Effect of Myo-Inositol in Treating Polycystic Ovary Syndrome (PCOS): A Review

Shameema Alam^*
5^th Year MBBCh Student, Dubai Medical College for Girls, Dubai, UAE.

Correspondence to: Shameema Alam, 5^th Year MBBCh Student, Dubai Medical College for Girls, Dubai, UAE.
Received date: August 16, 2024; Accepted date: August 31, 2024; Published date: September 7, 2024
Citation: Alam S. Effect of Myo-Inositol in Treating Polycystic Ovary Syndrome (PCOS): A Review. J Obst Gynecol Surg. 2024;5(1):6-13. doi:10.52916/jogs244039
Copyright: ©2024 Alam S. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.

Abstract

Introduction: Background: Women of reproductive age are often affected by Polycystic Ovary Syndrome (PCOS), a condition that can cause infertility and metabolic problems. Hormonal changes contribute to PCOS's mechanism. It involves three interrelated symptoms, namely ovulation disorders, androgen excesses, and Polycystic Ovarian Morphology (PCOM), which should all be treated appropriately. Inositol therapy has been shown to play a significant role in PCOS in several studies. Despite this, there is no comprehensive discussion of Myo-Inositol (MI) and D-Chiro-Inositol (DCI) in relation to particular symptoms.
Aim: The purpose of this review is to demonstrate how well Myo-inositol treats PCOS symptoms. Additionally, the study emphasises on evaluating inositol consumption while considering their physiological characteristics and the process by which certain PCOS symptoms arise.
Methods: Using the databases PubMed and Google Scholar, a review of the literature was carried out using one of the following keywords: PCOS, myo-inositol, and insulin resistance.
Results: Multiple research studies have shown that the treatment of MI improved the function of ovaries and fertility in patients with Polycystic Ovarian Syndrome (PCOS), reduced symptoms of hyperandrogenism, including acne and hirsutism, beneficially affected metabolic aspects, and regulated a number of hormonal factors that are deeply connected to the function of the reproductive system and ovulation. Thus, using MI as a treatment has become a breakthrough approach to enhance spontaneous ovulation, stimulate ovulation, or minimise PCOS symptoms.
Conclusion: A physiological ratio of 40:1 between MI and DCI could prove to be advantageous for addressing the metabolic, hormonal, and reproductive components of PCOS, according to the existing clinical evidence.

Keywords:

Polycystic Ovary Syndrome, Inositol (PCOS), Myo-Inositol (MI), D-Chiro-Inositol (DCI), Ovulation, Androgen, Insulin resistance.

Funding

This review article did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Refernces

