Obesity and Male Infertility: A Practical Approach

Abstract

Obesity in men is associated with infertility in numerous studies, and the temporal trend for a decline in semen parameters parallels the increasing prevalence of obesity in the developed world. In addition to impaired semen quality, fertility among obese men may be affected by decreased libido and erectile dysfunction. This spectrum of expression of hypogonadism among obese men originates from multiple interacting factors including reduced levels of gonadotropins and testosterone, altered androgen-to-estrogen ratios, insulin resistance, and sleep apnea. No evidence-based treatment that increases the likelihood of pregnancy for the infertility associated with male obesity has been demonstrated to date. Interventions associated with improvement of intermediate outcomes that include the endocrine profile, semen parameters, and sexual function may be appropriately selected based on history, physical findings, as well as endocrine and metabolic evaluation. Among these interventions are weight loss through lifestyle change, relief from sleep apnea, use of aromatase inhibitors, gonadotropin administration, phosphodiesterase inhibitors, and insulin-sensitizing agents.

Keywords

male infertility - overweight - BMI - semen parameters - treatment - reproductive function

• References

• 1 Stephen EH, Chandra A. Declining estimates of infertility in the United States: 1982-2002. Fertil Steril 2006; 86 (3) 516-523
• 2 Oehninger S. Clinical and laboratory management of male infertility: an opinion on its current status. J Androl 2000; 21 (6) 814-821
• 3 Sharpe RM. Low sperm counts may be preventable. Science 2011; 333 (6048) 1380-1381
• 4 Swan SH, Elkin EP, Fenster L. The question of declining sperm density revisited: an analysis of 101 studies published 1934–1996. Environ Health Perspect 2000; 108 (10) 961-966
• 5 Mokdad AH, Serdula MK, Dietz WH, Bowman BA, Marks JS, Koplan JP. The spread of the obesity epidemic in the United States, 1991–1998. JAMA 1999; 282 (16) 1519-1522
• 6 Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999–2002. JAMA 2004; 291 (23) 2847-2850
• 7 Hammoud AO, Gibson M, Peterson CM, Hamilton BD, Carrell DT. Obesity and male reproductive potential. J Androl 2006; 27 (5) 619-626
• 8 Hammoud AO, Gibson M, Peterson CM, Meikle AW, Carrell DT. Impact of male obesity on infertility: a critical review of the current literature. Fertil Steril 2008; 90 (4) 897-904
• 9 MacDonald AA, Herbison GP, Showell M, Farquhar CM. The impact of body mass index on semen parameters and reproductive hormones in human males: a systematic review with meta-analysis. Hum Reprod Update 2010; 16 (3) 293-311
• 10 Sallmén M, Sandler DP, Hoppin JA, Blair A, Baird DD. Reduced fertility among overweight and obese men. Epidemiology 2006; 17 (5) 520-523
• 11 Ramlau-Hansen CH, Thulstrup AM, Nohr EA, Bonde JP, Sørensen TI, Olsen J. Subfecundity in overweight and obese couples. Hum Reprod 2007; 22 (6) 1634-1637
• 12 Nguyen RH, Wilcox AJ, Skjaerven R, Baird DD. Men's body mass index and infertility. Hum Reprod 2007; 22 (9) 2488-2493
• 13 Ohwaki K, Yano E. Body mass index as an indicator of metabolic disorders in annual health checkups among Japanese male workers. Ind Health 2009; 47 (6) 611-616
• 14 Pauli EM, Legro RS, Demers LM, Kunselman AR, Dodson WC, Lee PA. Diminished paternity and gonadal function with increasing obesity in men. Fertil Steril 2008; 90 (2) 346-351
• 15 Jokela M, Kivimäki M, Elovainio M, Viikari J, Raitakari OT, Keltikangas-Järvinen L. Body mass index in adolescence and number of children in adulthood. Epidemiology 2007; 18 (5) 599-606
• 16 Bakos HW, Henshaw RC, Mitchell M, Lane M. Paternal body mass index is associated with decreased blastocyst development and reduced live birth rates following assisted reproductive technology. Fertil Steril 2011; 95 (5) 1700-1704
