The use of inositol stereoisomers for the treatment of patients with clinical and biochemical signs of hyperandrogenism

Cover Page

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

For many years, the use of combined oral contraceptives (COC) with antiandrogenic effects was the main treatment of clinical and biochemical hyperandrogenism in patients with polycystic ovary syndrome (PCOS). At the same time, the creation of an alternative therapy regimen for patients who have contraindications to taking hormonal drugs, as well as planning pregnancy, is obvious. Various combinations of inositol stereoisomers (myoinositol ― MI, and D-chiro-inositol ― DCI) are being actively studied. The review reflects the current understanding of the etiology, pathogenesis of hyperinsulinemia and androgen-dependent dermatological manifestations of polycystic ovary syndrome. The mechanisms of action of inositols at the molecular level are normalization of carbohydrate metabolism in the body and the reduction of hyperinsulinemia, as well as the levels of male sex hormones in PCOS. A comparative analysis of studies with various combinations of inositols was conducted on the effectiveness of treatment of clinical manifestations of hyperandrogenism, such as hirsutism and acne. The use of MI in conjunction with DCI reduces the risk of developing metabolic syndrome and improves the endocrine profile and manifestations of insulin resistance, but further multicenter studies on this problem are required.

Full Text

Restricted Access

About the authors

Ol'ga S. Alyautdina

I.M. Sechenov First Moscow State Medical University

Author for correspondence.
Email: olasa@list.ru
ORCID iD: 0000-0003-0770-8020

Dr. Sci. (Med.), Professor

Russian Federation, Moscow

Viktoriya Y. Prilutskaya

I.M. Sechenov First Moscow State Medical University

Email: anturiumvika@mail.ru
ORCID iD: 0000-0003-3319-182X

graduate student

Russian Federation, Moscow

Ekaterina I. Krylova

I.M. Sechenov First Moscow State Medical University

Email: kr_katrin00@mail.ru
ORCID iD: 0000-0002-0220-0474

IV year student

Russian Federation, Moscow

References

  1. Azziz R, Carmina E, Dewailly D, et al. Positions statement: Criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: An Androgen Excess Society guideline. J Clin Endocrinol Metab. 2006;91:4237–4245. doi: 10.1210/jc.2006-0178
  2. Rasool SUA, Ashraf S, Nabi M, et al. Elevated fasting insulin is associated with cardiovascular and metabolic risk in women with polycystic ovary syndrome. Diabetes Metab Syndr. 2019;13:2098–2105. doi: 10.1016/j.dsx.2019.05.003
  3. Yureneva SV, Il’ina LM. Current recommendations for the treatment of polycystic ovary syndrome: the benefits of oral contraceptives with antiandrogenic progestins. Problemy reproduktsii. 2017;23(4): 56–64. (In Russ). doi: 10.17116/repro201723456-64
  4. Croze ML, Soulage ChO. Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie. 2013;95(10):1811–1827. doi: 10.1016/j.biochi.2013.05.011
  5. Genazzani AD. Inositol as putative integrative treatment for PCOS. Reprod Biomed Online. 2016;33(6):770–780.
  6. doi: 10.1016/j.rbmo.2016.08.024
  7. Nestler JE, Unfer V. Reflections on inositol(s) for PCOS therapy: steps toward success. Gynecol Endocrinol. 2015;31(7):501–505. doi: 10.3109/09513590.2015.1054802
  8. Azziz R, Adashi EY. Stein and Leventhal: 80 years on. Am J Obstet Gynecol. 2016;214(2):247.e1–247.e11.
  9. doi: 10.1016/j.ajog.2015.12.013
  10. Vander Borght M, Wyns C. Fertility and infertility: definition and epidemiology. Clin Biochem. 2018;62:2–10.
  11. doi: 10.1016/j.clinbiochem.2018.03.012
  12. Azziz R, Carmina E, Chen Z, et al. Polycystic ovary syndrome. Nat Rev Dis Primer. 2016;2:16057. doi: 10.1038/nrdp.2016.57
  13. Gambineri A, Patton L, Altieri P, et al. Polycystic ovary syndrome is a risk factor for type 2 diabetes: results from a long-term prospective study. Diabetes. 2012;61(9):2369–2374.
  14. doi: 10.2337/db11-1360
  15. Macut D, Bjekić-Macut J, Rahelić D, Doknić M. Insulin and the polycystic ovary syndrome. Diabetes Res Clin Pract. 2017;130:163–170. doi: 10.1016/j.diabres.2017.06.011
  16. Mayer SB, Evans WS, Nestler JE. Polycystic ovary syndrome and insulin: our understanding in the past, present and future. Womens Health. 2015;11(2):137–149. doi: 10.2217/whe.14.73
