Inositol is an effective and safe treatment in polycystic ovary syndrome: a  systematic review and meta-analysis of randomized controlled trials

Dorina Greff; Anna E Juhász; Szilárd Váncsa; Alex Váradi; Zoltán Sipos; Julia Szinte; Sunjune Park; Péter Hegyi; Péter Nyirády; Nándor Ács; Szabolcs Várbíró; Eszter M Horváth

doi:10.1186/s12958-023-01055-z

Therapeutics Metabolic and Endocrine Agents

Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials

Greff D, Juhász AE, Váncsa S, Váradi A, Sipos Z, Szinte J, Park S, Hegyi P, Nyirády P, Ács N, Várbíró S, Horváth EM

Published January 26, 2023 Reproductive Biology and Endocrinology : RB&E, 21(1), 10

DOI 10.1186/s12958-023-01055-z PMID 36703143 PMC PMC9878965

RRM Academy Synopsis

Inositol raised cycle regularity versus placebo in PCOS trials

A 2023 meta-analysis of 26 randomized trials in 1691 women with PCOS found that inositol raised the chance of a regular cycle compared with placebo. Inositol groups reported fewer side effects than metformin groups.

Key Findings

On two trials, women taking inositol were more likely to have a normal menstrual cycle than women on placebo (risk ratio 1.79, 95% CI 1.13 to 2.85).
The authors report myoinositol had similar efficacy to metformin for cycle normalization. The interval was wide (risk ratio 1.42, 95% CI 0.8 to 2.53).
Across eight trials, BMI fell more with inositol than placebo (mean difference -0.45 kg/m2, 95% CI -0.89 to -0.02). Total testosterone, free testosterone and androstenedione also fell more than with placebo.
Four trials compared inositol with metformin. Side effects occurred in 7% of inositol groups and 53% of metformin groups (risk ratio 0.16, 95% CI 0.09 to 0.28).
Pregnancy rates showed no difference from placebo when inositol was followed by additional therapy (risk ratio 1.24, 95% CI 0.85 to 1.81).

Interpretation

PCOS (polycystic ovary syndrome) now also goes by polyendocrine metabolic ovarian syndrome (PMOS). This meta-analysis pooled 26 randomized trials testing inositol in women with PCOS. The authors call inositol effective and safe. The authors note small studies and mixed populations among the trials pooled. The findings support larger trials of inositol for cycle regularity and pregnancy in PCOS.

RRM Context

Restorative Reproductive Medicine looks for what drives irregular cycles in PCOS. The paper names insulin resistance as a key driver in PCOS. Inositol acts on insulin signaling. The authors say guidelines do not yet list inositol as standard therapy.

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

Abstract

Background

Metformin is the gold standard insulin sensitizer, which is widely used to treat insulin resistance in polycystic ovary syndrome (PCOS). However, metformin may induce gastrointestinal side effects.

Objective

Inositols have long been debated as a potential alternative for metformin in treating PCOS. Therefore, the present systematic review aimed to evaluate the efficacy and safety of inositols in treating PCOS.

Methods

The present systematic search was performed in CENTRAL, MEDLINE, and Embase from the inception until October 20th, 2021. Eligible randomized controlled trials (RCTs) included women diagnosed with PCOS and compared any inositols with metformin or placebo. Our primary outcome was cycle normalization, whereas secondary outcomes were body mass index (BMI), parameters of carbohydrate metabolism and clinical and laboratory hyperandrogenism. Results are reported as risk ratios or mean differences (MDs) with 95% confidence intervals (CIs).

Results

Twenty-six RCTs were identified, including data of 1691 patients (806 inositol, 311 with placebo, and 509 metformin groups). In patients treated with inositols, the risk (CI: 1.13; 2.85) of having a regular menstrual cycle was found by 1.79 higher than in the case of placebo. Moreover, the inositols showed non-inferiority compared to metformin in this outcome. In the case of BMI (MD = -0.45; CI: -0.89; -0.02), free testosterone (MD = -0,41, CI: -0.69; -0.13), total testosterone (MD = -20.39, CI: -40.12; -0.66), androstenedione (MD = -0.69, CI: -1,16; -0.22), glucose (MD = -3.14; CI: -5.75; -0.54) levels and AUC insulin (MD = -2081.05, CI: -2745.32; -1416.78) inositol treatment induced greater decrease compared to placebo. Inositol increased sex-hormone-binding globulin significantly compared to placebo (MD = 32.06, CI:1.27; 62.85).

Conclusion

Inositol is an effective and safe treatment in PCOS. Moreover, inositols showed non-inferiority in most outcomes compared to the gold standard treatment; metformin.

Systematic Review Registration

CRD42021283275.

Topics

Therapeutics › Metabolic and Endocrine Agents › Insulin Sensitizing Agents · Reproductive Endocrinology › Ovarian Hormones › Androgens · Menstrual Cycle › Cycle Disorders › Ovulatory Disturbances

Dorina Greff, Anna E Juhász, Szilárd Váncsa, Alex Váradi, Zoltán Sipos, Julia Szinte, Sunjune Park, Péter Hegyi, Péter Nyirády, Nándor Ács, Szabolcs Várbíró, Eszter M Horváth

D Greff, A Juhász, S Váncsa, Alexander Váradi, Alexandra Váradi, A Váradi, Z Sipos, J Szinte, S Park, P Hegyi, P Nyirády, N Ács, S Várbíró, E Horváth

PMID 36703143 36703143 DOI 10.1186/s12958-023-01055-z 10.1186/s12958-023-01055-z Greff et al. 2023, Greff 2023

Keywords

Inositol, Hypoglycemic Agents, Metformin, Testosterone, Insulins