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Cited by 145Hormonal and reproductive studiesHypothalamic control of reproductive hormonesSperm and Testicular Function

Male Obesity-related Secondary Hypogonadism – Pathophysiology, Clinical Implications and Management

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Fernandez, Cornelius J, Department of Endocrinology & Metabolism, Pilgrim Hospital, United Lincolnshire Hospitals NHS Trust, Boston, UK;, Chacko, Elias C, Department of Endocrinology, Jersey General Hospital, St Helier, Jersey, Pappachan, Joseph M, Department of Endocrinology & Metabolism, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK·2019·European Endocrinology
DOI 10.17925/ee.2019.15.2.83PMC PMC6785957
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Abstract

The single most significant risk factor for testosterone deficiency in men is obesity. The pathophysiological mechanisms involved in male obesity-related secondary hypogonadism are highly complex. Obesity-induced increase in levels of leptin, insulin, proinflammatory cytokines and oestrogen can cause a functional hypogonadotrophic hypogonadism with the defect present at the level of the hypothalamic gonadotrophin-releasing hormone (GnRH) neurons. The resulting hypogonadism by itself can worsen obesity, creating a self-perpetuating cycle. Obesity-induced hypogonadism is reversible with substantial weight loss. Lifestyle-measures form the cornerstone of management as they can potentially improve androgen deficiency symptoms irrespective of their effect on testosterone levels. In selected patients, bariatric surgery can reverse the obesity-induced hypogonadism. If these measures fail to relieve symptoms and to normalise testosterone levels, in appropriately selected men, testosterone replacement therapy could be started. Aromatase inhibitors and selective oestrogen receptor modulators are not recommended due to lack of consistent clinical trial-based evidence.

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  • Obesity can be a cause of impaired fertility.

    “Obesity can be a cause of impaired fertility.98,121,122”

    From Definition and diagnostic criteria of clinical obesity (2025) · cites this paper as [121]

    The Pathophysiology section says obesity can cause testosterone deficiency in men, and the Management options section discusses erectile dysfunction in obese men. These passages support a link to impaired male reproductive function, but the paper does not directly state that obesity impairs fertility or extend the finding beyond men. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • In men, obesity is a cause of hypogonadotropic hypogonadism resulting in spermatogenesis disturbances and erectile dysfunction.

    “In men, obesity is a cause of hypogonadotropic hypogonadism resulting in spermatogenesis disturbances and erectile dysfunction.121–123”

    From Definition and diagnostic criteria of clinical obesity (2025) · cites this paper as [121]

    The Abstract and the ‘Obesity and hypogonadism – bidirectional relationship’ section describe obesity as a cause of functional hypogonadotrophic hypogonadism. The ‘Exercise alone’ section discusses recovery of erectile function in patients with MOSH. However, the paper attributes suppression of spermatogenesis to testosterone replacement therapy, not to obesity-induced hypogonadism; no page numbers are available in our copy. (LLM, conf=0.87)

