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A 71-year-old woman was referred to the endocrinology clinic to investigate postmenopausal hirsutism with 10 years of evolution. She had history of regular menses and menopause with 50 years old. Physical examination showed a male pattern facies, deepening of the voice, androgenic alopecia and hirsutism with a score of 23 according to the modified Ferriman-Gallwey scale. Testosterone and androstenedione were increased. Transvaginal ultrasound, abdominal and pelvic CT showed uterine fibroids with no pathological findings in the adrenals or ovaries. Since she had postmenopausal vaginal bleeding, uterine fibroids and suspicion of an ovarian source for her hyperandrogenism, total hysterectomy and bilateral oophorectomy were performed. Histopathological diagnosis was a Leydig cell tumour located in left ovary and endometrial carcinoma. Improvement of hirsutism was started to notice 1 month after the surgery and she was referred to the oncology clinic for adjuvant treatment.

Research question Do cumulative live birth rates (CLBR) differ between polycystic ovary syndrome (PCOS) phenotypes when a freeze-all strategy is used to prevent ovarian hyperstimulation syndrome (OHSS) after ovarian stimulation (OS)? Design This is a single-centre, retrospective cohort study including 422 women with PCOS as defined by Rotterdam criteria or with PCO-like ovarian morphology-only (PCOM) in whom, between January 2015 and December 2019, a freeze-all strategy was applied after GnRH agonist triggering in the context of hyper-response defined as ≥18 follicles of ≥11 mm in their first or second IVF/ICSI cycle in a tertiary referral hospital. The primary outcome was CLBR resulting from the transfer of all cryopreserved embryos from the same IVF/ICSI cycle. Analysis was performed by multivariate logistic regression analysis adjusting for confounders. Results In total, 91/422 (21.6%) patients had PCOS phenotype A (hyperandrogenism + ovulation disorder + PCOM = HOP), 33/422 (7.8%) had phenotype C (hyperandrogenism + PCOM = HP), 161/422 (38.2%) had phenotype D (ovulation disorder + PCOM = OP) and 137/422 (32.5%) had PCOM. Unadjusted CLBR was similar among the groups (69.2%, 69.7%, 79.5% and 67.9%, respectively; p= 0.11). The multivariate logistic regression model adjusting for age, BMI, number of oocytes, fertilization rate and embryo stage at vitrification confirmed that the PCOS/PCOM phenotype did not have any impact on CLBR [OR 0.72, CI 0.24-2.14 (phenotype C); OR 1.55, CI 0.71-3.36 (phenotype D); OR 0.84, CI 0.39-1.83 (PCOM); p= 0.2, with phenotype A as reference]. Conclusions In subfertile women with PCOS eligible for ART, hyper-response after OS confers excellent cumulative live birth rates of ∼70%, irrespective of the phenotype, when a freeze-all strategy is used. This contrasts with the unfavourable clinical outcomes that have previously been observed in hyperandrogenic PCOS women who underwent mild OS targeting normal ovarian response and fresh embryo transfer. The data should however be interpreted with caution as the retrospective nature of the study holds the possibility of unmeasured confounding factors. The results cannot be generalized to all ART cycles in women with polycystic ovaries as they pertain to those cycles in which hyper-response is observed after OS.

Research question Do women with polycystic ovary syndrome (PCOS) have a different fat intake pattern to women without PCOS? Design Case–control study of 276 women between 20 and 35 years old from the Murcia region of Spain. Cases (n = 121) attended the Department of Gynaecology and Obstetrics of the University Clinical Hospital and were diagnosed with PCOS using Rotterdam criteria. Controls (n = 155) were women without PCOS attending the gynaecological outpatient clinic for routine gynaecological examinations. Data from clinical, gynaecological and analytical examinations were collected, including a food frequency questionnaire. Associations between fat intake and presence of PCOS and its phenotypes were examined using multiple logistic regression, adjusting for potential confounding factors. Results Although no association was found between fatty acid intake and PCOS, significant associations were observed for some PCOS phenotypes. The PCOS phenotype characterized by hyperandrogenism + oligo/amenorrhoea + polycystic ovarian morphology (‘H+O+POM’) was significantly associated with a higher intake of polyunsaturated fat (odds ratio [OR] 4.0; 95% confidence interval [CI] 1.1–14.2; fourth quartile of highest intake [Q4] versus lowest intake quartile as reference [Q1]) and omega-6 fatty acids (OR 3.5; 95% CI 1.01–12.4; Q3 versus Q1). The ‘H+O’ phenotype was positively associated with saturated fat intake (OR 6.9; 95% CI 1.1–41.6; Q4 versus Q1). Conclusion This exploratory study suggests that higher intakes of specific fatty acids are related to some PCOS phenotypes although no association was found for PCOS on a global basis. It is recommended that studies with larger sample size be performed to further explore these associations, thus contributing to establishing recommendations about fat intake adapted to different PCOS phenotypes.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women of reproductive age. Although its essential clinical manifestation includes a plethora of symptoms and signs, which largely reflects the underlying hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology, PCOS may also be associated with many metabolic derangements. These metabolic derangements happen to overlap with many of the core constituents of the metabolic syndrome (MBS)—increased insulin resistance, central obesity, and dyslipidemia. The two disorders also display similarly increased risks for certain metabolic and vascular diseases, such as type 2 diabetes mellitus, hypertension, and cardiovascular diseases. Due to the many similarities between metabolic syndrome and PCOS, this review aims to examine the evidence concerning the overlapping features, the risks for comorbidities, possible shared mechanisms, and treatment strategies in patients with coexisting PCOS and MBS.

To determine the relationships between circulating sex hormone-binding globulin (SHBG) and oxidized low-density lipoprotein (ox-LDL), total oxidant status, total antioxidant capacity, oxidative stress index, malondialdehyde, and the high-density lipoprotein (HDL) inflammatory index in patients with polycystic ovary syndrome (PCOS) and to investigate the effect of oxidative stress on the expression of SHBG and its mechanism in HepG2 cells.Cross-sectional study.University hospital.A total of 533 women with PCOS and 292 control women were included.None.Circulating SHBG, hormones, and metabolic and oxidative stress indices were determined in all subjects. The effects of ox-LDL and ox-HDL on the mRNA and protein expression of SHBG and related transcription factors were observed in HepG2 cells.The HDL inflammatory index, total oxidant status, oxidative stress index, and malondialdehyde levels were significantly higher in the three PCOS subgroups with different SHBG levels than in the controls. The ox-LDL and total antioxidant capacity were higher in the PCOS subgroups with SHBG levels75th percentile compared with the controls or the PCOS subgroup with SHBG levels ≥75th percentile. In HepG2 cells, the SHBG concentration in the culture supernatant, the mRNA levels of SHBG and hepatocyte nuclear factor-4α (HNF-4α), and the protein levels of HNF-4α were significantly lower in ox-LDL- and ox-HDL-treated cells than in the control cells and lipoprotein-treated cells.Oxidative stress inhibits the expression and secretion of SHBG by downregulating HNF-4α in vitro and may be an important factor promoting the occurrence of hyperandrogenemia in PCOS.

Background: Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder characterized by high androgen levels. The aim of this study was to evaluate the effects of hyperandrogenism on the hypothalamus and subsequently on the food intake and obesity in females. Methods: A dihydroxy testosterone (DHT)-induced rat model was established to recapitulate the hyperandrogenism features of PCOS patients. Body weight and food intake of the rats were recorded. The food intake of DHT-induced rats was restricted by pair feeding to exclude possible effects of weight gain on the hypothalamus. The expression levels of relevant proteins and mRNAs in the hypothalamus and primary hypothalamic neurons exposed to DHT were analyzed by Western blotting and RT-PCR, respectively. The leptin levels in the serum and cerebrospinal fluid (CSF) were measured, and leptin was injected via the intracerebroventricular (ICV) route to test the leptin sensitivity of the hypothalamus. Results: The excessive prepuberty androgen levels in the DHT-induced rats markedly elevated food intake prior to weight gain. Consistent with this, the expression of neuropeptide Y and agouti-related peptide mRNAs was upregulated, which occurred prior to obesity and even with restricted food intake. In addition, the hypothalamic sensitivity to insulin and leptin was also impaired in the DHT-induced rats before obesity and with restricted food intake. DHT significantly reduced the leptin levels in the CSF, and ICV injection of leptin inhibited the DHT-induced increase in food intake. Conclusions: Androgen excess increased food intake in rats and promoted obesity by downregulating insulin and leptin signaling in the hypothalamus, most likely by suppressing leptin levels in the CSF.

