Inositols in PCOS/PMOS: therapeutic role, metabolic implications, and combination with metformin
DOI:
https://doi.org/10.12775/QS.2026.58.72611Keywords
PCOS, myo-inositol, D-chiro-inositol, metformin, insulin resistance, infertility, hyperandrogenismAbstract
Polycystic Ovary Syndrome (PCOS), increasingly referred to as polyendocrine metabolic ovarian syndrome (PMOS), is a heterogeneous endocrine–metabolic disorder associated with reproductive dysfunction, hyperandrogenism, insulin resistance, and increased cardiometabolic risk. Due to the central role of insulin resistance, insulin-sensitizing therapies such as myo-inositol (MI), D-chiro-inositol (DCI), and metformin have gained growing clinical attention.
Evidence from studies published between 2015 and 2026 suggests that MI and DCI may improve insulin sensitivity, hormonal balance, and reproductive outcomes, including menstrual cycle regularity and ovulation. The 40:1 MI/DCI ratio remains the most extensively studied formulation and appears to reflect physiological proportions. Metformin continues to play a key therapeutic role, particularly in women with insulin resistance, overweight, or obesity, while combination therapy with inositols may provide additional benefits in selected cases.
However, evidence remains heterogeneous, highlighting the need for further high-quality randomized controlled trials to clarify the long-term efficacy and optimal clinical use of inositols in PCOS/PMOS management.
References
1. Teede HJ, Tay CT, Laven JJE, Dokras A, Moran LJ, Piltonen TT, et al. Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2023 Sep 18;108(10):2447–69.
2. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009 Feb;91(2):456–88.
3. Baba T. Polycystic ovary syndrome: Criteria, phenotypes, race and ethnicity. Reprod Med Biol. 2025 Jan 22;24(1):e12630.
4. Ma Y-C, Law K-S, Wang W-S, Chang H-M. Phenotypic variations in polycystic ovary syndrome: metabolic risks and emerging biomarkers. J Endocrinol. 2025 Oct 1;267(1).
5. Spritzer PM, Marchesan LB, Santos BR, Fighera TM. Hirsutism, normal androgens and diagnosis of PCOS. Diagnostics (Basel). 2022 Aug 9;12(8).
6. Joshi A. PCOS stratification for precision diagnostics and treatment. Front Cell Dev Biol. 2024 Feb 8;12:1358755.
7. Lentscher JA, Decherney AH. Clinical presentation and diagnosis of polycystic ovarian syndrome. Clin Obstet Gynecol. 2021 Mar 1;64(1):3–11.
8. Teede HJ, Gibson M, Laven J, Dokras A, Moran LJ, Piltonin T, et al. International PCOS guideline clinical research priorities roadmap: a co-designed approach aligned with end-user priorities in a neglected women’s health condition. EClinicalMedicine. 2024 Dec;78:102927.
9. Zhao H, Zhang J, Cheng X, Nie X, He B. Insulin resistance in polycystic ovary syndrome across various tissues: an updated review of pathogenesis, evaluation, and treatment. J Ovarian Res. 2023 Jan 11;16(1):9.
10. Dong J, Rees DA. Polycystic ovary syndrome: pathophysiology and therapeutic opportunities. bmjmed. 2023 Oct 12;2(1):e000548.
11. Harada M. Pathophysiology of polycystic ovary syndrome revisited: Current understanding and perspectives regarding future research. Reprod Med Biol. 2022 Oct 8;21(1):e12487.
12. Xu Y, Qiao J. Association of Insulin Resistance and Elevated Androgen Levels with Polycystic Ovarian Syndrome (PCOS): A Review of Literature. J Healthc Eng. 2022 Mar 21;2022:9240569.
13. Torchen LC, Wu M, Thompson B, Beaudouin A. POLYCYSTIC OVARY SYNDROME: ORIGINS AND IMPLICATIONS: The significance of functional adrenal hyperandrogenism in polycystic ovary syndrome across the lifespan. Reproduction. 2025 Jun 1;169(6).