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  1. [2]Saboor-Aftab SA Kumar S Barber TM The role of obesity and type 2 diabetes mellitus in the development of male obesity-associated secondary hypogonadism. Clin Endocrinol (Oxf). 2013 78 330 7 23121123
  2. [3]Kelly DM Jones TH Testosterone and obesity. Obes Rev. 2015 16 581 606 25982085
  3. [4]Calderón B Gómez-Martín JM Vega-Piñero B Prevalence of male secondary hypogonadism in moderate to severe obesity and its relationship with insulin resistance and excess body weight. Andrology. 2016 4 62 7 26663756
  4. [5]Hofstra J Loves S van Wageningen B High prevalence of hypogonadotropic hypogonadism in men referred for obesity treatment. Neth J Med. 2008 66 103 9 18349465
  5. [7]Anderson JL May HT Lappé DL Impact of testosterone replacement therapy on myocardial infarction, stroke, and death in men with low testosterone concentrations in an integrated health care system. Am J Cardiol. 2016 117 794 9 26772440
  6. [8]Iglesias P Prado F Ridruejo E Hypogonadism and mortality in aged hospitalized male patients: A 5-year prospective observational study. Exp Clin Endocrinol Diabetes. 2015 123 589 93 26600053
  7. [9]Pye SR Huhtaniemi IT Finn JD Late-onset hypogonadism and mortality in aging men. J Clin Endocrinol Metab. 2014 99 1357 66 24423283
  8. [10]Rao PM Kelly DM Jones TH Testosterone and insulin resistance in the metabolic syndrome and T2DM in men. Nat Rev Endocrinol. 2013 9 (8) 479 93 23797822
  9. [11]Tajar A Forti G O’Neill TW Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European male ageing study. J Clin Endocrinol Metab. 2010 95 1810 18 20173018
  10. [12]Tsai EC Boyko EJ Leonetti DL Low serum testosterone level as a predictor of increased visceral fat in Japanese-American men. Int J Obes Relat Metab Disord. 2000 24 485 91 10805506
  11. [13]Georgiev IP Georgieva TM Ivanov V Effects of castration-induced visceral obesity and antioxidant treatment on lipid profile and insulin sensitivity in New Zealand white rabbits. Res Vet Sci. 2011 90 196 204 20542306
  12. [14]Saylor PJ Smith MR Metabolic complications of androgen deprivation therapy for prostate cancer. J Urol. 2013 189 S34 42 23234628
  13. [15]Wang N Zhai H Han B Visceral fat dysfunction is positively associated with hypogonadism in Chinese men. Sci Rep. 2016 6 19844 26796865 PMC4726157
  14. [16]Haymana C Sonmez A Aydogdu A Visceral adiposity index and triglyceride/high-density lipoprotein cholesterol ratio in hypogonadism. Arch Endocrinol Metab. 2017 61 282 7 28225990 PMC10118811
  15. [18]Escobar-Morreale HF Santacruz E Luque-Ramirez M Prevalence of ‘obesity-associated gonadal dysfunction’ in severely obese men and women and its resolution after bariatric surgery: a systematic review and meta-analysis. Hum. Reprod Update. 2017 23 390 408 28486593
  16. [19]Pellitero S Olaizola I Alastrue A Hypogonadotropic hypogonadism in morbidly obese males is reversed after bariatric surgery. Obes Surg. 2012 22 1835 42 22923309
  17. [21]Brand JS van der Tweel I Grobbee DE Testosterone, sex hormone-binding globulin and the metabolic syndrome: a systematic review and meta-analysis of observational studies. Int J Epidemiol. 2011 40 189 207 20870782
  18. [22]Garcia-Cruz E Piqueras M Huguet J Hypertension, dyslipidemia and overweight are related to lower testosterone levels in a cohort of men undergoing prostate biopsy. Int J Impot Res. 2012 24 110 3 22258063
  19. [23]O’Reilly MW Glisic M Kumarendran B Serum testosterone, sex hormone-binding globulin and sex-specific risk of incident type 2 diabetes in a retrospective primary care cohort. Clin Endocrinol (Oxf). 2018 90 145 54 30256433 PMC6334272
  20. [24]Bhasin S Jasjua GK Pencina M Sex hormone-binding globulin, but not testosterone, is associated prospectively and independently with incident metabolic syndrome in men: the Framingham heart study. Diabetes Care. 2011 34 2464 70 21926281 PMC3198304
  21. [25]Tripathy D Dhindsa S Garg R Hypogonadotropic hypogonadism in erectile dysfunction associated with type 2 diabetes mellitus: a common defect? Metab Syndr Relat Disord. 2003 1 75 80 18370627
  22. [27]Laaksonen DE Niskanen L Punnonen K The metabolic syndrome and smoking in relation to hypogonadism in middle-aged men: a prospective cohort study. J Clin Endocrinol Metab. 2005 90 712 9 15536158
  23. [28]Kelly DM Jones TH. Testosterone: a metabolic hormone in health and disease. J Endocrinol. 2013 217 R25 45 23378050
  24. [29]Singh R Artaza JN Taylor WE Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology. 2003 144 5081 8 12960001
  25. [30]Bianchi VE The anti-inflammatory effects of testosterone. J Endocr Soc. 2018 3 91 107 30582096 PMC6299269
  26. [31]Rasouli N Kern PA Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab. 2008 93 S64 73 18987272 PMC2585759
  27. [32]McArdle MA Finucane OM Connaughton RM Mechanisms of obesity-induced inflammation and insulin resistance: insights into the emerging role of nutritional strategies. Front Endocrinol (Lausanne). 2013 4 52 23675368 PMC3650620