Polycystic ovarian syndrome affects between 6% and 18% of women of reproductive age worldwide. This syndrome can lead to female hyperandrogenism, insulin resistance, and female infertility. The Rotterdam criteria is used to improve timely diagnosis and treatment. A detailed physical examination, laboratory testing, and ultrasound imaging help diagnose this condition. Treatment is based on individual needs and should include lifestyle modifications, medication, health screening, and patient education. The goal of care should be to provide an accurate diagnosis of polycystic ovarian syndrome so that a treatment plan can be developed and implemented based on individual needs.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Metformin is introduced for treatment of women with PCOS, and the beneficial effects of exercise in women with PCOS are found for a range of outcomes. Our aim is to compare the effects of metformin plus exercise with exercise intervention in PCOS on clinical, anthropometric, metabolic, and psychological parameters. MEDLINE, EMBASE, Web of Science and China National Knowledge Infrastructure were searched for studies. Nine studies were considered eligible for inclusion. The meta-analysis reveals that metformin offers additive benefits to exercise, leading to modest improvements in menstrual cycles, hyperandrogenism, and abdominal fat.

Inflammation and dyslipidemia are often present in polycystic ovary syndrome (PCOS). We determined the effect of saturated fat ingestion on circulating heat shock protein-70 (HSP-70) and mononuclear cell (MNC) toll-like receptor-2 (TLR2) gene expression, activator protein-1 (AP-1) activation, and matrix matalloproteinase-2 (MMP-2) protein in women with PCOS. Twenty reproductive-age women with PCOS (10 lean, 10 with obesity) and 20 ovulatory controls (10 lean, 10 with obesity) participated in the study. HSP-70 was measured in serum and TLR2 mRNA and protein, AP-1 activation, and MMP-2 protein were quantified in MNC from blood drawn while fasting and 2, 3, and 5 h after saturated fat ingestion. Insulin sensitivity was derived from an oral glucose tolerance test (IS(OGTT)). Androgen secretion was assessed from blood drawn while fasting and 24, 48, and 72 h after human chorionic gonadotropin (HCG) administration. In response to saturated fat ingestion, serum HSP-70, TLR2 gene expression, activated AP-1, and MMP-2 protein were greater in lean women with PCOS compared with lean controls and in women with PCOS and obesity compared with controls with obesity. Both PCOS groups exhibited lower IS(OGTT) and greater HCG-stimulated androgen secretion compared with control subjects of their respective weight classes. Lipid-stimulated proatherogenic inflammation marker responses were negatively correlated with IS(OGTT) and positively correlated with abdominal adiposity and HCG-stimulated androgen secretion. In PCOS, saturated fat ingestion stimulates proatherogenic inflammation independent of obesity. This effect is greater when PCOS is combined with obesity compared with obesity alone. Abdominal adiposity and hyperandrogenism may perpetuate proatherogenic inflammation. NEW & NOTEWORTHY This paper demonstrates that in polycystic ovary syndrome (PCOS), ingestion of saturated fat triggers a molecular pathway of inflammation known to drive atherogenesis. This effect is independent of obesity as it occurs in lean women with PCOS and not in lean ovulatory control subjects. Furthermore, the combined effects of PCOS and obesity are greater compared with obesity alone.

The cytochrome P450 family 17 (CYP17) is associated with hyperandrogenism in women, and the association between CYP17 gene polymorphism and the risk of polycystic ovary syndrome (PCOS) is not definitive. In order to determine whether the CYP17 T/C (rs74357) gene polymorphism is an exposure risk for PCOS, a comprehensive meta-analysis summarizing 19 studies was performed. The pooled odds ratio (OR) and the corresponding 95% CI were measured under five genetic models, and the stratified analyses by ethnicity, Hardy–Weinberg equilibrium, testosterone levels and BMI in controls were carried out to identify the causes of substantial heterogeneity. The overall results validated that the CYP17 T/C (rs74357) gene polymorphism was significantly associated with PCOS risk in four genetic models. Moreover, the outcomes of subgroup analysis by ethnicity indicated that the frequencies of the C allele of CYP17 T/C (rs74357) polymorphism were markedly higher in women from Asia than in Caucasians (T vs C: OR 0.85, 95% CI = 0.74–0.99, P < 0.05). Therefore, these findings suggested that the CYP17 T/C (rs74357) gene polymorphism played an indispensable part in increasing the susceptibility of PCOS when carrying the C allele, which proposed that the polymorphism of the CYP17 gene may be a predictive factor for the risk of PCOS or an important pathway in PCOS-associated metabolic and hormonal dysregulation.

Polycystic ovary syndrome (PCOS) is a global health concern for women of reproductive age, as 6.5% of women worldwide are affected by this syndrome. PCOS is marked by hyperandrogenism, anovulation, menstrual abnormalities, and polycystic ovaries. Metals such as arsenic, cadmium, lead and mercury are considered to be systemic toxicants/human carcinogens and seem to have devastating effects on humans, even at minimal exposures. One of the probable aetiological factors for PCOS has been identified as oxidative stress. In view of the probable associations among oxidative stress, metal toxicity and PCOS, the present study examined the role of heavy metals in the generation of oxidative stress among females. This prospective study included 106 women (56 women diagnosed with PCOS and 50 women who were not diagnosed with PCOS as control women). There were no significant differences in the sociodemographic characteristics between the two groups except for the irregularity of menses and the presence of acne. The serum As, Cd, Pb, and Hg levels increased and the serum glutathione (GSH) and superoxide dismutase (SOD) levels diminished significantly in the PCOS group compared to the control group at P P P P P P

Leydig cell tumours (LCTs) of the ovary are rare ovarian tumours that usually present with hyperandrogenism. Conventional radiological imagings are helpful in localising these tumours. However, some tumours may be too small to be localised before curative surgical removal. It is important to identify these androgen-secreting neoplasms which originate mostly from adrenals or ovaries because they are potentially malignant and require specific treatment. When conventional imagings are unrevealing, selective ovarian and adrenal venous sampling (SOAVS) is the next option. We report a case of LCT that was localised by SOAVS after results from other imaging modalities remained inconclusive.

Polycystic ovary syndrome (PCOS) is one of the most important gynecological disorders of women in the age of reproduction. Different hormonal and inflammatory cross-talks may play in the appearance of its eventual complications as a leading cause of infertility. Excessive production of reactive oxygen species over the power of the antioxidant system as oxidative stress is known to contribute to a variety of diseases like PCOS. Thus, the utilization of antioxidants can be efficient in preventing or assistant in treating these diseases. In this review, we describe the clinical trial studies that have examined the efficiency of antioxidant strategies against PCOS and the possible underlying mechanisms. The investigations presented here lead us to consider that targeting oxidative stress pathways is probably a powerful promising therapeutic approach towards PCOS. There is preparatory evidence of the effectiveness of antioxidant interventions in ameliorating some of the PCOS complications, including metabolic and hormonal disorders. Due to limited data and relatively few clinical trials, many of these interventions need further investigation before they can be considered effective agents for routine clinical use.

Introduction. About 10–20% of patients among women of reproductive age suffer from signs and symptoms of androgen excess in hyperandrogenism. Its skin symptoms may include hirsutism, acne, seborrhea and alopecia.Aim. To assess the effect of cyproterone acetate on skin symptoms of hyperandrogenism and improvement in the patients’ quality of life after treatment.Materials and methods. The study included 120 patients with skin symptoms of hyperandrogenism. The patients ranged in age from 18 to 35 years. The inclusion criteria were the main complaints of the patients as follows: acne, hirsutism and alopecia. The patients underwent a comprehensive clinical and laboratory examination. The drug of choice for the treatment of androgendependent dermatopathies was cyproterone acetate at a dose of 50–100 mg daily.Results and discussion. All patients were divided into three groups: 44 (37%) patients with hirsutism, 55 (53%) with acne, 12 (10%) with alopecia. Moreover, 32 (27%) patients had a mix of symptoms at the same time. Such patients were assigned to one of the groups depending on the predominant complaint. All patients were prescribed cyproterone acetate at a dose of 50-100 mg once daily, depending on the severity of symptoms from day 1 to day 10 of the menstrual cycle, and 54 (52%) patients were prescribed cyproterone acetate 20 mg and ethinyl estradiol 35 mg from day 1 to day 21 of the menstrual cycle. The study showed stabilization of the psychoemotional state, relief of anxiety, depressive disorders, enhancement of self-esteem and sociability, and improvement of the quality of life in its various manifestations in the majority of patients after the treatment.Сonclusion. When assessed using the dermatology life quality index questionnaires, all patients reported the stabilization of the psychoemotional state and the improvement in the quality of life after the treatment. The anxiety and depressive disorders decreased in 109 (91%) patients, which favourably influenced various areas of quality of life, enhanced self-esteem and sociability with a positive effect on personal relationships.

