In symptomatic older men with low testosterone, restoring levels of the hormone to those of young healthy men yielded moderate improvements in sexual function, mood, depressive symptoms, and some measures of physical function, according to initial results from the Testosterone Trials (T Trials) published in the New England Journal of Medicine.1
Nevertheless, the number of participants limited the ability to draw conclusions about the risk for adverse events associated with testosterone therapy in this patient population, the researchers noted in the study.
“For a long time, there has been interest in whether testosterone is an appropriate therapy for aging-related conditions in men,” National Institute of Aging Director Richard J. Hodes, MD, said in a press release from the National Institutes of Health. “This study clarifies questions about some of its potential benefits. As the researchers note, clarifying the risks requires further study.”
The T Trials
Testosterone generally decreases as men age, with some older men displaying symptoms and conditions similar to those caused by low testosterone levels in men with pituitary or testicular disease, such as decreased mobility, vitality, and sexual function.
“These parallels suggest that the lower testosterone levels in older men may contribute to these conditions,” the researchers wrote.
To date, however, evidence on the benefits and risks of testosterone therapy in older men is conflicting. While studies have shown that the treatment increases muscle mass and decreases fat mass in men aged older than 65 years, data on its effects on physical performance, sexual function, and energy remain inconsistent.
In 2003, the Institute of Medicine highlighted a need for more definitive randomized, controlled trials evaluating the efficacy of testosterone therapy in older men. The T Trials were designed with these recommendations in mind.2
The T Trials include 7 double-blind, placebo-controlled trials conducted at 12 sites and are intended to determine if testosterone therapy can mitigate symptoms associated with low testosterone in older men. The New England Journal of Medicine report describes data from the 3 main trials — the Sexual Function Trial, the Physical Function Trial, and the Vitality Trial. The other trials are assessing cardiovascular, bone density, cognitive, and anemia outcomes.
A total of 790 men aged at least 65 years with testosterone levels lower than 275 ng/dL and symptoms suggesting hypoandrogenism were included in at least 1 of 3 trials.
Researchers randomly assigned participants to testosterone gel (AndroGel 1%, AbbVie) or placebo gel for 1 year. Serum testosterone concentration was measured at 1, 2, 3, 6, 9, and 12 months. Initial daily dose was 5 mg, with adjustment after each measurement to maintain a testosterone concentration within the normal range for young men aged 19 to 40 years.
Modest Benefits of Testosterone Therapy
Results linked increased testosterone levels to increases in sexual activity, as measured by the Psychosexual Daily Questionnaire (P<.001), increased sexual desire, and increased erectile function, the researchers reported.1
In the Physical Function Trial, the researchers noted no significant difference between the testosterone therapy and placebo groups in the percentage of men who experienced an at least 50-meter increase in 6-minute walking distance. However, after including men in all 3 trials, improvement was observed in 20.5% of those who received testosterone vs 12.6% of those who received placebo (P=.003).1
Although men who received testosterone demonstrated no significant improvement in vitality, as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue scale, they did report slightly better mood and lower severity of depressive symptoms, as compared with those who received placebo.1
In terms of adverse events, data showed that 23 men in the testosterone group vs 8 men in the placebo group had an increment in the prostate-specific antigen level of at least 1.0 ng/mL during the treatment period. However, only 1 man in the testosterone group was diagnosed with prostate cancer during that time, and 2 in the testosterone group and 1 in the placebo group were diagnosed during the following year. Change in the International Prostate Symptom Score did not differ significantly between groups. Seven men in the testosterone group and 0 in the placebo group had a hemoglobin level of at least 17.5 g/dL.1