Sindromul MOSH – o nouă viziune a hipogonadismului dobândit

Victoria Ghenciu; Arian Iurii; Ion Dumbraveanu; Mariana Creciun; Emil Ceban

Autori

Victoria Ghenciu Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu“ https://orcid.org/0009-0000-5001-5137
Arian Iurii Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu“ https://orcid.org/0000-0003-1436-5230
Ion Dumbraveanu Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu“ https://orcid.org/0000-0003-1114-2189
Mariana Creciun Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu“ https://orcid.org/0000-0002-4771-5703
Emil Ceban Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu“ https://orcid.org/0000-0002-1583-2884

Cuvinte cheie:

MOSH, hipogonadism, obezitate, disfuncțiesexual-reproductivă masculină, infertilitate

Rezumat

Hipogonadismul masculin funcțional în asociere cu obezitatea a fost definit recent ca hipogonadism secundar indus de obezitate – sindrom MOSH. Manifestările clinice sunt explicate prin două mecanisme importante: deficitul de testosteron și țesutul adipos în exces. Sinteza a 50 de articole apărute preponderent în ultimii 10 ani și extrase din bazele de date Google Scholar, PubMed, ResearchGate, Wiley Online Library, Health Data Sience cu utilizarea cuvintelor-cheie „MOSH”, „hipogonadsim”, „obezitate”, „disfuncție sexualreproductivă masculină”, „infertilitate”. Prevalența MOSH în populația generală este de 45% și corelează pozitiv cu gradul obezității. Mecanismele patogenetice multifactoriale includ lipotoxicitatea, supresia axei hipotalamo-hipofizar-gonadale, leptinorezistența, hiperestrogenemia, stresul oxidativ, statutul proinflamator, insulinorezistența și endotoxemia metabolică, apneea de somn, modificările genetice și epigenetice, cu impact major asupra sănătății sexual-reproductive masculine. Strategia de tratament include scăderea masei corporale, care poate ameliora simptomele deficitului de androgeni, îmbunătăți profilul metabolic și fertilitatea. MOSH este un subtip al hipogonadismului funțional cu potențial reversibil odată cu pierderea substanțială în greutate.

Referințe

1. AHIMA, R.S., DIAS, J.P. Connecting Obesity and Reproductive Disorders. In: Ahima, R.S. (eds) Metabolic Syndrome. Springer, Cham. 2023. pp. 659-674. https://doi.org/10.1007/978-3-031-40116-9_54

2. AMERATUNGA, D., GEBEH A., AMOAKO, A. Obesity and male infertility. In: Best Practice & Research Clinical Obstetrics & Gynaecology, 2023, nr. 90. https://doi.org/10.1016/j.bpobgyn.2023.102393

3. ANTINOZZI, C., LISTA, M., CAPONECCHIA, L., et al. Exploratory analysis in the differences in blood serum and seminal plasma of adipose-tissue related peptides in obese and non-obese men and their correlations with semen parameters. In: Front. Endocrinol. 2021, nr. 12, pp. 681939. https://doi.org/10.3389/fendo.2021.681939

4. ARMENI, E. Male hypogonadism in overweight and obesity. In: Metabolism and Target Organ Damage. 2023, nr. 3(2):9.

https://doi.org/10.20517/mtod.2023.05

5. BARBER, T., VALSAMAKIS, G., MASTORAKOS, G., et al. Dietary influences on the microbiota-gut-brain axis. In: Int J Mol Sci 2021, nr. 22:3502.

https://doi.org/10.3390/ijms22073502

6. BASARIA, S. Male hypogonadism. In: Lancet. 2014; nr. 5; pp. 1250-63. https://doi.org/10.1016/S0140-6736(13)61126-5

7. BIANCHI, V. The anti-inflammatory effects of testosterone. In: J Endocr Soc. 2018, nr.3, pp. 91-107. https://doi.org/10.1210/js.2018-00186

8. BOSTRÖM, P., WU, J., JEDRYCHOWSKI, M. et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. In: Nature. 2012, nr. 481(7382), pp. 463-8. https://doi.org/10.1038/nature10777