Polycystic ovary syndrome (PCOS) is a heterogeneous condition that affects women of reproductive age. It is associated with menstrual disturbances, hyperandrogenism, and polycystic ovaries. In addition to this, it results in altered anthropometric parameters, insulin resistance, and subsequently untoward cardio-metabolic sequelae. Therapeutic approaches that target weight loss and improve insulin sensitivity are used to address the metabolic complications in PCOS. Curcumin is a phytochemical which exhibits anti-inflammatory and anti-oxidant properties, and therefore, its use in PCOS has been a subject of substantial interest and research. The aim of this study was to synthesize the existing evidence on the effects of curcumin on glycaemic and lipid parameters in PCOS. We searched PubMed, Embase, Web of Science, Scopus, and ClinicalTrials databases from inception to June 07, 2021. Only randomized controlled trials (RCT) presenting sufficient data on glycemic and lipid parameters in patients with PCOS at baseline and the end of the follow-up period in each group were included. Meta-analysis of five RCTs showed a significant reduction on fasting glucose (WMD: − 3.68 mg/dL, 95% CI: − 5.11, − 2.25, p

Background. Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders. About 90% of all children with CAH have 21-hydroxylase deficiency which is required for the synthesis of glucocorticoids and mineralocorticodes. The salt-wasting form of CAH develops with a deficiency of both types of hormones. This form of CAH results in infant death if not treated, therefore early disease detection and start of treatment are very important. Aim of research is to study the clinical features of the course of the disease and evaluate the treatment efficacy of children with salt-wasting form of CAH in the Perm region. Materials and methods. We conducted an analysis of the clinical features of the salt-wasting form of CAH in 40 children of the Perm region. To evaluate the treatment efficacy following symptoms were analyzed: salty food craving, hyperpigmentation of skin, hirsutism, delayed or accelerated growth, etc. and parameters of water-electrolytic balance, the level of 17-hydroxyprogesterone, adrenocorticotropic hormone, renin. Results and discussion. Despite the modern possibilities of diagnosing and treating CAH, the complete control of the disease cant be achieved in all children. Almost all the children examined had either symptoms of replacement therapy failure or overdose symptoms. Hormonal imbalance disorders were performed by a few children without any symptoms of the disease. Conclusion. During our research we concluded that young children often have issues with an overdose of hormonal drugs and frequent occurrence of salt-wasting crises against the background of associated diseases, while for teenagers, problems associated with an insufficient dose of glucocorticoid drugs are relevant. Also, significant difficulties in the treatment of children with CAH are associated with the short action of hydrocortisone. One way to solve these problems is to organize a school for parents of children with CAH. Creating motivation, explaining the principles of treatment and importance of regular taking of drugs, as well as algorithm in medical emergency is an important step in achieving control for the disease.

Tourette Disorder (TD) is a male predominant neurodevelopmental disorder characterized by tics and frequent psychiatric comorbidities. Girls with TD have later peak symptoms, less remission with age, and worse impairment from tics, particularly in adulthood. Female TD patients are less likely to have Attention Deficit Hyperactivity Disorder and more likely to have anxiety and mood disorders. Hyperandrogenism is associated with TD in both sexes, and neuroanatomic sexual dimorphism is reduced in adult TD patients. Some women report catamenial tics, which may relate to estrogen withdrawal or rises in allopregnanolone. Limited data suggest that several neuroanatomic alterations present in boys with TD are not present in girls with TD. Female sex predicts better response to haloperidol. Further research into female tic pathophysiology may influence sex-specific treatment development.

Background A virilizing ovarian tumor (VOT) is a rare cause of hyperandrogenism in pre- and postmenopausal women. Although transvaginal ultrasound is considered as the first-line imaging method for ovarian tumors, it is examiner-dependent. We aimed to summarize the clinical and ultrasound manifestations of VOTs to help establish the diagnosis with emphasis on those causing diagnostic difficulty. Method We retrospectively identified 31 patients with VOTs who underwent surgery at Peking Union Medical College Hospital. Results Patients with VOTs were predominantly premenopausal. All patients showed androgenic manifestations with serum testosterone levels elevated to varying degrees. The tumor size of VOTs was significantly correlated with age (P P = 0.018). Twenty-seven out of 31 VOTs were successfully identified by ultrasound. On ultrasound, VOTs are mostly solid and hypoechoic masses with enhanced vascularity. Four VOTs (0.7–1.5 cm) were radiologically negative, and they were the smallest among all patients. Conclusion Patients with VOTs showed androgenic manifestations with varying degrees of hyperandrogenemia. Older patients tend to have smaller VOTs. Ultrasound is an effective method for the detection of VOTs. Some VOTs can be very small and difficult to visualize radiologically, especially in postmenopausal patients. Examiners must remain vigilant about very small VOTs on the basis of endocrine symptoms.

OBJECTIVE A nonclassic form of 11β-hydroxylase deficiency (NC11β-OHD) has been reported to cause mild androgen excess symptoms. Currently, the gold standard for biochemical diagnosis is elevated 11-deoxycortisol (11-DOC) levels after corticotropin stimulation test (ACTHstimT). However, there are no clear 11-DOC level cutoffs. One of the accepted references for 11-DOC levels for the paediatric population was published in 1991 by Lashansky et al. AIM: To determine the correlation between 11-DOC levels measured during ACTHstimT and clinical symptoms attributed to NC11β-OHD. DESIGN A retrospective study including all paediatric patients who underwent ACTHstimT at Shamir Medical Center between 2007 and 2015. Clinical data were collected from the patients' medical files. Outcome measures included the number of patients with hyperandrogenism signs and predefined elevated 11-DOC cut-off levels according to Lashansky for sex and age, and according to commercial kit cut-offs. RESULTS Data were complete at presentation for 136 patients. Long-term clinical data were documented for 98 patients, mean follow-up duration of 3.1 years (1.37-5.09). There was no statistically significant difference in the number of cases with elevated 11-DOC according to both cut-offs and early puberty, premature adrenarche nor acne. Follow-up data demonstrated no statistically significant difference in the number of cases with elevated 11-DOC levels among patients with compromised final adult height, polycystic ovarian syndrome or hyperandrogenism. CONCLUSIONS Basal and corticotropin stimulated 11-DOC levels were not significantly elevated above the 1.5 times cut-offs according to paediatric-specific norms or the commercial assay in paediatric individuals with possible clinical suspicion of NC11β-OHD.

Duplication of MECP2 (methyl-CpG-binding protein 2) gene causes a serious neurological and developmental disorder called MECP2 duplication syndrome (MDS), which is usually found in males. A previous clinical study reported that MDS patient has precocious puberty with hyperandrogenism, suggesting increased MeCP2 may cause male hyperandrogenism. Here we use an MDS mouse model and confirm that MECP2 duplication significantly upregulates androgen levels. We show for the first time that MeCP2 is highly expressed in the Leydig cells of testis, where androgen is synthesized. Mechanistically, MECP2 duplication increases androgen synthesis and decreases androgen to estrogen conversion through either the upregulation of luteinizing hormone receptor (LHCGR) in testis, as a result of MeCP2 binds to G-quadruplex structure of Lhcgr promoter and recruits the transcription activator CREB1 or the downregulation of the expression of aromatase in testis by binding the CpG island of Rorα, an upstream regulator of aromatase. Taken together, we demonstrate that MeCP2 plays an important role in androgen synthesis, supporting a novel non-CNS function of MeCP2 in the process of sex hormone synthesis.

Polycystic ovary syndrome (PCOS), characterized by ovulatory dysfunction and hyperandrogenism, is one of the most common endocrine disorders in women of reproductive age. Early diagnosis can help clinicians address associated long-term metabolic and reproductive health complications and mitigate the negative effects of PCOS on a patient's mental health and quality of life. Clinicians often are challenged by the diagnosis and management of PCOS because of controversies around diagnostic criteria, especially for adolescents. The International Consortium of Paediatric Endocrinology 2017 Consensus Statement provides practical guidance for clinicians to implement best practices for the identification, diagnosis, and management of PCOS in adolescents.

