Can testosterone treatment benefit men at risk of developing insulin resistance?
Testosterone deficiency appears to amplify the risk of developing insulin resistance and put men with hypogonadism at a higher risk of developing type 2 diabetes mellitus. Additionally, men with prediabetes or type 2 diabetes frequently have low testosterone levels. The level of testosterone and its association with type 2 diabetes may be confounded by other factors such as visceral fat. However, it has been suggested that the relationship between testosterone deficiency and type 2 diabetes is not affected by body mass index (BMI), waist circumference (a surrogate marker for visceral fat), and age.
Results from a previous study, assessing the `incidence of hypogonadism in men who are lean, overweight, or obese with type 2 diabetes, indicate that the rate of testosterone deficiency was significantly higher in men with type 2 diabetes, compared to men without diabetes. Additionally, a recommendation update was added to the American Diabetes Association In 2018, indicating to measure testosterone in men with diabetes and signs and symptoms of hypogonadism. In a study conducted by Rancho Bernardo, data showed lower testosterone levels amongst men with impaired fasting glucose or impaired glucose tolerance in comparison to those with normal glucose tolerance, even after adjusting for age and BMI.
Since weight loss is one of the main prevention strategies for type 2 diabetes and long-term testosterone therapy in male patients with hypogonadism leads to a sustained weight loss, a new study hypothesized that long-term testosterone therapy in men with hypogonadism and prediabetes (HbA1c of 5.7– 6.4%), will result in either prevention or slower rate of developing type 2 diabetes.
A total of 316 men with prediabetes and maximum total testosterone level of 12.1 nmol/L., combined with symptoms of hypogonadism, were pooled from two ongoing urological registries. Parenteral testosterone undecanoate (TU) at the dose of 1,000 mg was administered to 229 individuals every 12 weeks after an initial 6-week interval (T-group). A total of 87 men with hypogonadism who opted against long-term testosterone therapy were considered as an untreated control group. All metabolic and anthropometric parameters, including total testosterone, weight, waist circumference, body weight, hemoglobin, hematocrit, fasting glucose, HbA1c, systolic blood pressure and diastolic blood pressure, heart rate, and lipids, were measured biannually for a total of 8 years.
Data gathered from both T and control groups were averaged each year, then the average yearly data were used to measure differences between the two groups, with adjustment for possible confounders such as age, weight, waist circumference, and BMI. By using a mixed-effects model the average changes over time were compared between both groups.
Results of data analysis showed a significant improvement in glycemic control in T-group. A significant reduction was noted in both fasting blood glucose and HbA1c values in the T-group when compared to the untreated group. On the 8-year follow up, T-group experienced approximately 0.39% reduction in their HbA1c level (P, 0.0001). In contrast, a rise of ~ 0.63% in HbA1c level was noted in the untreated group (P, 0.0001). furthermore, a significant difference in both blood glucose and HbA1c levels was observed between the two groups during the entire 8 years follow up time. All the participants who received long-term testosterone therapy had an average HbA1c of 6.5%, with 90% of them achieving normal HbA1c of 5.7%. A total of 35 (40.2%) patients in the untreated group developed type 2 diabetes (HbA1c of 6.5%) and HbA1c of 5.7% was only seen in one patient among this group.
Long-term testosterone therapy appeared to be associated with significant improvements in fasting glucose, total cholesterol, LDL, HDL, non-HDL, triglycerides, and Aging Males’ Symptoms (AMS) scale. Lastly, the rate of mortality was 7.4% with T-group in contrast to 16.1% in the untreated group (P < 0.05). The prevalence of mild myocardial infarction was 0.4% in the T-group and 5.7% in the untreated group (P < 0.005).
This study suggested that long-term testosterone therapy may completely prevent progression of prediabetes into development of type 2 diabetes in men with hypogonadism and prediabetes. Additionally, long-term testosterone therapy caused significant reduction of CVD risk by reducing body weight, waist circumference, and glycemia and improving dyslipidemia. Therefore, testosterone treatment seems to have a great potential for the prevention of diabetes amongst men with hypogonadism and prediabetes and should be further investigated in randomized controlled trials as well as real-life observational studies.
- Long-term testosterone therapy may completely prevent progression of prediabetes into development of type 2 diabetes, in men with hypogonadism and prediabetes.
- Most of the men in the T-group achieved normoglycemia with an HbA1c of 5.7%.
- HbA1c decreased by 0.39±0.03% (P< 0.0001) in the T-group and increased by 0.636± 0.1% (P < 0.0001) in the untreated group.
Yassin, Aksam, et al. “Testosterone Therapy in Men With Hypogonadism Prevents Progression From Prediabetes to Type 2 Diabetes: Eight-Year Data From a Registry Study.” Diabetes Care, American Diabetes Association, 8 Mar. 2019, care.diabetesjournals.org/content/early/2019/03/04/dc18-2388.
Gyawali P, Martin SA, Heilbronn LK, et al. The role of sex hormone-binding globulin (SHBG), testosterone, and other sex steroids, on the development of type 2 diabetes in a cohort of community-dwelling middle-aged to elderly men. Acta Diabetol 2018;55:861–872.
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Ghazal Blair, Pharm.D. Candidate 2019, LECOM School of Pharmacy