Skip to main content
SpringerLink
Log in

Metabolic impact of current therapeutic strategies in Polycystic Ovary Syndrome: a preliminary study

  • General Gynecology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

To investigate the metabolic impact of currently used therapies in polycystic ovary syndrome (PCOS).

Methods

This is an observational, retrospective and transversal protocol. A small cohort of 133 patients, aged 14–48 years, diagnosed with PCOS was divided into four experimental groups: 1) untreated PCOS patients (n = 51); 2) PCOS patients treated with one of the following therapies (n = 82): a) combined oral contraceptives (COC, n = 35); b) metformin (n = 11); and c) inositols (n = 36).

Results

Although only < 10% of patients included in this cohort can be strictly encompassed in the development of metabolic syndrome, approximately 20% had insulin resistance. In PCOS patients, COC treatment modified the hormonal profile and worsened lipid parameters (increasing cholesterol and triglyceride levels) and insulin resistance, whereas inositol therapies improved significantly insulin resistance and glycosylated hemoglobin, reducing cholesterol and triglyceride levels. In these women, obesity was associated with greater alterations in lipid and glycemic metabolism and with higher blood pressure levels. PCOS patients with phenotype A presented vaster alterations in lipid metabolism and higher values of glycosylated hemoglobin as well as blood pressure compared to other PCOS phenotypes.

Conclusions

Results in this paper suggest that inositol therapies (alone or combined with COC) are the most useful therapies with the best benefits against PCOS symptoms. Thus, integrative treatment may become a more efficient long-term choice to control PCOS symptoms. Furthermore, obesity can be considered as an adverse symptom and calorie restriction a key element of combined treatment in PCOS, not only for fertility management but also in long-term metabolic sequelae.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

COC :

Combined oral contraceptive

BMI :

Body mass index

IGFBPs :

IGF-1 binding proteins

DHEAs :

Dehydroepiandrosterone sulfate

DBP :

Diastolic blood pressure

ECLIA :

Electrochemiluminescence immunoassay

FSH :

Follicle-stimulating hormone

GH :

Growth hormone

HDL :

High-density lipoprotein

HbA1c :

Glycosylated hemoglobin

HOMA :

Homeostasis model assessment, common clinical index to estimate insulin resistance

IGF-1 :

Insulin-like growth factor 1

IR :

Insulin resistance

LDL :

Low-density lipoprotein

LH :

Luteinizing hormone

MBP :

Mean blood pressure

MetS :

Metabolic syndrome

OSA :

Obstructive sleep apnea

PCOS :

Polycystic ovary syndrome

SBP :

Systolic blood pressure

SHBG :

Sex hormone-binding globulin

SMD :

Standard mean deviation

TSH :

Thyroid-stimulating hormone

References

  1. March WA, Moore VM, Willson KJ et al (2010) The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod 25:544–551. https://doi.org/10.1093/humrep/dep399

    Article  PubMed  Google Scholar 

  2. Wolf W, Wattick R, Kinkade O, Olfert M (2018) Geographical prevalence of polycystic ovary syndrome as determined by region and race/ethnicity. Int J Environ Res Public Health 15:2589. https://doi.org/10.3390/ijerph15112589

    Article  PubMed Central  Google Scholar 

  3. Ding T, Hardiman PJ, Petersen I et al (2017) The prevalence of polycystic ovary syndrome in reproductive-aged women of different ethnicity: a systematic review and meta-analysis. Oncotarget 8:96351–96358. https://doi.org/10.18632/oncotarget.19180

    Article  PubMed  PubMed Central  Google Scholar 

  4. Bani Mohammad M, Majdi Seghinsara A (2017) Polycystic ovary syndrome (PCOS), diagnostic criteria, and AMH. Asian Pac J Cancer Prev 18:17–21. https://doi.org/10.22034/APJCP.2017.18.1.17

