researchers conclude.

Secondary outcomes also did not differ between the 2 groups. Frequency of attempts at sex, vaginal penetration, ejaculation, satisfaction, and percentage of successful encounters improved to similar degrees in both groups, indicating that sildenafil was responsible for the improvements, and not testosterone supplementation. Frequency of adverse events also did not differ between the testosterone and placebo groups.

A limitation of the study is that it did not examine whether testosterone improves ED without sildenafil or whether adding the hormone has other benefits, such as improving body composition, muscle strength, cognition, and metabolism.

"The bottom line is that addition of testosterone adds to PDE5 only in men who have very low testosterone levels. The men in the current study did not have these low levels," H. Ballentine Carter, MD, professor of urology and oncology at Johns Hopkins Medicine in Baltimore, Maryland, told Medscape Medical News. He pointed to a study finding a similar lack of effect of supplementary testosterone in men taking tadalafil (Cialis, Lilly) ( J Sexual Med. 2011:8:284-293). Dr. Carter was not involved in the current study.

Dr. Bhasin has consulted for Eli Lilly & Co and received grants from Abbott and Ligand. One coauthor has received grants from Endo Pharmaceuticals and Bayer Healthcare and has consulted for Eli Lilly & Co and Bayer Healthcare. The other authors and Dr. Carter have disclosed no relevant financial relationships.

Ann Intern Med. Published online November 19. 2012.

processing....