Male sexual dysfunction in obesity: The role of sex hormones and small fibre neuropathy

English version

Autoři: Jan Hoong Ho ^aff001; Safwaan Adam ^aff001; Shazli Azmi ^aff002; Maryam Ferdousi ^aff002; Yifen Liu ^aff002; Alise Kalteniece ^aff002; Shaishav S. Dhage ^aff001; Brian G. Keevil ^aff003; Akheel A. Syed ^aff004; Basil J. Ammori ^aff005; Tomás Ahern ^aff006; Rachelle Donn ^aff002; Rayaz A. Malik ^aff002; Handrean Soran ^aff001
Působiště autorů: Department of Medicine, Manchester University NHS Foundation Trust, Manchester, United Kingdom ^aff001; Cardiovascular Research Group, The University of Manchester, Manchester, United Kingdom ^aff002; Department of Biochemistry, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom ^aff003; Department of Diabetes & Endocrinology, Salford Royal NHS Foundation Trust, Salford, United Kingdom ^aff004; Department of Surgery, Salford Royal NHS Foundation Trust, Salford, United Kingdom ^aff005; Department of Endocrinology, Our Lady of Lourdes Hospital, RCSI Hospital Group, Drogheda, Ireland ^aff006; Department of Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar ^aff007
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0221992

Souhrn

Context

Multiple factors contribute to sexual dysfunction in men with obesity. Sex hormone levels are commonly abnormal in men with obesity and this abnormality is often the focus of management in clinical practice. The role of small fibre neuropathy in obesity-related sexual dysfunction is not well established.

Objective

We aimed to investigate the relationship between sexual function, sex hormone levels and small nerve fibre morphology in men with severe obesity.

Materials and methods

A prospective study of 29 men with severe obesity was undertaken. Sexual function was assessed using the European Male Ageing Study Sexual Function Questionnaire. Small nerve fibre morphology was quantified using corneal confocal microscopy. Sex hormone levels were measured by mass spectrophotometry.

Results

Erectile dysfunction was present in 72% of the cohort with a higher prevalence of diabetes among the symptomatic group (88% vs 38%, p = 0.006). Corneal nerve fibre length (CNFL) and corneal nerve fibre density (CNFD) were both significantly lower in participants with erectile dysfunction compared to those without (p = 0.039 and p = 0.048 respectively). The erectile function score correlated with CNFL (r = -0.418, p = 0.034) and CNFD (r = -0.411, p = 0.037). Total testosterone and calculated free testosterone levels did not differ significantly between men with or without erectile dysfunction (median 8.8 nmol/L vs 9.0 nmol/L, p = 0.914; and median 176 pmol/L vs 179 pmol/L, p = 0.351 respectively), infrequent sexual thoughts (median 8.1 nmol/L vs 9.2 nmol/L, p = 0.650; and median 184 pmol/L, vs 176 pmol/L, p = 0.619 respectively) and decreased morning erections (median 9.0 nmol/L vs 8.8 nmol/L, p = 0.655; and median 170 pmol/L vs 193 pmol/L, p = 0.278 respectively).

Conclusion

Sexual dysfunction is highly prevalent in men with severe obesity. We found an association between small fibre neuropathy with erectile dysfunction with presence of diabetes a likely a significant contributing factor. We found no associations between testosterone levels with sexual symptoms (including frequency of sexual thoughts). The influence of small nerve fibre neuropathy on response to therapeutic interventions and whether interventions that improve small fibre neuropathy can improve erectile function in this population merits further study.

