Polycystic Ovary Syndrome Phenotypes Research Articles

Developmental programming of the neuroendocrine axis by steroid hormones: Insights from the sheep model of PCOS.

The reproductive neuroendocrine system is a key target for the developmental programming effects of steroid hormones during early life. While gonadal steroids play an important role in controlling the physiological development of the neuroendocrine axis, human fetuses are susceptible to adverse programming due to exposure to endocrine disrupting chemicals with steroidal activity, inadvertent use of contraceptive pills during pregnancy, as well as from disease states that result in abnormal steroid production. Animal models provide an unparalleled resource to understand the effects of steroid hormones on the development of the neuroendocrine axis and their role on the developmental origins of health and disease. In female sheep, exposure to testosterone (T) excess during fetal development results in an array of reproductive disorders that recapitulate those seen in women with polycystic ovary syndrome (PCOS), including disrupted neuroendocrine feedback mechanisms, increased pituitary responsiveness to gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) hypersecretion, functional hyperandrogenism, multifollicular ovarian morphology, and premature reproductive failure. Similar to a large proportion of women with PCOS, these prenatally T-treated sheep also manifest insulin resistance and cardiovascular alterations, including hypertension. This review article focuses on the effects of prenatal androgens on the developmental programming of hypothalamic and pituitary alterations in the sheep model of PCOS phenotype, centering specifically on key neurons, neuropeptides, and regulatory pathways controlling GnRH and LH secretion. Insights obtained from the sheep model as well as other animal models of perinatal androgen excess can have important translational relevance to treat and prevent neuroendocrine dysfunction in women with PCOS and other fertility disorders.

Genetic variations in OLR1 gene associated with PCOS and atherosclerotic risk factors.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. The aim of this study was to investigate the association of oxidized low-density lipoprotein receptor 1 (OLR1) gene variations with the susceptibility of PCOS and to examine the relationship between the frequencies of OLR1 gene variations and atherosclerotic risk factors. Genomic DNA was extracted from blood samples collected from 49 patients with PCOS and 43 healthy controls. The variants in the OLR1 gene were identified using next-generation sequencing (NGS). Heterozygous rs11053646 (K167N), rs11611438, rs11611453, and rs35688880 genotype frequencies were significantly higher in the PCOS group than that of control group. Single nucleotide polymorphism (SNP) rs34163097 minor A allele increased the PCOS risk by ∼10-fold (p = 0.03). SNPs rs11053646, rs11611438, rs11611453, rs34163097, and rs35688880 were positively correlated with body mass index (BMI). The logistic regression model (area under the curve: 0.770, p = 0.000) further revealed a combination of 2-h plasma glucose (PG-2 h), dehydroepiandrosterone sulfate (DHEAS), and rs11053646 as predictors of PCOS phenotype. This is the first study reporting the NGS data of OLR1 gene variants which might be associated with the pathogenesis of PCOS and several atherosclerotic risk factors, particularly higher BMI and DHEAS. To fully understand the genetic basis of PCOS and the contribution of OLR1 gene variants to PCOS pathogenesis, additional large-scale studies are warranted.

The Implication of Mechanistic Approaches and the Role of the Microbiome in Polycystic Ovary Syndrome (PCOS): A Review.

As a complex endocrine and metabolic condition, polycystic ovarian syndrome (PCOS) affects women's reproductive health. These common symptoms include hirsutism, hyperandrogenism, ovulatory dysfunction, irregular menstruation, and infertility. No one knows what causes it or how to stop it yet. Alterations in gut microbiota composition and disruptions in secondary bile acid production appear to play a causative role in developing PCOS. PCOS pathophysiology and phenotypes are tightly related to both enteric and vaginal bacteria. Patients with PCOS exhibit changed microbiome compositions and decreased microbial diversity. Intestinal microorganisms also alter PCOS patient phenotypes by upregulating or downregulating hormone release, gut-brain mediators, and metabolite synthesis. The human body's gut microbiota, also known as the "second genome," can interact with the environment to improve metabolic and immunological function. Inflammation is connected to PCOS and may be caused by dysbiosis in the gut microbiome. This review sheds light on the recently discovered connections between gut microbiota and insulin resistance (IR) and the potential mechanisms of PCOS. This study also describes metabolomic studies to obtain a clear view of PCOS and ways to tackle it.

