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Ovarian Function and Obesity: PCOS, Menopause

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Multidisciplinary Approach to Obesity

Abstract

Ovarian function and energy metabolism are tightly connected and reciprocally regulated to enable reproduction in food-scarce environment. Reproductive disorders can lead to metabolic disorders and obesity both of which may in turn induce alterations of the menstrual cycle and fertility. A growing body of research documents the effects of endocrine-disrupting chemicals on the differentiation of adipocytes and the central nervous system circuits that control food intake and energy expenditure, as well as influence on reproduction and insulin secretion. Insulin resistance is related to abdominal obesity, and in women, it is often inextricably linked with ovarian dysfunctions, leading to clinical manifestations across the entire female reproductive life. Specifically, obesity in women manifests, as early menarche, subfertility, polycystic ovary syndrome, symptomatic menopause, and increased risk of breast cancer. Overall, obese women with superimposed reproductive complications including PCOS may be considered to be at high risk for further progression to metabolic syndrome, type 2 diabetes mellitus, and potentially cardiovascular diseases. These patients can then be targeted for early screening, lifestyle optimization, and the prevention of the subsequent metabolic derangement. Considering the reciprocal interactions between pathways that control fertility and energy metabolism and the key roles of molecules such as estrogens and IGF-1 in these pathways, it is possible to consider changing the current therapeutic strategies—amelioration of metabolic disorders, for example, might become an important goal of hormone replacement therapy (HRT) in menopausal obese women.

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References

  1. Della Torre S, Benedusi V, Fontana R et al (2014) Energy metabolism and fertility—a balance preserved for female health. Nat Rev Endocrinol 10:13–23

    Article  PubMed  Google Scholar 

  2. Shapira N (2013) Women’s higher health risks in the obesogenic environment: a gender nutrition approach to metabolic dimorphism with predictive, preventive, and personalized medicine. EPMA J 4:1

    Article  PubMed  PubMed Central  Google Scholar 

  3. Davis LK, Hiramatsu N, Hiramatsu K et al (2007) Induction of three vitellogenins by 17β-estradiol with concurrent inhibition of the growth hormone-insulin-like growth factor 1 axis in a euryhaline teleost, the tilapia (Oreochromis mossambicus). Biol Reprod 77:614–625

    Article  CAS  PubMed  Google Scholar 

  4. Olofsson LE, Pierce AA, Xu AW (2009) Functional requirement of AgRP and NPY neurons in ovarian cycle-dependent regulation of food intake. Proc Natl Acad Sci U S A 106:15932–15937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Oakley AE, Clifton DK, Steiner RA (2009) Kisspeptin signaling in the brain. Endocr Rev 30:713–743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Clegg DJ, Brown LM, Woods SC et al (2006) Gonadal hormones determine sensitivity to central leptin and insulin. Diabetes 55:978–987

    Article  CAS  PubMed  Google Scholar 

  7. Chervenak J (2009) Bioidentical hormones for maturing women. Maturitas 64:86–89

    Article  CAS  PubMed  Google Scholar 

  8. Villa A, Della Torre S, Stell A et al (2012) Tetradian oscillation of estrogen receptor α is necessary to prevent liver lipid deposition. Proc Natl Acad Sci U S A 109:11806–11811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Della Torre S, Rando G, Meda C et al (2011) Amino acid-dependent activation of liver estrogen receptor α integrates metabolic and reproductive functions via IGF-1. Cell Metab 13:205–214

    Article  CAS  PubMed  Google Scholar 

  10. D’Eon TM, Souza SC, Aronovitz M et al (2005) Estrogen regulation of adiposity and fuel partitioning. Evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways. J Biol Chem 280:35983–35991

    Article  PubMed  Google Scholar 

  11. Couse JF, Korach KS (1999) Estrogen receptor null mice: what have we learned and where will they lead us? Endocr Rev 20:358–417

    Article  CAS  PubMed  Google Scholar 

  12. Tiano JP, Delghingaro-Augusto V, Le May C et al (2011) Estrogen receptor activation reduces lipid synthesis in pancreatic islets and prevents β cell failure in rodent models of type 2 diabetes. J Clin Invest 121:3331–3342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Jovanovic L (2004) Advances in diabetes for the millennium: diabetes in women. MedGenMed 6:3

    PubMed  PubMed Central  Google Scholar 

  14. Racho’n D, Teede H (2010) Ovarian function and obesity—interrelationship, impact on women’s reproductive lifespan and treatment options. Mol Cell Endocrinol 316:172–179

    Article  Google Scholar 

  15. Diamanti-Kandarakis E, Bergiele A (2001) The influence of obesity on hyperandrogenism and infertility in the female. Obes Rev 2:231–238

    Article  CAS  PubMed  Google Scholar 

  16. Van der Steeg JW, Steures P, Eijkemans MJ et al (2008) Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women. Hum Reprod 23:324–328

