Skip to main content

Advertisement

Log in

Lean polycystic ovary syndrome (PCOS): an evidence-based practical approach

  • Research Article
  • Published:
Journal of Diabetes & Metabolic Disorders Aims and scope Submit manuscript

Abstract

Background

Polycystic ovary syndrome (PCOS) is a common endocrinopathy affecting women of reproductive age. Common features include menstrual irregularities, hyperandrogenism and polycystic ovarian morphology although the presentation can be heterogeneous. Insulin resistance is thought to be responsible for the hormonal and metabolic derangements observed. PCOS has two phenotypes, overweight/obese and lean, the latter being a much less common presentation of the syndrome.

Aims

The aim of the present review is to summarise cardinal features, and to devise diagnostic and treatment algorithms for lean PCOS based on recent literature.

Methods

We searched PubMed, EBSCOhost and Google Scholar using search terms such as ‘lean polycystic ovary syndrome’ OR ‘lean polycystic ovarian syndrome’ OR ‘lean PCOS’ OR ‘lean polycystic ovary disease’ OR ‘lean polycystic ovarian disease’ OR ‘lean PCOD’ OR ‘hyperandrogenism’ AND ‘low BMI OR ‘low body mass index’ to identify potential articles to be included in the review. Citation searches were subsequently performed in order to find relevant literature.

Results

Hormonal, metabolic and haematological profiles were altered in lean women with PCOS compared to healthy counterparts. However, the derangements were either comparable or less obvious compared to obese women with the syndrome. Insulin resistance seemed inherent in PCOS independent of obesity. Treatment options included weight maintenance, restoration of ovulation with insulin-sensitizers such as metformin, relief of symptoms such as hirsutism, acne and menstrual dysfunction, and assisted reproductive technologies in refractory cases, all of which showed promising results. The literature with evidence on lean PCOS is of low to moderate quality and there are still some uncertainties in the evidence base.

Conclusion

Carefully designed randomised controlled trials are required to confirm findings of previous studies in lean PCOS and to consolidate diagnostic and management algorithms proposed in this review. This paper will aid health professionals to improve their clinical approach in managing lean women with PCOS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89:2745–9.

    Article  PubMed  CAS  Google Scholar 

  2. Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG, et al. A survey of the polycystic ovary syndrome in the Greek Island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab. 1999;84:4006–11.

    Article  PubMed  CAS  Google Scholar 

  3. Knochenhauer ES, Key TJ, Kahsar-Miller M, Waggoner W, Boots LR, Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab. 1998;83:3078–82.

    PubMed  CAS  Google Scholar 

  4. Asunción M, Calvo RM, San Millán JL, Sancho J, Avila S, Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab. 2000;85:2434–8.

    PubMed  Google Scholar 

  5. Michelmore K, Balen A, Dunger D, Vessey M. Polycystic ovaries and associated clinical and biochemical features in young women. Clin Endocrinol. 1999;51:779–86.

    Article  CAS  Google Scholar 

  6. Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol. 2014;6:1–13.

    Google Scholar 

  7. Fauser B, Tarlatzis B, Rebar R, Legro R, Balen A, Lobo R, et al. Consensus on women's health aspects of polycystic ovary syndrome (PCOS). Hum Reprod. 2012;27:14–24.

    Article  Google Scholar 

  8. Azziz R, Sanchez LA, Knochenhauer ES, Moran C, Lazenby J, Stephens KC, et al. Androgen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab. 2004;89:453–62.

    Article  PubMed  CAS  Google Scholar 

  9. Ibáñez L, Oberfield SE, Witchel S, Auchus RJ, Chang RJ, Codner E, et al. An international consortium update: pathophysiology, diagnosis, and treatment of polycystic ovarian syndrome in adolescence. Horm Res Paediatr. 2017;88:371–95.

    Article  PubMed  CAS  Google Scholar 

  10. Hsueh AJW, Kawamura K, Cheng Y, Fauser BCJM. Intraovarian control of early Folliculogenesis. Endocr Rev. 2015;36:1–24.