14. Rudnicka E, Suchta K, Grymowicz M, Calik-Ksepka A, Smolarczyk K, Duszewska AM, et al. Chronic low grade inflammation in pathogenesis of PCOS. Int J Mol Sci. 2021 Apr 6;22(7).
15. Suthar M, Kaliberdenko V. Inflammation-Driven Pathogenesis of Polycystic Ovary Syndrome: Integrating Endocrine Imbalance, Reproductive Impairments, and Tissue-Level Change. Recent Adv Inflamm Allergy Drug Discov. 2026 Mar 26;
16. Aboeldalyl S, James C, Seyam E, Ibrahim EM, Shawki HE-D, Amer S. The Role of Chronic Inflammation in Polycystic Ovarian Syndrome-A Systematic Review and Meta-Analysis. Int J Mol Sci. 2021 Mar 8;22(5).
17. Zhao H, Xing C, Zhang J, He B. Comparative efficacy of oral insulin sensitizers metformin, thiazolidinediones, inositol, and berberine in improving endocrine and metabolic profiles in women with PCOS: a network meta-analysis. Reprod Health. 2021 Aug 18;18(1):171.
18. DiNicolantonio JJ, H O’Keefe J. Myo-inositol for insulin resistance, metabolic syndrome, polycystic ovary syndrome and gestational diabetes. Open Heart. 2022 Mar;9(1).
19. Fedeli V, Unfer V, Dinicola S, Laganà AS, Canipari R, Monti N, et al. Inositol restores appropriate steroidogenesis in PCOS ovaries both in vitro and in vivo experimental mouse models. Cells. 2024 Jul 9;13(14).
20. Bizzarri M, Monti N, Piombarolo A, Angeloni A, Verna R. Myo-Inositol and D-Chiro-Inositol as Modulators of Ovary Steroidogenesis: A Narrative Review. Nutrients. 2023 Apr 13;15(8).
21. Kalra B, Kalra S, Sharma JB. The inositols and polycystic ovary syndrome. Indian J Endocrinol Metab. 2016;20(5):720–4.
22. Fitz V, Graca S, Mahalingaiah S, Liu J, Lai L, Butt A, et al. Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines. J Clin Endocrinol Metab. 2024 May 17;109(6):1630–55.
23. Greff D, Juhász AE, Váncsa S, Váradi A, Sipos Z, Szinte J, et al. Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Reprod Biol Endocrinol. 2023 Jan 26;21(1):10.
24. Sortino MA, Salomone S, Carruba MO, Drago F. Polycystic Ovary Syndrome: Insights into the Therapeutic Approach with Inositols. Front Pharmacol. 2017 Jun 8;8:341.
25. Placidi M, Casoli G, Tatone C, Di Emidio G, Bevilacqua A. Myo-Inositol and Its Derivatives: Their Roles in the Challenges of Infertility. Biology (Basel). 2024 Nov 16;13(11).
26. Gupta D, Khan S, Islam M, Malik BH, Rutkofsky IH. Myo-Inositol’s Role in Assisted Reproductive Technology: Evidence for Improving the Quality of Oocytes and Embryos in Patients With Polycystic Ovary Syndrome. Cureus. 2020 May 12;12(5):e8079.
27. Russo M, Forte G, Montanino Oliva M, Laganà AS, Unfer V. Melatonin and Myo-Inositol: Supporting Reproduction from the Oocyte to Birth. Int J Mol Sci. 2021 Aug 5;22(16).
28. Pivazyan L, Krylova E, Obosyan L, Seregina V, Shapovalenko R, Ayryan E. Effectiveness of Myo-Inositol on Oocyte and Embryo Quality in Assisted Reproduction: Systematic Review and Meta-Analysis of Randomized Clinical Trials. Gynecol Obstet Invest. 2025;90(1):78–92.