Regenerative Medicine for Polycystic Ovary Syndrome: Stem Cell-Based Therapies and Brown Adipose Tissue Activation.

Polycystic ovary syndrome (PCOS) is a pathological condition prevalent among women of reproductive age: it is associated with varied etiological factors (lifestyle, genetic, environmental…) and characterized by an increased polycystic morphology of the ovaries leading to disturbances in the menstrual cycle and its correlated infertility. Interconnections between PCOS, obesity, and insulin resistance have been recently investigated thoroughly in the scientific community; these findings directed PCOS therapies into unraveling possibilities to target insulin resistance and central adiposity as efficient treatment. On the other hand, brown adipose tissue is known to possess a thermogenic activity that increases lipolysis and directly attenuates fat deposition. Therefore, brown adipose tissue activation lands itself as a potential target for reducing obesity and its induced insulin resistance, subsequently rescuing PCOS phenotypes. In addition, regenerative medicine has proven efficacy in resolving PCOS-associated infertility and its metabolic symptoms. In particular, many stem/progenitor cells have been verified to possess the differentiation capacity into functional brown adipocytes. Thus, throughout this review, we will discuss the different brown adipose tissue activation strategies and stem-cell-based therapies applied to PCOS models and the possible combination of both therapeutic approaches to synergistically act on the activation of brown adipose tissue and attenuate PCOS-correlated infertility and retract the consequences of the metabolic syndrome on the physiological state of patients.

ПАТОГЕНЕТИЧЕСКИЕ ОСОБЕННОСТИ ВЛИЯНИЯ ПЕРЕНЕСЕННОЙ КОРОНАВИРУСНОЙ ИНФЕКЦИИ У ЖЕНЩИН С СИНДРОМОМ ПОЛИКИСТОЗНЫХ ЯИЧНИКОВ

From July 1, 2022, restrictions related to the spread of COVID-19 were lifted in Russia. But until now, according to experts, COVID-19 remains one of the most important medical problems for the global community. In 2023, 11 thousand people died from COVID-19 in the world, about 3 million were infected. There are cases known for complications from other organ systems in patients with COVID-19. However, in the general population, the course of COVID-19 is more severe in people with dyslipidaemia, obesity and hypertension. Often, these comorbidities are associated with polycystic ovary syndrome (PCOS). It is possible that women with PCOS will experience more severe clinical manifestations in the future. For 2020–2023 many women reported experiencing menstrual irregularities for the first time, which raised concerns about the impact of SARS-CoV-2 on reproductive function. There are currently insufficient clinical and statistically significant data to establish the causes of these disorders. This material is devoted to the analysis of the probable causes of menstrual irregularities in women with PCOS after a coronavirus infection: the possible direct effect of SARS-CoV-2 on the organs of the female reproductive system depending on the PCOS phenotype.

A Study of Serum Adiponectin Levels in Patients with Polycystic Ovarian Syndrome and its Correlation with Various Cardiometabolic Risk Markers.

Polycystic ovarian syndrome (PCOS) is the most common metabolic disorder in the reproductive age group, the pathogenesis of which is constantly evolving with the discovery of novel molecules and the lookout for potential therapeutic targets. The aim of the present study was to estimate the circulating levels of serum adiponectin in patients with PCOS compared to controls and to find its correlation with markers of cardiovascular risk, with special emphasis on circulating levels of oxidised low-density lipoprotein (oxLDL). In this cross-sectional observational study recently diagnosed, PCOS subjects were compared with age- and body mass index (BMI)-matched controls. All the included subjects underwent detailed clinical, biochemical and hormonal evaluation, including lipid profile, 75 g oral glucose tolerance test, fasting serum insulin, fasting serum adiponectin, oxLDL, total testosterone and anti-Mullerian hormone. Appropriate statistical methods were performed using SPSS (version 21) and Microsoft Excel (2019). A total of 56 PCOS cases and 32 controls were included in the study. Mean values of serum adiponectin (μg/mL) in our study were found to be significantly lower in PCOS cases (11.53 ± 4.74) versus controls (14.73 ± 5.61) irrespective of BMI. Mean values of serum oxLDL (μg/dL) were found to be higher in PCOS cases (157.96 ± 53.89) versus controls (117.52 ± 45.44), with a significant negative correlation between adiponectin and oxLDL in cases. No difference in levels of adiponectin was found between the different PCOS phenotypes. Hypoadiponectinaemia was found to be associated with PCOS irrespective of obesity in PCOS subjects. Serum oxLDL can complement adiponectin as early predictor of CV risk in PCOS.

