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Dose-Dependent Effects of Testosterone on Regional Adipose Tissue Distribution in Healthy Young Men

Division of Endocrinology, Metabolism, and Molecular Medicine (L.J.W., N.G., M.B., A.B.S., S.B.), Charles R. Drew University of Medicine and Science, Los Angeles, California 90059; School of Rehabilitation Sciences (L.J.W.), McMaster University, Hamilton, Ontario Canada L8S 1C7; School of Physical and Health Education (R.R.), Queen’s University, Kingston, Ontario, Canada, K7L 3N6; and Harbor-University of California, Los Angeles Medical Center (J.P.), Torrance, California 90502

Address all correspondence and requests for reprints to: Linda Woodhouse, McMaster University, School of Rehabilitation Science, 1400 Main Street West, Hamilton, Ontario, Canada L8S 1C7. E-mail: woodhou{at}mcmaster.ca.

Testosterone supplementation reduces total body adipose tissue (AT), but we do not know whether the effects are uniformly distributed throughout the body or are region specific, or whether they are dose related.

We determined the effects of graded doses of testosterone on regional AT distribution in 54 healthy men (18–35 yr) in a 20-wk, randomized, double-blind study of combined treatment with GnRH agonist plus one of five doses (25, 50, 125, 300, or 600 mg/wk) of testosterone enanthate (TE). Total body, appendicular, and trunk AT and lean body mass were measured by dual-energy x-ray absorptiometry, and sc, intermuscular, and intraabdominal AT of the thigh and abdomen were measured by magnetic resonance imaging. Treatment regimens resulted in serum nadir testosterone concentrations ranging from subphysiological to supraphysiological levels. Dose-dependent changes in AT mass were negatively correlated with TE dose at all sites and were equally distributed between the trunk and appendices. The lowest dose was associated with gains in sc, intermuscular, and intraabdominal AT, with the greatest percent increase occurring in the sc stores. At the three highest TE doses, thigh intermuscular AT volume was significantly reduced, with a greater percent loss in intermuscular than sc depots, whereas intraabdominal AT stores remained unchanged. In conclusion, changes in testosterone concentrations in young men are associated with dose-dependent and region-specific changes in AT and lean body mass in the appendices and trunk. Lowering testosterone concentrations below baseline increases sc and deep AT stores in the appendices and abdomen, with a greater percent increase in sc depots. Conversely, elevating testosterone concentrations above baseline induces a greater loss of AT from the smaller, deeper intermuscular stores of the thigh.

This work was supported by primarily by National Institutes of Health Grant 1RO1AG14369. Additional support was provided by Grants U54HD041748-01, 1RO1DK49296-05, 1RO1DK59627-01, and 1RO1HD043348-01; the Clinical Trials Unit Grant U01-DK54047; Research Centers in Minority Institutions (RCMI) Clinical Research Infrastructure Initiative (P20RR11145); RCMI Grants G12RR03026 and U54RR14616 and Universitywide AIDS Research Program Drew Cares HIV Center; and a General Clinical Research Center Grant MO-00425. BioTechnology General Corp. (Iselin, NJ) provided testosterone enanthate, and DebioPharm (Martigny, Suisse) provided GnRH agonist (Decapeptyl).

Abbreviations: AT, Adipose tissue; DEXA, dual-energy x-ray absorptiometry; LBM, lean body mass; LPL, lipoprotein lipase; MRI, magnetic resonance imaging; TE, testosterone enanthate.

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