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Androgen Therapy Induces Muscle Protein Anabolism in Older Women

Departments of Internal Medicine (M.S.-M., S.L.C., C.G., E.V., J.J., R.J.U.) and Surgery (D.P.-J., S.E.W., J.I.R.), University of Texas Medical Branch at Galveston, Galveston, Texas 77555-1060

Address all correspondence and requests for reprints to: Randall J. Urban, M.D., Chairman and Professor of Internal Medicine, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555-0569. E-mail: rurban{at}utmb.edu.

Context: Normal healthy men and women undergo a gradual loss of skeletal muscle mass and strength with advancing age. While androgens are protein anabolic in older men, the metabolic effects in older women are poorly understood.

Objective and Design: The objective of this study was to determine whether oral administration of a synthetic derivative of testosterone [oxandrolone, Oxandrin (OX)] (7.5 mg orally twice daily for 14 d) to five older women (age, 65 ± 2 yr) would enhance skeletal muscle anabolic biomarkers including mixed muscle fractional synthetic rate (FSR), net phenylalanine balance, androgen receptor, and IGF-I protein expression at d 0, 5, and 14 of treatment. As a positive control, seven older men were examined after 14 d of OX (10 mg orally twice daily).

Setting: The study was performed at the General Clinical Research Center.

Results: Fourteen days of OX significantly increased skeletal muscle FSR in older women (d 0, 0.073 ± 0.006 vs. d 5, 0.092 ± 0.006 vs. d 14, 0.115 ± 0.007%/h) (P < 0.05, d 0 vs. d 14). Conversely, OX stimulated FSR in older men after only 5 d (d 0, 0.061 ± 0.003 vs. d 5, 0.101 ± 0.01 vs. d 14, 0.084 ± 0.01%/h) (P < 0.05, d 0 vs. d 5). Androgen receptor expression was significantly increased in older men by d 14, but had not increased in older women. No change was noted in IGF-I expression in either group. We conclude that the skeletal muscle of older women and men responds to androgen administration, although the time course of anabolism appears to be gender specific.

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