Inositol and Metformin Administration in Mediterranean Diet and Low-Carbohydrate Diets in Women With PCOS

Overview

Polycystic ovary syndrome (PCOS) is a common endocrine disorder frequently associated with obesity, insulin resistance (IR), and metabolic dysfunction. Although lifestyle modification is recommended as first-line therapy, the optimal dietary approach for women with PCOS remains uncertain. This randomized, controlled, open-label, parallel-group trial aims to compare the effects of a Mediterranean diet (MD) and a low-carbohydrate diet (LCD), each combined with metformin, inositol, or folic acid (active control), in obese women with PCOS and IR. A total of 102 participants will be randomly assigned to one of six intervention groups and followed for two months. Anthropometric measurements, body composition, biochemical parameters, and hedonic hunger will be assessed at baseline and after the intervention. The primary outcome is the change in insulin resistance, assessed by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), from baseline to 2 months. Secondary outcomes include changes in body composition, metabolic and biochemical parameters, and hedonic hunger.

Polycystic ovary syndrome (PCOS) is a complex and widespread endocrine disorder of unknown etiology, affecting 5-20% of women of reproductive age worldwide according to different diagnostic criteria. According to the Rotterdam criteria, PCOS is characterized by the presence of two of the following: hyperandrogenism, chronic anovulation, and polycystic ovary morphology. While the causes of PCOS are not yet fully defined, insulin resistance (IR) is considered one of the key etiological components. IR, frequently observed in PCOS, often mediates increased total and abdominal fat accumulation. The close relationship between PCOS, hyperandrogenism, hyperinsulinemia, and IR also increases the risk of metabolic syndrome. As a result of the lifelong pathological condition of PCOS, these women are at high risk for obesity, metabolic dysfunction, vascular dysfunction, malignancy, reproductive complications, and mood disorders. For many years, effective methods have been sought to treat hormonal imbalances associated with PCOS in order to restore regular menstrual cycles and ovulation. It has been reported that women with PCOS should reduce their energy intake through diet and implement dietary models that promote weight loss. While various dietary interventions in the literature, such as the ketogenic diet (KD), low-carbohydrate diet (LCD), and Mediterranean diet (MD), have shown positive effects on PCOS as a first-line treatment method, the definition of PCOS-specific medical nutritional therapy is not clear. Since PCOS is a chronic disease requiring lifelong management, and considering the side effect profile and difficulty of implementing the ketogenic diet, which appears promising in the short term, this study will evaluate the effects of the Mediterranean diet and a non-ketogenic low-carbohydrate diet. Metformin and inositol treatments will also be included in this comparison, and thanks to an active control group (folic acid), the effect of these dietary models alone against these pharmacological treatments can also be examined. This will allow for the evaluation of the effects of existing treatment approaches both individually and in combination. The study is designed as a randomized controlled, open-label, parallel design. The study will include 102 obese women diagnosed with PCOS and insulin resistance, who will be randomly assigned to two diet groups (AD and DKD). Each diet group will be further divided into three subgroups, and these subgroups will also receive metformin, inositol, or active control (folic acid) treatments. The intervention period of the study is two months, and adherence to diet and medication will be monitored at regular intervals. Biochemical findings, anthropometric measurements, body composition measurements, and the Nutritional Power Scale will be repeated at the beginning and end of the two-month study. The findings of this study will contribute to determining the optimal sequence or combination of dietary models, increasingly common food supplements, and existing medical agents in terms of treatment effectiveness.