Comparative Effects of Myo-Inositol, Metformin, Berberine, and Combination Therapy on Metabolic, Anthropometric and Hormonal Parameters in Women with Polycystic Ovary Syndrome: A 6-Month Observational Cohort Study

Background: Polycystic ovary syndrome (PCOS) is the most prevalent endocrine condition among women of reproductive age. It is marked by metabolic and reproductive irregularities and is often linked to insulin resistance, dyslipidemia, and obesity. Diverse methods of treatment are employed to enhance metabolic and hormonal parameters, including inositol-based supplements, metformin, and novel compounds such as berberine. Objective: To describe changes observed over six months in anthropometric, metabolic, lipid, and hormonal metrics among women with PCOS undergoing myo-inositol, metformin, berberine, or a combination of metformin and berberine in standard clinical settings, and to investigate if disparities among treatment groups remained after controlling for initial characteristics. Materials and Methods: This retrospective observational cohort study included 148 women with PCOS diagnosed according to the Rotterdam criteria who completed six months of treatment with myo-inositol (n = 38), metformin (n = 52), berberine (n = 28), or combined metformin–berberine therapy (n = 30). Anthropometric, metabolic, lipid, and androgen parameters were assessed at baseline and after six months. Within-group changes were evaluated with correction for multiple testing using the Holm method. Given the non-random treatment allocation and baseline differences among groups, supplementary baseline-adjusted analyses were performed for the continuous outcomes. Results: Treatment groups differed significantly in several baseline metabolic variables including body mass index (BMI), fasting plasma glucose (FPG), fasting insulin and homeostatic model assessment of insulin resistance (HOMA-IR). After Holm correction for multiple testing, the metformin group showed significant reductions in BMI, FPG, markers of insulin resistance, lipid parameters, and androgen-related hormonal parameters, together with an increase in high-density lipoprotein cholesterol (HDL-C). In the myo-inositol group, significant reductions were observed in fasting insulin, HOMA-IR, total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, androstenedione, and dehydroepiandrosterone sulfate (DHEAS). In the berberine group, significant reductions were observed in BMI, fasting insulin, HOMA-IR, total cholesterol, triglycerides, and androstenedione. In the combined metformin–berberine group, significant reductions were observed in BMI, fasting insulin, HOMA-IR, total cholesterol, LDL-C, triglycerides, testosterone, androstenedione, DHEAS, and 17-hydroxyprogesterone, together with an increase in HDL-C. In the baseline-adjusted analyses, no significant overall treatment-group effects remained for the principal metabolic outcomes after correction for multiple testing, whereas significant overall treatment-group effects were observed for DHEAS and 17-hydroxyprogesterone. Conclusions: In this real-world observational cohort, six months of treatment with metformin, myo-inositol, berberine, or combined metformin–berberine therapy was associated with changes in several metabolic and hormonal parameters. However, substantial baseline differences among the clinically selected treatment groups and the absence of significant baseline-adjusted between-group effects for the principal metabolic outcomes preclude conclusions regarding comparative treatment efficacy. The observed between-group differences in selected hormonal outcomes warrant further investigation in prospective comparative studies.