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Effects of testosterone administration on cognitive function in hysterectomized women with low testosterone levels: a dose–response randomized trial

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Abstract

Purpose

To determine the dose-dependent effects of testosterone administration on cognition in women with low testosterone levels.

Methods

71 hysterectomized women with or without oophorectomy with total testosterone <31 ng/dl and/or free testosterone <3.5 pg/ml received a standardized transdermal estradiol regimen during the 12-week run-in period and were then randomized to receive weekly intramuscular injections of placebo, 3, 6.25, 12.5, or 25 mg testosterone enanthate for 24 weeks. Total testosterone was measured in serum by LC–MS/MS, and free testosterone levels were measured by equilibrium dialysis. Cognitive function was evaluated using a comprehensive battery of standardized neuropsychological tests at baseline and 24 weeks.

Results

46 women who had baseline and end-of-treatment cognitive function data constituted the analytic sample. The five groups were similar at baseline. Mean on-treatment nadir total testosterone concentrations were 15, 89, 98, 134, and 234 ng/dl in the placebo, 3, 6.25, 12.5, and 25 mg groups, respectively. No significant changes in spatial ability, verbal fluency, verbal memory, or executive function were observed in any treatment arm compared to placebo even after adjustment for baseline cognitive function, age, and education. Multiple regression analysis did not show any significant relation between changes in testosterone concentrations and change in cognitive function scores.

Conclusion

Short-term testosterone administration over a wide range of doses for 24 weeks in women with low testosterone levels was neither associated with improvements nor worsening of cognitive function.

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Acknowledgments

This study was supported by Grants 5U54HD041748-04 (to Charles Drew University of Medicine and Science) and 2008 TF D2274G (sub award to Boston University) from the National Institute of Child Health and Human Development and the Boston Claude D. Pepper Older Americans Independence Center Grant #5P30AG031679 from the National Institute of Aging. Watson Pharmaceuticals provided the transdermal estradiol patch for this trial. ENDO Pharmaceuticals provided testosterone injections for this trial.

Data safety monitoring board

Dr. Jan Shifren, Massachusetts General Hospital, Boston, Massachusetts (Chair); Dr. Raja Sayegh, Boston Medical Center; and Dr. Anita Nelson, Harbor-UCLA Medical Center.

Additional contributions

We are grateful to Maithili Davda for her contribution to the statistical programming and data analysis for this manuscript. We thank the staff of the General Clinical Research Unit of Boston University’s Clinical and Translational Science Institute and the Clinical Research Center of Charles Drew University of Medicine and Science for their help with these studies and the study participants for their commitment and generosity.

Conflict of interest

Dr. Basaria has received Grant support from Abbott Pharmaceuticals for investigator-initiated studies unrelated to this study and has previously consulted for Eli Lilly, Inc. Dr. Bhasin has received research Grant support from Abbott Pharmaceuticals and Eli Lilly, Inc. for investigator-initiated research unrelated to this study. Dr. Bhasin has served as a consultant to Regeneron, Merck, and Eli Lilly, Inc.

Author information

Authors and Affiliations

  1. Section of Men’s Health: Aging and Metabolism, Harvard Medical School, Brigham and Women’s Hospital, BLI-5, 221 Longwood Avenue, Boston, MA, 02115, USA

    G. Huang, T. G. Travison, S. Bhasin & S. Basaria

  2. Department of Neurology, Emory University, WWHC 1841 Clifton Rd., NE, Atlanta, GA, 30329, USA

    W. Wharton

  3. Division of Endocrinology, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, 90059, USA

    M. H. Ho

  4. School of Medicine and Public Health, University of Wisconsin, Madison, WI, 53792, USA

    C. Gleason & S. Asthana

  5. Geriatric Research, Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI, 53705, USA

    C. Gleason & S. Asthana

  6. Wisconsin Alzheimer’s Disease Research Center, Madison, WI, 53792, USA

    C. Gleason & S. Asthana

Authors
  1. G. Huang
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  2. W. Wharton
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  3. T. G. Travison
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  4. M. H. Ho
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  5. C. Gleason
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  6. S. Asthana
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  7. S. Bhasin
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  8. S. Basaria
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Corresponding author

Correspondence to G. Huang.

Additional information

Clinical Trials Registration Number: NCT00494208.

G. Huang and W. Wharton authors contributed equally to this manuscript.

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Huang, G., Wharton, W., Travison, T.G. et al. Effects of testosterone administration on cognitive function in hysterectomized women with low testosterone levels: a dose–response randomized trial. J Endocrinol Invest 38, 455–461 (2015). https://doi.org/10.1007/s40618-014-0213-3

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  • DOI: https://doi.org/10.1007/s40618-014-0213-3

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