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Abstract
Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that impairs ovulation, hormonal balance, and metabolic function. Lean women with PCOS present a unique challenge, as insulin resistance and hyperandrogenism may occur despite normal body weight. Metformin and myo-inositol are insulin-sensitizing agents widely used in PCOS, but evidence comparing their individual and combined effects in lean women is limited.
Objective: Compare changes in ovulation frequency, AMH, and androgen levels across three arms. Measure insulin sensitivity and gastrointestinal side effects. Assess patient-reported symptoms (acne, hirsutism). Determine which baseline factors predict best response.
Methods: A three-arm randomized controlled trial was conducted at a tertiary hospital in Balochistan, Pakistan. Ninety lean women with PCOS (BMI 18.5–24.9 kg/m²) were randomized equally into three groups: metformin (500 mg three times daily), myo-inositol (2 g twice daily), or combination therapy. Participants were followed monthly for six months. Primary outcomes included ovulation frequency, serum AMH, and total testosterone. Secondary outcomes included HOMA-IR, gastrointestinal side effects, and clinical symptoms (hirsutism and acne). Data were analyzed using ANOVA, chi-square, and paired t-tests, with p < 0.05 considered significant.
Results: All three interventions improved ovulation, hormonal, and metabolic parameters. Combination therapy yielded the greatest increase in ovulatory cycles (mean 4.8 ± 1.2) and the largest reductions in AMH (−2.5 ± 0.7 ng/mL) and total testosterone (−18 ± 5 ng/dL), compared to metformin and myo-inositol monotherapy (p < 0.05). Insulin sensitivity improved across all groups, with HOMA-IR reduction most pronounced in the combination arm. Gastrointestinal side effects were highest in the metformin group (30%), whereas myo-inositol monotherapy and combination therapy were better tolerated. Clinical symptoms of hirsutism and acne improved in all groups, with combination therapy showing superior symptom relief.
Conclusions: In lean women with PCOS, combination therapy with metformin and myo-inositol offers superior improvements in ovulatory function, hormonal balance, insulin sensitivity, and symptom control compared to monotherapy. These findings support the use of combination therapy for phenotype-specific management of lean PCOS and highlight the importance of individualized treatment strategies that consider both efficacy and tolerability.