9. CALDERÓN, B., GÓMEZ-MARTIN, J., VEGA-PIÑERO, B., et al. Prevalence of male secondary hypogonadism in moderate to severe obesity and its relationship with insulin resistance and excess body weight. In: Andrology. 2016, nr. 4(1), pp. 62-7. https://doi.org/10.1111/andr.12135

10. CALTABIANO, R., CONDORELLI, D., PANZA, S., et al. Glucagon-like peptide-1 receptor is expressed in human and rodent testis. In: Andrology. 2020, nr. 8(6), pp. 1935-1945. https://doi.org/10.1111/andr.12871

11. CAMPBELL, J., DRUCKER, D. Pharmacology, physiology, and mechanisms of incretin hormone action. In: Cell Metab. 2013, nr. 17(6), pp. 819-837. https://doi.org/10.1016/j.cmet.2013.04.008

12. CANNARELLA et al, Obesity and male fertility disorders. In: Molecular Aspects of Medicine. 2024, nr. 97:101273.

https://doi.org/10.1016/j.mam.2024.101273

13. CHAUDHURI, G., DAS, A., KESH, S. et al. Obesity and male infertility: multifaceted reproductive disruption. In: Middle East Fertil Soc J. 2022, nr. 27, 8. https://doi.org/10.1186/s43043-022-00099-2

14. COBETA, P., OSORIO, A., CUADRADO-AYUSO, M. et al. Sleeve Gastrectomy and Gastric Bypass Decrease the Carotid Intima-Media Thickness in Obese Men: Association with Weight Loss, Cardiovascular Risk Factors, and Circulating Testosterone. In: Obes Surg. 2020, nr. 30(3):851-859. https://doi.org/10.1007/s11695-020-04405-7

15. CORONA, G., RASTRELLI, G., MONAMI, M. et al. Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis. In: European J.of Endocrinology. 2013, nr. 168(6), pp. 829-843. https://doi.org/10.1530/EJE-12-0955

16. CORONA, G., RASTRELLI, G., SPARANO, C., VIGNOZZI, L., SFORZA, A., MAGGI, M. Advances in the treatment of functional male hypogonadism. In: Expert Review of Endocrinology & Metabolism. 2024, nr. 19(2), pp. 163-177.

https://doi.org/10.1080/17446651.2023.2296022

17. DENG, Y., LI, Y., HUANG, S. et al. Association of life course adiposity with risk of incident dementia: A prospective cohort study of 322,336 participants. In: Mol. Psychiatry. 2022, nr. 27(8), pp. 3385-3395. https://doi.org/10.1038/s41380-022-01604-9

18. FERNANDEZ, C., CHACKO, E., PAPPACHAN, J. Male Obesity-related Secondary Hypogonadism - Pathophysiology, Clinical Implications and Management. In: Eur Endocrinol. 2019, nr. 15(2), pp. 83-90. https://doi.org/10.17925/EE.2019.15.2.83

19. GAGGI, G., BARBAGALLO, F., DE TONI, L., BUCCI, I. Editorial: Endocrine disruptors: mechanism of action and implications for human health. In: Frontiers in Cell and Developmental Biology. 2024, nr. 12. https://doi.org/10.3389/fcell.2024.1378345

20. GEORGE, B., JHANCY, M., DUBE, R. et al. The Molecular Basis of Male Infertility in Obesity: A Literature Review. In: Int. J. Mol. Sci. 2024, nr. 25:179. https://doi.org/10.3390/ijms25010179

21. GHADERPOUR, S., GHIASI, R., HEYDARI, H. et al. The relation between obesity, kisspeptin, leptin, and male fertility. In: Horm Mol Biol Clin Investig. 2021, nr. 43(2), pp. 235-247. https://doi.org/10.1515/hmbci-2021-0058

22. GURAYAH, A., MASON, M., MASTERSON, J. et al. U-shaped association between prevalence of secondary hypogondism and body mass index: a retrospective analysis of men with testosterone deficiency. In: Int J Impot Res. 2023, nr. 35, pp. 374-7. https://doi.org/10.1038/s41443-022-00533-z

