Testosterone stimulates extra-hepatic but not hepatic fat oxidation (Fox): comparison of oral and transdermal testosterone administration in hypopituitary men.

BACKGROUND: Fat mass is increased in hypogonadal men and the changes are reversed by testosterone replacement. Testosterone administration enhances whole body fat oxidation (Fox). Fat is oxidized in the liver and in extra-hepatic tissues. OBJECTIVE: To determine whether the stimulation of Fox by testosterone arises primarily from the liver or from extra-hepatic tissues. DESIGN/PATIENTS: This was an open-label cross-over study. Thirteen men with hypopituitarism (age 53.1 +/- 4.1 years) with both growth hormone (GH) and testosterone deficiency were studied sequentially after 2 weeks of treatment with transdermal testosterone (5 mg), no treatment, and stepwise incremental doses of oral crystalline testosterone (10, 20, 40 and 80 mg) in the absence of GH replacement. MEASUREMENTS: Serum testosterone, IGF-I, metabolic effects [resting energy expenditure (REE) and Fox], SHBG, and thyroid binding globulin (TBG) as markers of excessive hepatic androgen exposure, were measured at the end of each treatment period. RESULTS: When compared to the no-treatment phase, mean blood testosterone levels rose into the physiological range after transdermal testosterone delivery but did not significantly change after 10, 20, 40 or 80 mg oral testosterone treatment. Blood SHBG and TBG fell significantly with 80 mg oral testosterone dose but were unaffected by any other testosterone treatment. Fox increased significantly with transdermal but not with any dose of oral testosterone. Mean plasma IGF-I and REE were unaffected by testosterone, regardless of the route or dose. CONCLUSIONS: Short-term testosterone administration does not stimulate hepatic fat oxidation but enhances whole body fat oxidation by acting on extra-hepatic tissues.