Klíčová slova:

Biology and life sciences – Cell biology – Biochemistry – Neuroscience – Cellular types – Animal cells – Anatomy – Medicine and health sciences – Physiology – Physiological parameters – Endocrinology – Endocrine disorders – Metabolic disorders – Body weight – Hormones – Urology – Neurology – Obesity – Lipid hormones – Cellular neuroscience – Neurons – Nerve fibers – Ocular system – Ocular anatomy – Androgens – Testosterone – Cornea – Neuropathy – Sex hormones – Sexual dysfunction – Erectile dysfunction

Zdroje

1. Steffen KJ, King WC, White GE, Subak LL, Mitchell JE, Courcoulas AP, et al. Sexual functioning of men and women with severe obesity before bariatric surgery. Surg Obes Relat Dis. 2016. Epub Sep 16. doi: 10.1016/j.soard.2016.09.022 27986585

2. Kandeel FR, Koussa VK, Swerdloff RS. Male sexual function and its disorders: physiology, pathophysiology, clinical investigation, and treatment. Endocr Rev. 2001;22(3):342–88. Epub 2001/06/16. doi: 10.1210/edrv.22.3.0430 11399748.

3. Soran H, Wu FC. Endocrine causes of erectile dysfunction. Int J Androl. 2005;28 Suppl 2:28–34. Epub 2005/10/21. doi: 10.1111/j.1365-2605.2005.00596.x 16236061.

4. Wang C, Jackson G, Jones TH, Matsumoto AM, Nehra A, Perelman MA, et al. Low testosterone associated with obesity and the metabolic syndrome contributes to sexual dysfunction and cardiovascular disease risk in men with type 2 diabetes. Diabetes Care. 2011;34(7):1669–75. Epub 2011/06/29. doi: 10.2337/dc10-2339 21709300.

5. Diaz-Arjonilla M, Schwarcz M, Swerdloff RS, Wang C. Obesity, low testosterone levels and erectile dysfunction. Int J Impot Res. 2009;21(2):89–98. Epub 2008/10/10. doi: 10.1038/ijir.2008.42 18843273.

6. Wu FC, Tajar A, Pye SR, Silman AJ, Finn JD, O’Neill TW, et al. Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab. 2008;93(7):2737–45. Epub 2008/02/14. doi: 10.1210/jc.2007-1972 18270261.

7. Mulligan T, Frick MF, Zuraw QC, Stemhagen A, McWhirter C. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract. 2006;60(7):762–9. Epub 2006/07/19. doi: 10.1111/j.1742-1241.2006.00992.x 16846397.

8. Hofstra J, Loves S, van Wageningen B, Ruinemans-Koerts J, Jansen I, de Boer H. High prevalence of hypogonadotropic hypogonadism in men referred for obesity treatment. Neth J Med. 2008;66(3):103–9. Epub 2008/03/20. 18349465.

9. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536–59. Epub 2010/06/09. doi: 10.1210/jc.2009-2354 20525905.

10. Giltay EJ, Tishova YA, Mskhalaya GJ, Gooren LJ, Saad F, Kalinchenko SY. Effects of testosterone supplementation on depressive symptoms and sexual dysfunction in hypogonadal men with the metabolic syndrome. J Sex Med. 2010;7(7):2572–82. Epub 2010/06/08. doi: 10.1111/j.1743-6109.2010.01859.x 20524974.

11. Jones TH, Arver S, Behre HM, Buvat J, Meuleman E, Moncada I, et al. Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study). Diabetes Care. 2011;34(4):828–37. Epub 2011/03/10. doi: 10.2337/dc10-1233 21386088.

12. Gianatti EJ, Dupuis P, Hoermann R, Zajac JD, Grossmann M. Effect of testosterone treatment on constitutional and sexual symptoms in men with type 2 diabetes in a randomized, placebo-controlled clinical trial. J Clin Endocrinol Metab. 2014;99(10):3821–8. Epub 2014/07/01. doi: 10.1210/jc.2014-1872 24978674.

13. Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, 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 26886521.

14. Bleustein CB, Arezzo JC, Eckholdt H, Melman A. The neuropathy of erectile dysfunction. Int J Impot Res. 2002;14(6):433–9. Epub 2002/12/21. doi: 10.1038/sj.ijir.3900907 12494274.

15. Miscio G, Guastamacchia G, Brunani A, Priano L, Baudo S, Mauro A. Obesity and peripheral neuropathy risk: a dangerous liaison. J Peripher Nerv Syst. 2005;10(4):354–8. Epub 2005/11/11. doi: 10.1111/j.1085-9489.2005.00047.x 16279984.