1. Norman RJ, Dewailly D, Legro RS, et al. Polycystic ovary syndrome. Lancet. 2007;370(9588):685-697.
2. Jin P, Xie Y. Treatment strategies for women with polycystic ovary syndrome. Gynecol Endocrinol. 2018;34(4):272-277.
3. 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(11):4237-4245.
4. Teede H, Deeks A, Moran L. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med. 2010;8:41.
5. Aversa A, La Vignera S, Rago R, et al. Fundamental Concepts and Novel Aspects of Polycystic Ovarian Syndrome: Expert Consensus Resolutions. Front Endocrinol (Lausanne). 2020;11:516.
6. Usadi RS, Legro RS. Reproductive impact of polycystic ovary syndrome. Curr Opin Endocrinol Diabetes Obes. 2012;19(6):505-511.
7. Moran L, Gibson-Helm M, Teede H, et al. Polycystic ovary syndrome: a biopsychosocial understanding in young women to improve knowledge and treatment options. J Psychosom Obstet Gynaecol. 2010;31(1):24-31.
8. Deeks AA, Gibson-Helm ME, et al. Is having polycystic ovary syndrome a predictor of poor psychological function including anxiety and depression?. Hum Reprod. 2011;26(6):1399-1407.
9. Teede HJ, Tay CT, Laven JJE, et al. Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2023;108(10):2447-2469.
10. 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(1):19-25.
11. Franks S, Mason H, Willis D. Follicular dynamics in the polycystic ovary syndrome. Mol Cell Endocrinol. 2000;163(1-2):49-52.
12. Carmina E, Rosato F, Jannì A, et al. 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.
13. de Melo AS, Dias SV, Cavalli Rde C, et al. Pathogenesis of polycystic ovary syndrome: multifactorial assessment from the foetal stage to menopause. Reproduction. 2015;150(1):R11-R24.
14. Fuster JJ, Andrés V. Telomere biology and cardiovascular disease. Circ Res. 2006;99(11):1167-1180.
15. Diamanti-Kandarakis E, Kandarakis H, Legro RS. The role of genes and environment in the etiology of PCOS. Endocrine. 2006;30(1):19-26.
16. Fornes R, Maliqueo M, Hu M, et al. The effect of androgen excess on maternal metabolism, placental function and fetal growth in obese dams. Sci Rep. 2017;7(1):8066.
17. Jahromi MS, Tehrani FR, Noroozzadeh M, et al. Elevated expression of steroidogenesis pathway genes; CYP17, GATA6 and StAR in prenatally androgenized rats. Gene. 2016;593(1):167-171.
18. https://www.uptodate.com/contents/etiology-and-pathophysiology-of-polycystic-ovary-syndrome-pcos-in-adolescents
19. Nelson VL, Qin KN, Rosenfield RL, et al. The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2001;86(12):5925-5933.
20. Unfer V, Porcaro G. Updates on the myo-inositol plus D-chiro-inositol combined therapy in polycystic ovary syndrome. Expert Rev Clin Pharmacol. 2014;7(5):623-631.
21. Genazzani AD. Inositol as putative integrative treatment for PCOS. Reprod Biomed Online. 2016;33(6):770-780.
22. Meier RK. Polycystic Ovary Syndrome. Nurs Clin North Am. 2018;53(3):407-420.
23. Al-Suod H, Ligor M, Rațiu I-A, et al. A Window on Cyclitols: Characterization and Analytics of Inositols. Phytochem Lett. 2017;20:507-519.
24. Jóźwik M, Jóźwik M, Teng C, et al. Human breast milk sugars and polyols over the first 10 puerperium days. Am J Hum Biol. 2013;25(2):198-204.
25. 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.
26. Holub BJ. The nutritional significance, metabolism, and function of myo-inositol and phosphatidylinositol in health and disease. Adv Nutr Res. 1982;4:107-141.
27. Asplin I, Galasko G, Larner J. Chiro-inositol deficiency and insulin resistance: a comparison of the chiro-inositol- and the myo-inositol-containing insulin mediators isolated from urine, hemodialysate, and muscle of control and type II diabetic subjects. Proc Natl Acad Sci U S A. 1993;90(13):5924-5928.
28. Unfer V, Proietti S, Gullo G, et al. Polycystic Ovary Syndrome: Features, Diagnostic Criteria and Treatments. Endocrinol Metab Syndr. 2014;3(3):136.
29. Larner J, Huang LC, Tang G, et al. Insulin mediators: structure and formation. Cold Spring Harb Symp Quant Biol. 1988;53 Pt 2:965-971.
30. 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.
31. Januszewski M, Issat T, Jakimiuk AA, et al. Metabolic and hormonal effects of a combined Myo-inositol and d-chiro-inositol therapy on patients with polycystic ovary syndrome (PCOS). Ginekol Pol. 2019;90(1):7-10.
32. Balen AH, Rutherford AJ. Managing anovulatory infertility and polycystic ovary syndrome. BMJ. 2007;335(7621):663-666.
33. Chiu TT, Tam PP. A correlation of the outcome of clinical in vitro fertilization with the inositol content and embryotrophic properties of human serum. J Assist Reprod Genet. 1992;9(6):524-530.
34. Laganà AS, Rossetti P, Buscema M, et al. Metabolism and Ovarian Function in PCOS Women: A Therapeutic Approach with Inositols. Int J Endocrinol. 2016;2016:6306410.
