The effect of myoinositol and D-chiroinositol in a ratio of 40:1 on hormonal and metabolic parameters in women with polycystic ovary syndrome

Pustotina О.А., Rasulova I.A.

1) F.I. Inozemtsev Academy of Medical Education, St. Petersburg, Russia; 2) H-Clinic LLC, Moscow, Russia
Background: Insulin resistance (IR) and compensatory hyperinsulinemia are considered to trigger pathogenetic changes in women with polycystic ovary syndrome (PCOS); however, insulin-sensitizing therapy shows contradictory results. Objective: To evaluate the incidence of metabolic disorders in patients with PCOS and the effect of a combination of myoinositol (MI) and D-chiroinositol (DHI) in a ratio of 40:1 on hormonal and metabolic parameters. Materials and methods: This was an open prospective study including 34 patients with the classic PCOS phenotype who received 2255 mg of inositol per day for 3 months (MI and DHI in a ratio of 40:1). Serum levels of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, total and free testosterone, sex hormone binding globulin (SHBG), anti-Mullerian hormone, glucose, insulin, HOMA-IR index and body mass index (BMI) were evaluated before and after administration. Results: The classic PCOS phenotype is associated with a high incidence of metabolic disorders: 55.9% of the examined women were overweight or obese, 50% had IR, 17.6% had a history of gestational diabetes mellitus, 61.8% had a family history of type 2 diabetes mellitus. After 3 months of taking a combination of MI and DHI in a ratio of 40:1, the parameters significantly decreased, namely, BMI (p=0.0029) and IR index (p=0.0007); the number of patients with elevated insulin levels in the blood decreased by 2.4 times. There was an improvement in markers of ovarian steroidogenesis: the serum level of total testosterone decreased (1.51±0.52 vs. 2.02±0.73 nmol/L, p<0.0001), free testosterone reduced (2.0 (1.0; 2.5) vs. 2.9 (1.6; 4.5) pg/ml, p=0.0002) and LH decreased (6.03±2.12 vs. 7.10±2.66 mME/ml, p=0.0058); concentrations of SHBG (69.15±21.66 vs. 40.78±22.66 nmol/L, p<0.0001) and estradiol (190 (150; 316) vs. 148 (111; 286) pmol/L, p=0.0003) increased. Conclusion: The combined administration of MI and DCI in a ratio of 40:1 improves metabolic and hormonal parameters in patients with the classic PCOS phenotype. Authors’ contributions: Pustotina O.A. – collecting the clinical data and creating an electronic database of the obtained results, analyzing the results of statistical processing of clinical material and their interpretation, writing, correcting and editing the article before submitting it for publication; Rasulova I.A. – collecting the clinical data and creating an electronic database of the obtained results, approval of the final version of the article before submitting it for publication. Conflicts of interest: The authors declare no possible conflicts of interest and guarantee that the article is the original work of the authors. Funding: The development and conducting of the study, the collection, analysis and interpretation of the data, as well as the preparation, review and approval of the manuscript were not sponsored. Ethical Approval: The study was approved by the Ethical Review Board of the F.I. Inozemtsev Academy of Medical Education (Protocol No.1 – 21/01/2022). Patient Consent for Publication: All patients signed an informed consent for the publication of their data. Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator. For citation: Pustotina О.А., Rasulova I.A. The effect of myoinositol and D-chiroinositol in a ratio of 40:1 on hormonal and metabolic parameters in women with polycystic ovary syndrome. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2023; (9): 170-178 (in Russian) https://dx.doi.org/10.18565/aig.2023.203