16. Herman RM, Brower JB, Stoddard DG, Casano AR, Targovnik JH, Herman JH, et al. Prevalence of somatic small fiber neuropathy in obesity. Int J Obes (Lond). 2007;31(2):226–35. Epub 2006/06/14. doi: 10.1038/sj.ijo.0803418 16770330.

17. Malik RA, Kallinikos P, Abbott CA, van Schie CH, Morgan P, Efron N, et al. Corneal confocal microscopy: a non-invasive surrogate of nerve fibre damage and repair in diabetic patients. Diabetologia. 2003;46(5):683–8. Epub 2003/05/10. doi: 10.1007/s00125-003-1086-8 12739016.

18. Pritchard N, Edwards K, Russell AW, Perkins BA, Malik RA, Efron N. Corneal confocal microscopy predicts 4-year incident peripheral neuropathy in type 1 diabetes. Diabetes Care. 2015;38(4):671–5. Epub 2015/01/13. doi: 10.2337/dc14-2114 25573881.

19. Chen X, Graham J, Dabbah MA, Petropoulos IN, Ponirakis G, Asghar O, et al. Small nerve fiber quantification in the diagnosis of diabetic sensorimotor polyneuropathy: comparing corneal confocal microscopy with intraepidermal nerve fiber density. Diabetes Care. 2015;38(6):1138–44. Epub 2015/03/22. doi: 10.2337/dc14-2422 25795415.

20. Azmi S, Ferdousi M, Alam U, Petropoulos IN, Ponirakis G, Marshall A, et al. Small-fibre neuropathy in men with type 1 diabetes and erectile dysfunction: a cross-sectional study. Diabetologia. 2017;60(6):1094–101. Epub 2017/03/31. doi: 10.1007/s00125-017-4245-z 28357503.

21. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:i–xii, 1–253. Epub 2001/03/10. 11234459.

22. Tajar A, Forti G, O’Neill TW, Lee DM, Silman AJ, Finn JD, et al. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. J Clin Endocrinol Metab. 2010;95(4):1810–8. Epub 2010/02/23. doi: 10.1210/jc.2009-1796 20173018.

23. (NICE) NIfHaCE. NICE Public Health Guideline 38. Type 2 diabetes: prevention in people at high risk. 2012.

24. O’Connor DB, Corona G, Forti G, Tajar A, Lee DM, Finn JD, et al. Assessment of sexual health in aging men in Europe: development and validation of the European Male Ageing Study sexual function questionnaire. The journal of sexual medicine. 2008;5(6):1374–85. Epub 2008/03/12. doi: 10.1111/j.1743-6109.2008.00781.x 18331267.

25. Wu FC, 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 Med. 2010;363(2):123–35. Epub 2010/06/18. doi: 10.1056/NEJMoa0911101 20554979.

26. Derby CA, Araujo AB, Johannes CB, Feldman HA, McKinlay JB. Measurement of erectile dysfunction in population-based studies: the use of a single question self-assessment in the Massachusetts Male Aging Study. Int J Impot Res. 2000;12(4):197–204. Epub 2000/11/18. 11079360.

27. Tavakoli M, Malik RA. Corneal confocal microscopy: a novel non-invasive technique to quantify small fibre pathology in peripheral neuropathies. Journal of visualized experiments: JoVE. 2011;(47). Epub 2011/01/21. doi: 10.3791/2194 21248693.

28. Kalteniece A, Ferdousi M, Adam S, Schofield J, Azmi S, Petropoulos I, et al. Corneal confocal microscopy is a rapid reproducible ophthalmic technique for quantifying corneal nerve abnormalities. PLoS One. 2017;12(8):e0183040. Epub 2017/08/18. doi: 10.1371/journal.pone.0183040 28817609.

29. Tavakoli M, Quattrini C, Abbott C, Kallinikos P, Marshall A, Finnigan J, et al. Corneal confocal microscopy: a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy. Diabetes Care. 2010;33(8):1792–7. Epub 2010/05/04. doi: 10.2337/dc10-0253 20435796.

