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The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 3 1903
Copyright © 2005 by The Endocrine Society

Letter to the Editor

Frequent Occurrence of Hypogonadotropic Hypogonadism in Type 2 Diabetes

Adam Morton

Diabetes Centre, Raymond Terrace, Brisbane, QLD 4101, Australia

Address correspondence to: Adam Morton, Mater Hospital, South Brisbane, Australia 4101. E-mail: Amorton{at}mater.org.au.

To the editor:

Dhindsa et al. (1) recently described the frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes mellitus and the progressive fall in total, bioavailable, and free testosterone levels with increase in body mass index. They considered possible mechanisms including increased plasma levels of proinflammatory cytokines. Another practically important mechanism of hypogonadism in individuals with type 2 diabetes is obstructive sleep apnea (OSA). In one study (2), the prevalence of severe OSA in diabetic hypertensive men was 36%, significantly higher than the prevalence of 14.5% in normoglycemic hypertensive subjects. OSA is also associated with other insulin-resistant states, occurring 30 times more commonly in women with polycystic ovary syndrome than in matched controls (3). OSA is associated with hypogonadotropic hypogonadism, with improvements in testosterone levels after intervention with continuous positive airway pressure (CPAP) and surgery (4, 5, 6). CPAP treatment also improves insulin sensitivity (7). Dhindsa et al. also raise the question of testosterone replacement in hypogonadal men with type 2 diabetes, citing the need for prospective randomized trials to answer this question. Before entering such trials, it would be important that OSA be excluded as a cause of hypogonadism, not only because CPAP treatment may resolve their hypogonadism and symptoms, but also because exogenous testosterone may precipitate or aggravate OSA in susceptible individuals (8, 9). Hemochromatosis would also need to be excluded, given that it may be complicated by hypogonadotropic hypogonadism and type 2 diabetes mellitus.

Received November 25, 2004.

References

  1. Dhindsa S, Prabhakar S, Sethi M, Bandyopadhyay A, Chaudhuri A, Dandona P 2004 Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. J Clin Endocrinol Metab 89:5462–5468[Abstract/Free Full Text]
  2. Elmasry A, Lindberg E, Berne C, Janson C, Gislason T, Awad Tageldin M, Boman G 2001 Sleep-disordered breathing and glucose metabolism in hypertensive men: a population-based study. J Intern Med 249:153–161[CrossRef][Medline]
  3. Vgontzas AN, Legro RS, Bixler EO, Grayev A, Kales A, Chrousos GP 2001 Polycystic ovary syndrome is associated with obstructive sleep apnea and daytime sleepiness: role of insulin resistance. J Clin Endocrinol Metab 86:517–520[Abstract/Free Full Text]
  4. Grunstein RR, Handelsman DJ, Lawrence SJ, Blackwell C, Caterson ID, Sullivan CE 1989 Neuroendocrine dysfunction in sleep apnea: reversal by continuous positive airways pressure therapy. J Clin Endocrinol Metab 68:352–358[Abstract]
  5. Luboshitzky R, Lavie L, Shen-Orr Z, Lavie P 2003 Pituitary-gonadal function in men with obstructive sleep apnea. The effect of continuous positive airways pressure treatment. Neuro Endocrinol Lett 24:463–467[Medline]
  6. Santamaria JD, Prior JC, Fleetham JA 1988 Reversible reproductive dysfunction in men with obstructive sleep apnoea. Clin Endocrinol (Oxf) 28:461–470[Medline]
  7. Harsch IA, Schahin SP, Bruckner K, Radespiel-Troger M, Fuchs FS, Hahn EG, Konturek PC, Lohmann T, Ficker JH 2004 The effect of continuous positive airway pressure treatment on insulin sensitivity in patients with obstructive sleep apnoea syndrome and type 2 diabetes. Respiration 71:252–259[CrossRef][Medline]
  8. Liu PY, Yee B, Wishart SM, Jimenez M, Jung DG, Grunstein RR, Handelsman DJ 2003 The short-term effects of high-dose testosterone on sleep, breathing, and function in older men. J Clin Endocrinol Metab 88:3605–3613[Abstract/Free Full Text]
  9. Matsumoto AM, Sandblom RE, Schoene RB, Lee KA, Giblin EC, Pierson DJ, Bremner WJ 1985 Testosterone replacement in hypogonadal men: effects on obstructive sleep apnoea, respiratory drives, and sleep. Clin Endocrinol (Oxf) 22:713–721[Medline]




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