Testosterone therapy may improve body composition, lipids for men with prediabetes
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Testosterone replacement therapy combined with lifestyle modification may contribute to improved metabolic and glucose profiles for men with hypogonadism and prediabetes, according to a review article.
In findings published in Andrology, Giovanni Corona, MD, PhD, an endocrinologist and andrologist at Maggiore-Bellaria Hospital in Bologna, Italy, and colleagues reviewed data from multiple studies and meta-analyses on the role testosterone plays in the development of diabetes. The researchers found people with impaired fasting glucose tended to have lower total and free testosterone levels than controls, and testosterone replacement may improve body composition and insulin resistance. However, they concluded more research is needed to analyze whether testosterone replacement can help men lose weight or prevent the development of type 2 diabetes.
“Experimental and clinical evidence clearly indicates that metabolic derangements even in preclinical stages are characterized by significantly lower testosterone circulating levels,” the researchers wrote. “In the latter circumstances, testosterone replacement therapy can improve body composition, metabolic profiles and insulin resistance, whereas the data on body weight are more conflicting.”
Researchers conducted a systematic review using studies and meta-analyses available in the Medline, Embase and Cochrane databases from 1969 to April 2022. Meta-analyses were preferred over individual studies. Searchers were conducted for papers analyzing the relationships between testosterone, diabetes and prediabetes. Researchers also analyzed data from a study of 4,682 patients who received care for sexual dysfunction at the University of Florence.
Lower testosterone linked to impaired fasting glucose
In the cohort with low testosterone from the University of Florence, 16.9% had IFG. Among men with IFG, the prevalence of secondary hypogonadism was two times higher than the prevalence observed in the general population. After adjusting for age, BMI and waist circumference were the best predictors for IFG-related low testosterone. Researchers also analyzed findings from eight similar studies, of which 3,625 participants had IFG and 6,205 had normal glucose. Men with IFG had a 3 nmol/L lower total testosterone and a 1.8 times higher risk for hypogonadism compared with controls. Waist circumference and BMI were again the strongest predictors for low testosterone.
Researchers found three meta-analyses investigating the effects of low testosterone among men with type 2 diabetes. Men with type 2 diabetes had lower total and free testosterone than controls without diabetes. Additionally, men who developed type 2 diabetes during follow-up had lower total testosterone at baseline than those who never developed diabetes.
Testosterone therapy may improve body composition, lipids
Researchers found two studies evaluating the use of testosterone replacement in people with hypogonadism and prediabetes. In an open-label observational study, 90% of men with low testosterone and prediabetes treated with injectable testosterone undecanoate (Nebido, Grünenthal) for up to 8 years achieved an HbA1c of less than 5.7% at follow-up. Those receiving testosterone replacement also had greater improvements in body composition, lipid profile and fasting glucose compared with controls. In a randomized controlled trial where men with low testosterone and prediabetes were randomly assigned to an intramuscular injection of testosterone undecanoate or placebo, participants in the testosterone group had greater improvements in fat mass, lean mass and waist circumference, but not body weight, compared with controls. Testosterone replacement was also associated with a greater reduction in fasting glucose, but not HbA1c.
Researchers analyzed data from four meta-analyses investigating the effect of testosterone replacement in people with type 2 diabetes. Testosterone replacement was associated with greater improvements in fasting glucose, HbA1c, fasting insulin and insulin resistance compared with placebo. However, data between the meta-analyses were conflicting for body composition. None of the meta-analyses found a change in BMI with testosterone replacement and only one found testosterone replacement reduced fat mass. For lipids, all of the meta-analyses found an improvement in triglycerides for men receiving testosterone compared with placebo, but findings varied for all remaining lipid parameters.
“It is our opinion that the combined approach of testosterone replacement therapy and lifestyle changes should be used in symptomatic hypogonadal men to better motivate patients to perform physical activity eventually resulting in weight loss and sexual function improvement,” the researchers wrote. “Whether or not these approaches can prevent the development of type 2 diabetes from preclinical conditions require more longitudinal well-performed studies.”
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