• 17 Braga DP, Halpern G, Figueira RD, Setti AS, Iaconelli Jr A, Borges Jr E. Food intake and social habits in male patients and its relationship to intracytoplasmic sperm injection outcomes. Fertil Steril 2012; 97: 53-59
• 18 Pham KN, Sandlow JI. The effect of body mass index on the outcomes of varicocelectomy. J Urol 2012; 187 (1) 219-221
• 19 Hammoud AO, Wilde N, Gibson M, Parks A, Carrell DT, Meikle AW. Male obesity and alteration in sperm parameters. Fertil Steril 2008; 90 (6) 2222-2225
• 20 Jensen TK, Andersson AM, Jørgensen N , et al. Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Fertil Steril 2004; 82 (4) 863-870
• 21 Magnusdottir EV, Thorsteinsson T, Thorsteinsdottir S, Heimisdottir M, Olafsdottir K. Persistent organochlorines, sedentary occupation, obesity and human male subfertility. Hum Reprod 2005; 20 (1) 208-215
• 22 Fejes I, Koloszár S, Szöllosi J, Závaczki Z, Pál A. Is semen quality affected by male body fat distribution?. Andrologia 2005; 37 (5) 155-159
• 23 Kort HI, Massey JB, Elsner CW , et al. Impact of body mass index values on sperm quantity and quality. J Androl 2006; 27 (3) 450-452
• 24 Miller DC, Hollenbeck BK, Smith GD , et al. Processed total motile sperm count correlates with pregnancy outcome after intrauterine insemination. Urology 2002; 60 (3) 497-501
• 25 Håkonsen LB, Thulstrup AM, Aggerholm AS , et al. Does weight loss improve semen quality and reproductive hormones? Results from a cohort of severely obese men. Reprod Health 2011; 8: 24
• 26 O'Brien JH, Lazarou S, Deane L, Jarvi K, Zini A. Erectile dysfunction and andropause symptoms in infertile men. J Urol 2005; 174 (5) 1932-1934 , discussion 1934
• 27 Bacon CG, Mittleman MA, Kawachi I, Giovannucci E, Glasser DB, Rimm EB. Sexual function in men older than 50 years of age: results from the health professionals follow-up study. Ann Intern Med 2003; 139 (3) 161-168
• 28 Feldman HA, Johannes CB, Derby CA , et al. Erectile dysfunction and coronary risk factors: prospective results from the Massachusetts male aging study. Prev Med 2000; 30 (4) 328-338
• 29 Hammoud A, Gibson M, Hunt SC , et al. Effect of Roux-en-Y gastric bypass surgery on the sex steroids and quality of life in obese men. J Clin Endocrinol Metab 2009; 94 (4) 1329-1332
• 30 Seftel A. Male hypogonadism. Part II: etiology, pathophysiology, and diagnosis. Int J Impot Res 2006; 18 (3) 223-228
• 31 Brody S. Slimness is associated with greater intercourse and lesser masturbation frequency. J Sex Marital Ther 2004; 30 (4) 251-261
• 32 Sullivan ME, Thompson CS, Dashwood MR , et al. Nitric oxide and penile erection: is erectile dysfunction another manifestation of vascular disease?. Cardiovasc Res 1999; 43 (3) 658-665
• 33 Chung WS, Sohn JH, Park YY. Is obesity an underlying factor in erectile dysfunction?. Eur Urol 1999; 36 (1) 68-70
• 34 Tajar A, Forti G, O'Neill TW , et al. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. The Journal of Clinical Endocrinology and Metabolism 2010; 95 (4) 1810-1818
• 35 Giagulli VA, Kaufman JM, Vermeulen A. Pathogenesis of the decreased androgen levels in obese men. J Clin Endocrinol Metab 1994; 79 (4) 997-1000
• 36 Tchernof A, Despres JP, Belanger A , et al. Reduced testosterone and adrenal C19 steroid levels in obese men. Metabolism 1995; 44 (4) 513-519
• 37 Grossmann M. Low testosterone in men with type 2 diabetes: significance and treatment. The Journal of Clinical Endocrinology and Metabolism 2011; 96 (8) 2341-2353
• 38 Schneider G, Kirschner MA, Berkowitz R, Ertel NH. Increased estrogen production in obese men. J Clin Endocrinol Metab 1979; 48 (4) 633-638
• 39 Akingbemi BT. Estrogen regulation of testicular function. Reprod Biol Endocrinol 2005; 3: 51
