Polycystic ovary syndrome is a disorder characterised by insulin resistance, low-grade inflammation and increased adipose tissue. The very low-carbohydrate ketogenic diet has been suggested to reduce obesity risks in polycystic ovary syndrome. This study aimed to update the evidence on the effects of the very low-carbohydrate ketogenic diet in women with polycystic ovary syndrome. Searches were conducted in electronic databases for randomised clinical trials addressing the research question. The values for the meta-analysis were presented as weighted mean difference (WMD). Twelve studies were included in the qualitative analysis and eleven in the quantitative analysis. Significant reductions were observed in anthropometric outcomes: weight (WMD: −9·57 kg; P < 0·0001), waist circumference (WMD: −7·75 cm; P < 0·0009), fat body mass (WMD: −7·44 kg; P = 0·0008), BMI (WMD: −3·45 kg/m2; P < 0·0001) and waist-to-hip ratio (WMD: −0·02; P < 0·0034). Hormonal improvements included free testosterone (WMD: −0·31 ng/dl; P < 0·0001), total testosterone (WMD: −7·21 ng/dl; P < 0·0001), sex hormone-binding globulin (WMD: 15·22 nmol/l; P = 0·0035), luteinising hormone (WMD: −3·97 U/L; P = 0·0008) and luteinising hormone:follicle-stimulating hormone ratio (WMD: −1·04; P = 0·0053), but not for follicle-stimulating hormone levels (WMD: 1·23 mUI/ml; P = 0·12). Significant changes in metabolic markers were seen in blood glucose (WMD: −9·65 mg/dl; P = 0·0031), insulin (WMD: −2·41 mg/dl; P = 0·0387), homeostatic model assessment for insulin resistance (WMD: −2·46; P = 0·0123) and TAG (WMD: −29·95 mg/dl; P = 0·0188). The very low-carbohydrate ketogenic diet shows significant benefits in managing body composition, reducing hyperandrogenism, balancing sex hormones and improving glucose metabolism in polycystic ovary syndrome.

High carbohydrate intake and low-grade inflammation cooperate with insulin resistance and hyperandrogenism to constitute an interactive continuum acting on the pathophysiology of polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age characterised by oligo-anovulatory infertility and cardiometabolic disorders. The role of insulin in PCOS is pivotal both in regulating the activity of ovarian and liver enzymes, respectively involved in androgen production and in triggering low-grade inflammation usually reported to be associated with an insulin resistance, dyslipidaemia and cardiometabolic diseases. Although an acute hyperglycaemia induced by oral glucose loading may increase inflammation and oxidative stress by generating reactive oxygen species through different mechanisms, the postprandial glucose increment, commonly associated with the Western diet, represents the major contributor of chronic sustained hyperglycaemia and pro-inflammatory state. Together with hyperinsulinaemia, hyperandrogenism and low-grade inflammation, unhealthy diet should be viewed as a key component of the ‘deadly quartet’ of metabolic risk factors associated with PCOS pathophysiology. The identification of a tight diet–inflammation–health association makes the adoption of healthy nutritional approaches a primary preventive and therapeutic tool in women with PCOS, weakening insulin resistance and eventually promoting improvements of reproductive life and endocrine outcomes. The intriguing nutritional–endocrine connections operating in PCOS underline the role of expert nutritionists in the management of this syndrome. The aim of the present review is to provide an at-a-glance overview of the possible bi-directional mechanisms linking inflammation, androgen excess and carbohydrate intake in women with PCOS.

Androgens may directly modulate early ovarian follicular development in preantral stages and androgen excess before puberty may disrupt this physiological process. Therefore, the aim of this study was to investigate the dynamics of follicular morphology and circulating androgen and estradiol levels in prepubertal Wistar rats acutely exposed to androgens. Prepubertal female Wistar rats were distributed into three groups: control, equine chorionic gonadotropin (eCG) intervention and eCG plus dehydroepiandrosterone (DHEA) intervention (eCG+DHEA). Serum DHEA, testosterone and estradiol levels were determined, and ovarian morphology and morphometry were assessed. The eCG+DHEA group presented increased serum estradiol and testosterone levels as compared with the control group (P<0.01), and higher serum DHEA concentration v. the eCG-only and control groups (P<0.01). In addition, the eCG+DHEA group had a higher number of, and larger-sized, primary and secondary follicles as compared with the control group (P<0.05). The eCG group presented intermediate values for number and size of primary and secondary follicles, without significant differences as compared with the other two groups. The number of antral follicles was higher in the eCG+DHEA and eCG groups v. controls (P<0.05). The number of primordial, atretic and cystic follicles were similar in all groups. In conclusion, the present experimental model using an acute eCG+DHEA intervention was useful to investigate events involved in initial follicular development under hyperandrogenic conditions, and could provide a reliable tool to study defective follicular development with possible deleterious reproductive consequences later in life.