  28. [33]Sarchielli E Comeglio P Squecco R Tumor Necrosis Factor-α impairs kisspeptin signalling in human gonadotropin-releasing hormone primary neurons. J Clin Endocrinol Metab. 2017 102 46 56 27736314 PMC5413096
  29. [34]Morelli A Sarchielli E Comeglio P Metabolic syndrome induces inflammation and impairs gonadotropin-releasing hormone neurons in the preoptic area of the hypothalamus in rabbits. Mol Cell Endocrinol. 2014 382 107 19 24064031
  30. [35]Grossmann M Testosterone and glucose metabolism in men: current concepts and controversies. J Endocrinol. 2014 220 R37 55 24353306
  31. [36]Pitteloud N Mootha VK Dwyer AA Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabetes Care. 2005 28 1636 42 15983313
  32. [37]Clarke H Dhillo WS Jayasena CN Comprehensive review on kisspeptin and its role in reproductive disorders. Endocrinol Metab (Seoul). 2015 30 124 41 26194072 PMC4508256
  33. [38]George JT Millar RP Anderson RA. Hypothesis: kisspeptin mediates male hypogonadism in obesity and type 2 diabetes. Neuroendocrinology. 2010 91 302 7 20628262
  34. [39]Sanchez-Garrido MA Ruiz-Pino F Manfredi-Lozano M Obesity-induced hypogonadism in the male: premature reproductive neuroendocrine senescence and contribution of Kiss1-mediated mechanisms. Endocrinology. 2014 155 1067 79 24424048
  35. [40]Harter CJL Kavanagh GS Smith JT The role of kisspeptin neurons in reproduction and metabolism. J Endocrinol. 2018 238 R173 R183 30042117
  36. [41]Caprio M Isidori AM Carta AR Expression of functional leptin receptors in rodent Leydig cells. Endocrinology. 1999 140 4939 47 10537117
  37. [42]Isidori AM Caprio M Strollo F Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab. 1999 84 3673 80 10523013
  38. [43]Roseweir AK Millar RP The role of kisspeptin in the control of gonadotrophin secretion. Hum Reprod Update. 2009 15 203 12 19109311
  39. [44]Quennell JH Mulligan AC Tups A Leptin indirectly regulates gonadotropin-releasing hormone neuronal function. Endocrinology. 2009 150 2805 12 19179437 PMC2732287
  40. [45]Tremellen K McPhee N Pearce K Endotoxin-initiated inflammation reduces testosterone production in men of reproductive age. Am J Physiol Endocrinol Metab. 2018 314 E206 E213 29183872 PMC5899218
  41. [46]Goldman AL Bhasin S Wu FCW A reappraisal of testosterone’s binding in circulation: physiological and clinical implications. Endocr Rev. 2017 38 302 24 28673039 PMC6287254
  42. [48]Kim SD Cho KS Obstructive sleep apnea and testosterone deficiency. World J Mens Health. 2019 37 12 8 29774669 PMC6305865
  43. [49]Wu FC Tajar A Beynon JM EMAS Group. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010 363 123 35 20554979
  44. [50]Hackett G Kirby M Edwards D British society for sexual medicine guidelines on adult testosterone deficiency, with statements for UK practice. J Sex Med. 2017 14 1504 23 29198507
  45. [55]Wing RR Rosen RC Fava JL Effects of weight loss intervention on erectile function in older men with type 2 diabetes in the Look AHEAD trial. J Sex Med. 2010 7 156 65 19694925 PMC4461030
  46. [57]Hu TY Chen YC Lin P Testosterone-associated dietary pattern predicts low testosterone levels and hypogonadism. Nutrients. 2018 10 (11) pii E1786 PMC6266690 30453566
  47. [59]Yeo JK Cho SI Park SG Which exercise is better for increasing serum testosterone levels in patients with erectile dysfunction? World J Mens Health. 2018 36 147 52 29623694 PMC5924956
  48. [60]Hayes LD Elliott BT Short-term exercise training inconsistently influences basal testosterone in older men: a systematic review and meta-analysis. Front Physiol. 2019 9 1878 30692929 PMC6339914
  49. [61]Cho DY Yeo JK Cho SI Exercise improves the effects of testosterone replacement therapy and the durability of response after cessation of treatment: a pilot randomized controlled trial. Asian J Androl. 2017 19 602 7 27427553 PMC5566857
  50. [62]Villareal DT Chode S Parimi N Sinacore Weight loss, exercise, or both and physical function in obese older adults. N Engl J Med. 2011 364 1218 29 21449785 PMC3114602
  51. [63]Khoo J Tian HH Tan B Comparing effects of low- and high-volume moderate-intensity exercise on sexual function and testosterone in obese men. J Sex Med. 2013 10 1823 32 23635309
  52. [65]Jensterle M Podbregar A Goricar K Effects of liraglutide on obesity-associated functional hypogonadism in men. Endocr Connect. 2019 8 195 202 30707677 PMC6391904
  53. [66]Corona G Rastrelli G Monami M Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis. Eur J Endocrinol. 2013 168 829 43 23482592
  54. [67]Calderon B Galdon A Calanas A Effects of bariatric surgery on male obesity-associated secondary hypogonadism: comparison of laparoscopic gastric bypass with restrictive procedures. Obes Surg. 2014 24 1686 92 24664512
  55. [68]Boonchaya-Anant P Laichuthai N Suwannasrisuk P Changes in testosterone levels and sex hormone-binding globulin levels in extremely obese men after bariatric surgery. Int J Endocrinol. 2016 2016 1416503 27725831 PMC5048048
  56. [69]Glina FPA de Freitas-Barboza JW Nunes VM What is the impact of bariatric surgery on erectile function? A systematic review and meta-analysis. Sex Med Rev. 2017 5 393 402 28526630