Polycystic ovary syndrome (PCOS) is one of the most common hormonal disorders and causes of infertility in women in reproductive age. Diagnostic criteria of PCOS in adult women include: ovulation disorders, hyperandrogenism and polycystic ovaries. According to most recommendations, 2 out of these 3 criteria are confirm the diagnosis of PCOS. In girls during puberty and in the first years after menarche, different diagnostic criteria of menstrual disorders should be taken into account (variable length of menstrual cycles, monophasic cycles) and the limited usefulness of ultrasound examination for PCOS diagnosis within 8 years after menarche. Fairly extensive differential diagnosis is also necessary, especially – exclusion of adrenal hyperandrogenism. Moreover, the diagnostic criteria of PCOS do not take into account the metabolic disorders found in most patients (obesity, insulin resistance, type 2 diabetes), which should be diagnosed as early as possible and treated appropriately. This is especially true for teenagers, in whom the unequivocal diagnosis of PCOS or its exclusion may be very difficult. Current recommendations regard hormonal contraception as the first-line therapy in PCOS, in both adult women and adolescents. Together with its beneficial effect on the reduction of hyperandrogenism and obtaining regular bleeding (which in fact are not menstruations), the unfavorable metabolic effects of hormonal contraception are emphasized, as well as the inadequacy of its use if it is expected to achieve or restore ovulation and fertility. The latest reports indicate the legitimacy of treatment aimed at correcting disorders of carbohydrate metabolism and its greater effectiveness compared to the use of oral contraceptives in both adult women and girls with PCOS. In the pharmacotherapy of insulin resistance, metformin is of fundamental importance, the use of pioglitazone, GLP-1 receptor agonists or inositols is also proposed. Adequate lifestyle and dietary modification are of major importance in the treatment and prevention of PCOS. The mechanisms of "inheritance" of PCOS and insulin resistance with the participation of epigenetic modifications are still better understood, taking into account the effects of exposure to androgen excess in utero, intrauterine growth retardation, and maternal obesity and hyperalimentation. This creates new possibilities for PCOS prophylaxis.

Background: The menstrual cycle describes the healthy reproductive system of the women which is controlled by different hormones. Aim: The goal of the study is to evaluate the prevalence of irregular menstruation in different endocrine changes and to identify their association with the age of women in reproductive life. Methodology: It was a cross-sectional study conducted on women attending the gynecological clinic of Karachi from March 2019 to June 2019. Of the 165 women with different hormonal changes 100 presented with menstrual cycle abnormality. Results: Among the women with menstrual irregularities 51% women presented with insulin resistance, 23% with hyperandrogenism, 19% with hypothyroidism and 7% hyperprolactinemia. Age-related association was observed in menstrual irregularities women with insulin resistant and hyperandrogenism. Conclusion: Menstrual cycle is a physiological process, any irregularities in cycle can be caused by even minimal hormonal imbalance. As a result, it is critical to address endocrine abnormalities in order to improve women's reproductive health.

Aim of the study: to study the clinicodiagnostic features of polycystic ovarian syndrome (PCOS) against the background of insulin resistance (IR) and hyperandrogenism (HA).Material and methods. We examined 120 women with PCOS and HA, 76 (63.3%) of the total number had IR. The average age of women was 28.54 ± 0.74 (20–44). In women with HA and PCOS against the background of IR, the levels of follicle-stimulating (hFSH), luteinizing (LH), thyrotropic (TТH) hormones were detected, as well as LH/hFSH ratio, prolactin (PRL), estradiol (E2), estrone (E1), total testosterone (T-total), DHEAS, androstenedione (Adione), cortisol (C), 17 hydroxyprogesterone (17-OPG), free triiodothyronine (T3), free thyroxine (T4), SHBG and Anti- Mullerian Hormone (AMH). The levels of carbohydrate metabolism, including glucose, insulin (on an empty stomach), after glucose loading, were determined as well as the HOMA and CARO indices.Results. It was found that according to the Ferriman–Gallwey score, hirsutism was within the range of 16.15 ± 0.34 (11–24) points, hormones — 13.17 ± 0.30 (9–20) points in the examined patients. The indiff erent number was 2.93 ± 0.11 (2–4) points. The average weight of patients was 74.1 ± 1.79 (50–134) kg, height 1.62 ± 0.005 (1.52–1.78) m, Index of Mass Corporal was within 28.56 ± 0.66 (19.5–51.4) kg/m2. In 81.5% of patients with HA and PCOS, absolute sterility was noted on the background of IR. According to hormones studies, there was a statistically signifi cant increase in LH (14.0 ± 0.87 mIU/ml), LH/hFSH (2.39 ± 0.15), TSH (2.83 ± 0.23 mIU/ml), DHEAS (3.32 ± 0.21 pg / ml), 17-OPG (1.0 ± 0.08 ng/ml), Adione (3.94 ± 0.1 ng/ml), T-total (1, 15 ± 0.006 ng/ml), K (125.39 ± 2.86 ng/ml), AMH (7.84 ± 0.36 ng/ml), E1 (153.36 ± 4.56 ng/ml) and decrease in E2 (65.32 ± 2.38 pg/ml), SHBG (36.1 ± 2.0 nmol/l). The study of carbohydrate metabolism and some anthropometric parameters revealed an increase in OB (100.66 ± 1.76 cm), OB / OT (0.86 ± 0.005), glucose and insulin (on an empty stomach) parameters and after glucose loading and HOMA index with a signifi cant decrease in the SAR index. According to the ultrasound data, patients with HA and PCOS against the background of IR revealed a statistically signifi cant decrease in the length and width of the uterus and an increase in the length, thickness, volume of the endometrium, the number of atresic follicles in both ovaries compared to similar data in practically healthy women (p

KłosińskaMartyna, Kaczyńska Agnieszka. Polycystic ovarian syndrome - management and treatment.Journal of Education, Healthand Sport. 2021;11(9):123-130. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2021.11.09.017 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2021.11.09.017 https://zenodo.org/record/5484900 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2021; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 25.08.2021. Revised: 26.08.2021. Accepted: 07.09.2021. POLYCYSTIC OVARIAN SYNDROME - MANAGEMENT AND TREATMENT Martyna Kłosińska1, Agnieszka Kaczyńska1 Martyna Kłosińska, martynaklosinska69@gmail.com, https://orcid.org/0000-0001-7649-085X Agnieszka Kaczyńska, agaagnieszkakk@gmail.com, https://orcid.org/0000-0002-8943-9401 (1) Faculty of Medicine, Medical University of Lublin, Aleje Racławickie 1, 20-059 Lublin, Poland SUMMARY The polycystic ovarian syndrome is an endocrine disorder with a high prevalence affecting reproductive-aged women and adolescent girls. The most common symptoms are infertility, numerous ovarian cysts, hyperandrogenism, menstrual cycle abnormalities. The disease has a great impact on patients, impairing their quality of life. Bearing that in mind, innovative therapeutic approaches are needed. We aim to describe current management and treatment concepts adopted in PCOS therapy. The analysis of previously published studies was conducted by using the PubMed, Google Scholar, and Scopus databases. Mentioned studies show that lifestyle changes may benefit PCOS therapy in multiple ways. Dietary and exercise interventions have a notable influence on women’s body composition as well as biochemical parameters. The reduction of body weight or BMI is a therapeutic achievement likewise patients’ contribution to managing PCOS. Pharmacotherapy provides plentiful treatment choices to adopt. Studies show that hormonal contraceptive has a significant impact on both hyperandrogenism and menstrual abnormalities. Metformin is proven to reduce BMI, improve LDL levels, and lower the risk of OHSS in women undergoing IVF/ICSI-ET. A meta-analysis proved metformin’s monotherapy superiority over clomifene citrate or their combination in treating infertility. However, both substances are not recommended as the first-line choice. Regrettably, many studies mention short of evidence, lack of larger sample sizes, or insufficient duration preventing further research. The conclusion we draw is that approaches of managing and treating PCOS are constantly advancing and updating. However, there is a necessity for future studies to expand their research by gathering more data and considering diverse cases. Key words: polycystic ovarian syndrome; endocrine productive disorder; infertility; hyperandrogenism; hormonal contraceptive; metformin; clomifene citrate