    Article  PubMed  Google Scholar 

  5. Ebersole AM, Bonny AE (2020) Diagnosis and treatment of polycystic ovary syndrome in adolescent females. Clin Obstet Gynecol. https://doi.org/10.1097/GRF.0000000000000538

    Article  PubMed  Google Scholar 

  6. Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R (2011) Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 7:219–231. https://doi.org/10.1038/nrendo.2010.217

    Article  CAS  PubMed  Google Scholar 

  7. Sirmans SM, Pate KA (2013) Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol 6:1–13. https://doi.org/10.2147/CLEP.S37559

    Article  PubMed  PubMed Central  Google Scholar 

  8. Dumesic DA, Oberfield SE, Stener-Victorin E et al (2015) Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome. Endocr Rev 36:487–525. https://doi.org/10.1210/er.2015-1018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Aguirre GA, De Ita JR, de la Garza RG, Castilla-Cortazar I (2016) Insulin-like growth factor-1 deficiency and metabolic syndrome. J Transl Med 14:3. https://doi.org/10.1186/s12967-015-0762-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Khorshidi A, Azami M, Tardeh S, Tardeh Z (2019) The prevalence of metabolic syndrome in patients with polycystic ovary syndrome: a systematic review and meta-analysis. Diabetes Metab Syndr 13:2747–2753. https://doi.org/10.1016/j.dsx.2019.06.008

    Article  PubMed  Google Scholar 

  11. Grundy SM (2006) Metabolic syndrome: connecting and reconciling cardiovascular and diabetes worlds. J Am Coll Cardiol 47:1093–1100. https://doi.org/10.1016/j.jacc.2005.11.046

    Article  CAS  PubMed  Google Scholar 

  12. Ford ES, Li C, Sattar N (2008) Metabolic syndrome and incident diabetes: current state of the evidence. Diabetes Care 31:1898–1904. https://doi.org/10.2337/dc08-0423

    Article  PubMed  PubMed Central  Google Scholar 

  13. Wolk R, Somers VK (2007) Sleep and the metabolic syndrome. Exp Physiol 92:67–78. https://doi.org/10.1113/expphysiol.2006.033787

    Article  PubMed  Google Scholar 

  14. Ip MSM, Lam B, Ng MMT et al (2002) Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med 165:670–676. https://doi.org/10.1164/ajrccm.165.5.2103001

    Article  PubMed  Google Scholar 

  15. Alberti KGMM, Eckel RH, Grundy SM et al (2009) Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; american heart association; world heart federation; international. Circulation 120:1640–1645. https://doi.org/10.1161/CIRCULATIONAHA.109.192644

    Article  CAS  PubMed  Google Scholar 

  16. Kim HJ, Kim HJ, Lee KE et al (2004) Metabolic significance of nonalcoholic fatty liver disease in nonobese, nondiabetic adults. Arch Intern Med 164:2169–2175. https://doi.org/10.1001/archinte.164.19.2169

    Article  PubMed  Google Scholar 

  17. Kotronen A, Westerbacka J, Bergholm R et al (2007) Liver fat in the metabolic syndrome. J Clin Endocrinol Metab 92:3490–3497. https://doi.org/10.1210/jc.2007-0482

    Article  CAS  PubMed  Google Scholar 

  18. Parish JM, Adam T, Facchiano L (2007) Relationship of metabolic syndrome and obstructive sleep apnea. J Clin Sleep Med 3:467–472

    Article  PubMed  PubMed Central  Google Scholar 

  19. Gami AS, Somers VK (2004) Obstructive sleep apnoea, metabolic syndrome, and cardiovascular outcomes. Eur Heart J 25:709–711. https://doi.org/10.1016/j.ehj.2004.03.008