Keywords

polycystic ovary syndrome
insulin resistance
myoinositol
D-chiroinositol

References

  1. Tosi F., Bonora E., Moghetti P. Insulin resistance in a large cohort of women with polycystic ovary syndrome: A comparison between euglycaemic-hyperinsulinaemic clamp and surrogate indexes. Hum. Reprod. 2017; 32(12): 2515-21. https://dx.doi.org/10.1093/humrep/dex308.
  2. Cassar S., Misso M.L., Hopkins W.G., Shaw C.S., Teede H.J., Stepto N.K. Insulin resistance in polycystic ovary syndrome: A systematic review and meta-analysis of euglycaemic-hyperinsulinaemic clamp studies. Hum. Reprod. 2016; 31(11): 2619-31. https://dx.doi.org/10.1093/humrep/dew243.
  3. Lim S.S., Davies M.J., Norman R.J., Moran L.J. Overweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum. Reprod. Update. 2012; 18(6): 618-37.https://dx.doi.org/10.1093/humupd/dms030.
  4. Ovalle F., Azziz R. Insulin resistance, polycystic ovary syndrome, and type 2 diabetes mellitus. Fertil. Steril. 2002; 77(6): 1095-105.https://dx.doi.org/10.1016/s0015-0282(02)03111-4.
  5. Patel S. Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy. J. Steroid Biochem. Mol. Biol. 2018; 182: 27-36.https://dx.doi.org/10.1016/j.jsbmb.2018.04.008.
  6. Tuorila K., Ollila M.M., Jarvenlin M.R., Tapanainen J.S., Franks S. et al. Hyperandrogenemia in early adulthood is an independent risk factor for abnormal glucose metabolism in middle age. J. Clin. Endocrinol. Metabol. 2021; 106(11): e4621-33. https://dx.doi.org/10.1210/clinem/dgab456.
  7. Carlomagno G., Unfer V., Roseff S. The D-chiro-inositol paradox in the ovary. Fertil. Steril. 2011; 95(8): 2515-6. https://dx.doi.org/10.1016/j.fertnstert.2011.05.027.
  8. Joham A.E., Norman R.J., Stener-Victorin E., Legro R.S., Franks S., Moran L.J. et al. Polycystic ovary syndrome. Lancet Diabetes Endocrinol. 2022; 10(9):668-80. https://dx.doi.org/10.1016/S2213-8587(22)00163-2.
  9. Unluhizarci K., Karaca Z., Kelestimur F. Role of insulin and insulin resistance in androgen excess disorders. World J. Diabetes. 2021; 12(5): 616-29.https://dx.doi.org/10.4239/wjd.v12.i5.616.
  10. Unfer V., Carlomagno G., Papaleo E., Vailati S., Candiani M., Baillargeon J.P. Hyperinsulinemia alters myoinositol to d-chiroinositol ratio in the follicular fluid of patients with PCOS. Reprod. Sci. 2014; 21(7): 854-8.https://dx.doi.org/10.1177/1933719113518985.
  11. Heimark D., McAllister J., Larner J. Decreased myo-inositol to chiro-inositol (M/C) ratios and increased M/C epimerase activity in PCOS theca cells demonstrate increased insulin sensitivity compared to controls. Endocr. J. 2014; 61(2): 111-7. https://dx.doi.org/10.1507/endocrj.ej13-0423.
  12. Laganà A.S., Garzon S., Casarin J., Franchi M., Ghezzi F. Inositol in Polycystic Ovary Syndrome: restoring fertility through a pathophysiology-based approach. Trends Endocrinol. Metab. 2018; 29(11): 768-80. https://dx.doi.org/10.1016/j.tem.2018.09.001.
  13. Monastra G., Vazquez-Levin M., Bezerra Espinola M.S., Bilotta G., Laganà A.S., Unfer V. D-chiro-inositol, an aromatase down-modulator, increases androgens and reduces estrogens in male volunteers: a pilot study. Basic Clin. Androl. 2021; 31(1): 13. https://dx.doi.org/10.1186/s12610-021-00131-x.
  14. Nordio M., Basciani S., Camajani E. 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. 2019; 23(12): 5512-21.https://dx.doi.org/10.26355/eurrev_201906_18223.
  15. Bevilacqua A., Dragotto J., Giuliani A., Bizzarri M. Myo-inositol and D-chiro-inositol (40:1) reverse histological and functional features of polycystic ovary syndrome in a mouse model. J. Cell. Physiol. 2019; 234(6): 9387-98.https://dx.doi.org/10.1002/jcp.27623.
  16. Teede H.J., Misso M.L., Costello M.F., Dokras A., Laven J., Moran L. et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil. Steril. 2018; 110(3): 364-79. https://dx.doi.org/10.1016/j.fertnstert.2018.05.004.
  17. Пустотина О.А. Фенотипы синдрома поликистозных яичников. Фарматека. 2023; 30(4-5): 156-63. [Pustotina O.A. Polycystic ovary syndrome phenotypes. Farmateka. 2023; 30(4-5): 156-63. (in Russian)].https://dx.doi.org/10.18565/pharmateca.2023.4-5.156-163.
  18. Unfer V., Dinicola S., Russo M. A PCOS Paradox: does inositol therapy find a rationale in all the different phenotypes? Int. J. Mol. Sci. 2023; 24(7): 6213. https://dx.doi.org/10.3390/ijms24076213.
