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Prevalence and Consequences of Androgen Deficiency in Young Male Cancer Survivors in a Controlled Cross-Sectional Study

Academic Units of Clinical Oncology (D.M.G., R.E.C., B.W.H.), School of Health and Related Research (S.J.W.), Bone Metabolism (R.E.), Child Health (H.A.D.), Haematology (J.A.S.), Endocrinology and Reproduction (R.J.M.R.), University of Sheffield, Sheffield S10 2JF, United Kingdom; Department of Endocrinology (S.M.S.), Christie Hospital Manchester, Manchester M20 4BX, United Kingdom; and Center for Sexual Medicine at Sheppard Pratt (L.D.), Baltimore, Maryland 21204

Address all correspondence and requests for reprints to: Professor R. J. M. Ross, Professor of Endocrinology, Head of Section Endocrinology and Reproduction, University of Sheffield, Room 112 Floor M, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, United Kingdom. E-mail: r.j.ross{at}sheffield.ac.uk.

Background: Testosterone replacement in hypogonadal males improves body composition, sexual function, and health-related quality of life. Male cancer survivors are at risk of androgen deficiency; however, when and in whom testosterone should be replaced remain unanswered questions.

Objective: The aim of our study was to define the prevalence of androgen deficiency in this patient group through assessment of testosterone levels and related measures.

Design: This was a cross-sectional, observational study of cases and controls. We recruited 176 cancer survivors and 213 controls, aged 25–45 yr.

Results: Of cancer survivors, 97% had received chemotherapy and 40% radiotherapy. Cancer survivors had lower total testosterone (tT) levels than controls (mean difference 2.67 nmol/liter; 95% confidence interval 1.58–3.76; P = 0.003), and 24 of 176 (13.6%; 95% confidence interval 9.3–19.5) had a tT less than 10 nmol/liter, which was less than 2.5% centile for controls. Cancer survivors had a greater fat mass, higher fasting insulin and glucose levels, increased fatigue, and reduced sexual function and health-related quality of life. In both cohorts, the tT correlated negatively with insulin levels and negatively with body fat mass; however, the difference in tT between them was independent of fat mass. We measured tT and SHBG and calculated bioavailable testosterone. The changes in calculated bioavailable testosterone were similar to tT.

Conclusions: A significant proportion of young male cancer survivors had a frankly low tT associated with an increased fat mass and insulin level compared with controls. These factors would be predicted to improve in response to testosterone replacement therapy and provide a powerful argument for an interventional study of testosterone therapy in young male cancer survivors.