35. Sortino MA, Salomone S, Carruba MO, et al. Polycystic Ovary Syndrome: Insights into the Therapeutic Approach with Inositols. Front Pharmacol. 2017;8:341.
36. Cabrera-Cruz H, Oróstica L, Plaza-Parrochia F, et al. The insulin-sensitizing mechanism of myo-inositol is associated with AMPK activation and GLUT-4 expression in human endometrial cells exposed to a PCOS environment. Am J Physiol Endocrinol Metab. 2020;318(2):E237-E248.
37. Donà G, Sabbadin C, Fiore C, et al. Inositol administration reduces oxidative stress in erythrocytes of patients with polycystic ovary syndrome. Eur J Endocrinol. 2012;166(4):703-710.
38. 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.
39. Benelli E, Del Ghianda S, Di Cosmo C, et al. A 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.
40. Shokrpour M, Foroozanfard F, Afshar Ebrahimi F, et al. Comparison of myo-inositol and metformin on glycemic control, lipid profiles, and gene expression related to insulin and lipid metabolism in women with polycystic ovary syndrome: a randomized controlled clinical trial. Gynecol Endocrinol. 2019;35(5):406-411.
41. 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.
42. Minozzi M, Nordio M, Pajalich R. The Combined therapy myo-inositol plus D-Chiro-inositol, in a physiological ratio, reduces the cardiovascular risk by improving the lipid profile in PCOS patients. Eur Rev Med Pharmacol Sci. 2013;17(4):537-540.
43. Minozzi M, D'Andrea G, Unfer V. Treatment of hirsutism with myo-inositol: a prospective clinical study. Reprod Biomed Online. 2008;17(4):579-582.
44. Regidor PA, Schindler AE, Lesoine B, et al. 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).
45. Papaleo E, Unfer V, Baillargeon JP, et al. Myo-inositol in patients with polycystic ovary syndrome: a novel method for ovulation induction. Gynecol Endocrinol. 2007;23(12):700-703.
46. Papaleo E, Unfer V, Baillargeon JP, et al. Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. Fertil Steril. 2009;91(5):1750-1754.
47. Raffone E, Rizzo P, Benedetto V. Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women. Gynecol Endocrinol. 2010;26(4):275-280.
48. Ciotta L, Iozza I, Rubbino G, et al. Treatment of hyperandrogenism by myo-inositol. In Proceedings of the 14th World Congress of Gynecological Endocrinology, Firenze, Italy, 4-7 March 2010.
49. Di Berardino OM, Monteleone P, Valentino V, et al. Myo-inositol administration in pcos patients after IVF. In Proceedings of the 14th World Congress of Gynecological Endocrinology, Firenze, Italy, 4-7 March 2010.
50. Kamenov Z, Kolarov G, Gateva A, et al. Ovulation induction with myo-inositol alone and in combination with clomiphene citrate in polycystic ovarian syndrome patients with insulin resistance. Gynecol Endocrinol. 2015;31(2):131-135.
51. Papaleo E, De Santis L, Baillargeon J, et al. Comparison of myo-inositol plus folic acid vs clomiphene citrate for first line treatment in women with polycystic ovary syndrome. In Proceedings of the 24th Annual Meeting of ESHRE, Barcelona, Spain, 6-9 July 2008.
52. Morgante G, Orvieto R, Di Sabatino A, et al. The role of inositol supplementation in patients with polycystic ovary syndrome, with insulin resistance, undergoing the low-dose gonadotropin ovulation induction regimen. Fertil Steril. 2011;95(8):2642-2644.
53. Gerli S, Mignosa M, Di Renzo GC. Effects of inositol on ovarian function and metabolic factors in women with PCOS: a randomized double blind placebo-controlled trial. Eur Rev Med Pharmacol Sci. 2003;7(6):151-159.
54. Costantino D, Minozzi G, Minozzi E, et al. Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double-blind trial. Eur Rev Med Pharmacol Sci. 2009;13(2):105-110.
55. Regidor PA, Schindler AE. Myoinositol as a Safe and Alternative Approach in the Treatment of Infertile PCOS Women: A German Observational Study. Int J Endocrinol. 2016;2016:9537632.
56. Zacchè 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.
57. Unfer V, Dinicola S, Laganà AS, et al. Altered Ovarian Inositol Ratios May Account for Pathological Steroidogenesis in PCOS. Int J Mol Sci. 2020;21(19):7157.
58. Genazzani AD, Lanzoni C, Ricchieri F, et al. Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecol Endocrinol. 2008;24(3):139-144.
59. Le Donne M, Alibrandi A, Giarrusso R, et al. Diet, metformin and inositol in overweight and obese women with polycystic ovary syndrome: effects on body composition. Minerva Ginecol. 2012;64(1):23-29.
60. Pizzo A, Laganà AS, Barbaro L. Comparison between effects of myo-inositol and D-chiro-inositol on ovarian function and metabolic factors in women with PCOS. Gynecol Endocrinol. 2014;30(3):205-208.
61. Nestler JE, Unfer V. Reflections on inositol(s) for PCOS therapy: steps toward success. Gynecol Endocrinol. 2015;31(7):501-505.
