AT THE AUA ANNUAL MEETING

NEW ORLEANS (FRONTLINE MEDICAL NEWS) – Testosterone 2% solution resulted in improved sex drive and increased energy in most hypogonadal men, according to a study presented by Dr. Gerald B. Brock at the annual meeting of the American Urological Association. In addition, testosterone levels returned to the normal range in this cohort, he reported.

“The treatment of hypogonadism has become very controversial in the U.S., Canada, and worldwide,” said Dr. Brock, a professor in the division of urology, department of surgery at St. Joseph’s Health Centre in London, Ontario. “Part of the problem is a lack of well-designed, placebo-controlled multicenter trials that specifically look at the symptomatic benefit [of testosterone replacement therapy] in these men. Symptoms are what drive men in for treatment, and as a result, we think it’s important to evaluate that endpoint.”

Dr. Brock and his colleagues assessed a broad population of hypogonadal men in order to determine the effect of testosterone solution 2% vs. placebo on serum total testosterone (TT) concentration, sexual drive, and energy.

In this multicenter, randomized, double-blind study, hypogonadal men ≥18 years (serum TT < 300 ng/dL) were assigned testosterone or placebo for 12 weeks. Men enrolled were required to have at least one symptom of testosterone deficiency (decreased energy or decreased sexual drive).

The primary objective was to compare the effect of testosterone and placebo on the proportion of hypogonadal men with serum TT levels falling within the normal range (300-1,050 ng/dL) after 12 weeks of treatment.

At entry into the study, men were given 60 mg of testosterone solution 2% or placebo, once daily. Two screening visits were conducted (baseline and randomization), and subsequent visits at weeks 2, 4, 6, 8, and 12 of treatment.

“An important part of this protocol was that the testosterone was dose-adjusted in a blinded fashion,” Dr. Brock said. “Based on results, patients could either be upped or lowered in their testosterone levels by 30-mg intervals at the 2-week interval visits.” Dosage adjustments were based on an algorithm used at weeks 4 and 8, using blinded TT levels determined at the preceding visit.

Secondary endpoints measured the effect of testosterone on sexual drive and energy level using two new patient-reported outcome instruments: the Sexual Arousal, Interest, and Drive ( SAID ) scale, for patients with low sex drive, and the Hypogonadism Energy Diary (HED), for patients with low sexual energy and overall energy. “Looking at these two facets was one of the novel aspects of the study,” Dr. Brock said.

Both SAID and HED were self-administered through the use of a handheld device. The SAID scale measures five items: thinking about sex (two items), arousal (one item), and level of interest in sex and sex drive (two items) as recalled in the past 7 days. Each item received a score of 1-5, and all scores were averaged to constitute the total SAID score.

HED was administered through two questions asked three times per day for 7 days, and addressed patients’ real-time energy levels (extent to which the respondent feels energetic or has feelings of tiredness/exhaustion). Each item was scored 0-10, and the total score was the sum of 7-day average scores for six items.

Exploratory measures included assessments of Patient Global Impression of Improvement ( PGI-I ), International Index of Erectile Dysfunction ( IIEF ), and the Psychosexual Daily Questionnaire (PDQ).

Overall, 715 patients (mean age, 55 years) were randomized to placebo (n = 357) or testosterone (n = 358); 82% (n = 294) of men assigned to placebo and 84% (n = 302) assigned to testosterone completed the 12-week study.

The study population was predominantly white, with a wide international enrollment. Low energy or decreased sex drive were present in roughly 75% of the study population, 50% of whom had previously received testosterone.

Comorbidities were common among participants – 30% had diabetes, 50% had hypertension, 38% had high cholesterol, and about 90% had hypogonadism from unknown reasons. “This was really a good representation of the general hypogonadal population,” Dr. Brock said.

“The results at 12 weeks were as expected,” he said. Normalization of testosterone (300-1,050 ng/dL) was found in 217 men (73%) in the active arm, compared with 43 (15%) in the placebo arm (P < 0.001).

“But perhaps the more exciting analyses show that the SAID and HED scales showed significant improvement,” he noted. “The preset levels of 0.01 were met with the SAID scale, and we received a significance level of 0.019 for the HED scale.”

Upon evaluation of exploratory measures, Dr. Brock and his coinvestigators found a significant difference between treatment groups across all domains of IIEF – orgasmic and erectile function, sexual desire, and intercourse and overall satisfaction (P < .05). The PDQ showed that statistical significance was reached in sexual desire, enjoyment, and sexual activity in the treated group compared with placebo (P < .05). The PGI-I also showed a significant effect of testosterone solution on energy level and sexual drive (P < .001 for treatment group difference).

“Perhaps the most important aspect of this trial is the safety, especially with all of the controversy about cardiovascular concerns,” Dr. Brock said. “There was no evidence of cardiovascular events in the treated arm and a single ischemic stroke in the placebo arm among the 356 patients in that group.”

Dr. Brock and his colleagues found that testosterone solution 2% therapy in hypogonadal men resulted in TT levels returning to the normal range in most of the cases. The testosterone solution also led to statistically significant improvements in sex drive and energy levels.

“The safety in this study was clear, and as a result, I think this is an important study that gives us new insight into the treatment of the hypogonadal male,” he asserted.

This study was funded by Eli Lilly. Dr. Brock has served as a consultant, done research in clinical trials, and served on advisory boards for several pharmaceutical companies. He owns stock in Lilly, in addition to Pfizer, Johnson & Johnson, GlaxoSmithKline, Abbott, and Astellas Pharma.

imnews@frontlinemedcom.com

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