23. HACKETT, G., KIRBY, M., EDWARDS, D. et al. British society for sexual medicine guidelines on adult testosterone deficiency, with statements for UK practice. In: J Sex Med. 2017, nr. 14, pp. 1504-23. https://doi.org/10.1016/j.jsxm.2017.10.067

24. HAMMOUD, A., CARRELL, D., GIBSON, M., et al. Updates on the relation of weight excess and reproductive function in men: sleep apnea as a new area of interest. In: Asian Journal of Andrology. 2012, nr. 14, pp. 77-81. https://doi.org/10.1038/aja.2011.64

25. HU, T., CHEN, Y., LIN, P., et al. Testosterone-associated dietary pattern predicts low testosterone levels and hypogonadism. In: Nutrients. 2018, nr. 10((11)), pp. E1786. https://doi.org/10.3390/nu10111786

26. IZZO, G., IULIANO, C., MOLETTIERI, P., et al. Male obesity secondary hypogonadism: effectiveness of ketogenic diet on testicular function. In: Explor Foods Foodomics. 2023, nr. 1, pp. 178-91. https://doi.org/10.37349/eff.2023.00014

27. JENSTERLE, M., PODBREGAR, A., GORICAR, K., et al. Effects of liraglutide on obesity-associated functional hypogonadism in men. In: Endocrine Connections. 2019, nr. 8(3), pp. 195-202. https://doi.org/10.1210/js.2019-SUN-221

28. KAWWASS, J., SUMMER, R., KALLEN, C. Direct effects of leptin and adiponectin on peripheral reproductive tissues: A critical review. In: Mol. Hum. Reprod. 2015, nr. 1, pp. 617-632. https://doi.org/10.1093/molehr/gav025

29. LA VIGNERA, S., CONDORELLI, R., CALOGERO, A., et al. Sexual and Reproductive Outcomes in Obese Fertile Men with Functional Hypogonadism after Treatment with Liraglutide: Preliminary Results. In: Journal of Clinical Medicine. 2023, nr. 12(2), pp. 672. https://doi.org/10.3390/jcm12020672

30. LIU, Y., HU, X., XIONG, M., et al. Association of BMI with erectile dysfunction: A cross-sectional study of men from an andrology clinic. In: Front Endocrinol (Lausanne). 2023, nr. 14, pp. 1135024. https://doi.org/10.3389/fendo.2023.1135024

31. MINUZZI, R., PETRY, C., SANTOS, F., et al. The Role of Hypogonadism in the Body Composition of Obese Men in the Preoperative Period of Bariatric Surgery. In: Endocrine Practice. 2024. https://doi.org/10.1016/j.eprac.2024.04.005

32. MORELLI, A., FILIPPI, S., COMEGLIO, P., et al. Physical activity counteracts metabolic syndrome-induced hypogonadotropic hypogonadism and erectile dysfunction in the rabbit. In: Am J Physiol Endocrinol Metab. 2019, nr. 316, pp. E519-E535. https://doi.org/10.1152/ajpendo.00377.2018

33. PAVLI, P., TRIANTAFYLLIDOU, O., KAPANTAIS, E., et al. Infertility Improvement after Medical Weight Loss in Women and Men: A Review of the Literature. In: Int. Journal of Molecular Sciences. 2024, nr. 25(3), pp. 1909. https://doi.org/10.3390/ijms25031909

34. PEARCE, K., HILL, A., TREMELLEN, K. Obesity related metabolic endotoxemia is associated with oxidative stress and impaired sperm DNA integrity. In: Basic Clin Androl 2019, nr. 29(6). https://doi.org/10.1186/s12610-019-0087-5

35. PIZZOL, D., SMITH, L., FONTANA, L., et al. Associations between body mass index, waist circumference and erectile dysfunction: a systematic review and META-analysis. In: Rev Endocr Metab Disord. 2020, nr. 21(4), pp. 657-666. https://doi.org/10.1007/s11154-020-09541-0