ContextNonalcoholic fatty liver disease (NAFLD) describes a spectrum of liver damage due to excessive hepatic lipid accumulation. Recent research has demonstrated a high prevalence of NAFLD in women with polycystic ovary syndrome (PCOS).ResultsStrong associations independent of body mass index (BMI) have been found between high androgen levels characteristic of PCOS, as well as insulin resistance, and the presence of NAFLD in these women, suggesting that these factors contribute to liver injury more significantly than obesity. Current studies indicate the occurrence of NAFLD in normal weight women with PCOS in addition to the commonly researched women who are overweight and obese. While the majority of studies address NAFLD in adult, premenopausal women (ages 25-40 years), the occurrence of NAFLD in young and adolescent women has gone largely unaddressed. Research in this field lacks diversity; a majority of studies either focus on populations of White women or are missing demographic information entirely.ConclusionsFuture studies should include larger, more racially and ethnically inclusive populations and particular attention should be paid to how excess androgens and insulin resistance contribute to the increased risk of NAFLD seen in women with PCOS of varying weights, ages, and ethnicities.Objective and MethodsHere, we review NAFLD in women with PCOS with subsections focused on the impact of hyperandrogenism, BMI, insulin resistance and age. Most notably, we present the most up-to-date racially and ethnically diverse worldwide prevalence of NAFLD in women with PCOS compared with women without PCOS (51.56% vs 29.64%, P < .001, respectively).

Поширеність та можливі наслідки гіперандрогенних станів у жінок репродуктивного віку обумовлюють важливість своєчасної диференційної діагностики гіпер­андрогеній. З урахуванням рівня розвитку радіологічних та лабораторних методів досліджень можлива постановка точного діагнозу, особливо при діагностиці гіперандрогеній наднирникового генезу, які часто перебігають без яскравої клінічної симптоматики, але супроводжуються порушеннями менструального циклу, безпліддям, невиношуванням вагітності.

Background. The polycystic ovary syndrome (PCOS) is the most frequent form of endocrine pathology and occurs in 5–10 % women of reproductive age and makes up 80 %, and according to some data, even 90 % of all forms of hyperandrogenism. The information about pathogenesis of PCOS is contradictory. The main step of the SPCO pathogenesis is hyperproduction of LH of by the hypophysis, revealed in 40–80 % patients. According to one of numerous theories, an increase secretion results in the increase of LH by the hypothalamus of the gonadotropin-releasing hormone (GRH), secreted in the discrete mode under control sexual steroid hormones, monoamines and opioid peptides. The aim of the investigation is to study the functional status of hypophysis — gonads axis for women with SPCO. Material and methods. In the department of neuroendocrinology of the Center of Endocrinology of Health Ministry of the Republic of Uzbekistan in a period from September 2015 till July 2016 120 outpatients of fertile age with PCOS were inspected. Mean age of patients was 25.5 ± 4.3 years. The duration of the disease hesitated from 7 months to 9 years. 20 healthy women of corresponding age made a control group. The complex of researches, including clinical, biochemical (glycemia, glucose tolerance test), hormonal (LH, FSH, prolactin, estradiol, progesterone, dehydroepiandrostendion (ДGEA), 17-oxyprogesterone, аntimuller hormone (АМH), insulin) was performed in all patients, ultrasonic examination of uterus and ovaries (transabdominal and transvaginal) on the 14th day of cycle with folliculometria in dynamics, and also magnetically-resonant tomography of hypophysis and questionnaire of patients were carried out. Results. Patients were divided into two groups: with primary sterility (94 cases) and with secondary sterility (26 cases). In the first group of patients with primary sterility the reliable decline of both pituitary and ovarian hormones was determined on a background of hyperandrogenemia and hyperprolactinemia. So, as compared to the group of control on the 14th day of cycle LH, FSH, and estradiol, progesterone, while free testosterone, DGEA were enhanced as compared to control data. In the second group of patients the reliable decline of pituitary hormones was also educed on a background of hyperandrogenemia and hyperprolactinemia while an ovarian function was within the normal limits. So, as compared to the group of control on the 14th day of cycle the LH, FSH, here free testosterone, DGEA and АМH levels were enhanced as compared to control data. The neuroimaging of hypophysis in patients with PCOS educed hyperplasia (adenomatosis) of hypophysis in 49 from 120 (40.8 %), that can be explained by ovarian insufficiency in these patients. On the second place by incidence there was the syndrome of the empty sella (26 cases, 21.6 %), and on the third — the microadenoma of hypophysis in 16 persons (13.3 %). Conclusions. In the first group of patients with primary sterility the reliable decline of both pituitary and ovarian hormones was marked on a background of hyperandrogenemia and hyperprolactinemia. In the second group of patients the significant decline of pituitary hormones was also educed on a background of hyperanrogenemia and hyperprolactinemia, while an ovarian function was within the normal limits. In both groups of patients hypogonadotropinemia occurred combined with moderate hyperprolactinemia and hyperandrogenemia. Thus, the most expressed violations of the system of pituitary — ovarian function were found out in the first group of patients with PCOS with primary sterility, at that the significant decline of the functional status of pituitary — gonads axis was marked, namely decline of LH, FSH, estradiol and progesterone levels on the 14th day of menstrual cycle, that was confirmed by ultrasouns examination of uterus and ovaries by impoverishment of follicle vehicle of ovaries, anovulation signs. Thus, the most expressed violations of the system of pituitary-ovarial function were found out in the first group of patients with PCOS with primary sterility, at that the significant decline of the functional state of hypophysis-gonads was marked, namely decline of LH, FSH, estradiol and progesterone levels that was confirmed by ultrasound investigation of uterus and ovaries.

Cysts of the external female genitalia are uncommon findings and can be either congenital or acquired. Congenital cysts of the external female genitalia may be discovered from the initial newborn examination and cause concern for clitoromegaly or ambiguous genitalia. We describe a clitoral cyst presenting as apparent clitoromegaly in a newborn; this is the third reported case in the literature. We also review the differential and evaluation for clitoromegaly in a newborn. We present a case of a 1-day-old newborn, with concern for clitoromegaly on initial newborn examination. Multiple anatomy ultrasounds were performed during pregnancy and no genital abnormality was noted. On physical examination, a 1 × 1 cm cyst was found on the clitoral hood obstructing the clitoris and vaginal opening. There were no signs of virilization or hyperandrogenism on examination. The cyst was aspirated, with clear, serous fluid removed. Normal female anatomy and normal clitoris size were noted after aspiration. She had no recurrence of the cyst in the months after discharge. Clitoral cysts of the female external genitalia are rare findings. Barring signs of virilization of hyperandrogenism, conservative management and watchful waiting or cyst drainage are reasonable approaches.

OBJECTIVE: The purpose of this study was to ascertain the extent to which the ocular surface of women with polycystic ovary syndrome is impacted. STUDY DESIGN: Included in this case-control study were 23 eyes of 23 patients (Group I) with polycystic ovary syndrome and 10 eyes of 10 healthy subjects (Group II). Polycystic ovary syndrome was diagnosed when two of the following conditions were met: oligo- or anovulation, clinical and/or biochemical signs of hyperandrogenism, and ultrasonographic documentation of polycystic ovaries. Ocular surface disease grading was performed using the Ocular Surface Disease Index questionnaire, slit lamp examination, meibomian gland secretion scoring, tear film breakup time, staining scores of ocular surfaces, the Schirmer's test, and tear osmolarity assessment. RESULTS: The study observed no significant difference in age (p=0.896). Group I was found to have a significantly higher median luteinizing hormone level (p=0.027). The Ocular Surface Disease Index scores in group I were significantly higher than those in group II (p=0.031). The prevalence of anterior blepharitis was significantly greater in group I (p=0.05). Tear film breakup time was higher in group I than in group II (p=0.026). The ocular surface disease severity was found to be significantly higher in group I (p=0.03). In group I, Ocular Surface Disease Index scores were significantly positively correlated with free testosterone, while tear osmolarity was significantly positively correlated with estradiol levels but significantly negatively correlated with dehydroepiandrosterone sulfate levels (p

Context Polycystic ovary syndrome (PCOS), a highly prevalent endocrine disorder characterized by hyperandrogenism, is the leading cause of anovulatory infertility. Objective This proof-of-concept study evaluated clinical efficacy and safety of the neurokinin 3 (NK3) receptor antagonist fezolinetant in PCOS. Methods This was a phase 2a, randomized, double-blind, placebo-controlled, multicenter study (EudraCT 2014-004409-34). The study was conducted at 5 European clinical centers. Women with PCOS participated in the study. Interventions included fezolinetant 60 or 180 mg/day or placebo for 12 weeks. The primary efficacy end point was change in total testosterone. Gonadotropins, ovarian hormones, safety and tolerability were also assessed. Results Seventy-three women were randomly assigned, and 64 participants completed the study. Adjusted mean (SE) changes in total testosterone from baseline to week 12 for fezolinetant 180 and 60 mg/day were −0.80 (0.13) and −0.39 (0.12) nmol/L vs −0.05 (0.10) nmol/L with placebo (P .10). Fezolinetant was well tolerated. Conclusion Fezolinetant had a sustained effect to suppress hyperandrogenism and reduce the LH-to-FSH ratio in women with PCOS.