  17. Chen MJ, Yang WS, Yang JH, et al. Low sexhormone-binding globulin is associated with low high-density lipoprotein cholesterol and metabolic syndrome in women with PCOS. Hum Reprod. 2006;21(9):2266–2271. doi: 10.1093/humrep/del175
  18. National Institutes of Health. Polycystic Ovary Syndrome Workshop Panel Final Report. Pathways to Prevention (P2P). Evidence-Based Methodology Workshop on Polycystic Ovary Syndrome (PCOS). National Institutes of Health, December 3, 2012.
  19. Spritzer PM, Barone CR, Oliveira FB. Hirsutism in polycystic ovary syndrome: pathophysiology and management. Current Pharmaceutical Design. 2016;22(36):5603–5613.
  20. doi: 10.2174/1381612822666160720151243
  21. Jones GL, Benes K, Clark TL, et al. The polycystic ovary syndrome health related quality of life questionnaire (PCOSQ): a validation. Hum Reprod. 2004;19:371–377. doi: 10.1093/humrep/deh048
  22. Carmina E, Rosato F, Janni A, Rizzo M, Longo RA. Extensive clinical experience: relative prevalence of different androgen excess disorders in 950 women referred because of clinical hyperandrogenism. J Clin Endocrinol Metab. 2006;91(1):2–6.
  23. doi: 10.1210/jc.2005-1457
  24. Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol. 2018;14(5):270–284. doi: 10.1038/nrendo.2018.24
  25. Sir-Petermann T, Maliqueo M, Codner E, et al. Early metabolic derangements in daughters of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2007;92:4637–4642.
  26. doi: 10.1210/jc.2007-1036
  27. Wojciechowska A, Osowski A, Jozwik M, Gorecki R. Inositol’s importance in the improvement of the endocrine-metabolic profile in PCOS. Int J Mol Sci. 2019;20(22):5787. doi: 10.3390/ijms20225787
  28. Milewska EM, Czyzyk A, Meczekalski B, Genazzani AD. Inositol and human reproduction: From cellular metabolism to clinical use. Gynecol Endocrinol. 2016;32:690–695.
  29. doi: 10.1080/09513590.2016.1188282
  30. Beemster P, Groenen P, Steegers-Theunissen R. Involvement of Inositol in Reproduction. Nutr Rev. 2002;60(3):80–87. doi: 10.1301/00296640260042748
  31. Unfer V, Carlomagno G, Papaleo E, et al. Hyperinsulinemia alters myoinositol to d-chiroinositol ratio in the follicular fluid of patients with PCOS. Reprod Sci. 2014;21(7):854–858.
  32. doi: 10.1177/1933719113518985
  33. Unfer V, Dinicola S, Laganà AS, Bizzarri M. Altered ovarian inositol ratios may account for pathological steroidogenesis in PCOS. Int J Mol Sci. 2020;21(19):7157. doi: 10.3390/ijms21197157
  34. Carlomagno G, Unfer V, Roseff S. The D-chiro-inositol paradox in the ovary. Fertil Steril. 2011;95(8):2515–2516.
  35. doi: 10.1016/j.fertnstert.2011.05.027
  36. Paul C, Laganà AS, Maniglio P, Triolo O, Brady DM. Inositol’s and other nutraceuticals’ synergistic actions counteract insulin resistance in polycystic ovarian syndrome and metabolic syndrome: state-of-the-art and future perspectives. Gynecol Endocrinol. 2016;32(6):431–438. doi: 10.3109/09513590.2016.1144741
  37. Baillargeon JP, Iuorno MJ, Apridonidze T, Nestler JE. Uncoupling between insulin and release of a D-chiro-inositol-containing inositolphosphoglycan mediator of insulin action in obese women with polycystic ovary syndrome. Metab Syndr Relat Disord. 2010;8(2):127–135. doi: 10.1089/met.2009.0052
  38. Larner J. D-chiro-inositol – its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res. 2002;3(1):47–60. doi: 10.1080/15604280212528
  39. Chiu TTY, Rogers MS, Briton-Jones C, Haines C. Effects of myo-inositol on the in-vitro maturation and subsequent development of mouse oocytes. Hum Reprod. 2003;18(2):408–416.
  40. doi: 10.1093/humrep/deg113
  41. Dinicola S, Chiu TTY, Unfer V, Carlomagno G, Bizzarri M. The rationale of the myo-inositol and D-chiro-inositol combined treatment for polycystic ovary syndrome. J Clin Pharmacol. 2014;54(10):1079–1092. doi: 10.1002/jcph.362
  42. Artini PG, Di Berardino OM, Papini F, et al. Endocrine and clinical effects of myo-inositol administration in polycystic ovary syndrome. A randomized study. Gynecol Endocrinol. 2013;29(4):375–379. doi: 10.3109/09513590.2012.743020
  43. Costantino D, Minozzi G, Minozzi F, Guaraldi C. Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: A double-blind trial. Eur Rev Med Pharmacol Sci. 2009;13:105–110.
  44. Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD, Allan G. Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med. 1999;340(17):1314–1320.