• 40 de Boer H, Verschoor L, Ruinemans-Koerts J, Jansen M. Letrozole normalizes serum testosterone in severely obese men with hypogonadotropic hypogonadism. Diabetes Obes Metab 2005; 7 (3) 211-215
• 41 Dhindsa S, Furlanetto R, Vora M, Ghanim H, Chaudhuri A, Dandona P. Low estradiol concentrations in men with subnormal testosterone concentrations and type 2 diabetes. Diabetes Care 2011; 34 (8) 1854-1859
• 42 Hammoud A, Carrell DT, Meikle AW , et al. An aromatase polymorphism modulates the relationship between weight and estradiol levels in obese men. Fertil Steril 2010; 94 (5) 1734-1738
• 43 Hammoud AO, Griffin J, Meikle AW, Gibson M, Peterson CM, Carrell DT. Association of aromatase (TTTAn) repeat polymorphism length and the relationship between obesity and decreased sperm concentration. Hum Reprod 2010; 25 (12) 3146-3151
• 44 Vermeulen A, Kaufman JM, Deslypere JP, Thomas G. Attenuated luteinizing hormone (LH) pulse amplitude but normal LH pulse frequency, and its relation to plasma androgens in hypogonadism of obese men. J Clin Endocrinol Metab 1993; 76 (5) 1140-1146
• 45 Blank DM, Clark RV, Heymsfield SB, Rudman DR, Blank MS. Endogenous opioids and hypogonadism in human obesity. Brain Res Bull 1994; 34 (6) 571-574
• 46 Dandona P, Dhindsa S. Update: Hypogonadotropic hypogonadism in type 2 diabetes and obesity. The Journal of clinical endocrinology and metabolism 2011; 96 (9) 2643-2651
• 47 Stellato RK, Feldman HA, Hamdy O, Horton ES, McKinlay JB. Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study. Diabetes Care 2000; 23 (4) 490-494
• 48 Tsai EC, Matsumoto AM, Fujimoto WY, Boyko EJ. Association of bioavailable, free, and total testosterone with insulin resistance: influence of sex hormone-binding globulin and body fat. Diabetes Care 2004; 27 (4) 861-868
• 49 Luboshitzky R, Lavie L, Shen-Orr Z, Herer P. Altered luteinizing hormone and testosterone secretion in middle-aged obese men with obstructive sleep apnea. Obes Res 2005; 13 (4) 780-786
• 50 Luboshitzky R, Zabari Z, Shen-Orr Z, Herer P, Lavie P. Disruption of the nocturnal testosterone rhythm by sleep fragmentation in normal men. J Clin Endocrinol Metab 2001; 86 (3) 1134-1139
• 51 Hammoud AO, Walker JM, Gibson M , et al Sleep Apnea, Reproductive Hormones and Quality of Sexual Life in Severely Obese Men. Obesity (Silver Spring) 2011;
• 52 Axelsson J, Ingre M, Akerstedt T, Holmbäck U. Effects of acutely displaced sleep on testosterone. J Clin Endocrinol Metab 2005; 90 (8) 4530-4535
• 53 Boyar RM, Rosenfeld RS, Kapen S , et al. Human puberty. Simultaneous augmented secretion of luteinizing hormone and testosterone during sleep. J Clin Invest 1974; 54 (3) 609-618
• 54 Luboshitzky R, Zabari Z, Shen-Orr Z, Herer P, Lavie P. Disruption of the nocturnal testosterone rhythm by sleep fragmentation in normal men. J Clin Endocrinol Metab 2001; 86 (3) 1134-1139
• 55 Schiavi RC, White D, Mandeli J. Pituitary-gonadal function during sleep in healthy aging men. Psychoneuroendocrinology 1992; 17 (6) 599-609
• 56 Goyal HO, Robateau A, Braden TD, Williams CS, Srivastava KK, Ali K. Neonatal estrogen exposure of male rats alters reproductive functions at adulthood. Biol Reprod 2003; 68 (6) 2081-2091
• 57 Oliva A, Spira A, Multigner L. Contribution of environmental factors to the risk of male infertility. Hum Reprod 2001; 16 (8) 1768-1776
• 58 Sharpe RM. Lifestyle and environmental contribution to male infertility. Br Med Bull 2000; 56 (3) 630-642
• 59 Jimenez Torres M, Campoy Folgoso C, Canabate Reche F , et al. Organochlorine pesticides in serum and adipose tissue of pregnant women in Southern Spain giving birth by cesarean section. Sci Total Environ 15 2006; 372 (1) 32-38
• 60 Munoz-de-Toro M, Beldomenico HR, Garcia SR , et al. Organochlorine levels in adipose tissue of women from a littoral region of Argentina. Environ Res 2006; 102 (1) 107-112