    Article  PubMed  CAS  Google Scholar 

  11. Franks S, Stark J, Hardy K. Follicle dynamics and anovulation in polycystic ovary syndrome. Hum Reprod Update. 2008;14:367–78.

    Article  PubMed  CAS  Google Scholar 

  12. Lebbe M, Woodruff TK. Involvement of androgens in ovarian health and disease. Mol Hum Reprod. 2013;19:828–37.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Kumari AS, Haq A, Jayasundaram R, Abdel-Wareth LO, Al Haija SA, Alvares M. Metformin monotherapy in lean women with polycystic ovary syndrome. Reprod BioMed Online. 2005;10:100–4.

    Article  PubMed  CAS  Google Scholar 

  14. Amiel SA, Sherwin RS, Simonson DC, Lauritano AA, Tamborlane WV. Impaired insulin action in puberty. A contributing factor to poor glycemic control in adolescents with diabetes. N Engl J Med. 1986;315:215–9.

    Article  PubMed  CAS  Google Scholar 

  15. Saenger P. Metabolic consequences of growth hormone treatment in paediatric practice. Horm Res. 2000;53(Suppl. 1):60–9.

    PubMed  CAS  Google Scholar 

  16. Geffner ME, Golde DW. Selective insulin action on skin, ovary, and heart in insulin-resistant states. Diabetes Care. 1988;11:500–5.

    Article  PubMed  CAS  Google Scholar 

  17. Nestler JE, Jakubowicz DJ. Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17α activity and serum androgens. J Clin Endocrinol Metab. 1997;82:4075–9.

    PubMed  CAS  Google Scholar 

  18. Dunaif A, Segal KR, Shelley DR, Green G, Dobrjansky A, Licholai T. Evidence for distinctive and intrinsic defects in insulin action in polycystic ovary syndrome. Diabetes. 1992;41:1257–66.

    Article  PubMed  CAS  Google Scholar 

  19. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81:19–25.

    Google Scholar 

  20. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. Criteria for defining polycystic ovary syndrome as a predominantly Hyperandrogenic syndrome: an androgen excess society guideline. J Clin Endocrinol Metab. 2006;91:4237–45.

    Article  PubMed  CAS  Google Scholar 

  21. Lujan ME, Jarrett BY, Brooks ED, Reines JK, Peppin AK, Muhn N, et al. Updated ultrasound criteria for polycystic ovary syndrome: reliable thresholds for elevated follicle population and ovarian volume. Hum Reprod. 2013;28:1361–8.

    Article  PubMed  Google Scholar 

  22. Rajpert-De Meyts E, Jørgensen N, Græm N, Müller J, Cate RL, Skakkebæk NE. Expression of anti-Müllerian hormone during Normal and pathological gonadal development: association with differentiation of Sertoli and granulosa cells. J Clin Endocrinol Metab. 1999;84:3836–44.

    PubMed  Google Scholar 

  23. Dumont A, Robin G, Catteau-Jonard S, Dewailly D. Role of anti-Müllerian hormone in pathophysiology, diagnosis and treatment of polycystic ovary syndrome: a review. Reprod Biol Endocrinol. 2015;13:137.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  24. Salmon NA, Handyside AH, Joyce IM. Oocyte regulation of anti-Müllerian hormone expression in granulosa cells during ovarian follicle development in mice. Dev Biol. 2004;266:201–8.

    Article  PubMed  CAS  Google Scholar 

  25. Durlinger A, Visser JA, Themmen A. Regulation of ovarian function: the role of anti-Mullerian hormone. Reproduction. 2002;124(5):601–9.

    Article  PubMed  CAS  Google Scholar 

  26. Durlinger AL, Kramer P, Karels B, de Jong FH, Uilenbroek JTJ, Grootegoed JA, et al. Control of primordial follicle recruitment by anti-Mullerian hormone in the mouse ovary. Endocrinology. 1999;140(12):5789–96.