    Article  PubMed  Google Scholar 

  20. Gruber A, Horwood F, Sithole J et al (2006) Obstructive sleep apnoea is independently associated with the metabolic syndrome but not insulin resistance state. Cardiovasc Diabetol 5:22. https://doi.org/10.1186/1475-2840-5-22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Tasali E, Van Cauter E (2002) Sleep-disordered breathing and the current epidemic of obesity: consequence or contributing factor? Am J Respir Crit Care Med 165:562–563. https://doi.org/10.1164/ajrccm.165.5.2201001b

    Article  PubMed  Google Scholar 

  22. Cizza G, Skarulis M, Mignot E (2005) A link between short sleep and obesity: building the evidence for causation. Sleep 28:1217–1220. https://doi.org/10.1093/sleep/28.10.1217

    Article  PubMed  Google Scholar 

  23. Vgontzas AN, Bixler EO, Chrousos GP (2005) Sleep apnea is a manifestation of the metabolic syndrome. Sleep Med Rev 9:211–224. https://doi.org/10.1016/j.smrv.2005.01.006

    Article  PubMed  Google Scholar 

  24. Franks S, McCarthy MI, Hardy K (2006) Development of polycystic ovary syndrome: involvement of genetic and environmental factors. Int J Androl 29:278–285. https://doi.org/10.1111/j.1365-2605.2005.00623.x(discussion 286-90)

    Article  CAS  PubMed  Google Scholar 

  25. World Medical Association (2013) World medical association declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 310(20):2191–2194. https://doi.org/10.1001/jama.2013.281053

    Article  CAS  Google Scholar 

  26. Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19:41–47

    Article  Google Scholar 

  27. National Institutes of Health (2002) High Blood Cholesterol Evaluation Treatment Detection National Cholesterol Education Program Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report.

  28. Nuttall FQ (2015) Body mass index. Nutr Today 50:117–128. https://doi.org/10.1097/NT.0000000000000092

    Article  PubMed  PubMed Central  Google Scholar 

  29. La Marca A, Grisendi V, Dondi G et al (2015) The menstrual cycle regularization following D-chiro-inositol treatment in PCOS women: a retrospective study. Gynecol Endocrinol 31:52–56. https://doi.org/10.3109/09513590.2014.964201

    Article  CAS  PubMed  Google Scholar 

  30. Nestler JE, Jakubowicz DJ, Iuorno MJ (2000) Role of inositolphosphoglycan mediators of insulin action in the polycystic ovary syndrome. J Pediatr Endocrinol Metab 13(Suppl 5):1295–1298

    PubMed  Google Scholar 

  31. Costantino D, Minozzi G, Minozzi E, Guaraldi C (2009) Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double-blind trial. Eur Rev Med Pharmacol Sci 13:105–110

    CAS  PubMed  Google Scholar 

  32. Dinicola S, Chiu TTY, Unfer V et al (2014) The rationale of the myo-inositol and D-chiro-inositol combined treatment for polycystic ovary syndrome. J Clin Pharmacol 54:1079–1092. https://doi.org/10.1002/jcph.362

    Article  CAS  PubMed  Google Scholar 

  33. Unfer V, Porcaro G (2014) Updates on the myo-inositol plus D-chiro-inositol combined therapy in polycystic ovary syndrome. Expert Rev Clin Pharmacol 7:623–631. https://doi.org/10.1586/17512433.2014.925795

    Article  CAS  PubMed  Google Scholar 

  34. Facchinetti F, Bizzarri M, Benvenga S et al (2015) Results from the international consensus conference on myo-inositol and d-chiro-inositol in obstetrics and gynecology: the link between metabolic syndrome and PCOS. Eur J Obstet Gynecol Reprod Biol 195:72–76. https://doi.org/10.1016/j.ejogrb.2015.09.024

    Article  CAS  PubMed  Google Scholar 

  35. Pizzo A, Laganà AS, Barbaro L (2014) Comparison between effects of myo-inositol and D-chiro-inositol on ovarian function and metabolic factors in women with PCOS. Gynecol Endocrinol 30:205–208. https://doi.org/10.3109/09513590.2013.860120