Hyperandrogenic syndrome is a pathological condition caused by an excessive production of androgens by ovaries and/or adrenal glands or increased local tissue sensitivity to circulating androgens. This is the most common endocrinopathy in women. The importance of timely diagnosis of hyperandrogenic states is due to their consequences: androgen-dependent dermopathy, menstrual disorders, endocrine infertility, increased risk of non-pregnancy, preterm labor, gestational diabetes. The prevalence and possible consequences of hyperandrogenism in women of reproductive age predetermine the importance of timely differential diagnosis of the major syndromes of hyperandrogenic states — adrenogenital syndrome and polycystic ovary syndrome. Since the symptoms of these syndromes have much in common, based on the data of literature review and own observations, a differential diagnosis is supplemented and presented in the form of an original table that to some extent will help endocrinologists and gynecologists to distinguish between these pathological conditions.

Polycystic ovary syndrome (PCOS) is a common disorder in reproductive-age women. In 2018, an international evidence-based guideline announced recommendations spanning a wide range of issues on the assessment and management of PCOS. From the 166 recommendations, the present study reviews those that are of particular clinical relevance for daily practice and introduces other relevant studies that have been published since the global guideline. The 2018 guideline increased the antral follicle count cutoff for the diagnosis of PCOS from 12 to 20 when using a high-frequency probe. Hirsutism was defined as having a score of ≥4–6 based on a lower percentile of 85%–90% or cluster analysis, which was lower than the traditionally used 95th percentile-based cutoff. The diagnosis of PCOS in adolescents is challenging, and irregular menstruation was defined carefully according to years from menarche. The use of ultrasonography for the diagnosis of PCOS was restricted to those 8 years after menarche. As medication for non-fertility indications, combined oral contraceptives are the first-line drug. Metformin, in addition to lifestyle modifications, should be considered for adult patients with a body mass index ≥25 kg/m2 for the management of weight and metabolic outcomes. An aromatase inhibitor is the recommended first-line medication for ovulation induction, a subsequent individual patient data meta-analysis also reported the same conclusion. Whether the new global guideline will be fully adopted by many specialists and change clinical practice is open to question. Further studies are needed to better understand and manage PCOS patients well.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathies affecting the early reproductive age in women, whose pathophysiology perplexes many researchers till today. This syndrome is classically categorized by hyperandrogenism and/or hyperandrogenemia, menstrual and ovulatory dysfunction, bulky multi follicular ovaries on Ultrasonography (USG), and metabolic abnormalities such as hyperinsulinemia, dyslipidemia, obesity. The etiopathogenesis of PCOS is not fully elucidated, but it seems that the hypothalamus-pituitary-ovarian axis, ovarian, and/or adrenal androgen secretion may contribute to developing the syndrome. Infertility and poor reproductive health in women’s lives are highly associated with elevated levels of androgens. Studies with ovarian theca cells taken from PCOS women have demonstrated increased androgen production due to augmented ovarian steroidogenesis attributed to mainly altered expression of critical enzymes (Cytochrome P450 enzymes: CYP17, CYP21, CYP19, CYP11A) in the steroid hormone biosynthesis pathway. Despite the heterogeneity of PCOS, candidate gene studies are the widely used technique to delineate the genetic variants and analyze for the correlation of androgen biosynthesis pathway and those affecting the secretion or action of insulin with PCOS etiology. Linkage and association studies have predicted the relationship between genetic variants and PCOS risk among families or populations. Several genes have been proposed as playing a role in the etiopathogenesis of PCOS, and the presence of mutations and/or polymorphisms has been discovered, which suggests that PCOS has a vital heritable component. The following review summarizes the influence of polymorphisms in crucial genes of the steroidogenesis pathway leading to intraovarian hyperandrogenism which can result in PCOS.

Некласична вроджена гіперплазія кори надниркових залоз (НВГКНЗ) унаслідок дефіциту 21-гідроксилази є однією з актуальних причин гіперандрогенних проявів у різні вікові проміжки часу. Своєчасна діагностика цього захворювання потребує обов’язкового включення визначення базальних рівнів 17-оксипрогестерону (17-ОПГ) у комплексне обстеження пацієнтів різних вікових груп із клінічними проявами надлишку андрогенів. Особливо це важливо при обстеженні дівчаток-підлітків і жінок репродуктивного віку з клінікою гіперандрогенії. В обов’язковий комплекс обстеження жінок при встановленні діагнозу синдрому полікістозних яєчників має входити виключення некласичної ВГКНЗ відповідно до всіх світових рекомендацій. При отриманні рівнів 17-ОПГ у діапазоні 2–10 нг/мл необхідно провести пробу з козинтропіном, що визнана у світі як стандарт діагностики ВГКНЗ. Діагностичним порогом постановки діагнозу ВГКНЗ унаслідок дефіциту 21-гідроксилази є рівень 17-ОПГ, базальний чи стимульований у пробі, понад 10 нг/мл. Проведення генетичного тестування — визначення мутацій у гені CYP21A2 — є важливим і необхідним інструментом не тільки підтвердження діагнозу, але й визначення тактики лікування пацієнта з діагнозом некласичної ВГКНЗ і виявлення ризиків появи класичної форми в майбутньої дитини за наявності алелі, пов’язаної з класичною формою вродженої дисфункції кори надниркових залоз у майбутніх батьків. За основу лабораторних критеріїв постановки діагнозу взято рекомендації останнього керівництва Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline, 2018.

Hyperandrogenism, a pathological condition caused by the effect of excess production of androgens on target organs and tissues, is one of the most common hormonal disorders observed in 5–20 % of women of reproductive age in the population and in 35–41 % of women suffering from infertility due to chronic ano­vulation. Hyperandrogenism is manifested by a combination of signs of damage to the skin and its appendages (seborrhea, acne, hirsutism, alopecia) and is defined by the term androgen-dependent dermopathy. In combination with other manifested signs of virilization, hyperandrogenism greatly aggravates socio-psychological, interpersonal relationships in most patients, often cau­sing anxiety, depression, and a decrease in the quality of life. In this regard, the problem of hyperandrogenism is not only of medical but also of social significance. An urgent problem, widely studied by both endocrinologists and gynecologists, is a clinical variant of hyperandrogenism syndrome such as polycystic ovary syndrome. The article presents a discussion of the National Consensus on the management of patients with hyperandrogenism (2016), makes proposals and additions to the diagnosis and management of patients with syndromic forms of hyperandrogenism (pubertal dyspituitarism and its equivalent in adults — hypothalamic-pituitary dysfunction, nonclassical form of congenital dysfunction of the cortex adrenal glands). The key positions concerning the assessment of the state of carbohydrate metabolism in patients with polycystic ovary syndrome are considered. The regimens of treatment with antiandrogens and the expediency of their use in patients with polycystic ovary of endocrine origin are discussed.

The importance of insulin resistance, compensatory hyperinsulinemia, and its effects, many of which have adverse effects on both the metabolic and reproductive organs. Treatment options for insulin resistance/hyperinsulinemia include lifestyle changes, exercise, weight loss, and or the use of thiazolidinediones (TZDs) or metformin. Weight loss measures are essential to the treatment of this condition. Lifestyle, exercise, and dietary changes, weight loss has been shown to reduce hyperandrogenism, increase ovulation and pregnancy rates, and improve immune conflict. Numerous studies have suggested that metformin plays an important role in the treatment of PCOS including restoring ovulation, weight loss, reducing androgen cycle levels, reducing the risk of miscarriage, and reducing the risk of gestational diabetes (GDM).PCOS patients may develop severe dyslipidemia, such as increased LDL-C and TG levels and decreased HDL-C levels associated with hyperandrogenism, IR, and chronic inflammation. Therefore, statins are widely used in the treatment of PCOS patients to reduce inflammation, oxidative stress, hyperandrogenemia, and other metabolic disorders. Statins have been reported to block HMG-CoA inhibiting mevalonate synthesis, which is a necessary substrate for cholesterol production and can be used to synthesize other important lipid links, therefore, statins can improve lipid status and hyperandrogenism. Keywords: PCOS, LH, FSH, GnRH, CAH, VA, BMI, IR, HDL, LDL, VLDL, MetS, HOMA.

