Although low serum levels of total and free testosterone hormones were found in 38.3 and 21.7%, respectively, of patients with COPD, the diagnostic criteria of LOH – which depend on the presence of low serum testosterone and the presence of sexual symptoms – were found only in 25% of COPD patients. This difference may be because of patient-to-patient variation in the testosterone threshold where symptoms of hypogonadism become manifest 12,28,29. This is the first study, to our knowledge, that applies the EMAS criteria 10 for the diagnosis of LOH in patients with COPD in comparison with their age-matched controls. Application of this strict criteria for the diagnosis of LOH will prevent overdiagnosis of LOH as there is a considerable overlap between the symptoms of LOH and symptoms of both aging and COPD, and will prevent overdescription of testosterone replacement therapy 30.
Hypoxia can affect the hypothalamic–pituitary–gonadal axis at multiple levels and was found to suppress testosterone secretion independent of glucocorticoid therapy in men with COPD 1. Hypogonadism in COPD in the present study appears to be caused primarily by a testicular dysfunction that is manifested as decreased serum level of total testosterone. In addition, the presence of a low concentration of serum FSH in patients with COPD and the absence of a compensatory increase of LH despite a low serum testosterone level indicates an affection of the pituitary gland and reinforces the previous proposal of hypoxic inhibition of pituitary gland LH secretion in those patients 39. The findings of Aasebo et al.40 supported these data as they found that that long-term oxygen treatment increased sexual function and testosterone levels in COPD patients.
Previous studies suggested that smoking increases total testosterone, whereas cessation of smoking decreases testosterone 31. In the present study, smoking index was not significantly different among cases and controls with LOH or among cases with LOH and without hypogonadism, a result that is in agreement with the recent view of absence of an association between current smoking and testosterone level or hypogonadism 41.
Administration of glucocorticoids either systemically or by inhalation methods is a common modality in the management of COPD cases and most patients receive short or long courses of steroids according to their severity 36. It was believed that high-dose glucocorticoid in the management of COPD may result in hypogonadism either primary by direct inhibitory effects on testicular function or by secondary inhibition of hypothalamic gonadotropin-releasing hormone secretion 42,43. Inhalation corticosteroid therapy in the present study was not significantly different among COPD cases with LOH and COPD cases without hypogonadism. This result reinforces the findings of recent studies on COPD that failed to show a significant correlation between glucocorticoid therapy and testosterone deficiency in men 13–15.
Among patients with COPD in the present study, comparing those with LOH with patients in a eugonadal state, patients with hypogonadism were found to have worse quality of life manifested by having less physical activity, worse psychological symptoms, and more muscle wasting. However, although Laghi et al.14 found hypogonadism to be common among men with COPD, they found that hypogonadism did not worsen the quality of life in men with COPD when compared with men with COPD and normal testosterone levels. The difference between their results and the results of the present study may be because of the wider age difference in the present study (78.8 years for patients with LOH vs. 58.6 for patients without hypogonadism) or may be because the diagnosis of hypogonadism in Laghi’s study depended only on estimation of serum levels of sex hormones without evaluation of patients’ symptoms.
Hence, combining the biochemical hormonal assay and the symptomatic complaints of the patients for the diagnosis of LOH seems to be more realistic in evaluation of a patient’s endocrine condition than the snapshot evaluation of serum level of sex hormones in previous studies. This will enable patients with COPD to receive testosterone replacement, which would improve erectile function and sexual thoughts and motivations 32.
Patients with COPD are more prone to developing LOH even at a younger age than their controls with normal pulmonary functions. There is an overlap between the symptoms of hypogonadism and those of aging and COPD. Therefore, application of strict criteria for screening for hypogonadism should be considered in these patients to allow for testosterone replacement therapy for only those patients who need it.
There are no conflicts of interest.
1. Svartberg J.Androgens and chronic obstructive pulmonary disease
.Curr Opin Endocrinol Diabetes Obes2010;17:257–261.