PHENOTYPES OF POLYCYSTIC OVARY SYNDROME AND THEIR ASSOCIATION WITH METABOLIC SYNDROME- A NORTH INDIAN TERTIARY CARE CENTER BASED STUDY

Background PCOS (Polycystic Ovary Syndrome) is a widely recognized endocrine disorder of the reproductive age group. PCOS women are known to have insulin resistance and an increased tendency for weight gain, leading to an alteration in the metabolic prole. Objectives To categorize women diagnosed as PCOS into various phenotypes and study their correlation with metabolic syndrome. Methods A study was conducted in the department of Obstetrics and Gynecology, GMC Patiala from Jan 2019 to June 2020 and the PCOS were diagnosed and classied into 4 Phenotypes and prevalence of metabolic syndrome as per ATP III/ NCEP criteria was studied in various phenotypes. Results During the study period 116 patients were diagnosed as PCOS. The mean age of the PCOS cases was 24.86 ± 4.96 years (n=116). The PCOS Phenotype A had the maximum prevalence, 52.59%, followed by Phenotype B 18.97%, Phenotype D 16.38%, and Phenotype C 12.06%. The lipid prole was maximally deranged in Phenotype D. The metabolic syndrome was present in 26.72% of cases, with maximum cases belonging to Phenotype A. Conclusion The PCOS cases have a higher prevalence of deranged metabolic proles at a young age. An early multidisciplinary approach in PCOS cases is essential, to lower the prevalence of deranged metabolic prole and long term co-morbidities.

Comparing Assisted Reproductive Outcomes in Women with Different Polycystic Ovary Syndrome Phenotypes Undergoing Frozen Embryo Transfer.

Patients with polycystic ovarian syndrome (PCOS) have unique characteristics depending on its phenotype. Therefore, prediction of controlled ovarian stimulation (COS) response and assisted reproductive technique (ART) outcome in these becomes challenging. To assess the outcomes of assisted reproductive technology (ART) in various polycystic ovary syndrome (PCOS) phenotypes and to evaluate the predictive value of anti-Mullerian hormone (AMH) and total testosterone on ART success. Clinical pregnancy rate (CPR) was measured as the primary outcome. This was a prospective observational study conducted at a tertiary care centre. A total of 190 infertile women with PCOS (Rotterdam criteria) were enrolled and were subdivided into four phenotypes. Baseline screening and transvaginal scan were done. All patients underwent COS using antagonist protocol with recombinant follicle-stimulating hormone, and an agonist trigger was given for follicular maturation. One or two blastocysts were transferred in a frozen-thawed embryo transfer cycle. Luteal phase support was given with vaginal progesterone. For quantitative variables, we employed the Kruskal-Wallis Test with post hoc Tukey's analysis. For continuous or ordinal variables, the Mann-Whitney U test was utilized. The analysis of categorical data was conducted using the Chi-square (χ2) test with SPSS 21 software. Phenotype A was the most prevalent (37%). CPR was the highest in phenotype D (57.7%), followed by phenotype C (53.06%), A (43%) and B (36%). The mean serum AMH level was the highest in phenotype A (9.7 ± 4.3 ng/dL) and the lowest in phenotype B (5.9 ± 1.8 ng/dL). The mean total testosterone level was 103 ± 15.68 ng/mL in Type A, 109.46 ± 37.08 ng/mL in Type B and 48.52 ± 17.07 ng/ml in Type D. Phenotype D showed higher CPR and lower miscarriage rate compared to other phenotypes (not significant) and was associated with good clinical outcome. No correlation could be established with serum AMH, total testosterone levels and CPR.

Type 2 Diabetes and Precursors in Community Dwelling Asian Indian Adult Youth.

