Independent Effects of Testosterone on Lipid Oxidation and VLDL-TG Production

A Randomized, Double-Blind, Placebo-Controlled, Crossover Study

  1. Claus H. Gravholt1
  1. 1Department of Endocrinology and Internal Medicine and the Medical Research Laboratories, Clinical Institute, Aarhus University Hospital, Aarhus, Denmark
  2. 2Department of Clinical Pharmacology, Aarhus University, Aarhus, Denmark
  3. 3Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark
  4. 4Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota
  1. Corresponding author: Christian Høst,{at}


Low testosterone (T) levels in men have been shown to predict development of the metabolic syndrome, but the effects of T on lipid metabolism are incompletely understood. In a randomized, double-blind, placebo-controlled, crossover study, 12 healthy, young males received gonadotropin-releasing hormone agonist treatment 1 month prior to 3 of 4 trial days to induce castrate levels of T. On trial days, T gel was applied to the body containing either high or low physiological T dose or placebo. On the 4th trial day, participants constituted their own eugonadal controls. Each study comprised a 5-h basal period and a 3-h hyperinsulinemic-euglycemic clamp. Short-term hypogonadism did not affect VLDL triglyceride (TG) secretion, nor did it affect VLDL-TG concentrations. It was, however, characterized by lower total lipid oxidation. In addition, acute rescue with high physiological T increased VLDL-TG secretion during both basal and clamp conditions. These data show that T can act through fast nongenomic pathways in the liver. In addition, the early hypogonadal state is characterized by decreased total lipid oxidation, but whether these changes represent early hypogonadal metabolic dysfunction warrants further investigations. Testosterone is not a major determinant of resting VLDL-TG kinetics in men.

  • Received April 19, 2012.
  • Accepted September 4, 2012.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See for details.