29. Unfer V, Dinicola S, Laganà AS, Bizzarri M. Altered ovarian inositol ratios may account for pathological steroidogenesis in PCOS. Int J Mol Sci. 2020 Sep 28;21(19).
30. Dinicola S, Unfer V, Soulage CO, Yap-Garcia MIM, Bevilacqua A, Benvenga S, et al. d-Chiro-Inositol in Clinical Practice: A Perspective from the Experts Group on Inositol in Basic and Clinical Research (EGOI). Gynecol Obstet Invest. 2024 Feb 19;89(4):284–94.
31. Monastra G, Unfer V, Harrath AH, Bizzarri M. 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. 2017 Jan;33(1):1–9.
32. A double-edge sword: the role of D-chiro-inositol in oocyte and embryo quality - EGOI-PCOS [Internet]. 2019 [cited 2026 May 19]. Available from: https://www.egoipcos.com/a-double-edge-sword-the-role-of-d-chiro-inositol-in-oocyte-and-embryo-quality/
33. Minini M, Monastra G, Dinicola S. A double-edge sword: the role of D-chiro-inositol in oocyte and embryo quality. 2019 Dec 10;
34. Laganà AS, Myers SH, Forte G, Naem A, Krentel H, Allahqoli L, et al. Inositols in treating polycystic ovary syndrome and non-insulin dependent diabetes mellitus: now and the future. Expert Opin Drug Metab Toxicol. 2024 Jan 22;20(1–2):61–72.
35. 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 Jun;23(12):5512–21.
36. Kelly FA, de Oliveira Macena Lôbo A, Cardoso JHCO, de Moraes FCA. Comparison of metformin with inositol versus metformin alone in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Endocrine. 2025 Feb;87(2):389–99.
37. Saadati S, Mason T, Godini R, Vanky E, Teede H, Mousa A. Metformin use in women with polycystic ovary syndrome (PCOS): Opportunities, benefits, and clinical challenges. Diabetes Obes Metab. 2025 Jun;27 Suppl 3(Suppl 3):31–47.
38. Russo M, Oliva MM, Nordio M, Porcaro G, Unfer V. Metformin and Myo-Inositol: A Comparative Analysis. Gynecol Obstet Invest. 2025 Nov 21;1–13.
39. Attia GM, Almouteri MM, Alnakhli FT. Role of Metformin in Polycystic Ovary Syndrome (PCOS)-Related Infertility. Cureus. 2023 Aug 31;15(8):e44493.
40. Sadeghi HM, Adeli I, Calina D, Docea AO, Mousavi T, Daniali M, et al. Polycystic ovary syndrome: A comprehensive review of pathogenesis, management, and drug repurposing. Int J Mol Sci. 2022 Jan 6;23(2).
41. Li Y, Wang Y, Liu H, Zhang S, Zhang C. Association between HOMA-IR and ovarian sensitivity index in women with PCOS undergoing ART: A retrospective cohort study. Front Endocrinol (Lausanne). 2023 Mar 9;14:1117996.
42. González-González JG, Violante-Cumpa JR, Zambrano-Lucio M, Burciaga-Jimenez E, Castillo-Morales PL, Garcia-Campa M, et al. HOMA-IR as a predictor of Health Outcomes in Patients with Metabolic Risk Factors: A Systematic Review and Meta-analysis. High Blood Press Cardiovasc Prev. 2022 Nov;29(6):547–64.
43. Tahapary DL, Pratisthita LB, Fitri NA, Marcella C, Wafa S, Kurniawan F, et al. Challenges in the diagnosis of insulin resistance: Focusing on the role of HOMA-IR and Tryglyceride/glucose index. Diabetes Metab Syndr. 2022 Aug;16(8):102581.
44. Lete I, Martínez A, Lasaga I, Centurión E, Vesga A. Update on the combination of myo-inositol/d-chiro-inositol for the treatment of polycystic ovary syndrome. Gynecol Endocrinol. 2024 Dec;40(1):2301554.
