Comparative Effects of Combined Inositols and Alpha-Lipoic Acid (ALA) On Metabolic, Hormonal, and Clinical Outcomes in Obese Hyperinsulinemic Women with Polyendocrine Metabolic Ovarian Syndrome (PCOS/PMOS): The Impact of Family History of Diabetes

Abstract

Background: Polyendocrine Metabolic Ovarian Syndrome (PCOS/PMOS) represents a complex metabolic-endocrine disorder in obese, hyperinsulinemic, and insulin-resistant women with a family history of diabetes. Myo-inositol (MI) and D-chiro-inositol (DCI) act as insulin-sensitizing agents, while alpha-lipoic acid (ALA) may provide additional metabolic benefits. However, comparative evidence regarding their combined effects in this high-risk population remains limited. Objective of the article is to compare the metabolic, hormonal, and clinical effects of MI, MI+DCI, and MI+DCI+ALA in obese, hyperinsulinemic women with PCOS/PMOS and a family history of diabetes.

Methods: In this randomized, double-blind, parallel-group clinical trial, 96 women aged 20–38 years with obesity (BMI ≥30 kg/m²), Rotterdam criteria-defined PCOS/PMOS, hyperinsulinemia, and insulin resistance were randomized to control, MI, MI+DCI (40:1), or MI+DCI+ALA groups. Participants were evaluated at baseline and after 12 and 24 weeks. Metabolic, hormonal, and clinical parameters, including insulin sensitivity, glucose metabolism, androgen status, lipid profile, anthropometric measures, and menstrual regularity, were assessed.

Results: After 24 weeks, all three treatment groups demonstrated improvements in metabolic and hormonal parameters compared with controls. The MI+DCI combination produced greater improvements in insulin resistance and glucose metabolism than MI alone, while the addition of ALA resulted in further improvement. Androgen levels decreased, and SHBG increased, accompanied by improved gonadotropin balance. Menstrual regularity was restored most frequently with MI+DCI+ALA, followed by MI+DCI and MI alone. Anthropometric and lipid parameters also improved, with the most pronounced overall metabolic effects observed with the triple combination. Improvements in hepatic insulin extraction and liver-related parameters were particularly evident following ALA addition.

Conclusions: In obese women with PCOS/PMOS, hyperinsulinemia, insulin resistance and a family history of diabetes, MI+DCI supplementation was associated with greater metabolic, hormonal and clinical benefits than MI alone, while the addition of ALA provided further improvement across key metabolic outcomes. These findings support the potential role of combined inositol and ALA therapy in managing PCOS/PMOS phenotypes characterized by increased metabolic risk.