62. Huang LC, Fonteles MC, Houston DB, et al. Chiroinositol deficiency and insulin resistance. III. Acute glycogenic and hypoglycemic effects of two inositol phosphoglycan insulin mediators in normal and streptozotocin-diabetic rats in vivo. Endocrinology. 1993;132(2):652-657.
63. Bevilacqua A, Carlomagno G, Gerli S, et al. Results from the International Consensus Conference on myo-inositol and D-chiro-inositol in Obstetrics and Gynecology--assisted reproduction technology. Gynecol Endocrinol. 2015;31(6):441-446.
64. Minozzi M, Costantino D, Guaraldi C, et al. The effect of a combination therapy with myo-inositol and a combined oral contraceptive pill versus a combined oral contraceptive pill alone on metabolic, endocrine, and clinical parameters in polycystic ovary syndrome. Gynecol Endocrinol. 2011;27(11):920-924.
65. Wu S, Divall S, Nwaopara A, et al. Obesity-induced infertility and hyperandrogenism are corrected by deletion of the insulin receptor in the ovarian theca cell. Diabetes. 2014;63(4):1270-1282.
66. Owczarczyk-Saczonek A, Lahuta LB, Ligor M, et al. The Healing-Promoting Properties of Selected Cyclitols-A Review. Nutrients. 2018;10(12):1891.
67. Genazzani AD, Santagni S, Rattighieri E, et al. Modulatory role of D-chiro-inositol (DCI) on LH and insulin secretion in obese PCOS patients. Gynecol Endocrinol. 2014;30(6):438-443.
68. Nestler JE, Jakubowicz DJ, Reamer P, et al. Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med. 1999;340(17):1314-1320.
69. Bevilacqua A, Bizzarri M. Physiological role and clinical utility of inositols in polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2016;37:129-139.
70. Chiu TT, Rogers MS, Law EL, et al. Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality. Hum Reprod. 2002;17(6):1591-1596.
71. Dell'Edera D, Sarlo F, Allegretti A, et al. The influence of D-chiro-inositol and D-myo-inositol in pregnant women with glucose intolerance. Biomed Rep. 2017;7(2):169-172.
72. Galazis N, Galazi M, Atiomo W. D-Chiro-inositol and its significance in polycystic ovary syndrome: a systematic review. Gynecol Endocrinol. 2011;27(4):256-262.
73. Colazingari S, Treglia M, Najjar R, et al. The combined therapy myo-inositol plus D-chiro-inositol, rather than D-chiro-inositol, is able to improve IVF outcomes: results from a randomized controlled trial. Arch Gynecol Obstet. 2013;288(6):1405-1411.
74. Wojciechowska A, Osowski A, Jóźwik M, et al. Inositols' Importance in the Improvement of the Endocrine-Metabolic Profile in PCOS. Int J Mol Sci. 2019;20(22):5787.
75. Dewailly D, Lujan ME, Carmina E, et al. Definition and significance of polycystic ovarian morphology: a task force report from the Androgen Excess and Polycystic Ovary Syndrome Society. Hum Reprod Update. 2014;20(3):334-352.
76. Bhide P, Homburg R. Anti-Müllerian hormone and polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2016;37:38-45.
77. Dinicola S, Chiu TT, Unfer V, et al. The rationale of the myo-inositol and D-chiro-inositol combined treatment for polycystic ovary syndrome. J Clin Pharmacol. 2014;54(10):1079-1092.
78. DeUgarte CM, Bartolucci AA, Azziz R. Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment. Fertil Steril. 2005;83(5):1454-1460.
79. Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev. 2012;33(6):981-1030.
80. Bevilacqua A, Dragotto J, Giuliani A, et al. 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):9387-9398.
81. Orio F, Muscogiuri G, Ascione A, et al. Effects of physical exercise on the female reproductive system. Minerva Endocrinol. 2013;38(3):305-319.
82. Szydlarska D, Grzesiuk W, Bar-andziak E. Controversies concerning the pathogenesis of polycystic ovary syndrome. Endokrynol Otył Zab Przem Mat. 2010;6(3):141-146.
83. Panidis D, Tziomalos K, Papadakis E, et al. Lifestyle intervention and anti-obesity therapies in the polycystic ovary syndrome: impact on metabolism and fertility. Endocrine. 2013;44(3):583-590.
84. Nybacka Å, Carlström K, Ståhle A, et al. Randomized comparison of the influence of dietary management and/or physical exercise on ovarian function and metabolic parameters in overweight women with polycystic ovary syndrome. Fertil Steril. 2011;96(6):1508-1513.
85. Domecq JP, Prutsky G, Mullan RJ, et al. Lifestyle modification programs in polycystic ovary syndrome: systematic review and meta-analysis. J Clin Endocrinol Metab. 2013;98(12):4655-4663.
86. Baillargeon JP, Diamanti-Kandarakis E, Ostlund RE Jr, et al. Altered D-chiro-inositol urinary clearance in women with polycystic ovary syndrome. Diabetes Care. 2006;29(2):300-305.
87. Crawford TJ, Crowther CA, Alsweiler J, et al. Antenatal dietary supplementation with myo-inositol in women during pregnancy for preventing gestational diabetes. Cochrane Database Syst Rev. 2015;2015(12):CD011507.