DOI: 10.6084/m9.figshare.28451030
title: Supplementary Material for: Impact of Ketogenic Diet on Weight, Metabolic, and Endocrine Parameters in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

description: Introduction
Polycystic ovary syndrome (PCOS) is a widespread disease among women of childbearing age. This pathology embraces a complex spectrum of clinical manifestations. An altered secretion of gonadotropins and high levels of androgens determine menstrual irregularities and ovulatory dysfunction, infertility, hirsutism, alopecia and acne. Moreover, hyperinsulinemia and insulin-resistance (IR) are common, leading to an increased metabolic risk. Whilst various pharmacological strategies have been studied to manage PCOS, the role of lifestyle should be emphasized. Numerous studies highlight the fundamental role that diet plays in the regulation of these hormonal imbalances. The hypothesis that a low-carbohydrate diet, such as the ketogenic diet (KD), may be beneficial in patients with PCOS has been evaluated in some clinical studies. The aim of the present systematic review and meta-analysis has been to evaluate through anthropometric, metabolic, and hormonal parameters the impact of KD in overweight or obese patients with PCOS.
Methods
A research question according to the PICOS framework was formulated, and a literature search following the PRISMA criteria for systematic review was performed. Studies that reported the following outcomes were included: weight loss, body mass index (BMI), circulating levels of glucose, insulin, Homeostasis Model Assessment – Insulin Resistance (HOMA-IR), LDL- cholesterol, HDL- cholesterol, triglycerides, luteinizing hormone (LH), follicle stimulating hormone (FSH), LH/FSH, estrogens, progesterone, anti-müllerian hormone (AMH), total-testosterone (total-T), free-testosterone (free-T), sex-hormone-binding-globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), pregnancies and live births. The extracted data were analyzed, and pooled results were expressed as standardized mean difference (SMD) with 95% Confidence Interval (CI).
Results
Seven studies were included in the systematic review. The results of the meta-analysis showed that after KD the patients had a significant weight loss (standard mean difference or SMD 1.31 Kg [95% CI 0.45, 2.17] p=0.003) and lower BMI (SMD 1.27 kg/m2 [95% CI 0.71, 1.83], p&lt;0.001). Blood glucose (SMD 1.36 mg/dL [95% CI 1.08, 1.64], p&lt;0.001), insulin (SMD 1.15 µU/mL 95% CI [0.60, 1.70], p&lt;0.001) and HOMA-IR (SMD 1.84 [95% CI 0.72, 2.96], p=0.001) were all decreased, and lipid profile was improved with higher HDL (SMD 0.38 mg/dL [95% IC 1.45, 0.68], p=0.48, not significant), lower LDL (SMD 0.73 mg/dL [95% CI 0.03, 1.42], p=0.04) and lower triglycerides (SMD 1.11 mg/dL [95% CI 0.53, 1.68], p&lt;0.001). Moreover, LH concentrations were significantly reduced (SMD 1.12 ng/dL [0.39, 1.84] p=0.003), FSH levels raised (SMD -0.76 ng/dL [-1.25, -0.28], p=0.002), the LH/FSH ratio decreased (SMD 2.04 (95% CI 1.04-3.03, p&lt;0.001); testosterone decreased (free-T SMD 0.57 ng/dL [95% CI 0.28, 0.86], p&lt;0.001; total-T SMD 0.54 ng/dL, 95% CI 0.28, 0.80, p&lt;0.001), and SHBG levels were significantly increased (SMD 0.79, 95% CI [1.24-0.34],p&lt;0.001). Data about estrogens, progesterone, DHEAS and pregnancies were too scarce to allow a comparison in the meta-analysis. 
Conclusion 
The ketogenic diet seems to offer a substantial benefit in improving all the anthropometric, metabolic and hormonal parameters evaluated. Studies on larger populations of PCOS patients may offer greater understanding of the benefits of low-glycemic diets in this category of patients.