Long-Term Testosterone Administration on Insulin Sensitivity in Older Men With Low or Low-Normal Testosterone Levels

• Published in: The journal of clinical endocrinology and metabolism Vol. 103; no. 4; pp. 1678 - 1685
• Main Authors: Huang, Grace, Pencina, Karol M, Li, Zhuoying, Basaria, Shehzad, Bhasin, Shalender, Travison, Thomas G, Storer, Thomas W, Harman, S Mitchell, Tsitouras, Panayiotis
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.04.2018; Copyright Oxford University Press; Oxford University Press
• Subjects: Age; Aged; Aging; Arteriosclerosis; Blood Glucose - analysis; Body Composition - drug effects; Body fat; Clinical s; Double-Blind Method; Dual energy X-ray absorptiometry; Glucose; Hormone replacement therapy; Humans; Insulin; Insulin - blood; Insulin resistance; Insulin Resistance - physiology; Male; Middle Aged; Octreotide; Placebos; Statistical analysis; Testosterone; Testosterone - administration & dosage; Testosterone - blood; Treatment Outcome
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2017-02545

Abstract Background Serum testosterone levels and insulin sensitivity both decrease with age. Severe testosterone deficiency is associated with the development of insulin resistance. However, the effects of long-term testosterone administration on insulin sensitivity in older men with low or low-normal testosterone levels remain unknown. Methods The Testosterone Effects on Atherosclerosis in Aging Men Trial was a placebo-controlled, randomized, double-blind trial. The participants were 308 community-dwelling men, ≥60 years old, with total testosterone 100 to 400 ng/dL or free testosterone <50 pg/mL. A subset of 134 nondiabetic men (mean age, 66.7 ± 5.1 years) underwent an octreotide insulin suppression test at baseline and at 3 and 36 months after randomization to measure insulin sensitivity. Insulin sensitivity was estimated as the steady-state plasma glucose (SSPG) concentration at equilibrium during octreotide and insulin administration. Secondary outcomes included total lean mass (TLM) and total fat mass (TFM) by dual energy x-ray absorptiometry. Results There was a significant (P = 0.003) increase in SSPG in the placebo group, whereas no change was seen in testosterone-treated subjects from baseline to 36 months; however, the between-group differences in change in SSPG over 3 years were not statistically significant (+15.3 ± 6.9 mg/dL in the placebo group vs +6.2 ± 6.4 mg/dL in the testosterone group; mixed-model effect, P = 0.17). Changes in SSPG with testosterone treatment were not associated with changes in serum total or free testosterone concentrations. Changes in TFM but not TLM were associated with increases in SSPG. Stratification by age or baseline total testosterone level did not show significant intervention effects. Conclusion Testosterone administration for 36 months in older men with low or low-normal testosterone levels did not improve insulin sensitivity. Testosterone levels and insulin sensitivity both decrease with age. We found that long-term testosterone therapy for 36 months in nondiabetic older men did not improve insulin sensitivity.