Impact of Acute Biochemical Castration on Insulin Sensitivity in Healthy Adult Men

Abstract

Introduction. Evidence supports an inverse relationship between serum testosterone (T) and insulin resistance in men. However, data with respect to causality are limited. The aim of this study was to explore the impact of acute biochemical castration on insulin sensitivity in healthy adult men. Methods. Ten healthy, adult males (mean age 41.0 ± 3.9 yr) were studied. Subjects were studied at baseline and after 2 and 4 weeks of biochemical castration. Outpatient hospital research setting. Body composition (dual-energy x-ray absorptiometry), energy expenditure (indirect calorimetry), abdominal and visceral adiposity (MRI), skeletal muscle intramyocellular lipid content ([IMCL] ¹H-MR spectroscopy), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) were assessed before and after 2 and 4 weeks of biochemical castration induced by a GnRH antagonist (acyline 300 μg/kg subcutaneous every 10–14 days). Serum T, insulin and glucose levels, body composition, abdominal visceral fat, IMCL, and glucose disposal rate (M) were measured. Results and Conclusion. Acyline administration suppressed serum T to frankly hypogonadal levels in all subjects for the duration of the study (P <0.009). No significant changes in body composition, energy expenditure, or M were observed at either 2 or 4 weeks of castration. Acyline is an effective GnRH antagonist inducing acute castration in all subjects. ii) Four weeks of biochemical castration has no impact on insulin sensitivity in healthy men likely due to unchanged body composition variables. iii) Insulin resistance associated with chronic low T levels may be largely driven by decreased fat free mass, increased percent body fat, and/or other metabolic regulatory factors.

Keywords:

• Testosterone
• Insulin Sensitivity
• Body Composition

ACKNOWLEDGMENTS

We gratefully acknowledge the MGH Reproductive Endocrine Unit Reference Laboratory, Ms. Gail Chin, and Ms. Apisadaporn Thambundit for their superb technical contributions to this study. The peptide, acyline, was synthesized at NeoMPS, Reproductive Health Branch, Center for Population Research, NICHD, NIH.

DECLARATION OF INTEREST

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.