30. Gallagher LM, Owen LJ, Keevil BG. Simultaneous determination of androstenedione and testosterone in human serum by liquid chromatography-tandem mass spectrometry. Ann Clin Biochem. 2007;44(Pt 1):48–56. Epub 2007/02/03. doi: 10.1258/000456307779595922 17270092.

31. Owen LJ, Wu FC, Buttler RM, Keevil BG. A direct assay for the routine measurement of testosterone, androstenedione, dihydrotestosterone and dehydroepiandrosterone by liquid chromatography tandem mass spectrometry. Ann Clin Biochem. 2016;53(Pt 5):580–7. Epub 2015/11/22. doi: 10.1177/0004563215621096 26589631.

32. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84(10):3666–72. Epub 1999/10/16. doi: 10.1210/jcem.84.10.6079 10523012.

33. Dehghani C, Pritchard N, Edwards K, Russell AW, Malik RA, Efron N. Risk Factors Associated With Corneal Nerve Alteration in Type 1 Diabetes in the Absence of Neuropathy: A Longitudinal In Vivo Corneal Confocal Microscopy Study. Cornea. 2016;35(6):847–52. Epub 2016/02/05. doi: 10.1097/ICO.0000000000000760 26845318.

34. Dehghani C, Pritchard N, Edwards K, Vagenas D, Russell AW, Malik RA, et al. Morphometric stability of the corneal subbasal nerve plexus in healthy individuals: a 3-year longitudinal study using corneal confocal microscopy. Invest Ophthalmol Vis Sci. 2014;55(5):3195–9. Epub 2014/04/26. doi: 10.1167/iovs.14-13959 24764058.

35. Klein R, Klein BE, Lee KE, Moss SE, Cruickshanks KJ. Prevalence of self-reported erectile dysfunction in people with long-term IDDM. Diabetes Care. 1996;19(2):135–41. Epub 1996/02/01. 8718433.

36. Malavige LS, Levy JC. Erectile dysfunction in diabetes mellitus. J Sex Med. 2009;6(5):1232–47. Epub 2009/02/13. doi: 10.1111/j.1743-6109.2008.01168.x 19210706.

37. Kim N, Azadzoi KM, Goldstein I, Saenz de Tejada I. A nitric oxide-like factor mediates nonadrenergic-noncholinergic neurogenic relaxation of penile corpus cavernosum smooth muscle. J Clin Invest. 1991;88(1):112–8. Epub 1991/07/01. doi: 10.1172/JCI115266 1647413.

38. de Tejada IS. Therapeutic strategies for optimizing PDE-5 inhibitor therapy in patients with erectile dysfunction considered difficult or challenging to treat. Int J Impot Res. 2004;16 Suppl 1:S40–2. Epub 2004/06/30. doi: 10.1038/sj.ijir.3901215 15224136.

39. Hatzimouratidis K, Burnett AL, Hatzichristou D, McCullough AR, Montorsi F, Mulhall JP. Phosphodiesterase type 5 inhibitors in postprostatectomy erectile dysfunction: a critical analysis of the basic science rationale and clinical application. Eur Urol. 2009;55(2):334–47. Epub 2008/11/07. doi: 10.1016/j.eururo.2008.10.028 18986755.

40. Srinivas-Shankar U, Roberts SA, Connolly MJ, O’Connell MD, Adams JE, Oldham JA, et al. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2010;95(2):639–50. Epub 2010/01/12. doi: 10.1210/jc.2009-1251 20061435.

41. Keevil BG, MacDonald P, Macdowall W, Lee DM, Wu FC, Team N. Salivary testosterone measurement by liquid chromatography tandem mass spectrometry in adult males and females. Ann Clin Biochem. 2014;51(Pt 3):368–78. doi: 10.1177/0004563213506412 24194586.

42. Vermeulen A, Verdonck G. Representativeness of a single point plasma testosterone level for the long term hormonal milieu in men. J Clin Endocrinol Metab. 1992;74(4):939–42. doi: 10.1210/jcem.74.4.1548361 1548361.