Insulin resistance is documented in clamp studies in 75% of women with polycystic ovary syndrome (PCOS). Although it is not included in the diagnostic criteria of PCOS, there is a crucial role of this metabolic impairment, which along with hormonal abnormalities, increase each other in a vicious circle of PCOS pathogenesis. Insulin resistance in this group of patients results from defects at the molecular level, including impaired insulin receptor-related signaling pathways enhanced by obesity and its features: Excess visceral fat, chronic inflammation, and reactive oxygen species. While lifestyle intervention has a first-line role in the prevention and management of excess weight in PCOS, the role of anti-obesity pharmacological agents in achieving and maintaining weight loss is being increasingly recognized. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) not only act by reducing body weight but also can affect the mechanisms involved in insulin resistance, like an increasing expression of glucose transporters in insulin-dependent tissues, decreasing inflammation, reducing oxidative stress, and modulating lipid metabolism. They also tend to improve fertility either by increasing LH surge in hypothalamus-pituitary inhibition due to estrogen excess connected with obesity or decreasing too high LH levels accompanying hyperinsulinemia. GLP1-RAs seem promising for effective treatment of obese PCOS patients, acting on one of the primary causes of PCOS at the molecular level.

In a healthy female reproductive system, a subtle hormonal and metabolic dance leads to repetitive cyclic changes in the ovaries and uterus, which make an effective ovulation and potential implantation of an embryo possible. However, that is not so in the case of polycystic ovary syndrome (PCOS), in which case the central mechanism responsible for entraining hormonal and metabolic rhythms during the menstrual cycle is notably disrupted. In this review we provide a detailed description of the possible scenario of PCOS pathogenesis. We begin from the analysis of how a set of genetic disorders related to PCOS leads to particular malfunctions at a molecular level (e.g., increased enzyme activities of cytochrome P450 (CYP) type 17A1 (17$\alpha$-hydroxylase), 3$\beta$-HSD type II and CYP type 11A1 (side-chain cleavage enzyme) in theca cells, or changes in the expression of aquaporins in granulosa cells) and discuss further cellular- and tissue-level consequences (e.g., anovulation, elevated levels of the advanced glycation end products in ovaries), which in turn lead to the observed subsequent systemic symptoms. Since gene-editing therapy is currently out of reach, herein special emphasis is placed on discussing what kinds of drug targets and which potentially active substances seem promising for an effective medication, acting on the primary causes of PCOS on a molecular level.

Background. Polycystic ovary syndrome (PCOS) and hypothyroidism are the most common endocrinological disorders among women of reproductive age. Since hypothyroidism occurs more frequently in PCOS patients, it is vital to explain its clinical impact. Aim. To evaluate the impact of subclinical hypothyroidism (SCH) and its treatment on the metabolic profile of patients with PCOS. Methods. 190 women with PCOS phenotype A were enrolled in the case-control study. They were divided into three groups: 38 women with PCOS and subclinical hypothyroidism, 76 women with PCOS and SCH under thyroid replacement therapy, and 76 women with PCOS and normal thyroid function (control group). Serum lipids, fasting glucose, and insulin, as well as oral glucose tolerance tests were performed. Results. In the analyzed parameters, there were no statistic differences between the groups in relation to thyroid function. BMI turned out to be the main factor dividing the patients in terms of serum lipids, fasting glucose, fasting insulin, and oral glucose tolerance test. TSH was associated with total cholesterol and LDL cholesterol levels, whereas BMI has a dominant impact on HDL cholesterol, triglycerides, glucose, and insulin resistance. Conclusions. SCH is associated with mild lipid serum alterations in women with PCOS, but it is BMI to have a dominant impact on glucose and insulin. It seems that treatment of SCH in PCOS does not significantly alter lipid and glucose metabolism.

Introduction: Polycystic ovary syndrome (PCOS) is a disorder that substantially affects women’s health. It is particularly diagnosed in young patients. Women with PCOS are burdened with excessive weight gain, overweight and obesity (74%) compared to a healthy female population. Excessive weight influences psychological state and emotional well-being, whereas in the meantime, psychological and behavioral dysfunction is increasingly being diagnosed among patients with PCOS. Aim: To assess depressive symptoms and emotional control among women with PCOS in relation to BMI. Methods: The study was conducted among 671 self-reported PCOS women. The standardized Beck Depression Inventory (BDI) was used to assess depressive disorders. Emotion control was assessed using the Courtauld Emotional Control Scale (CECS). Results: Moderate and severe depressive symptoms were more common in PCOS women with abnormal BMI compared to normal BMI subjects (p < 0.01). In total, 27.1% of obese women had moderate depression and 28.8% had severe depression. Among overweight women, 19.9% suffered from moderate and 25% from severe depressive symptoms. Underweight women also reported moderate (25.6%) and severe (33.3%) depressive signs. There were no statistically significant differences between the body weight of the women studied and the CECS scores. Conclusions: Depressive symptoms are more common in women with PCOS and abnormal BMI than in women with PCOS and proper BMI. The severity of depressive symptoms increases with BMI, but underweight women with PCOS are also at risk of depressive disorders. The level of suppression of negative emotions is independent of BMI in women with PCOS.