Treating men who have androgen deficiency with a 2% 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 online in the Journal of Urology, scheduled for its November issue.
Treatment with the 2% testosterone solution (Axiron, Lilly), 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% to 66% 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."
No Cardiovascular Signals in Latest Trial
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.
Dr Brock acknowledged that cardiovascular safety with testosterone has been "controversial," but this latest study "wasn't designed" to address this issue, he told Medscape Medical News.
Nevertheless, he said his new research adds to the literature in that it included a large number of men — 558 — taking testosterone for an extended period of time. And "there was absolutely no evidence of any concerning end point in this study — no cardiovascular signal whatsoever," he said.
Also, because the solution is applied under the arm, it doesn't have as much risk of transferring to a partner or children, Dr Brock said.
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.
Participants in both groups had similar baseline characteristics — to qualify for the trial, they had to be 18 years or older and have had two total testosterone levels < 300 ng/dL measured 1 week or more apart and at least one symptom of testosterone deficiency (low energy or low sex drive).
At the end of the open-label study, 60% of the formerly placebo group and 66% of the continuing-active group had normal testosterone levels.
Improved SAID and HED Scores
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 (P < .001 for both groups). 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 (P < .001 for both groups).
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.
There were no significant changes from week 0 to week 36 in body mass index, HbA1c, or insulin sensitivity for the formerly placebo or continuing-active groups.
"For the first time, we really have an understanding of what treatment with testosterone does to those men who become normalized in terms of their testosterone level," Dr Brock commented.
He and his coauthors acknowledge, however, that a limitation of the study is that there was no placebo control in the open-label phase. Without that, the observed improvements cannot be conclusively attributed to testosterone-replacement therapy, they caution.
Is It Thyroid, Depression, Low T, or Just Old Age?
Dr Brock says some primary-care physicians are stymied by patients who report low energy or low sexual interest as to whether it could be a thyroid problem, depression, or just old age.
"In the past 10 years many of us have begun to recognize that it may be, in some of these men, a direct effect of having low testosterone," he said.
In their editorial, Drs Loughlin and Klap note that testosterone may decline with aging to levels that are "below the normal range for healthy young men," but it's not clear whether coexisting symptoms, such as decrease in energy, "are a consequence of age-related decline in endogenous testosterone or whether they are a result of other factors, such as coexisting conditions, concomitant medications, or perhaps aging itself."
Findings from the first three of seven placebo-controlled, multicenter Testosterone Trials, published in February, indicate a year's worth of testosterone treatment in older men may help improve sexual function, mood, depressive symptoms, and possibly walking distance, but it doesn't seem to improve vitality, they note.
The accompanying editorial at the time concluded that although testosterone therapy did yield certain benefits, at this point their clinical importance is uncertain: "Therapy was not a panacea, and the findings alone might be insufficient to support a decision to initiate testosterone therapy in symptomatic older men."
Hence, the pressing need for proper quantification of age-adjusted testosterone levels, add Drs Loughlin and Klap, "because it is not unreasonable to posit that some of the explosion in testosterone products is due to the fact that some older men are being diagnosed as 'hypogonadal' based on serum levels that apply to men who are decades younger."
Dr Brock reports a financial relationship with Eli Lilly, Pfizer, Johnson & Johnson, and Astellas Pharma. Disclosures for the coauthors are listed in the article. The editorialists report no relevant financial relationships.
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J Urol. Published online April 25, 2016. Abstract, Editorial
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Cite this: 2% Testosterone Ups Sex Drive, Energy for Men With Low T - Medscape - Aug 24, 2016.
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