No adverse events reported in cohort of high-risk men receiv
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Testosterone therapy with intramuscular testosterone undecanoate did not result in any adverse cardiovascular or prostate events in a cohort of men with obesity, type 2 diabetes and functional hypogonadism, clinical trial data showed.

“Two years of testosterone therapy can be safe even in a high-risk population of obese men with functional hypogonadism and type 2 diabetes when appropriate safety practices outlined by the clinical guidelines are diligently followed,” said researchers. “Men on long-term testosterone therapy should be monitored with prostate-specific antigen, hematocrit and digital rectal examination.”

Researchers conducted a first-year double-blind, second-year open-label, randomized placebo-controlled trial with 55 white men aged 40 to 70 years with confirmed symptomatic hypogonadism, type 2 diabetes and obesity. Participants treated their diabetes with noninsulin antidiabetes medication and did not use medications to reduce weight, BMI or waist circumference. The trial was a single-center study conducted from 2014 to March 2018 at Celje General Hospital in Slovenia.

Participants were randomly assigned to a treatment group (n = 28, mean age, 58.18 years) receiving intramuscular testosterone undecanoate injections (Nebido, Bayer AG) or a matching placebo cohort (n = 27, mean age, 62.19 years). Placebo was limited to 1 year; in year 2 of the trial, the placebo group received testosterone undecanoate. The treatment cohort received testosterone undecanoate for 2 years.

The first injection of testosterone undecanoate or placebo was done at the first week, the second injection took place at 6 weeks, and further injections occurred every 10 weeks. All participants had a clinical, biochemical and hormonal assessment at baseline and 12 and 24 months. Researchers also checked prostate-specific antigen (PSA) and hematocrit levels 6 months after initiation of treatment to assess response to treatment. Safety tests were performed approximately every 3 months.

In the treatment group, hematocrit levels increased from a mean of 42.7% at baseline to 44.9% at 6 months and 45.3% at 1 year. In the placebo group, hematocrit increased from 44.4% at baseline to 45% at 6 months and 46.5% at 12 months. Individual hematocrit values never exceeded the upper safety limit of 52% in either group during the 2-year study duration.

“We showed that hematocrit increased gradually from the baseline in both groups within 3 to 6 months after the start of testosterone therapy,” the researchers wrote. “These findings are in accordance with several studies, which showed that the effects of testosterone therapy on hematocrit become apparent after 3 months and the plateau is reached within 9 to 12 months.”

The treatment cohort had an increase in PSA from 0.645 µg/L at baseline to 0.825 µg/L at 12 months and 1.175 µg/L at 24 months. In the placebo group, PSA increased from 0.67 µg/L at baseline to 0.89 µg/L at 12 months and to 0.95 µg/L at the end of the 12 months of testosterone undecanoate. Of the 55 participants, 52 never had a PSA level above 4 µg/L.

In the treatment group, mean total testosterone increased from 7.24 nmol/L at baseline to 17.04 nmol/L at 12 months and 23.5 nmol/L at 24 months. In the placebo group, a mean total testosterone level of 9.83 nmol/L at the start of testosterone undecanoate increased to 17.92 nmol/L after 12 months.

No adverse prostate carcinoma, erythrocytosis or CVD events were reported during the trial, and no side effects of the medication were observed. According to the researchers, this may be due to the limited study population size and does not constitute conclusive evidence that testosterone therapy has no negative effects on CVD and prostate health.

“Future research should require a dedicated focus on the evaluation of large multicentric cohorts of obese males with type 2 diabetes to better elucidate risks of testosterone therapy related to prostate carcinoma and erythrocytosis,” the researchers wrote.