Effect of testosterone replacement therapy on insulin sensitivity and body composition in congenital hypogonadism: A prospective longitudinal follow-up study

AIMS: To evaluate the prevalence of metabolic syndrome (MS) and whole-body composition in patients with congenital hypogonadism and investigate the effects of replacement therapy with testosterone undecanoate on MS, insulin resistance (IR), and whole-body composition in subset of patients. METHODS: In a single arm prospective longitudinal intervention study, 33 patients with congenital hypogonadism, ages 20–39 years, were recruited and their parameters of MS, whole-body composition by DXA were compared with age and BMI matched healthy controls. In 21 patients, after 9 months we prospectively studied the effect (pre–post difference) of injection testosterone undecanoate (1,000 mg) replacement on MS, IR, and whole-body compositions. RESULTS: The prevalence of MS was similar in patients and controls (27.3% vs. 9.1%, P = 0.05). Hypogonadism patients had higher prevalence of hypertension (33% vs. 3%, P < 0.01). Patients had decrease in lean body mass (P < 0.05) as compared to controls. After testosterone replacement, there was significant decrease in waist circumference (88.6 ± 13.1 cm vs. 83.9 ± 12.9 cm, P < 0.01), truncal fat (25.9 ± 7.3% vs. 24.0 ± 6.3%, P < 0.05), fasting C-peptide (2.1 ± 0.79 ng/ml vs. 0.68 ± 0.23 ng/ml, P < 0.01), serum proinsulin [1.43 (0.32– 13.4) vs. 0.5 (0.5–3.2) pmol/l, P < 0.001] and a significant increase in lean body mass (46,906 ± 8,876 gm vs. 50,083 ± 7,590 gm, P < 0.001). Homeostasis model assessment of insulin resistance (HOMA-IR) (4.6 ± 1.7 vs. 0.5 ± 0.2, P < 0.001) and homeostatic model for assessment of insulin sensitivity (HOMA%S) [21 (12–65) vs. 206 (125–714), P < 0.001] were improved significantly following testosterone replacement. CONCLUSION: In this study, 36 weeks of testosterone replacement resulted in significant decrease in waist circumference, IR, truncal fat, total body fat and improvement in lean body mass, and insulin sensitivity.