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Effects of Androgen Therapy on Adipose Tissue and Metabolism in Older Men

Department of Medicine and Division of Infectious Diseases (E.T.S., F.R.S.), General Clinical Research Center, Keck School of Medicine (L.Z., C.M., C.F., Y.S., C.A., F.R.S.), and Department of Biokinesiology and Physical Therapy (E.T.S., M.D.O., F.R.S.), University of Southern California, Los Angeles, California 90033

Address all correspondence and requests for reprints to: Dr. Fred R. Sattler, Departments of Medicine and Biokinesiology and Physical Therapy, University of Southern California, 1540 East Alcazar Street, CHP-155, Los Angeles, California 90033. E-mail: fsattler{at}usc.edu.

We investigated the effects of oxandrolone on regional fat compartments and markers of metabolism. Thirty-two 60- to 87-yr-old men (body mass index, 28.1 ± 3.4 kg/m²) were randomized to oxandrolone (20 mg/d; n = 20) or matching placebo (n = 12) treatment for 12 wk. Oxandrolone reduced total (–1.8 ± 1.0 kg; P < 0.001), trunk (–1.2 ± 0.6 kg; P < 0.001), and appendicular (–0.6 ± 0.6 kg; P < 0.001) fat, as determined by dual energy x-ray absorptiometry. The changes in total and trunk fat were greater (P < 0.001) than the changes with placebo. By magnetic resonance imaging, visceral adipose tissue decreased (–20.9 ± 12 cm²; P < 0.001), abdominal sc adipose tissue (SAT) declined (–10.7 ± 12.1 cm²; P = 0.043), the ratio VAT/SAT declined from 0.57 ± 0.23 to 0.49 ± 0.19 (P = 0.002), and proximal and distal thigh SC fat declined [–8.3 ± 6.7 cm² (P < 0.001) and –2.2 ± 3.0 kg (P = 0.004), respectively]. Changes in proximal and distal thigh SC fat with oxandrolone were different than with placebo (P = 0.018 and P = 0.059). A marker of insulin sensitivity (quantitative insulin sensitivity check index) improved with oxandrolone by 0.0041 ± 0.0071 (P = 0.018) at study wk 12. Changes in total fat, abdominal SAT, and proximal extremity SC fat were correlated with changes in fasting insulin from baseline to study wk 12 (r 0.45; P < 0.05). Losses of total fat and SAT were greater in men with baseline testosterone of 10.4 nmol/liter or less ( 300 ng/dl) than in those with higher levels [–2.5 ± 1.1 vs. –1.5 ± 0.8 kg (P = 0.036) and –24.1 ± 14.3 vs. –2.9 ± 21.3 cm² (P = 0.03), respectively]. Twelve weeks after discontinuing oxandrolone, 83% of the reductions in total, trunk, and extremity fat by dual energy x-ray absorptiometry scanning were sustained (P < 0.02). Androgen therapy, therefore, produced significant and durable reductions in regional abdominal and peripheral adipose tissue that were associated with improvements in estimates of insulin sensitivity. However, high-density lipoprotein cholesterol decreased by –0.49 ± 0.21 mmol/liter and directly measured low-density lipoprotein cholesterol increased by 0.57 ± 0.67 mmol/liter and non-high-density lipoprotein cholesterol increased by 0.54 ± 0.97 mmol/liter (P < 0.03 for each) during treatment with oxandrolone; these changes were largely reversible. Thus, therapy with an androgen that does not adversely affect lipids may be beneficial for some components of the metabolic syndrome in overweight older men with low testosterone levels.

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