Treating men who have androgen deficiency with a 2 percent testosterone solution helped improve their sex drive and energy for at least 9 months without adding adverse effects, researchers say.

Results from the study by Gerald Brock, MD, in the department of surgery, University of Western Ontario, London, and colleagues, were published in the Journal of Urology.

Treatment with the 2 percent testosterone solution, applied in the armpit, was well tolerated for the 9-month study period, which included a 3-month, double-blind, placebo-controlled part at the beginning (June 2013–October 2014), followed by a 6-month open-label extension, which ended in April 2015.

The 6-month extension demonstrated that the increases in sex drive and energy continued after the original double-blind phase and did not plateau after the first few months of therapy.

In an accompanying editorial, Drs. Kevin R Loughlin and Julia Klap, of the department of urology, Brigham and Women's Hospital, Boston, Massachusetts, say the results "suggest this form of testosterone is safe," but the efficacy outcomes "are somewhat more uncertain" as, at the end of the open-label phase, only 60 percent to 66 percent of participants in the formerly placebo and continuing active therapy groups, respectively, had total testosterone levels within the normal range.

And moreover, they state, what is needed more than anything is a quantification of age-adjusted testosterone levels. Increasing numbers of older men are being prescribed testosterone on the basis of low testosterone levels when compared with men aged 40 and younger. But it may just be that testosterone levels at older ages are slightly lower, in which case "it should not be unexpected that testosterone supplementation may not result in a significant clinical benefit," they observe.

"A prospective trial to better define age-adjusted testosterone levels is long overdue and should be near the top of our research agenda."

The US Food and Drug Administration (FDA) requires that all makers of prescription testosterone products make sure to indicate on the label that testosterone-replacement therapy is approved "only for men who have low testosterone levels due to disorders of the testicles, pituitary gland, or brain that cause hypogonadism" and not simply to relieve symptoms in men who have low testosterone for no apparent reason other than aging.

But regardless of this, "interest in testosterone-replacement therapy continues to intensify" — there was a more than threefold increase in use of testosterone from 2001 to 2011 among men in the US aged 40 years or older, say Drs. Loughlin and Klap in their editorial.

The FDA says testosterone shouldn't be used in men who don't have hypogonadism because the benefit/risk profile for such use hasn't been established, including cardiovascular risks, which remain unknown. But the EU medicines agency has taken a difference stance and concluded that there is "no consistent evidence" of an increased risk for heart problems with testosterone products.

Of the 558 participants, average age 55 years, in the open-label extension phase of the trial, 275 had previously received placebo and 283 had been treated with testosterone. They were recruited from a number of countries, including in North and South America, Europe, and South Korea.

At the end of the open-label study, 60 percent of the formerly placebo group and 66 percent of the continuing-active group had normal testosterone levels.

Participants completed two relatively new surveys: the five-item Sexual Arousal, Interest and drive (SAID) survey and the two-item Hypogonadism Energy Diary (HED).

Treatment with the testosterone solution significantly improved SAID scores during the open-label phase for both the formerly placebo and continuing-active groups: mean change for the formerly placebo group was 17.5 and continuing-active group was 9.3. This meant that testosterone improved sex drive, arousal, and erectile function.

Testosterone also improved HED scores from the beginning of the open-label phase to end point: mean change for the formerly placebo group was 8.9 and for the continuing-active group was 5.1.

The SAID and HED questionnaires help advance the clinical management of these men because they can help assess how profoundly affected they are at the beginning of treatment and after they start to respond to therapy, DR. Brock noted.