    Article  PubMed  CAS  Google Scholar 

  27. Laven JS, Mulders AG, Visser JA, Themmen AP, De Jong FH, Fauser BC. Anti-Mullerian hormone serum concentrations in normoovulatory and anovulatory women of reproductive age. J Clin Endocrinol Metab. 2004;89:318–23.

    Article  PubMed  CAS  Google Scholar 

  28. Pigny P, Merlen E, Robert Y, Cortet-Rudelli C, Decanter C, Jonard S, et al. Elevated serum level of anti-mullerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest. J Clin Endocrinol Metab. 2003;88:5957–62.

    Article  PubMed  CAS  Google Scholar 

  29. Dewailly D, Andersen CY, Balen A, Broekmans F, Dilaver N, Fanchin R, et al. The physiology and clinical utility of anti-Müllerian hormone in women. Hum Reprod Update. 2014;20:370–85.

    Article  PubMed  Google Scholar 

  30. Fanchin R, Taieb J, Lozano DHM, Ducot B, Frydman R, Bouyer J. High reproducibility of serum anti-Müllerian hormone measurements suggests a multi-staged follicular secretion and strengthens its role in the assessment of ovarian follicular status. Hum Reprod. 2005;20:923–7.

    Article  PubMed  CAS  Google Scholar 

  31. van Disseldorp J, Lambalk C, Kwee J, Looman C, Eijkemans M, Fauser B, et al. Comparison of inter-and intra-cycle variability of anti-Müllerian hormone and antral follicle counts. Hum Reprod. 2009;25:221–7.

    Article  PubMed  Google Scholar 

  32. Pellatt L, Hanna L, Brincat M, Galea R, Brain H, Whitehead S, et al. Granulosa cell production of anti-Mullerian hormone is increased in polycystic ovaries. J Clin Endocrinol Metab. 2007;92:240–5.

    Article  PubMed  CAS  Google Scholar 

  33. Villarroel C, Merino P, Lopez P, Eyzaguirre F, Van Velzen A, Iniguez G, et al. Polycystic ovarian morphology in adolescents with regular menstrual cycles is associated with elevated anti-Müllerian hormone. Hum Reprod. 2011;26:2861–8.

    Article  PubMed  CAS  Google Scholar 

  34. Williams RM, Ong KK, Dunger DB. Polycystic ovarian syndrome during puberty and adolescence. Mol Cell Endocrinol. 2013;373:61–7.

    Article  PubMed  CAS  Google Scholar 

  35. Saxena P, Prakash A, Nigam A, Mishra A. Polycystic ovary syndrome: is obesity a sine qua non? A clinical, hormonal, and metabolic assessment in relation to body mass index. Indian J Endocrinol Metab. 2012;16:996–9.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev. 2012;33:981–1030.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  37. Doh E, Mbanya A, Kemfang-Ngowa JD, Dohbit S, Tchana-Sinou M, Foumane P, et al. The relationship between adiposity and insulin sensitivity in African women living with the polycystic ovarian syndrome: a clamp study. Int J Endocrinol. 2016;2016:9201701.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  38. Bozkirli E, Bakiner O, Ertörer E, Anaforoglu I, Tütüncü NB, Demirag NG. Insulin resistance in non-obese polycystic ovary syndrome subjects and relation with family history of diabetes mellitus. Turk J Endocrinol Metab. 2015;19(2):55–9. https://doi.org/10.4274/tjem.2761.

    Article  Google Scholar 

  39. Majumdar A, Singh TA. Comparison of clinical features and health manifestations in lean vs. obese Indian women with polycystic ovarian syndrome. J Hum Reprod Sci. 2009;2:12–7.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Bik W, Baranowska-Bik A, Wolinska-Witort E, Chmielowska M, Martynska L, Baranowska B. The relationship between metabolic status and levels of adiponectin and ghrelin in lean women with polycystic ovary syndrome. Gynecol Endocrinol. 2007;23:325–31.

    Article  PubMed  CAS  Google Scholar 

  41. Meier U, Gressner A. Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. Clin Chem. 2004;50:1511–25.

    Article  PubMed  CAS  Google Scholar 

  42. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7:941–6.