    Article  PubMed  Google Scholar 

  17. Shalitin S, Phillip M (2003) Role of obesity and leptin in the pubertal process and pubertal growth – a review. Int J Obes Relat Metab Disord 27:869–874

    Article  CAS  PubMed  Google Scholar 

  18. Lakshman R, Forouhi N, Luben R et al (2008) Association between age at menarche and risk of diabetes in adults: results from the EPIC-Norfolk cohort study. Diabetologia 51:781–786

    Article  CAS  PubMed  Google Scholar 

  19. Carmina E, Bucchieri S, Esposito A et al (2007) Abdominal fat quantity and distribution in women with polycystic ovary syndrome and extent of its relation to insulin resistance. J Clin Endocrinol Metab 92:2500–2505

    Article  CAS  PubMed  Google Scholar 

  20. Hoeger KM (2014) Developmental origins and future fate in PCOS. Semin Reprod Med 32(03):157–158

    Article  CAS  PubMed  Google Scholar 

  21. Orio F, Palomba S (2014) New guidelines for the diagnosis and treatment of PCOS. Nat Rev Endocrinol 10:130–132

    Article  PubMed  Google Scholar 

  22. Moran LJ, Teede HJ (2009) Metabolic features of the reproductive phenotypes of polycystic ovary syndrome. Hum Reprod Update 15:477–488

    Article  CAS  PubMed  Google Scholar 

  23. Boudreaux MY, Talbott EO, Kip KE et al (2006) Risk of T2DM and impaired fasting glucose among PCOS subjects: results of an 8-year follow-up. Curr Diabetes Rep 6:77–83

    Article  CAS  Google Scholar 

  24. Toscano V, Bianchi P, Balducci R et al (1992) Lack of linear relationship between hyperinsulinaemia and hyperandrogenism. Clin Endocrinol Oxford 36:197–207

    Article  CAS  Google Scholar 

  25. Moran LJ, Hutchison SK, Meyer C et al (2009) A comprehensive assessment of endothelial function in overweight women with and without polycystic ovary syndrome. Clin Sci (Lond) 116(10):761–770

    Google Scholar 

  26. Orio F, Palomba S, Colao A (2006) Cardiovascular risk in women with polycystic ovary syndrome. Fertil Steril 86(Suppl 1):S20–S21

    Article  PubMed  Google Scholar 

  27. Misso M, Boyle J, Norman R, Teede H (2014) Development of evidenced-based guidelines for PCOS and implications for community health. Semin Reprod Med 32(3):230–240

    Article  CAS  PubMed  Google Scholar 

  28. Gambineri A, Patton L, Vaccina et al (2006) Treatment with flutamide, metformin, and their combination added to a hypocaloric diet in overweight-obese women with polycystic ovary syndrome: a randomized, 12-month, placebo-controlled study. J Clin Endocrinol Metab 91:3970–3980

    Article  CAS  PubMed  Google Scholar 

  29. Lubrano C, Genovesi G, Specchia P et al (2013) Obesity and metabolic comorbidities: environmental diseases? Oxid Med Cell Longev 2013:640673. doi:10.1155/2013/640673

    Article  PubMed  PubMed Central  Google Scholar 

  30. Schneider JE, Brozek JM, Keen-Rhinehart E (2014) Our stolen figures: the interface of sexual differentiation, endocrine disruptors, maternal programming, and energy balance. Horm Behav, http://dx.doi.org/10.1016/j.yhbeh.2014.03.011

  31. Barrett ES, Sobolewski M (2014) Polycystic ovary syndrome: do endocrine-disrupting chemicals play a role? Semin Reprod Med 32(03):166–176

    Article  PubMed  PubMed Central  Google Scholar 

  32. Legro RS, Arslanian SA, Ehrmann DA et al (2013) Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 98(12):4565–4592, http://dx.doi.org/10.1210/jc.2013-2350

    Article  CAS  PubMed  Google Scholar 

  33. Agapova SE, Cameo T, Sopher AB et al (2014) Diagnosis and challenges of polycystic ovary syndrome in adolescence. Semin Reprod Med 32(3):194–201

    Article  PubMed  PubMed Central  Google Scholar 

  34. Greco EA, Fornari R, Rossi F et al (2010) Is obesity protective for osteoporosis? Evaluation of bone mineral density in individuals with high body mass index. Int J Clin Pract 64:817–820. doi:10.1111/j.1742-1241.2009.02301.x

    Article  CAS  PubMed  Google Scholar 

  35. Greco EA, Francomano D, Fornari R et al (2013) Negative association between trunk fat, insulin resistance and skeleton in obese women. World J Diabetes 4:31–39

    Article  PubMed  PubMed Central  Google Scholar 

  36. Lovejoy JC, Champagne CM, de Jonge L et al (2008) Increased visceral fat and decreased energy expenditure during the menopausal transition. Int J Obes (Lond) 32:949–958

