Metabolism, Obesity, Thinness, and Reproduction

  • Alessia Prati
  • Antonella Napolitano
  • Giulia Despini
  • Alba Manzo
  • Martina Caroli
  • Alessandro D. Genazzani
Part of the ISGE Series book series (ISGE)


The physiology of reproduction is ruled by neuroendocrine signals that originate in many regions of the brain. Additionally, such signals are greatly modulated or affected by relevant signals derived from the periphery of our body. All such peripheral signals are concerned with specific sensorial and metabolic information that might positively or negatively modulate specific responses from the brain and from the affective neuroendocrine pathways of the endocrine glands. Such interconnections are at the basis of the modulation, which might block or restart reproductive functions by means of hypothalamus-pituitary control of ovarian function in humans either by body weight loss, as from anorexia nervosa, or by excessive body mass, as in obesity. The understanding of these mechanisms is of tremendous value to clinicians who face and resolve reproductive impairment.


Thinness Obesity Hypothalamus Neuroendocrinology Insulin Stress Adiposity Metabolic syndrome 


  1. 1.
    Schally A, Arimura A, Kastin A, Matsuo H, Baba Y, Redding T, Nair R, Debeljuk L, White W. Gonadotropin-releasing hormone: one polypeptide regulates secretion of luteinizing and follicle-stimulating hormones. Science. 1971;173:1036–8.CrossRefGoogle Scholar
  2. 2.
    Lebrethon M-C, Aganina A, Fournier M, Gerard A, Parent A-S, Bourguignon J-P. Effects of in vivo and in vitro administration of ghrelin, leptin and neuropeptide mediators on pulsatile gonadotrophin-releasing hormone secretion from male rat hypothalamus before and after puberty. J Neuroendocrinol. 2007;19:181–8.CrossRefGoogle Scholar
  3. 3.
    Gottsch M, Cunningham M, Smith J, Popa S, Acohido B, Crowley W, Seminara S, Clifton D, Steiner R. A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology. 2004;145:4073–7.CrossRefGoogle Scholar
  4. 4.
    Zhu J, Xu XH, Knight GE, He C, Burnstock G, Xiang Z. A subpopulation of gonadotropin-releasing hormone neurons in the adult mouse forebrain is γ-5 aminobutyric acidergic. J Neurosci Res. 2015;93:1611–21.CrossRefGoogle Scholar
  5. 5.
    Tsutsui K, Saigoh E, Ukena K, Teranishi H, Fujisawa Y, Kikuchi M, Ishii S, Sharp PJ. A novel avian hypothalamic peptide inhibiting gonadotropin release. Biochem Biophys Res Commun. 2000;275:661–7.CrossRefGoogle Scholar
  6. 6.
    Fourman LT, Fazeli PK. Neuroendocrine causes of amenorrhea: an update. J Clin Endocrinol Metab. 2015;100:812–24.CrossRefGoogle Scholar
  7. 7.
    Vigersky RA, Andersen AE, Thompson RH, Lauriaux DL. Hypothalamic dysfunction in secondary amenorrhea associated with simple weight loss. N Engl J Med. 1977;297:1141–6.CrossRefGoogle Scholar
  8. 8.
    Berga SL, Mortola SF, Girton L, Suh B, Laughlin G, Pham P, Yen SSC. Neuroendocrine aberrations in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab. 1989;68:301–8.CrossRefGoogle Scholar
  9. 9.
    Cameron JL, Helmreich DL, Schreihofer DA. Modulation of reproductive hormone secretion by nutritional intake: stress signals versus metabolic signals. Hum Reprod. 1993;8:162–7.CrossRefGoogle Scholar
  10. 10.
    Ringstrom SJ, Suter D, D’Agostino J, Hoestler JP, Scwartz NB. Effects of glucocorticoids on the hypothalamic-pituitary-gonadal axis. In: Genazzani AR, Nappi G, Petraglia F, Martignoni E, editors. Stress and related disorders from adaptation to dysfunction. Carnforth: Parthenon; 1991. p. 297–305.Google Scholar
  11. 11.
    Misra M, Klibanski A. Endocrine consequences of anorexia nervosa. Lancet Diabetes Endocrinol. 2014;2(7):581–92. Epub 2014 Apr 2CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Frisch RE, Revelle R. Height and weight at menarche and a hypothesis of critical body weights and adolescent events. Science. 1970;169:397–9. [PubMed: 5450378]CrossRefGoogle Scholar
