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Semin Reprod Med 2013; 31(04): 251-257
DOI: 10.1055/s-0033-1345272
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Big Enough for an Aromatase Inhibitor? How Adiposity Affects Male Fertility

Sahar M. Stephens
1   Department of Obstetrics and Gynecology, University of Colorado, Denver, Colorado
,
Alex J. Polotsky
1   Department of Obstetrics and Gynecology, University of Colorado, Denver, Colorado
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Publikationsverlauf

Publikationsdatum:
17. Juni 2013 (online)

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Abstract

Obesity is a pandemic and is associated with multiple medical problems including subfertility. Male obesity has been associated with altered semen parameters and reproductive hormonal levels, including a reduced testosterone:estradiol (T:E2) ratio. Treatment methods employed for obesity-related male subfertility include gonadotropin administration, weight loss, and aromatase inhibitors. Letrozole is a highly effective nonsteroidal aromatase inhibitor that has been used to treat male subfertility in several case series with promising results. Adequately designed randomized controlled studies are needed to produce evidence-based data on the role of aromatase inhibitors in male subfertility management and evaluate the side-effect profile.

Keywords

male obesity - infertility - aromatase inhibitor - letrozole
 

  • References

  • 1 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
    CrossrefPubMedGoogle Scholar
  • 2 US Department of Health and Human Services. Final review, healthy people 2010: Nutrition and overweight. Available at: http://www.cdc.gov/nchs/data/hpdata2010 . Accessed on April 29, 2013
    PubMedGoogle Scholar
  • 3 Organization TWH. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 2000; 894: i-xii , 1–253
    PubMedGoogle Scholar
  • 4 Ode JJ, Pivarnik JM, Reeves MJ, Knous JL. Body mass index as a predictor of percent fat in college athletes and nonathletes. Med Sci Sports Exerc 2007; 39 (3) 403-409
    PubMedGoogle Scholar
  • 5 Okorodudu DO, Jumean MF, Montori VM , et al. Diagnostic performance of body mass index to identify obesity as defined by body adiposity: a systematic review and meta-analysis. Int J Obes (Lond) 2010; 34 (5) 791-799
    CrossrefPubMedGoogle Scholar
  • 6 Organization TWH. Obesity and Overweight. WHO Media Centre; 2011
    Google Scholar
  • 7 Pasquali R, Pelusi C, Genghini S, Cacciari M, Gambineri A. Obesity and reproductive disorders in women. Hum Reprod Update 2003; 9 (4) 359-372
    CrossrefPubMedGoogle Scholar
  • 8 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
    CrossrefPubMedGoogle Scholar
  • 9 Nguyen RH, Wilcox AJ, Skjaerven R, Baird DD. Men's body mass index and infertility. Hum Reprod 2007; 22 (9) 2488-2493
    CrossrefPubMedGoogle Scholar
  • 10 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
    CrossrefPubMedGoogle Scholar
  • 11 Sallmén M, Sandler DP, Hoppin JA, Blair A, Baird DD. Reduced fertility among overweight and obese men. Epidemiology 2006; 17 (5) 520-523
    CrossrefPubMedGoogle Scholar
  • 12 Speakman JR, Djafarian K, Stewart J, Jackson DM. Assortative mating for obesity. Am J Clin Nutr 2007; 86 (2) 316-323
    PubMedGoogle Scholar
  • 13 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
    CrossrefPubMedGoogle Scholar
  • 14 Keltz J, Zapantis A, Jindal SK, Lieman HJ, Santoro N, Polotsky AJ. Overweight men: clinical pregnancy after ART is decreased in IVF but not in ICSI cycles. J Assist Reprod Genet 2010; 27 (9–10) 539-544
    CrossrefPubMedGoogle Scholar
  • 15 Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Evidence for decreasing quality of semen during past 50 years. BMJ 1992; 305 (6854) 609-613
    CrossrefPubMedGoogle Scholar
  • 16 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
    CrossrefPubMedGoogle Scholar
  • 17 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
    CrossrefPubMedGoogle Scholar
  • 18 Sermondade N, Faure C, Fezeu L, Lévy R, Czernichow S. Obesity-Fertility Collaborative Group. Obesity and increased risk for oligozoospermia and azoospermia. Arch Intern Med 2012; 172 (5) 440-442
    CrossrefPubMedGoogle Scholar
  • 19 Teerds KJ, de Rooij DG, Keijer J. Functional relationship between obesity and male reproduction: from humans to animal models. Hum Reprod Update 2011; 17 (5) 667-683
    CrossrefPubMedGoogle Scholar
  • 20 Amatruda JM, Hochstein M, Hsu TH, Lockwood DH. Hypothalamic and pituitary dysfunction in obese males. Int J Obes 1982; 6 (2) 183-189
    PubMedGoogle Scholar
  • 21 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
    CrossrefPubMedGoogle Scholar