2. Rochester DF.Malnutrition and the respiratory muscles.Clin Chest Med1986;7:91–99.
3. Zuwallack RL.Alterations in total and regional body composition in patients with moderate to severe obstructive lung disease.Monaldi Archives Chest Dis1996;51:507–509.
4. Kamischke A, Kemper DE, Castel MA, Lüthke M, Rolf C, Behre HM, et al..Testosterone levels in men with chronic obstructive pulmonary disease
with or without glucocorticoid therapy.Eur Respir J1998;11:41–45.
5. Araujo AB, Dixon JM, Suarez EA, Murad MH, Guey LT, Wittert GA.Endogenous testosterone and mortality in men: a systematic review and meta-analysis.J Clin Endocrinol Metab2011;96:3007–3019.
6. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM.Testosterone therapy in men with androgen deficiency syndromes: an endocrine society clinical practice guideline.J Clin Endocrinol Metab2010;95:2536–2559.
7. .American association of clinical endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hypogonadism
in adult male patients – 2002 update.Endocr Pract2002;8:439–456.
8. Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, et al..Investigation, treatment and monitoring of late-onset hypogonadism
in males.Int J Androl2009;32:1–10.
9. Dandona P, Rosenberg MT.A practical guide to male hypogonadism
in the primary care setting.Int J Clin Pract2010;64:682–696.
10. Huhtaniemi I, Forti G.Male late-onset hypogonadism
: pathogenesis, diagnosis and treatment.Nat Rev Urol2011;8:335–344.
11. Nigro N, Christ-Crain M.Testosterone treatment in the aging male: Myth or reality?Swiss Med Wkly2012;142Marchw13539.
12. Wu FCW, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, et al..Identification of late-onset hypogonadism
in middle-aged and elderly men.N Engl J Med2010;363:123–135.
13. Van Vliet M, Spruit MA, Verleden G, Kasran A, Van Herck E, Pitta F, et al..Hypogonadism
, quadriceps weakness, and exercise intolerance in chronic obstructive pulmonary disease
.Am J Respir Crit Care Med2005;172:1105–1111.
14. Laghi F, Antonescu-Turcu A, Collins E, Segal J, Tobin DE, Jubran A, Tobin MJ.Hypogonadism
in men with chronic obstructive pulmonary disease
: prevalence and quality of life.Am J Respir Crit Care Med2005;171:728–733.
15. Debigaré R, Marquis K, Côté CH, Tremblay RR, Michaud A, LeBlanc P, Maltais F.Catabolic/anabolic balance and muscle wasting in patients with COPD.Chest2003;124:83–89.
16. Karadag F, Ozcan H, Karul AB, Yilmaz M, Cildag O.Sex hormone alterations and systemic inflammation in chronic obstructive pulmonary disease
.Int J Clin Pract2009;63:275–281.
17. Pauwels RA, Buist AS, Calverley PMA, Jenkins CR, Hurd SS.Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease
: NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop summary.Am J Respir Crit Care Med2001;163:1256–1276.
18. Crapo RO, Hankinson JL, Irvin C, MacIntyre NR, Voter KZ, Wise RA, et al..Standardization of spirometry: 1994 Update.Am J Respir Crit Care Med1995;152:1107–1136.
19. Labrie F, Bélanger A, Bélanger P, Bérubé R, Martel C, Cusan L, et al..Androgen glucuronides, instead of testosterone, as the new markers of androgenic activity in women.J Steroid Biochem Mol Biol2006;994–5182–188.
20. Vermeulen A, Verdonck L, Kaufman JM.A critical evaluation of simple methods for the estimation of free testosterone in serum.J Clin Endocrinol Metab1999;84:3666–3672.
21. Han TS, Tajar A, O’Neill TW, Jiang M, Bartfai G, Boonen S, et al..Impaired quality of life and sexual function in overweight and obese men: the European male ageing study.Eur J Endocrinol2011;164:1003–1011.
22. Araujo AB, Johannes CB, Feldman HA, Derby CA, McKinlay JB.Relation between psychosocial risk factors and incident erectile dysfunction: prospective results from the Massachusetts male aging study.Am J Epidemiol2000;152:533–541.