    Article  PubMed  CAS  Google Scholar 

  43. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med. 2002;8:1288–95.

    Article  PubMed  CAS  Google Scholar 

  44. Broglio F, Arvat E, Benso A, Gottero C, Muccioli G, Papotti M, et al. Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. J Clin Endocrinol Metab. 2001;86:5083–6.

    Article  PubMed  CAS  Google Scholar 

  45. Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, et al. A role for ghrelin in the central regulation of feeding. Nature. 2001;409(6817):194–8.

    Article  PubMed  CAS  Google Scholar 

  46. Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, et al. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology. 2000;141:4325–8.

    Article  PubMed  CAS  Google Scholar 

  47. Hosoda H, Kojima M, Kangawa K. Biological, physiological, and pharmacological aspects of ghrelin. J Pharmacol Sci. 2006;100:398–410.

    Article  PubMed  CAS  Google Scholar 

  48. Han Y, Kim HS, Lee H-J, Oh J-Y, Sung Y-A. Metabolic effects of polycystic ovary syndrome in adolescents. Ann Pediatr Endocrinol Metab. 2015;20:136–42.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Song DK, Hong YS, Sung Y-A, Lee H. Insulin resistance according to β-cell function in women with polycystic ovary syndrome and normal glucose tolerance. PLoS One. 2017;12:e0178120.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  50. Ndrepepa G, Kastrati A. Gamma-glutamyl transferase and cardiovascular disease. Ann Transl Med. 2016;4(24):481. https://doi.org/10.21037/atm.2016.12.27.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  51. Berria R, Gastaldelli A, Lucidi S, Belfort R, De Filippis E, Easton C, et al. Reduction in hematocrit level after pioglitazone treatment is correlated with decreased plasma free testosterone level, not hemodilution, in women with polycystic ovary syndrome. Clin Pharmacol Ther. 2006;80:105–14.

    Article  PubMed  CAS  Google Scholar 

  52. Coviello AD, Kaplan B, Lakshman KM, Chen T, Singh AB, Bhasin S. Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. J Clin Endocrinol Metab. 2008;93:914–9.

    Article  PubMed  CAS  Google Scholar 

  53. Simmonds MJ, Milne N, Ong K, Brotherton E, McNamee AP, Horobin J, et al. Physical properties of blood are altered in young and lean women with polycystic ovary syndrome. PLoS One. 2016;11:e0167290.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  54. Sprung VS, Atkinson G, Cuthbertson DJ, Pugh CJA, Aziz N, Green DJ, et al. Endothelial function measured using flow-mediated dilation in polycystic ovary syndrome: a meta-analysis of the observational studies. Clin Endocrinol. 2013;78:438–46.

    Article  Google Scholar 

  55. Christian RC, Dumesic DA, Behrenbeck T, Oberg AL, Sheedy PF, Fitzpatrick LA. Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88:2562–8.

    Article  PubMed  CAS  Google Scholar 

  56. Okoroh EM, Hooper WC, Atrash HK, Yusuf HR, Boulet SL. Is polycystic ovary syndrome another risk factor for venous thromboembolism? United States, 2003–2008. Am J Obstet Gynecol. 2012;207:377-e1-8.

    PubMed  Google Scholar 

  57. Blair SA, Kyaw-Tun T, Young IS, Phelan NA, Gibney J, McEneny J. Oxidative stress and inflammation in lean and obese subjects with polycystic ovary syndrome. J Reprod Med. 2013;58(3–4):107–14.

    PubMed  CAS  Google Scholar 

  58. Bourdeau I, El Ghorayeb N, Gagnon N, Lacroix A. MANAGEMENT OF ENDOCRINE DISEASE: Differential diagnosis, investigation and therapy of Bilateral Adrenal Incidentalomas. Eur J Endocrinol. 2018;179(2):R57–R67.