  13. 13.
    Frisch RE, McArthur JW. Menstrual cycles: fatness as a determinant of minimum weight for height necessary for their maintenance or onset. Science. 1974;185:949–51. [PubMed: 4469672]CrossRefGoogle Scholar
  14. 14.
    Ahima RS, Saper CB, Flier JS, et al. Leptin regulation of neuroendocrine systems. Front Neuroendocrinol. 2000;21:263–307.CrossRefGoogle Scholar
  15. 15.
    Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996;334:292–5.CrossRefGoogle Scholar
  16. 16.
    Woods SC, D’Alessio DA. Central control of body weight and appetite. J Clin Endocrinol Metab. 2008;93(11 suppl 1):S37–50.CrossRefGoogle Scholar
  17. 17.
    Zigman JM, Elmquist JK. Minireview: From anorexia to obesity—the yin and yang of body weight control. Endocrinology. 2003;144:3749–56.CrossRefGoogle Scholar
  18. 18.
    Lanfranco F, Bonelli L, Baldi M, et al. Acylated ghrelin inhibits spontaneous luteinizing hormone pulsatility and responsiveness to naloxone but not that to gonadotropin-releasing hormone in young men: evidence for a central inhibitory action of ghrelin on the gonadal axis. J Clin Endocrinol Metab. 2008;93:3633–9.CrossRefGoogle Scholar
  19. 19.
    Pralong FP. Insulin and NPY pathways and the control of GnRH function and puberty onset. Mol Cell Endocrinol. 2010;324:82–6.CrossRefGoogle Scholar
  20. 20.
    Moret M, Stettler R, Rodieux F, et al. Insulin modulation of luteinizing hormone secretion in normal female volunteers and lean polycystic ovary syndrome patients. Neuroendocrinology. 2009;89:131–9.CrossRefGoogle Scholar
  21. 21.
    Barr VA, Malide D, Zarnowski MJ, et al. Insulin stimulates both leptin secretion and production by rat white adipose tissue. Endocrinology. 1997;138:4463–72.CrossRefGoogle Scholar
  22. 22.
    Roa J, Tena-Sempere M. Connecting metabolism and reproduction: roles of central energy sensors and key molecular mediators. Mol Cell Endocrinol. 2014;397:4–14.CrossRefGoogle Scholar
  23. 23.
    Wolfe A, Divall S, Wu S. The regulation of reproductive neuroendocrine function by insulin and insulin-like growth factor-1 (IGF-1). Front Neuroendocrinol. 2014;35:558–72.CrossRefGoogle Scholar
  24. 24.
    Luna AM, Wilson DM, Wibbelsman CJ, et al. Somatomedins in adolescence: a cross-sectional study of the effect of puberty on plasma insulin-like growth factor I and II levels. J Clin Endocrinol Metab. 1983;57:268–71.CrossRefGoogle Scholar
  25. 25.
    Gómez-Pinilla F. Brain foods: the effects of nutrients on brain function. Nat Rev Neurosci. 2008;9(7):568–78.CrossRefGoogle Scholar
  26. 26.
    Genazzani AD, Gamba O, Petraglia F. Estrogen replacement therapy modulates spontaneous GH secretion but does not affect GH-RH-induced GH response and low T3 syndrome in women with hypothalamic amenorrhea associated to weight-loss. J Endocrinol Invest. 1998;21:353–7.CrossRefGoogle Scholar
  27. 27.
    Genazzani AD, Petraglia F, Fabbri G, Monzani A, Montanini V, Genazzani AR. Evidence of luteinizing hormone secretion in hypothalamic amenorrhea associated with weight loss. Fertil Steril. 1990;54:222–6.CrossRefGoogle Scholar
  28. 28.
    World Health Organization. Obesity and overweight fact sheet 2016. Available at: Last accessed March 6, 2017.Google Scholar
  29. 29.
    Knight M, Kurinczuk JJ, Spark P, Brocklehurst P. Extreme obesity in pregnancy in the United Kingdom. Obstet Gynecol. 2010;115:989–97.CrossRefGoogle Scholar
  30. 30.
    Rachon D, Teede H. Ovarian function and obesity—interrelationship, impact on women’s reproductive lifespan and treatment options. Mol Cell Endocrinol. 2010;316:172–9.CrossRefGoogle Scholar
  31. 31.