In this study, levels of progranulin (PGRN) and tumor necrosis factor-alpha (TNF-α) were measured to detect the presence of inflammation in lean polycystic ovary (PCOS) patients.40 lean PCOS patients were assessed by Rotterdam criteria. Forty healthy women with regular menstrual cycles and without biochemical and clinical hyperandrogenism were involved in our study. Blood samples were taken from the patient and control groups for the measurement of progranulin (PGRN), tumor necrosis factor-alpha (TNF-α), lipid parameters, glucose, insulin, and other hormones.Serum PGRN and TNF-α levels were significantly higher in patients with lean PCOS, compared with the control group (PGRN is known as a ligand for the TNF-α receptor. PGRN level increase in lean PCOS patients may be due to inhibiting the inflammatory effects of TNF-α. To observe the PGRN and TNF-α connection in obesity, further study is needed in obese PCOS patients and obese control groups.

Research question: What is the effect of weight loss through different interventions (three-component lifestyle intervention with short message service [SMS+] versus three-component lifestyle intervention without SMS [SMS–] versus care as usual [CAU]) on polycystic ovary syndrome (PCOS) characteristics (ovulatory dysfunction, hyperandrogenism, polycystic ovarian morphology [PCOM]) and phenotype distribution? Design: Analysis of secondary outcome measures of a randomized controlled trial. Women diagnosed with PCOS (n = 183), who wished to become pregnant, with a body mass index above 25 kg/m², were assigned to a 1-year three-component (cognitive behavioural therapy, diet, exercise) lifestyle intervention group, with or without SMS, or to CAU (advice to lose weight). Results: The prevalence of biochemical hyperandrogenism was 30.9% less in the SMS- group compared with CAU after 1 year (P = 0.027). Within-group analyses revealed significant improvements in ovulatory dysfunction (SMS+: –39.8%, P = 0.001; SMS–: –30.5%, P = 0.001; CAU: –32.1%, P < 0.001), biochemical hyperandrogenism (SMS–: –27.8%, P = 0.007) and PCOM (SMS–: –14.0%, P = 0.034). Weight loss had a significantly favourable effect on the chance of having ovulatory dysfunction (estimate 0.157 SE 0.030, P < 0.001) and hyperandrogenism (estimate 0.097 SE 0.027, P < 0.001). Conclusions: All groups demonstrated improvements in PCOS characteristics, although these were more profound within the lifestyle intervention groups. Weight loss per se led to an amelioration of diagnostic characteristics and in the phenotype of PCOS. A three-component lifestyle intervention aimed at a 5–10% weight loss should be recommended for all women with PCOS before they become pregnant.

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and insulin resistance. The dual sodium-glucose co-transporter 1/2 inhibitor (SGLT1/2i) licogliflozin (LIK066) ameliorates hyperinsulinism in patients with diabetes and obesity. This study examines the effect of licogliflozin on androgens in women with PCOS. In a multicentre, randomized, placebo-controlled, double-blind, 2-week trial, patients with PCOS received licogliflozin 50 mg or placebo three times a day (TID). Changes in free testosterone (FT), other androgens and variables of insulin resistance were analysed. Concentration of FT did not change (TRLIK₀₆₆:TRPCB [FT]: 0.88; 90% CI: 0.70-1.11; P =.353). Licogliflozin reduced androstendione (A4) by 19% (TRLIK₀₆₆:TRPCB [A4]: 0.81; 90% CI: 0.68-0.99; P =.089) and dehydroepiandrosteron sulphate (DHEAS) by 24% (TRLIK₀₆₆:TRPCB [DHEAS]: 0.76; 90% CI: 0.65-0.89; P =.008). Hyperinsulinaemia was reduced by 70% by licogliflozin (highest insulin concentration [MAXI]; TRLIK₀₆₆:TRPCB [MAXI]: 0·26; 90% CI:0.20-0.34; P

PURPOSE We sought to compare the efficacy of the letrozole (LTZ) stair-step protocol with clomiphene citrate (CC) stair-step protocol in the management of 150 mg dose of CC-resistant polycystic ovary syndrome (PCOS) patients. METHODS We retrospectively compared a total of 61 patients diagnosed as being resistant to the traditional CC protocol who were subsequently managed using the LTZ stair-step protocol with CC-resistant 56 patients who were treated with CC stair-step protocol. The number of follicles ≥18 mm, endometrial thickness, time to ovulation, clinical pregnancy rates, multiple pregnancy rates, spontaneous abortion rates, live birth rates, and systemic side effects in patients were evaluated. RESULTS The mean time to ovulation was significantly shorter in the LTZ stair-step group than the CC stair-step group (17.3 ± 7.7 and 22.4 ± 8.1 days, respectively, p

Polycystic ovary syndrome (PCOS) causes anovulation and hyperandrogenism. Hormonal imbalance is known to contribute to systemic autoimmune diseases.To examine the frequency of certain rheumatic diseases in PCOS.This retrospective study utilized and analyzed electronic medical records from January 2004 through February 2020. A diagnosis of PCOS and specified rheumatic diseases was searched using ICD-9 and ICD-10 codes. A total of 754 adult patients with PCOS and 1,508 age- and body mass index-matched patients without PCOS were included. Frequencies of the rheumatic diseases were compared between PCOS and non-PCOS subjects or literature data.The prevalence of rheumatoid arthritis (RA) was found to be 2.25% (17/737) in the PCOS patients, numerically higher than 1.26% (19/1489) in the non-PCOS subjects. The difference was significant with a confidence level of 90% (1.04-3.15) but not at 95% with an odds ratio of 1.808 (95% CI = 0.934-3.4, p = 0.0747). When compared with the literature data from the US female population, the prevalence of RA in PCOS patients was significantly higher (2.25% vs. 1.40%, p 0.0001). Among the autoimmune diseases examined, both systemic sclerosis (0.40% vs. 0.0%, p = 0.0369) and undifferentiated connective tissue disease (0.53% vs. 0.0%, p = 0.0123) were significantly more frequent in the PCOS patients than the non-PCOS. Additionally, PCOS patients had a significantly higher frequency of osteoarthritis than non-PCOS patients (5.44% vs. 2.92%, p = 0.0030) with an odds ratio of 1.913 (95% CI = 1.239-2.955).We have shown unprecedentedly that certain rheumatic diseases are more prevalent in PCOS. This study provides important insight into autoimmunity in association with PCOS. Key Points • Polycystic ovary syndrome is postulated to cause systemic autoimmune disease due to its hormonal imbalance. • We conducted the first epidemiologic assessment of the prevalence of systemic autoimmune diseases. • Certain autoimmune and rheumatic diseases are more prevalent in polycystic ovary syndrome.

Objective: The aim of this study is to clarify, in girls with premature pubarche (PP), the influence of premature androgenization on the prevalence of polycystic ovary syndrome (PCOS). Design and patients: Ninety-nine PP girls, 63 who developed PCOS and 36 who did not develop PCOS, were retrospectively included. Clinical, anthropometric, and metabolic parameters were evaluated at the time of diagnosis of PP and after 10 years from menarche to find predictive factors of PCOS. Results: Young females with PP showed a PCOS prevalence of 64% and showed a higher prevalence of familial history of diabetes (P = 0.004) and a lower prevalence of underweight (P = 0.025) than PP-NO-PCOS. In addition, girls with PP-PCOS showed higher BMI (P < 0.001), waist circumference (P < 0.001), total testosterone (P = 0.026), visceral adiposity index (VAI) (P = 0.013), total cholesterol (P < 0.001), LDL-cholesterol (P < 0.001), non-HDL cholesterol (P < 0.001) and lower age of menarche (P = 0.015), ISI-Matsuda (P < 0.001), DIo (P = 0.002), HDL cholesterol (P = 0.026) than PP-NO-PCOS. Multivariate analysis showed that WC (P = 0.049), ISI-Matsuda (P < 0.001), oral disposition index (DIo) (P < 0.001), VAI (P < 0.001), total testosterone (P < 0.001) and LDL-cholesterol (P < 0.001) are independent predictive factors for PCOS in girls with PP. Conclusions: Our study established a strong association between multiple risk factors and development of PCOS in PP girls. These risk factors are predominantly related to the regulation of glucose, lipid, and androgen metabolism. Among these factors, WC, ISI-Matsuda, DIo, VAI, total testosterone, and LDL-cholesterol predict PCOS.