Recent studies have shown a high prevalence of Type-2-diabetes (T2DM) (24%) and prediabetes (18.1%) in Kerala. There is no community based study from South Asia regarding the prevalence of type 2 diabetes and its precursors in the young adult population. This community based study was done to find the prevalence of type 2 diabetes and its precursors in South Indian adult youth (18-30 years age) of Thiruvananthapuram district. Cross sectional design was used for this study. Multistage cluster sampling was used to enrol community dwelling youth of 18 to 30 years, residing in Thiruvananthapuram district. Six panchayath wards from rural and urban regions and 4 from coastal area were randomly selected as the primary sampling units. Trained staff nurses conducted the survey with the help of accredited-social-health-activists (ASHA). Socio-demographic data, anthropometry, clinical features of insulin resistance, and random capillary glucose (CG) and blood pressure were assessed and recorded. Oral Glucose tolerance test or HbA1c was done for participants with a CG ≥130 mg/dl for diagnosis of diabetes and prediabetes. A total of 1031 participants were included from the rural (n = 394), coastal (n = 269) and urban (n = 368) areas. Prevalence of hyperglycaemia i.e., T2DM and pre-diabetes was 0.48% (n = 5) and 2.4% (n = 25) respectively. Family-history of T2DM was present in 35.1% subjects. Prevalence of overweight, obesity and abdominal-obesity was 28.2%, 16.1% and 28.4% respectively. Clinical-features of insulin resistance (CFIR) were present in 27.1% subjects (acanthosis [17.7%], skin tags [1.7%] and PCOS phenotype [10.7%]). Among various anthropometric measurements and their derivatives, CFIR correlated best (r = 0.24, P < 0.01) with the product of BMI and the sum of abdominal circumference and hip circumference (Trivandrum Medical College [TMC] -adiposity-index), which is a newly proposed parameter. Hyperglycaemia was more common in males, did not correlate with waist hip ratio, and correlated best again with TMC-adiposity-index ((r = 0.13, P < 0.01). The burden of insulin resistance in the young South Indian population, hitherto unknown in any community based study, has been studied for the first time. The prevalence of precursors of T2DM is high in this population. Early identification of 'at risk' individuals could provide a window of opportunity for preventing or delaying future diabetes and its long term complications. TMC adiposity index could become a valuable tool in the anthropometric assessment for predicting future T2DM.

Endometrial Pathology and Reproductive Outcomes in Polycystic Ovary Syndrome (PCOS)

Introduction: The common and key in the pathogenesis of PCOS and chronic endometritis (CE) is the chronic course of inflammation. Persistent damage to the endometrium leads to impaired endometrial receptivity and creates conditions for the development of infertility. The purpose of the study was to identify the most common endometrial pathology in women with PCOS and infertility and to analyze the effectiveness of infertility treatment in women with this pathology, to evaluate reproductive outcomes. Materials and methods: Analyzed 240 case histories of patients of LLC “Clinic of Professor Pasman”, Novosibirsk Clinical Oncological Dispancery for the period 2012-2022, diagnosed with PCOS, Infertility. Patients were included in the study group by random sequential selection. The frequency of occurrence of each of the PCOS phenotypes was analyzed, as well as the prevalence of endometrial pathology. The most common pathology is chronic endometritis, therefore, in addition to the standard methods of treating infertility in PCOS, CE was additionally treated by the following methods: photodynamic therapy (PDT) and the introduction of a macrophage medium into the uterine cavity. Results and discussion: In 61% of cases, hysteroscopy was performed and endometrial pathology was detected, which indicates the need to diagnose the endometrium in women with PCOS, especially before using ART. The most common endometrial pathology is chronic endometritis (61.6%). PDT and the introduction of macrophage medium increase the effectiveness of the treatment of CE and infertility in PCOS. The results obtained indicate a high incidence of PCOS without hyperandrogenism and obesity.

Ovulatory Versus Anovulatory Polycystic Ovary Syndrome Phenotypes: is There Really Any Effect on Laboratory, Clinic and Metabolic Profiles for Turkish Women?

Ovulatory Versus Anovulatory Polycystic Ovary Syndrome Phenotypes: is There Really Any Effect on Laboratory, Clinic and Metabolic Profiles for Turkish Women?