    Article  CAS  PubMed  Google Scholar 

  36. Matarrelli B, Vitacolonna E, D’Angelo M et al (2013) Effect of dietary myo-inositol supplementation in pregnancy on the incidence of maternal gestational diabetes mellitus and fetal outcomes: a randomized controlled trial. J Matern Fetal Neonatal Med 26:967–972. https://doi.org/10.3109/14767058.2013.766691

    Article  CAS  PubMed  Google Scholar 

  37. Nestler JE, Jakubowicz DJ, Reamer P et al (1999) Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med 340:1314–1320. https://doi.org/10.1056/NEJM199904293401703

    Article  CAS  PubMed  Google Scholar 

  38. Gerli S, Papaleo E, Ferrari A, Di Renzo GC (2007) Randomized, double blind placebo-controlled trial: effects of myo-inositol on ovarian function and metabolic factors in women with PCOS. Eur Rev Med Pharmacol Sci 11:347–354

    CAS  PubMed  Google Scholar 

  39. Genazzani AD, Lanzoni C, Ricchieri F, Jasonni VM (2008) Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecol Endocrinol 24:139–144. https://doi.org/10.1080/09513590801893232

    Article  CAS  PubMed  Google Scholar 

  40. Monastra G, Unfer V, Harrath AH, Bizzarri M (2017) Combining treatment with myo-inositol and D-chiro-inositol (40:1) is effective in restoring ovary function and metabolic balance in PCOS patients. Gynecol Endocrinol 33:1–9. https://doi.org/10.1080/09513590.2016.1247797

    Article  CAS  PubMed  Google Scholar 

  41. Genazzani AD (2016) Inositol as putative integrative treatment for PCOS. Reprod Biomed Online 33:770–780. https://doi.org/10.1016/j.rbmo.2016.08.024

    Article  CAS  PubMed  Google Scholar 

  42. Facchinetti F, Orrù B, Grandi G, Unfer V (2019) Short-term effects of metformin and myo-inositol in women with polycystic ovarian syndrome (PCOS): a meta-analysis of randomized clinical trials. Gynecol Endocrinol 35:198–206. https://doi.org/10.1080/09513590.2018.1540578

    Article  CAS  PubMed  Google Scholar 

  43. Nordio M, Basciani S, Camajani E (2019) The 40:1 myo-inositol/D-chiro-inositol plasma ratio is able to restore ovulation in PCOS patients: comparison with other ratios. Eur Rev Med Pharmacol Sci 23:5512–5521. https://doi.org/10.26355/eurrev_201906_18223

    Article  CAS  PubMed  Google Scholar 

  44. Laganà AS, Garzon S, Casarin J et al (2018) Inositol in polycystic ovary syndrome: restoring fertility through a pathophysiology-based approach. Trends Endocrinol Metab 29:768–780. https://doi.org/10.1016/j.tem.2018.09.001

    Article  CAS  PubMed  Google Scholar 

  45. Tanbo T, Mellembakken J, Bjercke S et al (2018) Ovulation induction in polycystic ovary syndrome. Acta Obstet Gynecol Scand 97:1162–1167. https://doi.org/10.1111/aogs.13395

    Article  PubMed  Google Scholar 

  46. He Y, Tian J, Blizzard L et al (2020) Associations of childhood adiposity with menstrual irregularity and polycystic ovary syndrome in adulthood: the childhood determinants of adult health study and the bogalusa heart study. Hum Reprod 35:1185–1198. https://doi.org/10.1093/humrep/deaa069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Cena H, Chiovato L, Nappi RE (2020) Obesity, polycystic ovary syndrome and infertility: a new avenue for GLP-1 receptor agonists. J Clin Endocrinol Metab. https://doi.org/10.1210/clinem/dgaa285