  59. Pugeat M, Plotton I, de la Perrière AB, Raverot G, Déchaud H, Raverot V. MANAGEMENT OF ENDOCRINE DISEASE Hyperandrogenic states in women: pitfalls in laboratory diagnosis. Eur J Endocrinol. 2018;178:R141–54.

    Article  PubMed  CAS  Google Scholar 

  60. Pappachan JM, Hariman C, Edavalath M, Waldron J, Hanna FW. Cushing's syndrome: a practical approach to diagnosis and differential diagnoses. J Clin Pathol. 2017;70:350–9.

    Article  PubMed  CAS  Google Scholar 

  61. Katznelson L, Laws ER Jr, Melmed S, Molitch ME, Murad MH, Utz A, et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99:3933–51.

    Article  PubMed  CAS  Google Scholar 

  62. Goyal M, Dawood AS. Debates regarding lean patients with polycystic ovary syndrome: a narrative review. J Hum Reprod Sci. 2017;10:154–61.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Arentz S, Abbott JA, Smith CA, Bensoussan A. Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings. BMC Complement Altern Med. 2014;14:511.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Wright CE, Zborowski JV, Talbott EO, McHugh-Pemu K, Youk A. Dietary intake, physical activity, and obesity in women with polycystic ovary syndrome. Int J Obes Relat Metab Disord. 2004;28:1026–32.

    Article  PubMed  CAS  Google Scholar 

  65. Popova P, Ivanova L, Karonova T, Grineva E. Ovulation induction by metformin in lean and obese women with polycystic ovary syndrome. Endocr Abstr 2011;26(P90).

  66. Anastasiou OE, Canbay A, Fuhrer D, Reger-Tan S. Metabolic and androgen profile in underweight women with polycystic ovary syndrome. Arch Gynecol Obstet. 2017;296:363–71.

    Article  PubMed  CAS  Google Scholar 

  67. Atiomo W, Sinha A. The role of metformin in the treatment of infertile women with polycystic ovary syndrome. Obstet Gynaecol. 2004;6:145–51. https://doi.org/10.1576/toag.6.3.145.26996.

  68. Genazzani AD, Santagni S, Ricchieri F, Campedelli A, Rattighieri E, Chierchia E, et al. Myo-inositol modulates insulin and luteinizing hormone secretion in normal weight patients with polycystic ovary syndrome. J Obstet Gynaecol Res. 2014;40:1353–60.

    Article  PubMed  CAS  Google Scholar 

  69. Kar S. Anthropometric, clinical, and metabolic comparisons of the four Rotterdam PCOS phenotypes: a prospective study of PCOS women. J Hum Reprod Sci. 2013;6:194–200.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Orvieto R, Nahum R, Meltcer S, Homburg R, Rabinson J, Anteby EY, et al. Ovarian stimulation in polycystic ovary syndrome patients: the role of body mass index. Reprod BioMed Online. 2009;18:333–6.

    Article  PubMed  Google Scholar 

  71. Abu Hashim H, Foda O, El Rakhawy M. Unilateral or bilateral laparoscopic ovarian drilling in polycystic ovary syndrome: a meta-analysis of randomized trials. Arch Gynecol Obstet. 2018;297:859–70.

    Article  PubMed  CAS  Google Scholar 

  72. Mihailidis J, Dermesropian R, Taxel P, Luthra P, Grant-Kels JM. Endocrine evaluation of hirsutism. Int J Womens Dermatol. 2017;3(1 Suppl):S6–S10.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Asai Y, Baibergenova A, Dutil M, Humphrey S, Hull P, Lynde C, et al. Management of acne: Canadian clinical practice guideline. CMAJ. 2016;188:118–26.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, et al. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013;98:4565–92.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Joseph M. Pappachan.

Ethics declarations

Conflicts of interest

There no competing interests among authors of this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Toosy, S., Sodi, R. & Pappachan, J.M. Lean polycystic ovary syndrome (PCOS): an evidence-based practical approach. J Diabetes Metab Disord 17, 277–285 (2018). https://doi.org/10.1007/s40200-018-0371-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40200-018-0371-5

Keywords

Navigation