  57. [70]Mora M Aranda GB de Hollanda A Weight loss is a major contributor to improved sexual function after bariatric surgery. Surg Endosc. 2013 27 3197 204 23612762
  58. [71]Dimitriadis GK Randeva HS Aftab S Metabolic phenotype of male obesity-related secondary hypogonadism pre-replacement and post-replacement therapy with intra-muscular testosterone undecanoate therapy. Endocrine. 2018 60 175 84 29396841 PMC5845623
  59. [72]Haider A Saad F Doros G Hypogonadal obese men with and without diabetes mellitus type 2 lose weight and show improvement in cardiovascular risk factors when treated with testosterone: an observational study. Obes Res Clin Pract. 2014 8 e339 49 25091355
  60. [73]Francomano D Lenzi A Aversa A Effects of five-year treatment with testosterone undecanoate on metabolic and hormonal parameters in ageing men with metabolic syndrome. Int J Endocrinol. 2014 2014 527470 24688542 PMC3945028
  61. [74]Jones TH Arver S Behre HM TIMES2 Investigators. Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study). Diabetes Care. 2011 34 828 37 21386088 PMC3064036
  62. [75]Dhindsa S Ghanim H Batra M Hypogonadotropic hypogonadism in men with diabesity. Diabetes Care. 2018 41 1516 25 29934480 PMC6014549
  63. [78]Ng Tang Fui M Hoermann R Grossmann M Effect of testosterone treatment on adipokines and gut hormones in obese men on a hypocaloric diet. J Endocr Soc. 2017 1 302 12 29264488 PMC5686636
  64. [80]Ng Tang Fui M Hoermann R Nolan B Effect of testosterone treatment on bone remodelling markers and mineral density in obese dieting men in a randomized clinical trial. Sci Rep. 2018 8 9099 29904126 PMC6002535
  65. [81]Saad F Aversa A Isidori AM Testosterone as potential effective therapy in treatment of obesity in men with testosterone deficiency: a review. Curr Diabetes Rev. 2012 8 131 43 22268394 PMC3296126
  66. [83]Ng Tang Fui M Hoermann R Zajac JD The effects of testosterone on body composition in obese men are not sustained after cessation of testosterone treatment. Clin Endocrinol (Oxf). 2017 87 336 43 28561278
  67. [86]Corona G Rastrelli G Morgentaler A Meta-analysis of results of testosterone therapy on sexual function based on international index of erectile function scores. Eur Urol. 2017 72 1000 11 28434676
  68. [87]Saad F Yassin A Doros G Effects of long-term treatment with testosterone on weight and waist size in 411 hypogonadal men with obesity classes I-III: observational data from two registry studies. Int J Obes (Lond). 2016 40 162 70 26219417 PMC4722240
  69. [88]Saad F Haider A Doros G Long-term treatment of hypogonadal men with testosterone produces substantial and sustained weight loss. Obesity (Silver Spring). 2013 21 1975 81 23512691
  70. [89]Cai X Tian Y Wu T Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Asian J Androl. 2014 16 146 52 24369149 PMC3901874
  71. [90]Zhang J Yang B Xiao W Effects of testosterone supplement treatment in hypogonadal adult males with T2DM: a meta-analysis and systematic review. World J Urol. 2018 36 1315 26 29511802
  72. [91]Grossmann M Hoermann R Wittert G Effects of testosterone treatment on glucose metabolism and symptoms in men with type 2 diabetes and the metabolic syndrome: a systematic review and meta-analysis of randomized controlled clinical trials. Clin Endocrinol (Oxf). 2015 83 344 51 25557752
  73. [92]Onasanya O Iyer G Lucas E Association between exogenous testosterone and cardiovascular events: an overview of systematic reviews. Lancet Diabetes Endocrinol. 2016 4 943 56 27669646
  74. [93]Corona G Maseroli E Rastrelli G Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis. Expert Opin Drug Saf. 2014 13 1327 51 25139126
  75. [94]Hackett G Metabolic effects of testosterone therapy in men with type 2 diabetes and metabolic syndrome. Sex Med Rev. 2019 7 476 90 30803918
  76. [95]Wallis CJ Lo K Lee Y Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study. Lancet Diabetes Endocrinol. 2016 4 498 506 27165609
  77. [101]Grossmann M Matsumoto AM A Perspective on middle-aged and older men with functional hypogonadism: focus on holistic management. J Clin Endocrinol Metab. 2017 102 1067 75 28359097 PMC5477803
  78. [102]Magnussen LV Andersen PE Diaz A MR spectroscopy of hepatic fat and adiponectin and leptin levels during testosterone therapy in type 2 diabetes: a randomized, double-blinded, placebo-controlled trial. Eur J Endocrinol. 2017 177 157 68 28522646
  79. [103]Kalinchenko SY Tishova YA Mskhalaya GJ Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: the double-blinded placebo-controlled Moscow study. Clin Endocrinol. (Oxf). 2010 73 602 12 20718771
  80. [105]Bhasin S Parker RA Sattler F Effects of testosterone supplementation on whole body and regional fat mass and distribution in human immunodeficiency virus-infected men with abdominal obesity. J Clin Endocrinol Metab. 2007 92 1049 57 17164307
  81. [106]Grossmann M Hypogonadism and male obesity: Focus on unresolved questions. Clin Endocrinol (Oxf). 2018 89 11 21 29683196