    Article  PubMed  PubMed Central  Google Scholar 

  48. Hamilton-Fairley D, Kiddy D, Watson H et al (1992) Association of moderate obesity with a poor pregnancy outcome in women with polycystic ovary syndrome treated with low dose gonadotrophin. Br J Obstet Gynaecol 99:128–131. https://doi.org/10.1111/j.1471-0528.1992.tb14470.x

    Article  CAS  PubMed  Google Scholar 

  49. Pasquali R, Antenucci D, Casimirri F et al (1989) Clinical and hormonal characteristics of obese amenorrheic hyperandrogenic women before and after weight loss. J Clin Endocrinol Metab 68:173–179. https://doi.org/10.1210/jcem-68-1-173

    Article  CAS  PubMed  Google Scholar 

  50. Naderpoor N, Shorakae S, Joham A et al (2015) Obesity and polycystic ovary syndrome. Minerva Endocrinol 40:37–51

    CAS  PubMed  Google Scholar 

  51. Loh HH, Yee A, Loh HS et al (2020) Sexual dysfunction in polycystic ovary syndrome: a systematic review and meta-analysis. Hormones (Athens). https://doi.org/10.1007/s42000-020-00210-0

    Article  Google Scholar 

  52. Woodward A, Klonizakis M, Broom D (2020) Exercise and polycystic ovary syndrome. Adv Exp Med Biol. https://doi.org/10.1007/978-981-15-1792-1_8

    Article  PubMed  Google Scholar 

  53. Javed Z, Papageorgiou M, Madden LA et al (2020) The effects of empagliflozin versus metformin on endothelial microparticles in overweight/obese women with polycystic ovary syndrome. Endocr Connect. https://doi.org/10.1530/EC-20-0173

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors wish to express their gratitude to Dr. Mª Teresa Blanco Guillén, Cristina Alonso Gracia, María Cabrera Salinas, Raquel Romero Fernández, Alicia Guntiñas Castillo, Izaskun Méndez García, Alba Miranda Calvo, Antonio Ierullo, Carolina Cantos and Virginia Rodríguez Tabares, all of these MD of our team, for their generous help. This work was possible thank to the financial help of “Fundación de Investigación HM Hospitales”.

Funding

This work was supported by Fundación de Investigación HM Hospitales.

Author information

Authors and Affiliations

  1. Departments of Ginecology and Pediatry. HM Velazquez Cabinet, Fundación de Investigación HM Hospitales, Hospital “Puerta del Sur”, Velazquez 25, 28001, Madrid, Spain

    María Victoria De Diego, Olga Gómez-Pardo, Janette Kirk Groar, Alejandro López-Escobar, Inma Castilla-Cortázar & Miguel Ángel Rodríguez-Zambrano

  2. Tecnologico de Monterrey, Escuela de Medicina Y Ciencias de La Salud, Ave. Morones Prieto 3000, 64710, Monterrey, NL, Mexico

    Irene Martín-Estal & Inma Castilla-Cortázar

Authors
  1. María Victoria De Diego
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Olga Gómez-Pardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Janette Kirk Groar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alejandro López-Escobar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Irene Martín-Estal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Inma Castilla-Cortázar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Miguel Ángel Rodríguez-Zambrano
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MVDD: project development, data collection, data analysis; OGP: data collection; JKG: data collection; ALE: data collection; IME: manuscript writing/editing; ICC: project development, data analysis; MARZ: project development. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Inma Castilla-Cortázar or Miguel Ángel Rodríguez-Zambrano.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ethics Committee of the “Fundación de Investigación HM Hospitales de Madrid” (14.11.704-GHM).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

De Diego, M.V., Gómez-Pardo, O., Groar, J.K. et al. Metabolic impact of current therapeutic strategies in Polycystic Ovary Syndrome: a preliminary study. Arch Gynecol Obstet 302, 1169–1179 (2020). https://doi.org/10.1007/s00404-020-05696-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-020-05696-y

Keywords

Search

Navigation