45. Bodepudi R, Seher S, Khan SA, Emmanuel S, Shantha Kumar V, Nerella R, et al. Myoinositol versus metformin in the treatment of polycystic ovarian syndrome: A systematic review. Cureus. 2023 Jul 11;15(7):e41748.
46. Alenezi SA, Khan R, Amer S. The Impact of High BMI on Pregnancy Outcomes and Complications in Women with PCOS Undergoing IVF-A Systematic Review and Meta-Analysis. J Clin Med. 2024 Mar 10;13(6).
47. Guo F, Gong Z, Fernando T, Zhang L, Zhu X, Shi Y. The Lipid Profiles in Different Characteristics of Women with PCOS and the Interaction Between Dyslipidemia and Metabolic Disorder States: A Retrospective Study in Chinese Population. Front Endocrinol (Lausanne). 2022 Jul 4;13:892125.
48. Li S, Chu Q, Ma J, Sun Y, Tao T, Huang R, et al. Discovery of novel lipid profiles in PCOS: do insulin and androgen oppositely regulate bioactive lipid production? J Clin Endocrinol Metab. 2017 Mar 1;102(3):810–21.
49. Sharon P M, P M, Manivannan A, Thangaraj P, B M L. The Effectiveness of Myo-Inositol in Women With Polycystic Ovary Syndrome: A Prospective Clinical Study. Cureus. 2024 Feb 10;16(2):e53951.
50. Sene AA, Saeedzarandi M, Yazdizadeh M, Ghaffari SR, Amjadi F, Zandieh Z, et al. The effect of myo-inositol on assisted reproductive technology outcomes in women with polycystic ovarian syndrome: A systematic review and meta-analysis of randomized clinical trial studies. Int J Reprod Biomed. 2025 May;23(5):353–76.
51. Zhang J, Zhang H, Zhou W, Jiang M, Lin X. Effect of myo-inositol supplementation in mixed ovarian response IVF cohort: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2025 Mar 21;16:1520362.
52. Palomba S, Seminara G, Aversa A. Myo-inositol in reproductive management of women with PCOS: holy grail for medical practice or demon for scientific evidence? Reprod Biomed Online. 2026 Feb;52(2):105269.
53. Rashid R, Mir SA, Kareem O, Ali T, Ara R, Malik A, et al. Polycystic ovarian syndrome-current pharmacotherapy and clinical implications. Taiwan J Obstet Gynecol. 2022 Jan;61(1):40–50.
54. Wdowiak A, Bakalczuk S, Filip M, Laganà AS, Unfer V. The Clinical Use of Myo-Inositol in IVF-ET: A Position Statement from the Experts Group on Inositol in Basic and Clinical Research and on PCOS (EGOI-PCOS), the Polish Society of Andrology, and the International Scientific Association for the Support and Development of Medical Technologies. J Clin Med. 2025 Jan 16;14(2).
55. Beresniak A, Russo M, Forte G, Laganà AS, Oliva MM, Aragona C, et al. A Markov-model simulation of IVF programs for PCOS patients indicates that coupling myo-Inositol with rFSH is cost-effective for the Italian Health System. Sci Rep. 2023 Oct 18;13(1):17789.
56. Sharma P, Malvi A. Combination of metformin and myoinositol: a powerful weapon to combat polycystic ovary syndrome. Int J Reprod Contracept Obstet Gynecol. 2025 Jan 16;
57. Teede HJ, Khomami MB, Morman R, Laven JSE, Joham AE, Costello MF, et al. Polyendocrine metabolic ovarian syndrome, the new name for polycystic ovary syndrome: a multistep global consensus process. Lancet. 2026 May;
58. Rimmer A. PCOS name change to PMOS must be managed to avoid confusing patients, says expert. BMJ. 2026 May 15;393:s955.
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Copyright (c) 2026 Alicja Biskup, Agata Wnęk, Julia Smagowska, Natalia Staszko, Ewa Kala-Kaziszyn, Kamila Bała, Mikołaj Stańko
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