Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines

Victoria Fitz; Sandro Graca; Shruthi Mahalingaiah; Jing Liu; Lily Lai; Ali Butt; Mike Armour; Vibhuti Rao; Dhevaksha Naidoo; Alison Maunder; Guoyan Yang; Vaishnavi Vaddiparthi; Selma F Witchel; Alexia Pena; Poli Mara Spritzer; Rong Li; Chau Tay; Aya Mousa; Helena Teede; Carolyn Ee

doi:10.1210/clinem/dgad762

Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines

Fitz V, Graca S, Mahalingaiah S, Liu J, Lai L, Butt A, Armour M, Rao V, Naidoo D, Maunder A, Yang G, Vaddiparthi V, Witchel SF, Pena A, Spritzer PM, Li R, Tay C, Mousa A, Teede H, Ee C

Published May 17, 2024 The Journal of clinical endocrinology and metabolism

DOI 10.1210/clinem/dgad762 PMID 38163998 PMC PMC11099481

RRM Academy Synopsis

Inositol evidence for PCOS is limited and inconclusive

A 2024 review of 30 randomized trials in women with polycystic ovary syndrome (PCOS) found the evidence for inositol limited and inconclusive. In 2 trials each, metformin did better than myo-inositol for waist-hip ratio and hirsutism. Across 6 trials, myo-inositol likely caused fewer stomach side effects than metformin.

Key Findings

The review included 30 trials (n = 2230; 1093 intervention, 1137 control); 19 contributed to meta-analyses. Most outcomes were rated low to very low certainty.
D-chiro-inositol improved ovulation rate versus placebo in 2 trials (OR 11.50, 95% CI 3.40 to 38.91; 64 participants, low certainty).
Myo-inositol plus folic acid and folic acid alone did not differ for clinical pregnancy rate in 5 studies (OR 1.24, 95% CI 0.90 to 1.73).
Metformin outperformed myo-inositol for waist-hip ratio (MD 0.04, 2 trials) and Ferriman-Gallwey hirsutism score (MD 2.42, 2 trials).
Gastrointestinal adverse events were less common with myo-inositol than metformin (OR 0.09, 95% CI 0.02 to 0.37; 6 trials, I2 = 69%).

Interpretation

The authors pooled randomized trials of inositol, a supplement, in PCOS, also called PMOS (polyendocrine metabolic ovarian syndrome). They rated most results low to very low certainty. The authors note that risk of bias was generally high. The review informed the 2023 international evidence-based PCOS guideline.

RRM Context

Restorative reproductive medicine treats PCOS by working out which features each woman has. The D-chiro-inositol ovulation signal came from two small trials. Clinical pregnancy did not differ when myo-inositol was added to folic acid.

Our editorial summary of this paper, not the article's abstract.

Abstract

Context

Insulin resistance is common in women with polycystic ovary syndrome (PCOS). Inositol may have insulin sensitizing effects; however, its efficacy in the management of PCOS remains indeterminate.

Objective

To inform the 2023 international evidence-based guidelines in PCOS, this systematic review and meta-analysis evaluated the efficacy of inositol, alone or in combination with other therapies, in the management of PCOS.

Data Sources

Medline, PsycInfo, EMBASE, All EBM, and CINAHL from inception until August 2022.

Study Selection

Thirty trials (n = 2230; 1093 intervention, 1137 control), with 19 pooled in meta-analyses were included.

Data Extraction

Data were extracted for hormonal, metabolic, lipids, psychological, anthropometric, reproductive outcomes, and adverse effects by 1 reviewer, independently verified by a second.

Data Synthesis

Thirteen comparisons were assessed, with 3 in meta-analyses. Evidence suggests benefits for myo-inositol or D-chiro-inositol (DCI) for some metabolic measures and potential benefits from DCI for ovulation, but inositol may have no effect on other outcomes. Metformin may improve waist-hip ratio and hirsutism compared to inositol, but there is likely no difference for reproductive outcomes, and the evidence is very uncertain for body mass indexI. Myo-inositol likely causes fewer gastrointestinal adverse events compared with metformin; however, these are typically mild and self-limited.

Conclusion

The evidence supporting the use of inositol in the management of PCOS is limited and inconclusive. Clinicians and their patients should consider the uncertainty of the evidence together with individual values and preferences when engaging in shared decision-making regarding the use of inositol for PCOS.

Victoria Fitz, Sandro Graca, Shruthi Mahalingaiah, Jing Liu, Lily Lai, Ali Butt, Mike Armour, Vibhuti Rao, Dhevaksha Naidoo, Alison Maunder, Guoyan Yang, Vaishnavi Vaddiparthi, Selma F Witchel, Alexia Pena, Poli Mara Spritzer, Rong Li, Chau Tay, Aya Mousa, Helena Teede, Carolyn Ee

V Fitz, S Graca, S Mahalingaiah, J Liu, L Lai, A Butt, Michael Armour, M Armour, V Rao, D Naidoo, A Maunder, G Yang, V Vaddiparthi, S Witchel, A Pena, P Spritzer, R Li, C Tay, A Mousa, H Teede, C Ee

PMID 38163998 38163998 DOI 10.1210/clinem/dgad762 10.1210/clinem/dgad762 Fitz et al. 2024, Fitz 2024

Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines

Inositol evidence for PCOS is limited and inconclusive

Key Findings

Interpretation

RRM Context

Abstract

By this author

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