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Authors
Fernandez, C. J., Department of Endocrinology & Metabolism, P. H., Chacko, E. C., Department of Endocrinology, J. G. H., Pappachan, J. M., & Department of Endocrinology & Metabolism, L. T. H. N. F. T.
Affiliations
  • Pilgrim Hospital (GB)
  • Government of Jersey (JE)
  • Lancashire Teaching Hospitals NHS Foundation Trust (GB)
Corresponding author
Pappachan, Joseph M
ORCID
Venue
European Endocrinology
Publisher
Touch Medical Media, Ltd.
Published
2019
Volume
15
Issue
2
Pages
83
ISSN
1758-3772 (ISSN-L)
DOI
10.17925/ee.2019.15.2.83
PMC
PMC6785957
OpenAlex
W2970628515
Cited by
145
References
25
Citations by year
2026: 9 · 2025: 22 · 2024: 22 · 2023: 34 · 2022: 20 · 2021: 17 · 2020: 20
FWCI
2.20
Type
journal article
Language
en
Open access
Licence
Locations
  • touchREVIEWS in Endocrinology (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
This article is published under the Creative Commons Attribution Non-commercial License.
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
Keywords
male obesity, secondary hypogonadism, androgen deficiency, leptin, insulin, inflammatory cytokines, estrogen, weight loss, lifestyle intervention, bariatric surgery, testosterone replacement therapy, aromatase inhibitors, selective estrogen receptor modulators

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