    Jungheim ES, Moley KH. Current knowledge of obesity’s effects in the pre- and periconceptional periods and avenues for future research. Am J Obstet Gynecol. 2010;203:525–30.CrossRefGoogle Scholar
  32. 32.
    Pasquali R. Obesity and androgens: facts and perspectives. Fertil Steril. 2006;85:1319–40.CrossRefGoogle Scholar
  33. 33.
    Moran LJ, Norman RJ, Teede HJ. Metabolic risk in PCOS: phenotype and adiposity impact. Trends Endocrinol Metab. 2015;26:136–43.CrossRefGoogle Scholar
  34. 34.
    Ibanez L, et al. Precocious pubarche, hyperinsulinism, and ovarian hyperandrogenism in girls: relation to reduced fetal growth. J Clin Endocrinol Metab. 1998;83:3558–62.CrossRefGoogle Scholar
  35. 35.
    Morrison JL, Duffield JA, Muhlhausler BS, Gentili S, McMillen IC. Fetal growth restriction, catch-up growth and the early origins of insulin resistance and visceral obesity. Pediatr Nephrol. 2010;25(4):669–77.CrossRefGoogle Scholar
  36. 36.
    Zimmet P, Alberti G, Kaufman F, Tajima N, Silink M, Arslanian S, Wong G, Bennett P, Shaw J, Caprio S, International Diabetes Federation Task Force on Epidemiology and Prevention of Diabetes. The metabolic syndrome in children and adolescents. Lancet. 2007;369(9579):2059–61.CrossRefGoogle Scholar
  37. 37.
    Hannon TS, Gungor N. Arslanian SA. Type 2 diabetes in children and adolescents: a review for the primary care provider. Pediatr Ann. 2006;35(12):880–7.PubMedGoogle Scholar
  38. 38.
    Franks S. Polycystic ovary syndrome in adolescents. Int J Obes (Lond). 2008;32(7):1035–41.CrossRefGoogle Scholar
  39. 39.
    Franks S, Berga SL. Does PCOS have developmental origins? Fertil Steril. 2012;97(1):2–6.CrossRefGoogle Scholar
  40. 40.
    Chittenden BG, Fullerton G, Maheshwari A, Bhattacharya S. Polycystic ovary syndrome and the risk of gynaecological cancer: a systematic review. Reprod Biomed Online. 2009;19:398–405.CrossRefGoogle Scholar
  41. 41.
    Barbieri RL. The role of adipose tissue and hyperinsulinemia in the development of hyperandrogenism in women. In: Frisch RE, editor. Adipose tissue and reproduction. Basel: Karger; 2000. p. 42–57.Google Scholar
  42. 42.
    Conway GS, Jacobs HS, Holly JM, Wass JA. Effects of LH, insulin, insulin-like growth factor I and insulin-like growth factor small binding protein I in the polycystic ovary syndrome. Clin Endocrinol (Oxf). 1990;33:593–603.CrossRefGoogle Scholar
  43. 43.
    Behboudi-Gandevani S, Ramezani Tehrani F, Rostami Dovom M, Farahmand M, Bahri Khomami M, Noroozzadeh M, Kabir A, Azizi F. Insulin resistance in obesity and polycystic ovary syndrome: systematic review and meta-analysis of observational studies. Gynecol Endocrinol. 2016;32(5):343–5353.CrossRefGoogle Scholar
  44. 44.
    Salley KE, Wickham EP, Cheang KI, Essah PA, Karjane NW, Nestler JE. Glucose intolerance in polycystic ovary syndrome: a position statement of the Androgen Excess Society. J Clin Endocrinol Metab. 2007;92(12):4546–56.CrossRefGoogle Scholar
  45. 45.
    Genazzani AD. Inositol as putative integrative treatment for PCOS. Reprod Biomed Online. 2016;33:770–80.CrossRefGoogle Scholar
  46. 46.
    Genazzani AD, Shefer K, Della Casa D, Prati A, Napolitano A, Manzo A, Despini G, Simoncini T. Modulatory effects of alpha-lipoic acid (ALA) administration on insulin sensitivity in obese PCOS patients. J Endocrinol Invest. 2018;41(5):583–90.CrossRefGoogle Scholar

Copyright information

© International Society of Gynecological Endocrinology 2019

Authors and Affiliations

  • Alessia Prati
    • 1
  • Antonella Napolitano
    • 1
  • Giulia Despini
    • 1
  • Alba Manzo
    • 1
  • Martina Caroli
    • 1
  • Alessandro D. Genazzani
    • 1
  1. 1.Department of Obstetrics and Gynecology, Gynecological Endocrinology CenterUniversity of Modena and Reggio EmiliaModenaItaly

Personalised recommendations