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Published on: March 5, 2022
Metabolic Phenotype Predicts Biochemical Response to Inositol Supplementation in Polycystic Ovary Syndrome: A
Daniele Tienforti1, Gennaro Puocci1, Claudia Venditti1
1Andrology Unit, Department of Clinical Medicine, Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
Objective:
To evaluate the effect of inositol supplementation on biochemical hyperandrogenism in women with polycystic ovary syndrome (PCOS) and to explore whether metabolic phenotype modifies the endocrine response.
Design:
Systematic review and meta-analysis of randomized controlled trials conducted in accordance with PRISMA guidelines.
Patients:
Women diagnosed with PCOS according to established criteria (NIH, Rotterdam, or AE-PCOS). Nine eligible trials comprising a total of 440 participants were included.
Measurements:
Primary outcomes were serum total testosterone (TT), calculated free testosterone (cFT), free androgen index (FAI), and sex hormone-binding globulin (SHBG). Prespecified subgroup analyses explored differences according to body mass index (BMI) and insulin resistance (HOMA-IR).
Results:
Inositol supplementation was associated with significant reductions in TT (SMD -1.30; 95% CI -2.17 to -0.42), cFT, and FAI, together with an increase in SHBG. Substantial heterogeneity was observed for several outcomes. In subgroup analyses, the largest and most consistent reduction in TT was observed among normal-weight women (BMI < 25 kg/m²) (SMD -2.97; 95% CI -3.78 to -2.16), with minimal heterogeneity (I² = 9%). No significant improvements were detected in overweight or obese women, nor in women with insulin resistance when considered independently of BMI. These subgroup findings should be interpreted as exploratory.
Conclusions:
Inositol supplementation is associated with improvements in biochemical hyperandrogenism in women with PCOS, with evidence of phenotype-dependent variability. The most consistent biochemical response was observed in normal-weight individuals. These findings support a metabolically informed, hypothesis-generating framework and highlight the need for adequately powered, phenotype-stratified trials incorporating clinically meaningful outcomes, including standardized measures of hirsutism, ovulatory function, and patient-reported endpoints.
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