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The Short-Term Effects of High-Dose Testosterone on Sleep, Breathing, and Function in Older Men

Department of Andrology, ANZAC Research Institute and Concord Hospital (P.Y.L., S.M.W., M.J., D.J.H.), and Woolcock Institute of Medical Research and Royal Prince Alfred Hospital (B.Y., D.G.J., R.R.G.), University of Sydney, Sydney, 2139 Australia

Address all correspondence and requests for reprints to: Prof. David J. Handelsman, ANZAC Research Institute, Sydney NSW 2139 Australia. E-mail: djh{at}med.usyd.edu.au.

Androgen therapy may precipitate obstructive sleep apnea in men. Despite increasing androgen use in older men, few studies have examined sleep and breathing. Randomized, double-blind, placebo-controlled studies examining effects of testosterone simultaneously on sleep, breathing, and function in older men are not available. Seventeen community-dwelling healthy men over the age of 60 yr were randomized to receive three injections of im testosterone esters at weekly intervals (500 mg, 250 mg, and 250 mg) or matching oil-based placebo and then crossed over to the other treatment after 8 wk of washout. Polysomnography, anthropometry, and physical, mental, and metabolic function were assessed at baseline and after each treatment period. Testosterone treatment reduced total time slept (1 h), increased the duration of hypoxemia (5 min/night), and disrupted breathing during sleep (total and non-rapid eye movement respiratory disturbance indices both increased by approximately seven events per hour) (all P < 0.05). Despite expected effects on body composition (increase in total and lean mass, reduction in fat mass, P < 0.05, bioimpedance method), upper airway dimensions did not change (acoustic reflectometry). Driving ability (computer simulation), physical activity (accelerometry, Physical Activity Scale in the Elderly), quality of life (SF36, Functional Outcomes of Sleep Questionnaire), mood (Profile of Mood States Questionnaire), sleepiness (Epworth, Stanford scales), and insulin resistance (homeostasis model) also were not changed by treatment. Short-term administration of high-dose testosterone shortens sleep and worsens sleep apnea in older men but did not alter physical, mental, or metabolic function. These changes did not appear to be due to upper airway narrowing. Further study of longer-term lower-dose androgen therapy on sleep and breathing is needed to evaluate its safety in older men.

This work was supported by National Health and Medical Research Council of Australia Grants 142613 and 262025. There are no financial disclosures by any of the authors. This study was presented in part during the Clinical Trials Symposium of the 84th Annual Meeting of The Endocrine Society, San Francisco, California, June 20–23, 2002.

Abbreviations: BMI, Body mass index; FOSQ, Functional Outcomes of Sleep Questionnaire; IPSS, International Prostate Symptom Score; NREM, non-rapid eye movement; OSA, obstructive sleep apnea; PASE, Physical Activity Scale in the Elderly; POMS, Profile of Mood States Questionnaire; PSA, prostate-specific antigen; RDI, respiratory disturbance index; REM, rapid eye movement.

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