  19. Пустотина О.А., Дикке Г.Б., Остроменский В.В. Роль инозитола в репродукции человека. Акушерство и гинекология. 2022; 2: 111-8. [Pustotina O.A., Dikke G.B., Ostromensky V.V. Inositol and human reproduction. Obstetrics and Gynecology. 2022; (2): 111-8. (in Russian)]. https://dx.doi.org/10.18565/aig.2022.2.111-118.
  20. Чернуха Г.Е., Найдукова А.А., Каприна Е.К., Мирошина Е.Д., Донников А.Е. Молекулярно-генетические и эндокринные предикторы восстановления регулярного менструального ритма на фоне терапии метформином при синдроме поликистозных яичников. Акушерство и гинекология. 2022; 3: 80-8. [Chernukha G.E., Naidukova A.A., Kaprina E.K., Miroshina E.D., Donnikov A.E. Molecular genetic and endocrine predictors of menstrual cycle regulation in patients with polycystic ovary syndrome undergoing metformin treatment. Obstetrics and Gynecology. 2022; (3): 80-8. (in Russian)].https://dx.doi.org/10.18565/aig.2022.3.80-88.
  21. Хащенко Е.П., Наджарян А.Г., Уварова Е.В. Эффективность дифференцированного подхода к терапии пациентов с синдромом поликистозных яичников c использованием инозитолов и комбинированных оральных контрацептивов в раннем репродуктивном возрасте. Акушерство и гинекология. 2021; 3: 154-66. [Khashchenko E.P., Nadzharyan A.G., Uvarova E.V. Effectiveness of a differentiated approach to the treatment of patients with polycystic ovary syndrome using inositols and combined oral contraceptives in early reproductive age. Obstetrics and Gynecology. 2021; (3): 154-66. (in Russian)]. https://dx.doi.org/10.18565/aig.2021.3.154-166.
  22. Munro M.G., Balen A.H., Cho S.H., Critchley H.O.D., Diaz I., Ferriani R. et al. The FIGO ovulatory disorders classification system. Int. J. Gynecol. Obstet. 2022; 159(1): 1-20. https://dx.doi.org/10.1002/ijgo.14331.
  23. Genazzani A., Battipaglia C., Petrillo T., Alberti C., Patrizi B., Tomatis V. et al. HIE (hepatic insulin extraction) index in overweight/ obese. PCOS patients with or without familial diabetes. Gynecol. Reprod. Endocr. Metab. 2022; 3(1): 57-68. https://dx.doi.org/10.53260/grem.223019.
  24. Karkera S. The clinical manifestations of polycystic ovary syndrome (PCOS) and the treatment options. Eur. J. Biol. Med. Sci. Res. 2023; 11: 57-91.https://dx.doi.org/10.37745/ejbmsr.2013/vol11n15791.
  25. De Leo V., Musacchio M.C., Cappelli V., Massaro M.G., Morgante G., Petraglia F. Genetic, hormonal and metabolic aspects of PCOS: an update. Reprod. Biol. Endocrinol. 2016; 14(1): 38. https://dx.doi.org/10.1186/s12958-016-0173-x.
  26. Lie Fong S., Laven J.S.E., Duhamel A., Dewailly D. Polycystic ovarian morphology and the diagnosis of polycystic ovary syndrome: redefining threshold levels for follicle count and serum anti-Müllerian hormone using cluster analysis. Hum. Reprod. 2017; 32(8): 1723-31. https://dx.doi.org/10.1093/humrep/dex226.
  27. Wawrzkiewicz-Jałowiecka A., Kowalczyk K., Trybek P., Jarosz T., Radosz P., Setlak M., Madej P. In search of new therapeutics-molecular aspects of the PCOS pathophysiology: genetics, hormones, metabolism and beyond. Int. J. Mol. Sci. 2020; 21(19): 7054. https://dx.doi.org/10.3390/ijms21197054.
  28. Silva M.S.B., Giacobini P. New insights into anti-Müllerian hormone role in the hypothalamic-pituitary-gonadal axis and neuroendocrine development. Cell. Mol. Life Sci. 2021; 78(1): 1-16. https://dx.doi.org/10.1007/s00018-020-03576-x.
  29. Azziz R., Carmina E., Dewailly D., Diamanti-Kandarakis E., Escobar-Morreale H.F., Futterweit W. et al. The androgen excess and PCOS society criteria for the polycystic ovary syndrome: the complete task force report. Fertil. Steril. 2009; 91: 456-88. https://dx.doi.org/10.1016/j.fertnstert.2008.06.035.
  30. Sacchi S., Marinaro F., Tondelli D., Lui J., Xella S., Marsella T. et al. Modulation of gonadotrophin induced steroidogenic enzymes in granulosa cells by d-chiroinositol. Reprod. Biol. Endocrinol. 2016; 14(1): 52.https://dx.doi.org/10.1186/s12958-016-0189-2.

Received 23.08.2023

Accepted 05.09.2023

About the Authors

Olga A. Pustotina, Dr. Med. Sci., Professor at the Department of Obstetrics and Gynecology with a course in reproductive medicine, F.I. Inozemtsev Academy of Medical Education, +7(916)926-76-52, pustotina@gmail.com, https://orcid.org/0000-0001-6117-7270, 190013, Russia, St. Petersburg, Moskovsky Ave., 22M, office N.
Irina A. Rasulova, obstetrician-gynecologist, H-Clinic LLC, +7(916)354-43-25, irisha.harmony@gmail.com, 127083. Russia, Moscow, March 8 str., 6A-1.

Similar Articles

By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.