Are Phenotypes of PCOS and Vitamin D Levels Interlinked

Are Phenotypes of PCOS and Vitamin D Levels Interlinked

The molecular mechanism of miR-96-5p in the pathogenesis and treatment of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS), characterized by the androgen excess and arrest of antral follicles, is a common endocrine disorder among women lacking specific diagnostic biomarkers and therapeutic targets. Herein, we studied the molecular mechanism of miR-96-5p in the process of PCOS and its potential applications in PCOS. Clinically, we found that miR-96-5p significantly decreased in serum, follicular fluid and primary human granulosa cells (hGCs) of PCOS patients (n = 70) vs non-PCOS women (n = 60), as well as in the ovaries of 3-types of induced PCOS-like mice. Furthermore, we demonstrated that the elevated circulating miR-96-5p levels were significantly correlated with the PCOS disordered endocrine clinical features, and the area under the curve of receiver operating characteristic was 0.8344, with 75.71% specificity and 80% sensitivity. Mechanically, we identified miR-96-5p as an androgen-regulated miRNA that directly targets the forkhead transcription factor FOXO1. Inhibition of miR-96-5p decreased estrogen synthesis, while decreasing the cell proliferation index of KGN via regulating the expression of FOXO1 and its downstream genes. Inversely, inhibition of FOXO1 abrogated the effect of miR-96-5p on estrogen synthesis and proliferation index. Of note, ovarian intra-bursal injection of miR-96-5p agomir rescued the phenotypes of dehydroepiandrosterone-induced PCOS like mice. In conclusion, our results clarified a vital role of miR-96-5p in the pathogenesis of PCOS and might serve as a novel diagnostic biomarker and therapeutic target for PCOS.

The diagnostic performance of antimullerian hormone for polycystic ovarian syndrome and polycystic ovarian morphology.

The diagnosis of polycystic ovary syndrome (PCOS) remains a challenge to clinicians due to heterogeneous clinical presentation and diagnostic criteria. This study investigated the utilization of Anti-Müllerian hormone (AMH) alone or replacing polycystic ovarian morphology (PCOM) in the PCOS diagnostic criteria. A total of 401 women were categorised as PCOS (n:154), nonPCOS with polycystic ovarian morphology (PCOM) (n:105), and nonPCOS with normal ovarian morphology (NOM) (n:142). First, the diagnostic performance of AMH for PCOS diagnosis in Rotterdam, Androgen Excess Society, and National Institutes of Health (NIH) criteria was analyzed. Second, AMH was used instead of PCOM in Rotterdam criteria and we searched diagnostic performance for PCOS phenotypes. AMH levels were positively correlated with LH, testosterone, hirsutism score, menstrual cycle length, and antral follicle count (p < 0.05). AMH alone had specificity and sensitivity for PCOS diagnosis were 84.9% and 72.4% in Rotterdam (AUC: 0.866); 84.4% and 72% in Androgen Excess Society (AUC: 0.857); 83.3% and 66.4% in National Institute of Health criteria (AUC: 0.825). AMH alone had satisfactory diagnostic potential for phenotype A, but not other phenotypes. The replacement of PCOM with AMH in Rotterdam criteria had a high diagnostic potential for PCOS (AUC: 0.934, sensitivity:97.4%, specificity: 90.67%). Phenotype A and phenotype D were diagnosed with 100% sensitivity and 94.5% specificity. Phenotype C was recognised with 96.15% sensitivity and 94.5% specificity. AMH may be used with high diagnostic accuracy instead of PCOM in the Rotterdam PCOS criteria.

Establishing Normative Values to Determine the Prevalence of Biochemical Hyperandrogenism in Premenopausal Women of Different Ethnicities from Eastern Siberia.