Androgen-producing tumors in women are rare neoplasms that can cause secondary virilizing characteristics. Of patients presenting with symptoms of hyperandrogenism, these tumors are found in ∼0.2% of cases. Androgen-producing tumors can arise from the ovary or the adrenal gland. Those arising from the ovary are rare, accounting for

Background: Polycystic ovary syndrome (PCOS), a heterogeneous, complex genetic trait of unclear etiology, is an important cause of ovulatory and menstrual irregularity, subfertility and infertility, clinically evident hyperandrogenism, and metabolic dysfunction in women. It is recognized as one of the most common endocrine/metabolic disorders of women. Objective: To investigate the serum levels of insulin and leptin in and their correlation with the endocrine and metabolic peculiarities of PCOS. Patients and methods: This study was carried out on 100 females attending the outpatient clinic of Al Azhar University Hospital seeking conception assistance during the period between April 2019 and august 2020. All women were in the reproductive age group, had primary infertility and diagnosed as having PCOS according to Rotterdam criteria. All patients included within this study were classified under two equal groups: Patient group included women having PCOS, and control group include normal fertile healthy women received no hormonal medication during the last 3 months preceding the study. Results: The biochemical laboratory investigation, including follicle stimulating hormone (FSH) and luteinizing hormone (LH) showed no statistically significant difference between control and patient groups. In contrast, the serum levels of LH/ FSH, free testosterone, fasting insulin and leptin in the patient group showed a significant increase as compared with the control group. Serum leptin level was found to be significantly elevated in overweight and obese patients. No significant differences in serum leptin were noted in normal weight patients. Similarly, serum insulin level was significantly higher in overweight and obese patients compared to overweight and obese control group. The serum leptin levels were plotted against Body mass index (BMI) in both control and patient group, significant correlations were observed. Also, there was a significant positive correlation between serum leptin and serum insulin levels. Conclusion: Women with PCOS have altered leptin and insulin levels which were distinct differences between ovulating and non-ovulating women with PCOS. Also, there were significant differences in the levels of serum leptin levels and insulin levels between normal and overweight/obese women with PCOS.

Polycystic ovary syndrome (PCOS), i.e., anovulation, hyperandrogenemia and polycystic ovary, is an endocrine-metabolic disease affecting reproductive aged women. Women with PCOS are likely to develop obesity, dyslipidemia, type 2 diabetes mellitus (T2DM) and cardiovascular diseases at a younger age. Despite high frequency and severe disease burden, the pathophysiological mechanisms of PCOS remain poorly defined and correspondingly have no therapeutic options. Emerging evidence has demonstrated that PCOS is accompanied with low-grade chronic inflammation and biomarkers thereof. Interestingly, serum amyloid A (SAA) has recently been identified as a potential marker of infection and inflammation and a number of studies have reported an association with PCOS. In this review, we explore the relationship between SAA and hyperandrogenemia, inflammation, obesity and insulin resistance, and provide convincing evidence for SAA as a potential inflammatory biomarker in PCOS.

The most frequently diagnosed condition in women at the age of reproduction is the polycystic ovarian syndrome (PCOS).it could be related to a complex endocrine condition, due to its heterogeneity and uncertainty about its etiology, as the clinical highlights of PCOS incorporate those related to reproductive signs such as decreased frequency of ovulation, irregular menstrual cycles, decreased fertility. Carnitine plays a substantial role in weight loss, glucose tolerance, insulin function and fatty acid metabolism. Thus carnitine plays a crucial role in controlling obesity, insulin resistance, oxidative stress that are associated with PCOS .While, AGEs are a diverse group of reactive molecules that are formed endogenously by non-enzymatic reactions of carbonyl group of carbohydrates with free amino groups of proteins, nucleic acids or lipids. The soluble form of receptors of AGE (sRAGE) could play an important role in management obesity, insulin resistance, hyperandrogenism, oxidative stress which could be related to PCOS. This study was aimed to investigate serum levels of carnitine & soluble receptors for advanced glycation end products (sRAGE) in clomiphene resistant PCOS .Besides assessing the correlation between serum levels of carnitine ,as well as, soluble receptors of AGE with hormonal ( LH, FSH& Testosterone) and metabolic ( serum glucose , serum insulin & HOMA-IR) markers in these patients . The study included thirty women with clomiphene resistant PCOS and thirty apparently healthy women, as a control .In order to measure serum total carnitine and serum soluble receptor of advance glycation end product (sRAGE in PCOS and control groups. The results of our study have shown a decreased serum levels of total carnitine in PCOS group in comparison with control group (48.05 and 59.73 nmol/ml, respectively), but there was no significant elevation in serum levels of sRAGE in patients group as compared with control group .In addition to a significant correlation between serum total carnitine and serum sRAGE levels (r=0.45, P-value=0.03). In conclusion serum total carnitine level was low in Clomiphene resistant-PCOS patients in comparison with control group. Although, sRAGE levels in clomiphene resistant- PCOS patients were not significantly different from the age and BMI-matching controls, but a significant correlation between serum total carnitine and sRAGE was detected. Key words: Poly cystic ovarian syndrome, soluble receptor of advance glycation end products (sRAGE) , SerumTotal Carnitine

Introduction: PCOS is one of the common endocrine disorders in women leading to various complications like infertility, menstrual, psychological disturbances and metabolic syndrome. The objectives of this study were to study the clinical and biochemical parameters of metabolic syndrome in women of reproductive age group with PCOS. Materials and Methods: This cross-sectional study was conducted in a tertiary care centre from September 2018 to June 2020. Fifty six women diagnosed with PCOS, underwent clinical and laboratory assessments for the diagnosis of metabolic syndrome, as per international diabetes federation (IDF) criteria. Results: 14.3% subjects had metabolic syndrome. The prevalence of individual components of the metabolic syndrome among PCOS patients were: waist circumference >80cms in 100%, HDL 150mg/dl in 75%, blood pressure >130/85mmhg in 12.5%, fasting plasma glucose > 100 mg /dl in 87.5%. Subjects with metabolic syndrome had significantly higher BMI compared to those without metabolic syndrome (p=0.043). Conclusion: The metabolic syndrome and its individual components, like waist circumference and decreased HDL were found to be more common among PCOS patients in this study. As the risk of MetS increases with age and BMI, early screening and timely interventions like lifestyle changes will prevent metabolic complications like cardiovascular diseases and type II diabetes mellitus. Keywords: Polycystic ovarian syndrome, Metabolic syndrome, Central obesity, Insulin resistance, Hyperandrogenism.

We performed this updated systematic review and meta-analysis to evaluate anti-Müllerian hormone levels (AMH) in newborns of mothers with polycystic ovary syndrome (PCOS) compared with healthy controls. A search of the literature was conducted in the PubMed, MEDLINE, EMBASE, Cochrane Library, CBM, CNKI, WANFANG, and VIP for articles to assess AMH levels in offspring of PCOS and non-PCOS mothers irrespective of language. These databases were searched from their inception to December 7, 2020. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS) scoring system. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were adopted to calculate the overall estimates with random-effects models. A total of 6 studies with 846 participants were included. The pooled analysis found an increased AMH level in the umbilical cord blood in newborns of PCOS mothers (SMD =0.62, 95% CI [0.28, 0.95]). Subgroup analyses revealed an elevation of AMH concentrations in female neonates, neonates born to American and Asian PCOS mothers. In addition, higher AMH levels were also found in studies diagnosed by the National Institute of Health (NIH) criteria, maternal clinical/biochemical hyperandrogenism, or maternal body mass index (BMI) >30 kg/m2. Meta-regression analysis suggested that diagnostic criterion contributed mostly to the high heterogeneity. We demonstrated that AMH levels in neonates born to PCOS mothers were essentially higher, which indicates that AMH may act as an enigmatic role in the pathogenesis of PCOS which inhibits folliculogenesis in the fetal stage.