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 (17α-hydroxylase), 3β-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.

Leydig cell ovarian tumors constitute not only a medical problem for clinicians but also a social problemwhich is why women with symptoms of hirsutism relatively quickly contact physicians for medical consultation. Leydig cell ovarian tumor is a rare sex cord-gonadal stromal tumor which constitutes less than 0.5% of ovarian tumors. These cancers appear at all ages but the majority of the cases concern women in the perimenopause. In the majority of cases (70-85%), the growth is accompanied by androgen secretion, together with virilization and hirsutism. The presence of hormonally active ovarian cancers should be suspected in cases of rapidly growing symptoms of masculinization, especially when the level of free testosterone in the blood exceeds the upper limit for the given age more than three times. In diagnosing postmenopausal hyperandrogenism, it is necessary to take into account hormonally active ovarian tumors, as well as adrenal cancers. It is important to exclude other causes of hyperandrogenism, e.g. endocrinopathies (acromegaly or hypothyroidism), or iatrogenic and idiopathic factors. In order to make the diagnosis and implement the proper treatment method faster, an interdisciplinary team of physicians specializing in endocrinology, gynecology and oncology is crucial. This paper contains a study of two cases concerning Leydig cell ovarian tumors in women of postmenopausal age with symptoms of masculinization and hirsutism.

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