23. Ku DY, Park YS, Chang HJ, Kim SR, Ryu JW, Kim WJ.Depression and life quality in chronic renal failure patients with polyneuropathy on hemodialysis.Ann Rehabil Med2012;36:702–707.
24. Beck AT, Steer RA, Ball R, Ranieri WF.Comparison of Beck depression inventories-IA and -II in psychiatric outpatients.J Pers Assess1996;67:588–597.
25. .Physical status: The use and interpretation of anthropometry. WHO technical report series no.: 8541995.Geneva:WHO.
26. Araujo AB, O’Donnell AB, Brambilla DJ, Simpson WB, Longcope C, Matsumoto AM, McKinlay JB.Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts male aging study.J Clin Endocrinol Metab2004;89:5920–5926.
27. Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H.Position statement: utility, limitations, and pitfalls in measuring testosterone: an endocrine society position statement.J Clin Endocrinol Metab2007;92:405–413.
28. Travison TG, Shackelton R, Araujo AB, Hall SA, Williams RE, Clark RV, et al..The natural history of symptomatic androgen deficiency in men: onset, progression, and spontaneous remission.J Am Geriatr Soc2008;56:831–839.
29. Huhtaniemi IT, Pye SR, Holliday KL, Thomson W, O’Neill TW, Platt H, et al..Effect of polymorphisms in selected genes involved in pituitary-testicular function on reproductive hormones and phenotype in aging men.J Clin Endocrinol Metab2010;95:1898–1908.
30. Balasubramanian V, Naing S.Hypogonadism
in chronic obstructive pulmonary disease
: incidence and effects.Curr Opin Pulm Med2012;18:112–117.
31. Laghi F, Adiguzel N, Tobin MJ.Endocrinological derangements in COPD.Eur Respir J2009;34:975–996.
32. Svartberg J, Schirmer H, Medbø A, Melbye H, Aasebø U.Reduced pulmonary function is associated with lower levels of endogenous total and free testosterone. The Tromsø study.Eur J Epidemiol2007;22:107–112.
33. Makarevich AE.Disorders of sex hormone status in patients with chronic obstructive pulmonary disease
34. Semple PD, Beastall GH, Watson WS, Hume R.Serum testosterone depression associated with hypoxia in respiratory failure.Clin Sci1980;58:105–106.
35. Semple PD, Beastall GH, Brown TM, Stirling KW, Mills RJ, Watson WS.Sex hormone suppression and sexual impotence in hypoxic pulmonary fibrosis.Thorax1984;39:46–51.
36. Creutzberg EC, Casaburi R.Endocrinological disturbances in chronic obstructive pulmonary disease
.Eur Respir J Suppl2003;22:76s–80s.
37. Crawford BAL, Liu PY, Kean MT, Bleasel JF, Handelsman DJ.Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment.J Clin Endocrinol Metab2003;88:3167–3176.
38. Nierman DM, Mechanick JI.Hypotestosteronemia in chronically critically ill men.Crit Care Med1999;27:2418–2421.
39. Gosney JR.Atrophy of Leydig cells in the testes of men with longstanding chronic bronchitis and emphysema.Thorax1987;42:615–619.
40. Aasebo U, Gyltnes A, Bremnes RM, Aakvaag A, Slordal L.Reversal of sexual impotence in male patients with chronic obstructive pulmonary disease
and hypoxemia with long term oxygen therapy.J Steroid Biochem Mol Biol1993;46:799–803.
41. Kirbas G, Abakay A, Topcu F, Kaplan A, Ünlü M, Peker Y.Obstructive sleep apnoea, cigarette smoking and serum testosterone levels in a male sleep clinic cohort.J Int Med Res2007;35:38–45.
42. MacAdams MR, White RH, Chipps BE.Reduction of serum testosterone levels during chronic glucocorticoid therapy.Ann Intern Med1986;104:648–651.
43. Creutzberg EC, Schols AMWJ.Anabolic steroids.Curr Opin Clin Nutr Metab Care1999;2:243–253.