    Article  CAS  Google Scholar 

  37. Wing RR, Matthews KA, Kuller LH et al (1991) Weight gain at the time of menopause. Arch Intern Med 151:97–102

    Article  CAS  PubMed  Google Scholar 

  38. Kudesia B, Neal-Perry G (2014) Menopausal implications of polycystic ovarian syndrome. Semin Reprod Med 32(03):222–229

    Article  PubMed  Google Scholar 

  39. Marini H, Bitto A, Altavilla D et al (2010) Efficacy of genistein aglycone on some cardiovascular risk factors and homocysteine levels: a follow-up study. Nutr Metab Cardiovasc Dis 20:332–340. doi:10.1016/j.numecd.2009.04.012

    Article  CAS  PubMed  Google Scholar 

  40. Marini H, Bitto A, Altavilla D, Burnett BP et al (2008) Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: a follow-up study. J Clin Endocrinol Metab 93:4787–4796. doi:10.1210/jc.2008-1087

    Article  CAS  PubMed  Google Scholar 

  41. Atteritano M, Marini H, Minutoli L et al (2007) Effects of the phytoestrogen genistein on some predictors of cardiovascular risk in osteopenic, postmenopausal women: a two-year randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 92:3068–3075

    Article  CAS  PubMed  Google Scholar 

  42. Palomba S, Giallauria F, Falbo A et al (2008) Structured exercise training programme versus hypocaloric hyperproteic diet in obese polycystic ovary syndrome patients with anovulatory infertility: a 24-week pilot study. Hum Reprod 23:642–650

    Article  CAS  PubMed  Google Scholar 

  43. Meyer C, McGrath BP, Teede HJ (2007) Effects of medical therapy on insulin resistance and the cardiovascular system in polycystic ovary syndrome. Diabetes Care 30:471–478

    Article  CAS  PubMed  Google Scholar 

  44. Pi-Sunyer FX (2008) The effects of pharmacologic agents for type 2 diabetes mellitus on body weight. Postgrad Med 120:5–17

    Article  PubMed  Google Scholar 

  45. Panidis D, Farmakiotis D, Rousso D et al (2008) Obesity, weight loss, and the polycystic ovary syndrome: effect of treatment with diet and orlistat for 24 weeks on insulin resistance and androgen levels. Fertil Steril 89:899–906

    Article  PubMed  Google Scholar 

  46. Puurunen J, Piltonen T, Puukka K et al (2013) Statin therapy worsens insulin sensitivity in women with polycystic ovary syndrome (PCOS): a prospective, randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 98(12):4798–4807, http://dx.doi.org/10.1210/jc.2013-2674

    Article  CAS  PubMed  Google Scholar 

  47. Palomba S, Falbo A, Zullo F et al (2009) Evidence-based and potential benefits of metformin in the polycystic ovary syndrome: a comprehensive review. Endocr Rev 30:1–50

    Article  CAS  PubMed  Google Scholar 

  48. Misso ML, Costello MF, Garrubba M et al (2013) Metformin versus clomiphene citrate for infertility in non-obese women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 19:2–11

    Article  CAS  PubMed  Google Scholar 

  49. Lubrano C, Cornoldi A, Pili M et al (2004) Reduction of risk factors for cardiovascular diseases in morbid-obese patients following biliary-intestinal bypass: 3 years’ follow-up. Int J Obes Relat Metab Disord 28:1600–1606

    Article  CAS  PubMed  Google Scholar 

  50. Lubrano C, Mariani S, Badiali M et al (2010) Metabolic or bariatric surgery? Long-term effects of malabsorptive vs restrictive bariatric techniques on body composition and cardiometabolic risk factors. Int J Obes (Lond) 34:1404–1414. doi:10.1038/ijo.2010.54

    Article  CAS  Google Scholar 

  51. Eid GM, Cottam DR, Velcu LM et al (2005) Effective treatment of polycystic ovarian syndrome with Roux-en-Y gastric bypass. Surg Obes Relat Dis 1:77–80

    Article  PubMed  Google Scholar 

  52. Petrangeli E, Lubrano C, Ortolani F et al (1994) Estrogen receptors: new perspectives in breast cancer management. J Steroid Biochem Mol Biol 49:327–331

    Article  CAS  PubMed  Google Scholar 

  53. Petrangeli E, Lubrano C, Ravenna L et al (1995) Gene methylation of oestrogen and epidermal growth factor receptors in neoplastic and perineoplastic breast tissues. Br J Cancer 72:973–975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Amadou A, Ferrari P, Muwonge R et al (2013) Overweight, obesity and risk of premenopausal breast cancer according to ethnicity: a systematic review. Obes Rev 14:665–678

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Carla Lubrano .

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Lubrano, C., Gnessi, L., Migliaccio, S. (2015). Ovarian Function and Obesity: PCOS, Menopause. In: Lenzi, A., Migliaccio, S., Donini, L. (eds) Multidisciplinary Approach to Obesity. Springer, Cham. https://doi.org/10.1007/978-3-319-09045-0_7

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  • DOI: https://doi.org/10.1007/978-3-319-09045-0_7

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