Androgen assessment is a key element for diagnosing polycystic ovary syndrome (PCOS), and defining a "normal" level of circulating androgens is critical for epidemiological studies. We determined the upper normal limits (UNLs) for androgens in a population-based group of premenopausal "healthy control" women, overall and by ethnicity (Caucasian and Asian), in the cross-sectional Eastern Siberia PCOS Epidemiology and Phenotype (ESPEP) Study (ClinicalTrials.gov ID: NCT05194384) conducted in 2016-2019. Overall, we identified a "healthy control" group consisting of 143 healthy premenopausal women without menstrual dysfunction, hirsutism, polycystic ovaries, or medical disorders. We analyzed serum total testosterone (TT) by using liquid chromatography with tandem mass spectrometry (LC-MS/MS), and DHEAS, sex-hormone-binding globulin (SHBG), TSH, prolactin, and 17-hydroxyprogesterone (17OHP) were assessed with an enzyme-linked immunosorbent assay (ELISA). The UNLs for the entire population for the TT, free androgen index (FAI), and DHEAS were determined as the 98th percentiles in healthy controls as follows: 67.3 (95% confidence interval (CI): 48.1, 76.5) ng/dl, 5.4 (3.5, 14.0), and 355 (289, 371) μg/dl, respectively. The study results demonstrated that the UNLs for TT and FAI varied by ethnicity, whereas the DHEAS UNLs were comparable in the ethnicities studied.

Polycystic Ovary Syndrome and Gut Microbiota: Phenotype Matters.

Abnormalities in gut microbiota diversity are considered important mechanisms in metabolic disorders in polycystic ovarian syndrome (PCOS). However, the data on the association of these disorders with the PCOS phenotype remain controversial. The objectives of this study were to estimate the alpha diversity of the gut microbiota of healthy women and PCOS patients depending on phenotype. The study participants (184 premenopausal women: 63 with PCOS, 121 without PCOS) were recruited during the annual employment assessment in the Irkutsk Region and the Buryat Republic (Russia) in 2016-2019. For PCOS diagnosis, we used the Rotterdam (2003) criteria and definitions of PCOS phenotypes. Five indexes of alpha diversity (ASV, Shannon, Simpson, Chao, and ACE) were estimated for the gut microbiota in all participants using amplicon metasequencing. As a result, two out of five alpha diversity indexes showed a statistical difference between the non-PCOS and PCOS groups. We did not find a significant difference in the alpha diversity of gut microbiota in the subgroups of women with hyperandrogenic PCOS phenotypes vs non-androgenic phenotype D and the group of women with the presence of only one of the PCOS criteria. Nevertheless, "classic" PCOS phenotypes demonstrated the most significant decrease in alpha diversity compared with healthy women without any signs of PCOS.

Insight Towards Induction of Reproductive-Metabolic Phenotypes of Polycystic Ovarian Syndrome

Insight Towards Induction of Reproductive-Metabolic Phenotypes of Polycystic Ovarian Syndrome

The effects of melatonin and metformin on histological characteristics of the ovary and uterus in letrozole-induced polycystic ovarian syndrome mice: A stereological study.

Polycystic ovarian syndrome (PCOS) with anovulation, hyperandrogenism, ovarian and uterine histological changes, menstrual irregularities, etc. signs is an infertility type. It seems that melatonin and metformin can improve these abnormalities. To evaluate the effects of melatonin and metformin on the ovary and uterus in PCOS-induced mice using stereological methods. Seventy-two adult female BALB/c mice (8-wk-old, 20-30 gr) were randomly divided into control (distilled water, gavage), PCOS (90 µg/kg letrozole, gavage), PCOS+metformin (500 mg/kg, gavage), PCOS+melatonin (10 mg/kg, intraperitoneal injection), and PCOS+melatonin control (0.5% ethanol saline) groups (n = 12/each). Another PCOS group was kept for a month to ensure that PCOS features remained. Finally, a stereological evaluation of the uterus and ovary was carried out, and vaginal cytology and serum testosterone levels were assessed. PCOS mice treated with metformin and melatonin had lower testosterone levels, body weight, and more regular estrus cycles than the PCOS group (p 0.001). A significant decrease in conglomerate and daughter gland numbers, and primary, secondary, atretic, and cystic follicles numbers with a significant increase in primordial and Graafian follicles, and corpus luteum numbers (p 0.001) was seen in these treated mice. Also, endometrial vessels' volume and length significantly increased, but ovarian, endometrial, myometrial, stromal, and glands volume, and endometrial and myometrial thickness dramatically declined (p 0.001). It appears that metformin and melatonin could restore the PCOS phenotype including estrus cycle irregularity, high testosterone level, and ovarian and uterine micromorphology to the control levels. However, the 2 treatments had similar effects on the examined parameters.