  45. doi: 10.1056/NEJM199904293401703
  46. Benelli E, Del Ghianda S, Di Cosmo C, Tonacchera MA. Combined therapy with myo-inositol and D-chiro-inositol improves endocrine parameters and insulin resistance in PCOS young overweight women. Int J Endocrinol. 2016;2016:3204083.
  47. doi: 10.1155/2016/3204083
  48. Regidor PA, Schindler AE, Lesoine B, Druckman R. Management of women with PCOS using myo-inositol and folic acid. New clinical data and review of the literature. Horm Mol Biol Clin Investig. 2018;34(2). doi: 10.1515/hmbci-2017-0067
  49. Chernukha GE, Tabeeva GI, Udovichenko MA. Unused opportunities for the correction of endocrine and metabolic disorders in polycystic ovary syndrome. Akusherstvo i ginekologiya. 2019;(10). doi: 10.18565/aig.2019.10.140-147
  50. Januszewski M, Issat T, Jakimiuk AA. Metabolic and hormonal effects of a combined myo-inositol and D-chiro-inositol therapy on patients with polycystic ovary syndrome (PCOS). Ginekol Polska. 2019;90(1):7–10. doi: 10.5603/GP.2019.0002
  51. Nordio M, Proietti E. The combined therapy with myo-inositol and D-chiro-inositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone. Eur Rev Med Pharmacol Sci. 2012;16(5):575–581.
  52. Minozzi M, Andrea G, Unfer V. Treatment of hirsutism with myo-inositol: a prospective clinical study. Reprod Biomed Online. 2008;17(4):579–582. doi: 10.1016/s1472-6483(10)60248-9
  53. Genazzani AD, Lanzoni C, Ricchieri F, Jasonni VM. Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweith patients with polycystic ovary syndrome. Gynecol Endocrinol. 2008;24(3):139–144. doi: 10.1080/09513590801893232
  54. Zacche MM, Caputo L, Filippis S, et al. Efficacy of myo-inositol in the treatment of cutaneous disorders in young women with polycystic ovary syndrome. Gynecol Endocrinol. 2009;25(8):508–513. doi: 10.1080/09513590903015544
  55. Minozzi M, Costantino D, Guaraldi C, Unfer V. The effect of a combination therapy with myo-inositol and combined oral contraceptive pill versus a combined oral contraceptive pill alone on metabolic, endocrine and clinical parameterd in polycystic ovarian syndrome. Gynecol Endocrinol. 2011;27(11):920–924. doi: 10.3109/09513590.2011.564685
  56. Ozay AC, Ozay OE, Okyay RE, et al. Different effects of myoinositol plus folic acid versus combined oral treatment on androgen levels in PCOS women. Int J Endocrinol. 2016;2016:3206872. doi: 10.1155/2016/3206872
  57. Ranwa M, Nagaria T, Jaiswal J. Study of effect of myoinositol on menstrual irregularities and skin problems in polycystic ovarian syndrome cases. Int J Reprod Contracept Obstet Gynecol. 2017;6(6):2310–2317. doi: 10.18203/2320-1770.ijrcog20172120
  58. Le Donne M, Metro D, Alibrandi A, Papa M, Benvenga S. Effects of three treatment modalities (diet, myoinositol or myoinositol associated with D-chiro-inositol) on clinical and body composition outcomes in women with polycystic ovary syndrome. Eur Rev Med Pharmacol Sci. 2019;23(5):2293–2301.
  59. doi: 10.26355/eurrev_201903_17278
  60. Advani K, Batra M, Tajpuriya S, Gupta R, et al. Efficacy of combination therapy of inositols, antioxidants and vitamins in obese and non-obese women with polycystic ovary syndrome: an observational study. J Obstet Gynaecol. 2020;40(1):96–101. doi: 10.1080/01443615.2019.1604644
  61. Ramanan A, Ravi S, Radha Anbu K, Michael M. Efficacy and safety of Tracnil administration in patients with dermatological manifestations of PCOS: an open-label single-arm study. Dermatol Res Pract. 2020;2020:7019126. doi: 10.1155/2020/7019126
  62. Oboskalova TA, Vorontsova AV, Zvychainyi MA, Gushchina KG, Maitesyan MM. Results of the use of a combination of myoinositol and D-chiroinositol in a ratio of 5:1 in women with polycystic ovary syndrome. Ginekologiya. 2020;22(6):84–89. (In Russ). doi: 10.26442/20795696.2020.6.200548
  63. Pezza M, Carlomagno V. Inositol in women suffering from acne and PCOS: a randomized study. Glob Dermatol. 2017;4(1):1–4. doi: 10.15761/GOD.1000203.

Supplementary files

Supplementary Files
Action
1. Fig. Scheme of interaction of hyperandrogenism and hyperinsulinemia in the pathogenesis of polycystic ovary syndrome.

Download (219KB)

Statistics

Views

Abstract: 104

Article Metrics

Metrics Loading ...

Refbacks

  • There are currently no refbacks.

Copyright (c) 2021 Eco-Vector



This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies