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Testosterone dose-response relationships in hysterectomized women with or without oophorectomy: effects on sexual function, body composition, muscle performance and physical function in a randomized trial

Huang, Grace MD1; Basaria, Shehzad MD1; Travison, Thomas G. PhD1,2; Ho, Matthew H. MD, PhD3,4; Davda, Maithili MPH1,2; Mazer, Norman A. MD, PhD1; Miciek, Renee MS1; Knapp, Philip E. MD1; Zhang, Anqi PhD1; Collins, Lauren RNP1; Ursino, Monica BS1; Appleman, Erica MA1; Dzekov, Connie BA3; Stroh, Helene BA1; Ouellette, Miranda BA1; Rundell, Tyler BA1; Baby, Merilyn BA1; Bhatia, Narender N. MD4; Khorram, Omid MD, PhD4; Friedman, Theodore MD, PhD3; Storer, Thomas W. PhD1; Bhasin, Shalender MD1

doi: 10.1097/GME.0000000000000093
Original Articles

Objective: This study aims to determine the dose-dependent effects of testosterone on sexual function, body composition, muscle performance, and physical function in hysterectomized women with or without oophorectomy.

Methods: Seventy-one postmenopausal women who previously underwent hysterectomy with or without oophorectomy and had total testosterone levels less than 31 ng/dL or free testosterone levels less than 3.5 pg/mL received a standardized transdermal estradiol regimen during the 12-week run-in period and were randomized to receive weekly intramuscular injections of placebo or 3, 6.25, 12.5, or 25 mg of testosterone enanthate for 24 weeks. Total and free testosterone levels were measured by liquid chromatography–tandem mass spectrometry and equilibrium dialysis, respectively. The primary outcome was change in sexual function measured by the Brief Index of Sexual Functioning for Women. Secondary outcomes included changes in sexual activity, sexual distress, Derogatis Interview for Sexual Functioning, lean body mass, fat mass, muscle strength and power, and physical function.

Results: Seventy-one women were randomized; five groups were similar at baseline. Sixty-two women with analyzable data for the primary outcome were included in the final analysis. The mean on-treatment total testosterone concentrations were 19, 78, 102, 128, and 210 ng/dL in the placebo, 3-mg, 6.25-mg, 12.5-mg, and 25-mg groups, respectively. Changes in composite Brief Index of Sexual Functioning for Women scores, thoughts/desire, arousal, frequency of sexual activity, lean body mass, chest-press power, and loaded stair-climb power were significantly related to increases in free testosterone concentrations; compared with placebo, changes were significantly greater in women assigned to the 25-mg group, but not in women in the lower-dose groups. Sexual activity increased by 2.7 encounters per week in the 25-mg group. The frequency of androgenic adverse events was low.

Conclusions: Testosterone administration in hysterectomized women with or without oophorectomy for 24 weeks was associated with dose and concentration-dependent gains in several domains of sexual function, lean body mass, chest-press power, and loaded stair-climb power. Long-term trials are needed to weigh improvements in these outcomes against potential long-term adverse effects.

From the 1Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine and Boston Medical Center, Boston, MA; 2Department of Biostatistics, Boston University School of Public Health, Boston, MA; 3Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA; and 4Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, University of California, Los Angeles, CA.

Received April 22, 2013; revised and accepted August 8, 2013.

T.G.T. and M.H.H. contributed equally to this work.

Funding/support: This study was supported by grants 5U54HD041748-04 (to Charles Drew University of Medicine and Science) and 2008 TF D2274G (subaward to Boston University) from the National Institute of Child Health and Human Development and by the Boston Claude D. Pepper Older Americans Independence Center (grant 5P30AG031679 from the National Institute on Aging).

Financial disclosure/conflicts of interest: S.B. has received research grant support from Abbott Pharmaceuticals and Eli Lilly and Co for investigator-initiated research unrelated to this study. S.B. has served as a consultant to Regeneron, Merck, and Eli Lilly and Co. No other potential conflict of interest relevant to this article was reported.

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Address correspondence to: Shalender Bhasin, MD, Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115. E-mail: sbhasin@partners.org

© 2014 by The North American Menopause Society.