What are the proven benefits and side effects of testosterone therapy in my elderly male patient with hypogonadism?

The benefits and side-effects of testosterone therapy (TTh) in male hypogonadism, a common condition among elderly men, have been explored in several trials, demonstrating variable health benefits without significant side effects.1-4

A large 2016 randomized placebo-controlled trial of testosterone replacement for one year in elderly men found that TTh modestly improves muscle mass and strength (by 5%) without significant reduction in falls or frailty.1 This study also showed significant improvement in sexual desire and erectile dysfunction, but the effect of TTh on erections was weaker than that of phosphodiesterase inhibitors. Of interest, TTh did not improve fatigue in this study.1 This is important because lack of energy is probably the commonest complaint by men in ambulatory setting requesting that a serum testosterone level be checked.

Interestingly, in one study, cognition was not improved by TTh.2 Additionally, although TTh has been shown to improve bone density,3  it is not known if it has any impact on the risk of fractures due to lack of proper studies.  Hence, TTh should not be considered for treatment of osteoporosis at this time.  

TTh has been shown to be associated with a rise in hemoglobin by ~1 g/dl.4 However, some men may develop polycythemia, especially if they achieve supranormal levels of serum testosterone with therapy. Testosterone and hemoglobin concentrations should be monitored during TTh.3

Although there have been concerns about risks of cardiovascular events and prostate cancer with TTh, a recent randomized placebo controlled cardiovascular trial showed no effect of TTh on the incidence of major adverse cardiovascular events.4 TTh also does not appear to increase the risk of prostate cancer in the short term (up to 3 years), but long- term prospective trials have not yet been conducted to exclude this possibility.3

Feel free to use the above summary while discussing the pros and cons of TTh with your patients.

Bonus Pearl: Did you know that, according to the Endocrine Society Clinical Practice Guideline,3 in men with symptoms and signs consistent with testosterone deficiency, measuring fasting morning total testosterone concentrations followed by repeat testing for confirmation is recommended.  In men whose total testosterone is near the lower limit of normal or who have condition that alters sex hormone binding globulin, a free testosterone concentration using either equilibrium dialysis or estimating it using an accurate formula is recommended. 3

Contributed by Sandeep Dhindsa, MD, Director, Division of Endocrinology, Diabetes and Metabolism, St. Louis University Medical School, St. Louis, Missouri

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  1. Snyder PJ, Bhasin S, Cunningham GR, et al. Effects of testosterone treatment in older Men. N Engl J Med. 2016;374(7):611-24. Epub 2016/02/18. doi: 10.1056/NEJMoa1506119. PubMed PMID: 26886521.
  2. Snyder PJ, Bhasin S, Cunningham GR, et al. Lessons from the testosterone trials. Endocr Rev. 2018;39(3):369-86. Epub 2018/03/10. doi: 10.1210/er.2017-00234. PubMed PMID: 29522088; PMCID: PMC6287281.
  3. Bhasin S, Brito JP, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715-44. Epub 2018/03/22. doi: 10.1210/jc.2018-00229. PubMed PMID: 29562364.
  4. Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular safety of testosterone-replacement therapy. N Engl J Med. 2023;389(2):107-17. Epub 2023/06/16. doi: 10.1056/NEJMoa2215025. PubMed PMID: 37326322.


Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What are the proven benefits and side effects of testosterone therapy in my elderly male patient with hypogonadism?

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