Metabolic and endocrine effects of myo-inositol versus metformin in women with insulin-resistant polyendocrine metabolic ovarian syndrome: an open-label, randomized controlled trial

Insulin resistance (IR) plays a key role in Polyendocrine Metabolic Ovarian Syndrome (PMOS), previously known as Polycystic Ovary Syndrome (PCOS). This study compared myo-inositol (MYO) and metformin (MET) in women with insulin-resistant PMOS across all Rotterdam phenotypes. Primary outcomes were hormonal and metabolic parameters; secondary outcomes included menstrual cyclicity, anthropometric, clinical, ovarian ultrasound, and safety parameters. A prospective, randomized, open-label clinical trial assigned 60 women with insulin-resistant PMOS to receive either MYO (2 g plus folic acid 200 µg twice daily; n = 30) or MET (850 mg twice daily; n = 30) for 6 months. Hormonal (LH, FSH, total and free testosterone, androstenedione, DHEA-S, SHBG), metabolic (fasting glucose and insulin, OGTT, HOMA-IR, QUICKI, Matsuda–DeFronzo Index), anthropometric (weight, BMI, waist and hip circumference), clinical (menstrual cyclicity, acne, Ferriman–Gallwey score), and safety parameters were assessed at baseline, 3, and 6 months; ovarian ultrasound was performed at baseline and 6 months. Both MYO and MET significantly improved menstrual cyclicity ( p < 0.01), acne ( p < 0.01), and waist circumference ( p < 0.01). MET significantly improved the waist-to-hip ratio( p < 0.05). Total testosterone showed a trend toward reduction in both groups (MET: p = 0.076; MYO: p = 0.055). MYO was superior to MET in reducing dehydroepiandrosterone sulfate (DHEA-S) levels (between-group difference: −323 ng/mL; 95% CI: −587 to − 59.2; p = 0.009). MET significantly improved HOMA-IR ( p < 0.01) and outperformed MYO in the AUC for the glucose-to-insulin ratio [(mg/dL)/(µIU/mL)] × min during the OGTT (between-group difference: −88; 95% CI: −160 to − 16.3; p = 0.016). MET also significantly improved the presence of a dominant follicle ( p < 0.01). Adverse effects were significantly more frequent with MET at 3 months ( p < 0.001) and 6 months ( p = 0.023). Treatment satisfaction exceeded 85% in both groups. Both MYO and MET appear to be effective options for improving menstrual cyclicity in women with insulin-resistant PMOS. Their distinct clinical, metabolic, and tolerability profiles suggest that treatment selection may be individualized according to patient characteristics and therapeutic priorities. https://clinicaltrials.gov on March 8, 2021. Clinical trial identification number: NCT04892186.