  • 22 Jain A, Polotsky AJ, Rochester D , et al. Pulsatile luteinizing hormone amplitude and progesterone metabolite excretion are reduced in obese women. J Clin Endocrinol Metab 2007; 92 (7) 2468-2473
    CrossrefPubMedGoogle Scholar
  • 23 Dhillo WS, Chaudhri OB, Patterson M , et al. Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab 2005; 90 (12) 6609-6615
    CrossrefPubMedGoogle Scholar
  • 24 George JT, Millar RP, Anderson RA. Hypothesis: kisspeptin mediates male hypogonadism in obesity and type 2 diabetes. Neuroendocrinology 2010; 91 (4) 302-307
    CrossrefPubMedGoogle Scholar
  • 25 Hammoud A, Carrell D, Gibson M, Peterson C, Meikle A. Updates on the relation of weight excess and reproductive function in men: sleep apnea as a new area of interest. Asian J Androl 2012; 14: 77-81
    CrossrefPubMedGoogle Scholar
  • 26 Kamischke A, Nieschlag E. Analysis of medical treatment of male infertility. Hum Reprod 1999; 14 (Suppl. 01) 1-23
    PubMedGoogle Scholar
  • 27 Attia AM, Al-Inany HG, Farquhar C, Proctor M. Gonadotrophins for idiopathic male factor subfertility. Cochrane Database Syst Rev 2007; (4) CD005071
    PubMedGoogle Scholar
  • 28 Stanik S, Dornfeld LP, Maxwell MH, Viosca SP, Korenman SG. The effect of weight loss on reproductive hormones in obese men. J Clin Endocrinol Metab 1981; 53 (4) 828-832
    CrossrefPubMedGoogle Scholar
  • 29 Strain GW, Zumoff B, Miller LK , et al. Effect of massive weight loss on hypothalamic-pituitary-gonadal function in obese men. J Clin Endocrinol Metab 1988; 66 (5) 1019-1023
    CrossrefPubMedGoogle Scholar
  • 30 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
    CrossrefPubMedGoogle Scholar
  • 31 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. Hum Reprod 2005; 20 (4) 997-998
    CrossrefPubMedGoogle Scholar
  • 32 Sermondade N, Massin N, Boitrelle F , et al. Sperm parameters and male fertility after bariatric surgery: three case series. Reprod Biomed Online 2011; 2012; 24 (2) 206-210
    CrossrefPubMedGoogle Scholar
  • 33 Palmer NO, Bakos HW, Owens JA, Setchell BP, Lane M. Diet and exercise in an obese mouse fed a high-fat diet improve metabolic health and reverse perturbed sperm function. Am J Physiol Endocrinol Metab 2012; 302 (7) E768-E780
    CrossrefPubMedGoogle Scholar
  • 34 Elkhiat Y, Fahmy I. Aromatase inhibitors in the treatment of male infertility. Human Andrology 2011; 1: 35-38
    CrossrefPubMedGoogle Scholar
  • 35 Raman JD, Schlegel PN. Aromatase inhibitors for male infertility. J Urol 2002; 167 (2, Pt 1) 624-629
    CrossrefPubMedGoogle Scholar
  • 36 de Ronde W, de Jong FH. Aromatase inhibitors in men: effects and therapeutic options. Reprod Biol Endocrinol 2011; 9: 93
    CrossrefPubMedGoogle Scholar
  • 37 Zumoff B, Miller LK, Strain GW. Reversal of the hypogonadotropic hypogonadism of obese men by administration of the aromatase inhibitor testolactone. Metabolism 2003; 52 (9) 1126-1128
    CrossrefPubMedGoogle Scholar
  • 38 Roth MY, Amory JK, Page ST. Treatment of male infertility secondary to morbid obesity. Nat Clin Pract Endocrinol Metab 2008; 4 (7) 415-419
    CrossrefPubMedGoogle Scholar
  • 39 Patry G, Jarvi K, Grober ED, Lo KC. Use of the aromatase inhibitor letrozole to treat male infertility. Fertil Steril 2009; 92 (2) e1-e2
    CrossrefPubMedGoogle Scholar
  • 40 Cavallini G, Beretta G, Biagiotti G. Preliminary study of letrozole use for improving spermatogenesis in non-obstructive azoospermia patients with normal serum FSH. Asian J Androl 2011; 13 (6) 895-897
    CrossrefPubMedGoogle Scholar
  • 41 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
    CrossrefPubMedGoogle Scholar
  • 42 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
    CrossrefPubMedGoogle Scholar
  • 43 Richardson D, Goldmeier D, Frize G , et al. Letrozole versus testosterone. a single-center pilot study of HIV-infected men who have sex with men on highly active anti-retroviral therapy (HAART) with hypoactive sexual desire disorder and raised estradiol levels. J Sex Med 2007; 4 (2) 502-508
    CrossrefPubMedGoogle Scholar
  • 44 Saylam B, Efesoy O, Cayan S. The effect of aromatase inhibitor letrozole on body mass index, serum hormones, and sperm parameters in infertile men. Fertil Steril 2011; 95 (2) 809-811
    CrossrefPubMedGoogle Scholar
  • 45 Gonzales GF, Tapia V, Gasco M, Gonzales-Castañeda C. Aromatase activity after a short-course of letrozole administration in adult men at sea level and at high altitude (with or without excessive erythrocytosis). Horm Metab Res 2012; 44 (2) 140-145
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 46 Lapauw B, T'Sjoen G, Mahmoud A, Kaufman JM, Ruige JB. Short-term aromatase inhibition: effects on glucose metabolism and serum leptin levels in young and elderly men. Eur J Endocrinol 2009; 160 (3) 397-402
    CrossrefPubMedGoogle Scholar