• 61 Brindley GS. Deep scrotal temperature and the effect on it of clothing, air temperature, activity, posture and paraplegia. Br J Urol 1982; 54 (1) 49-55
• 62 Bujan L, Daudin M, Charlet JP, Thonneau P, Mieusset R. Increase in scrotal temperature in car drivers. Hum Reprod 2000; 15 (6) 1355-1357
• 63 Figa-Talamanca I, Cini C, Varricchio GC , et al. Effects of prolonged autovehicle driving on male reproduction function: a study among taxi drivers. Am J Ind Med 1996; 30 (6) 750-758
• 64 Jung A, Schill WB. [Male infertility. Current life style could be responsible for infertility]. MMW Fortschr Med 14 2000; 142 (37) 31-33
• 65 Mieusset R, Bujan LE, Massat G, Mansat A, Pontonnier F. Inconstant ascending testis as a potential risk factor for spermatogenesis in infertile men with no history of cryptorchism. Hum Reprod 1997; 12 (5) 974-979
• 66 Momen MN, Fahmy I, Amer M, Arafa M, Zohdy W, Naser TA. Semen parameters in men with spinal cord injury: changes and aetiology. Asian J Androl 2007; 9 (5) 684-689
• 67 Shafik A, Olfat S. Lipectomy in the treatment of scrotal lipomatosis. Br J Urol 1981; 53 (1) 55-61
• 68 Aston KI, Krausz C, Laface I, Ruiz-Castane E, Carrell DT. Evaluation of 172 candidate polymorphisms for association with oligozoospermia or azoospermia in a large cohort of men of European descent. Hum Reprod 2010; 25 (6) 1383-1397
• 69 Bezold G, Lange M, Peter RU. Homozygous methylenetetrahydrofolate reductase C677T mutation and male infertility. N Engl J Med 2001; 344 (15) 1172-1173
• 70 Blomberg Jensen M, Bjerrum PJ, Jessen TE , et al. Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa. Hum Reprod 2011; 26 (6) 1307-1317
• 71 Blomberg Jensen M, Nielsen JE, Jorgensen A , et al. Vitamin D receptor and vitamin D metabolizing enzymes are expressed in the human male reproductive tract. Hum Reprod 2010; 25 (5) 1303-1311
• 72 Ebisch IM, van Heerde WL, Thomas CM, van der Put N, Wong WY, Steegers-Theunissen RP. C677T methylenetetrahydrofolate reductase polymorphism interferes with the effects of folic acid and zinc sulfate on sperm concentration. Fertil Steril 2003; 80 (5) 1190-1194
• 73 Ramlau-Hansen CH, Moeller UK, Bonde JP, Olsen J, Thulstrup AM. Are serum levels of vitamin D associated with semen quality? Results from a cross-sectional study in young healthy men. Fertil Steril 29 2010
• 74 Singh K, Singh SK, Sah R, Singh I, Raman R. Mutation C677T in the methylenetetrahydrofolate reductase gene is associated with male infertility in an Indian population. Int J Androl 2005; 28 (2) 115-119
• 75 Seftel A. Male hypogonadism. Part II: etiology, pathophysiology, and diagnosis. International Journal of Impotence Research 2006; 18 (3) 223-228
• 76 Heidelbaugh JJ. Management of erectile dysfunction. Am Fam Physician 2010; 81 (3) 305-312
• 77 Handel LN, Shetty R, Sigman M. The relationship between varicoceles and obesity. J Urol 2006; 176 (5) 2138-2140 ; discussion 2140
• 78 Shin JI, Lee JS. Re: The relationship between varicoceles and obesity. J Urol 2007; 178 (5) 2223-2224 ; author reply 2224
• 79 Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. The Journal of clinical endocrinology and metabolism 1999; 84 (10) 3666-3672
• 80 Kaukua J, Pekkarinen T, Sane T, Mustajoki P. Sex hormones and sexual function in obese men losing weight. Obes Res 2003; 11 (6) 689-694
• 81 Niskanen L, Laaksonen DE, Punnonen K, Mustajoki P, Kaukua J, Rissanen A. Changes in sex hormone-binding globulin and testosterone during weight loss and weight maintenance in abdominally obese men with the metabolic syndrome. Diabetes Obes Metab 2004; 6 (3) 208-215
• 82 Bastounis EA, Karayiannakis AJ, Syrigos K, Zbar A, Makri GG, Alexiou D. Sex hormone changes in morbidly obese patients after vertical banded gastroplasty. Eur Surg Res 1998; 30 (1) 43-47