36. RAEE, P., SHARMS MOFARAHE, Z., NAZARIAN, H., et al. Male obesity is associated with sperm telomere shortening and aberrant mRNA expression of autophagy-related genes. In: Basic Clin Androl, 2023, nr. 33(1), pp. 13. https://doi.org/10.1186/s12610-023-00188-w

37. SANTACROCE, L., IMBIMBO, C., BALLINI, A., et al. Testicular immunity and its connection with the microbiota. physiological and clinical implications in the light of personalized medicine. In: J Pers Med. 2022, nr. 12, pp. 1335. https://doi.org/10.3390/jpm12081335

38. SANTI, D., LOTTI, F., SPARANO, C., RASTERLLI, G., et al, Does an increase in adipose tissue weight affect male fertility? A systematic review and meta-analysis based on semen analysis performed using the WHO 2010 criteria. In: Andrology. 2024, nr. 12(1), pp. 123-136. https://doi.org/10.1111/andr.13460

39. SCHULZE, M. Metabolic health in normal-weight and obese individuals. In: Diabetologia. 2019, nr. 62, pp. 558-66. https://doi.org/10.1007/s00125-018-4787-8

40. SERVICE, C., PURI, D., AL AZZAWI, S., et al. The impact of obesity and metabolic health on male fertility: a systematic review. In: Fertility and Sterility. 2023, nr. 120(6), pp. 1098-1111. https://doi.org/10.1016/j.fertnstert.2023.10.017

41. SHIMIZU, T., SATO, T., TSUKIYAMA, K., et al. Food intake affects sperm-egg fusion through the GIP/PSG17 Axis in mice. In: Endocrinology. 2017, nr. 158(7), pp. 2134- 2144. https://doi.org/10.1210/en.2016-1861

42. STANDFORD, F., TAUQEER, Z., KYLE, T. Media and its influence on obesity. In: Curr Obes Rep. 2018, nr. 7, pp. 186-92.

https://doi.org/10.1007/s13679-018-0304-0

43. STARKA, L., HILL, M., POSPIŠILOVÁ, H., DUŠKOVÁ, M. Estradiol, obesity and hypogonadism. In: Physiol Res. 2020, nr. 69(2), pp. S273-S278. https://doi.org/10.33549/physiolres.934510

44. SULEIMAN, J., NNA, V., OTHMAN, Z., et al. Orlistat attenuates obesity-induced decline in steroidogenesis and spermatogenesis by up-regulating steroidogenic genes. In: Andrology. 2020, nr. 8, pp. 1471-1485. https://doi.org/10.1111/andr.12824

45. TREMELLEN, K. Gut endotoxin leading to a decline in gonadal function (GELDING) - a novel theory for the development of late onset hypogonadism in obese men. In: Basic Clin Androl. 2016, nr. 26:7. https://doi.org/10.1186/s12610-016-0034-7

46. VARNUM, A., POZZI, E., DEEBEL, N., et al. Impact of GLP-1 Agonists on Male Reproductive Health - A Narrative Review. In: Medicina. 2024, nr. 60(1), pp. 50. https://doi.org/10.3390/medicina60010050

47. WHO: World Health Organisation. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight

48. WITHERSPOON, L., FLANNIGAN, R. It puts the T's in fertility: testosterone and spermatogenesis. In: Int J Impot Res. 2022, nr. 34, pp. 669-672. https://doi.org/10.1038/s41443-022-00531-1

49. YARDIMCI, A., ULKER, N., BULMUS, O., et al. Irisin improves high-fat diet-induced sexual dysfunction in obese male rats. In: Neuroendocrinology. 2022, nr. 112(11), pp. 1087-110. https://doi.org/10.1159/000523689

50. YAZICI, D., SEZER, H. Insulin Resistance, Obesity and Lipotoxicity. In: Adv Exp Med Biol. 2017, nr. 960, pp. 277-304.

https://doi.org/10.1007/978-3-319-48382-5_12