Dysregulation of intraovarian redox status and steroidogenesis pathway in letrozole-induced PCOS rat model: a possible modulatory role of l-Carnitine

Abstract Background Polycystic ovarian syndrome (PCOS) is a reproductive disorder associated with several endocrine and metabolic alterations. The mechanism underlying this syndrome is controversial. On the other hand, drugs used for the treatment are associated with several side effects and poor in controlling PCOS phenotype. l-Carnitine (LC) has been reported to have a significant regulatory function on the redox and metabolic status of female reproductive system. Nevertheless, its regulatory pathways to regulate PCOS are still under investigation. Therefore, this study aimed to evaluate the effects of LC on the steroidogenic pathways, oxidative stress markers and metabolic profile in letrozole (LTZ)-induced PCOS rat model. Methods For this aim, animals were divided into four groups (n = 6). Control group, untreated letrozole-induced PCOS group (1 mg/kg bwt) for 21 days, PCOS group treated with l-Carnitine (100 mg/kg bwt) for 14 days and PCOS group treated with clomiphene citrate (2 mg/kg bwt) for 14 days. Finally, body and ovarian weight, metabolic state(glucose and lipid profile), hormonal assays (testosterone, 17 β estradiol, LH and FSH levels), intraovarian relative gene expression (CYP17A1, StAR, CYP11A1 and CYP19A1 genes), ovarian redox state (malondialdehyde (MDA), reduced glutathione content (GSH) and catalase enzyme activity (CAT)) as well as serum total antioxidant capacity (TAC) were detected. Also, histomorphometric ovarian evaluation (number and diameter of cystic follicles, granulosa cell thickness and theca cell thickness) as well as immune expression of caspase-3 of granulosa cells of cystic follicles were determined. Results LC significantly improved ovarian redox state (GSH, MDA and CAT), steroidogenic pathways gene expression (CYP17A1, StAR, CYP11A1 and CYP19A1 genes), hormonal profile (Follicle stimulating hormone (FSH) and luteinizing hormone (LH), testosterone and estradiol), metabolic state (Glucose and lipid profile) histomorphometric alterations and decreased caspase 3 immune reaction of granulosa cells. Conclusion l-Carnitine supplementation can ameliorate the PCOS phenotype through its energetic, antioxidant and antiapoptotic functions as well as steroidogenesis regulatory role. This protocol could be modified to produce the best therapeutic benefits, and it could be regarded as a prospective therapeutic intervention for PCOS.

ASSESSMENT OF VITAMIN D AND CALCIUM LEVELS IN WOMEN WITH PCOS: AN OBSERVATIONAL STUDY

Objectives: Polycystic ovarian syndrome (PCOS) is a prevalent endocrinal disorder in the women of reproductive age group. The present study aims to investigate the correlation between Vitamin D and calcium levels in PCOS subjects as well as to establish the correlation between body mass index, hyperandrogenism, and metabolic syndrome in various phenotypes of PCOS. Methods: In the present prospective and observational study, a total of 80 patients diagnosed with PCOS were recruited. The recruited patients were divided in the following two groups - study group (60 women diagnosed with PCOS based on Rotterdam criteria); and control group (20 women without PCOS recruited from outpatient department and infertility clinics). Baseline characteristics, Vitamin D level, and serum calcium levels were measured in the two groups and then compared. Results: The mean age of patients in both the groups was found to be comparable (study group: 26.45±5.95 years versus control group: 28.40±6.65 years; p=0.221). The difference of mean 25-Hydroxy Vitamin D3 level was found to be statistically highly significant (study group 14.71 [±9.12] ng/mL versus control group was 22.47 [±6.71] ng/mL; p=0.0008). The difference of mean serum calcium level was also found to be statistically highly significant (study group 9.14 [±0.50] mg/mL, and control group 9.74 [±0.45] mg/mL; p&lt;0.0001). Conclusion: Women with PCOS have a significantly lower serum 25-hydroxyvitamin D and calcium levels as compared to controls. There is need for routine Vitamin D3 and calcium screening in all patients of PCOS for better insight into its role in the syndrome. Screening and correction of Vitamin D3 and calcium deficiency may prevent PCOS and its manifestations.