• 83 Globerman H, Shen-Orr Z, Karnieli E, Aloni Y, Charuzi I. Inhibin B in men with severe obesity and after weight reduction following gastroplasty. Endocr Res 2005; 31 (1) 17-26
• 84 di Frega AS, Dale B, Di Matteo L, Wilding M. Secondary male factor infertility after Roux-en-Y gastric bypass for morbid obesity: case report. Human Reproduction 2005; 20 (4) 997-998
• 85 Sermondade N, Massin N, Boitrelle F , et al. Sperm parameters and male fertility after bariatric surgery: three case series. Reproductive Biomedicine online Nov 3 2011;
• 86 Reis LO, Zani EL, Saad RD, Chaim EA, de Oliveira LC, Fregonesi A. Bariatric Surgery Does not Interfere With Sperm Quality--A Preliminary Long-Term Study. Reprod Sci 2012; 19 (10) 1057-1062
• 87 Esposito K, Giugliano F, Di Palo C , et al. Effect of lifestyle changes on erectile dysfunction in obese men: a randomized controlled trial. JAMA 2004; 291 (24) 2978-2984
• 88 Semple PA, Graham A, Malcolm Y, Beastall GH, Watson WS. Hypoxia, depression of testosterone, and impotence in pickwickian syndrome reversed by weight reduction. Br Med J (Clin Res Ed) 1984; 289 (6448) 801-802
• 89 Grunstein RR, Handelsman DJ, Lawrence SJ, Blackwell C, Caterson ID, Sullivan CE. Neuroendocrine dysfunction in sleep apnea: reversal by continuous positive airways pressure therapy. J Clin Endocrinol Metab 1989; 68 (2) 352-358
• 90 Luboshitzky R, Lavie L, Shen-Orr Z, Lavie P. Pituitary-gonadal function in men with obstructive sleep apnea. The effect of continuous positive airways pressure treatment. Neuro Endocrinol Lett 2003; 24 (6) 463-467
• 91 Santamaria JD, Prior JC, Fleetham JA. Reversible reproductive dysfunction in men with obstructive sleep apnoea. Clin Endocrinol (Oxf) 1988; 28 (5) 461-470
• 92 Bratel T, Wennlund A, Carlstrom K. Pituitary reactivity, androgens and catecholamines in obstructive sleep apnoea. Effects of continuous positive airway pressure treatment (CPAP). Respiratory Medicine 1999; 93 (1) 1-7
• 93 Meston N, Davies RJ, Mullins R, Jenkinson C, Wass JA, Stradling JR. Endocrine effects of nasal continuous positive airway pressure in male patients with obstructive sleep apnoea. J Intern Med 2003; 254 (5) 447-454
• 94 Zumoff B, Miller LK, Strain GW. Reversal of the hypogonadotropic hypogonadism of obese men by administration of the aromatase inhibitor testolactone. Metabolism: Clinical and Experimental 2003; 52 (9) 1126-1128
• 95 Loves S, Ruinemans-Koerts J, de Boer H. Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism. Eur J Endocrinol 2008; 158 (5) 741-747
• 96 Roth MY, Amory JK, Page ST. Treatment of male infertility secondary to morbid obesity. Nat Clin Pract Endocrinol Metab 2008; 4 (7) 415-419
• 97 Pavlovich CP, King P, Goldstein M, Schlegel PN. Evidence of a treatable endocrinopathy in infertile men. J Urol 2001; 165 (3) 837-841
• 98 Raman JD, Schlegel PN. Aromatase inhibitors for male infertility. J Urol 2002; 167 (2 Pt 1) 624-629
• 99 Attia AM, Al-Inany HG, Farquhar C, Proctor M. Gonadotrophins for idiopathic male factor subfertility. Cochrane Database Syst Rev 2007; (4) CD005071
• 100 Shabsigh R, Kaufman JM, Steidle C, Padma-Nathan H. Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. J Urol 2004; 172 (2) 658-663
• 101 Ozata M, Oktenli C, Bingol N, Ozdemir IC. The effects of metformin and diet on plasma testosterone and leptin levels in obese men. Obesity research 2001; 9 (11) 662-667
• 102 Casulari LA, Caldas AD, Domingues Casulari Motta L, Lofrano-Porto A. Effects of metformin and short-term lifestyle modification on the improvement of male hypogonadism associated with metabolic syndrome. Minerva endocrinologica 2010; 35 (3) 145-151
• 103 Morgante G, Tosti C, Orvieto R, Musacchio MC, Piomboni P, De Leo V. Metformin improves semen characteristics of oligo-terato-asthenozoospermic men with metabolic syndrome. Fertil Steril 2011; 95 (6) 2150-2152