Treatment Of PCOS Research Articles

Anti-mullerian hormone as an emerging promising marker in the prognosis of PCOS

Aims: To correlation of AMH with clinical, hormonal and ultrasound findings; and determine the role of AMH as prognostic marker.
 Methods: This was a prospective cross sectional study on women attending Gynaecology outpatient department of Medial College and Hospital, Kolkata, from January 2018 to June 2019. Study comprised of 70 newly diagnosed cases of PCOS using Rotterdam criteria 2003. Clinical history included menstrual complaint, hirsutism and weight gain; examination included BMI and Ferriman-Gallwey score; and investigations included FBS, 2hr PPBS, TSH, Prolactin, total testosterone, LH, AMH level and pelvic USG before starting intervention and same parameters were rechecked after 3 months of treatment completion.
 Results: A total of 70 PCOS patients were included in a study conducted within 1 year time period. The most common Phenotype in our study is Phenotype A (O+H+P) which was almost 85.71%, followed by Phenotype B (O+H) 7.14% and the least we got Phenotype C (H+P) that is 2.86%. There was statistically significant (p<0.05) decrease in AMH level following treatment of PCOS (before treatment mean AMH level was 9.634.42 and after treatment the level was 5.812.77).
 Conclusions: The most frequent PCOS phenotype in Indian women is A (O+H+P). Therapy in PCOS women with raised AMH reduces the AMH levels. Measurement of serum AMH provides a high specificity and sensitivity by which it can act as a prognostic marker for PCOS.

TCM Treatment of Polycystic Ovaries and PCOS Using Integrated Medical Diagnosis---- 58 Cases Study

TCM Treatment of Polycystic Ovaries and PCOS Using Integrated Medical Diagnosis---- 58 Cases Study

Metabolomic Biomarkers in Polycystic Ovary Syndrome: A Review of the Evidence.

Polycystic ovary syndrome (PCOS) is an endocrinologic condition affecting one in five women of reproductive age. PCOS is often characterized by disruptions to the menstrual cycle, development of male-pattern hair growth (hirsutism), and polycystic ovary morphology. Recently, PCOS has been linked to metabolic dysfunction, with 40 to 80% of women characterized as overweight or obese. Despite these well-known negative health effects of PCOS, 75% of sufferers remain undiagnosed. This is most likely due to the variability in symptom presentation and the lack of a definitive test for the condition. Metabolomics, which is a platform used to analyze and characterize a large number of metabolites, has recently been proposed as a potential tool for investigating the metabolic pathways that could be involved in the pathophysiology of PCOS. In doing so, novel biomarkers could be identified to improve diagnosis and treatment of PCOS. This review aims to summarize the findings of recent metabolomic studies that highlight metabolic-specific molecules which are deranged in PCOS, to identify potential biomarkers for the condition. Current limitations for metabolomic studies are discussed, as well as future directions to progress the field toward further validation and integration into clinical practice.

Involvement of BMP-15 in Glucocorticoid Actions on Ovarian Steroidogenesis by Rat Granulosa Cells

Glucocorticoid receptor (GR) are known to be expressed in the ovary and glucocorticoids are shown to exert direct effects on granulosa cell functions. In the clinical setting, menstrual abnormality, amenorrhea and hypermenorrhea can be shown in patients with glucocorticoid excess. On the other hand, glucocorticoids can also be used for the treatment of PCOS with hyperandrogenism. However, the effects of glucocorticoids on the reproductive system have not been fully elucidated. In the present study, we investigated the influence of glucocorticoids on follicular steroidogenesis using primary culture of rat granulosa cells, by focusing on the ovarian bone morphogenetic proteins (BMPs) acting as a luteinizing inhibitor. Granulosa cells isolated from female immature rats were treated with follicle-stimulating hormone (FSH) in the presence of dexamethasone (Dex) in serum-free conditions. After treatment with Dex for 48 h, the changes of estradiol (E2) and progesterone (P4) production and cAMP synthesis induced by FSH treatments were measured by ELISA. Total RNAs of granulosa cells treated with FSH, Dex and BMPs were extracted and mRNA levels of steroidogenetic factors and enzymes, BMP receptors and Id-1 were quantified by real-time RT-PCR. Phosphorylation of Smad1/5/9 induced by BMPs was evaluated by Western blotting using cell lysates in the presence or absence of Dex. As a result, it was revealed that Dex treatment decreased FSH-induced E2 production by granulosa cells. In accordance with the steroid results, Dex suppressed FSH-induced P450arom mRNA expression as well as FSH-induced cAMP synthesis by granulosa cells. By contrast, Dex treatment augmented FSH-induced P4 production by granulosa cells in a concentration-dependent manner. Dex treatment was found to enhance basal and FSH-induced mRNA levels of P4-synthetic enzymes including P450scc and 3βHSD. Of note, Dex treatment activated the BMP target gene Id-1 transcription and Smad1/5/9 phosphorylation, in particular, induced by BMP-15 among various BMP ligands including BMP-2, -4, -6, -7, -9 and -15. It was also revealed that Dex treatment increased mRNA levels of ALK-6, a type-I receptor for BMP-15, and that BMP-15 treatment in turn upregulated GR mRNA levels expressed by granulosa cells. Given that BMP-15 acts as an inhibitor for P4 production by suppressing FSH-receptor actions, it was suggested that glucocorticoid is functionally linked to the enhancement of endogenous BMP-15, leading to the negative feedback toward the P4 overproduction induced by FSH and Dex in granulosa cells. Collectively, it was revealed that glucocorticoids elicit differential effects on the ovarian steroidogenesis of E2 and P4, in which GR and BMP-15 actions are mutually enhanced in granulosa cells.

The Imbalance in Th17 and Treg Cells in Polycystic Ovarian Syndrome Patients with Autoimmune Thyroiditis

ABSTRACT The ratio of T helper (Th) 17 and T regulatory (Treg) cells in patients with polycystic ovary syndrome complicated with autoimmune thyroiditis (PCOS-AIT) remains unreported. The study aimed to determine the Th17/Treg cell paradigm in PCOS-AIT patients. In peripheral blood mononuclear cells from PCOS patients and controls, the percentages of Th17 and Treg cells were measured by flow cytometry, the mRNA levels of a Th17-related transcription factor (ROR-γt) and a Treg-specific transcription factor (Foxp3) were determined by qRT-PCR, and the levels of Th17-related cytokines and Treg-related cytokines were measured by ELISA. Additionally, to examine the effect of testosterone on the Th17/Treg cell balance in vitro, cultured PCOS-AIT CD4+ T cells were treated with 10 μM testosterone for 24 h, and the Th17/Treg cell proportions and expression of Th17/Treg cell-associated transcription factors and cytokines were analyzed by flow cytometry, qRT-PCR, and ELISA. The Th17 cell percentage, Th17/Treg cell ratio, and expression of Th17-related ROR-γt and IL-17 were significantly higher in peripheral blood mononuclear cells from PCOS-AIT patients than in those from controls. In CD4+ T cells derived from PCOS-AIT patients, testosterone significantly decreased the Th17 cell percentage, Th17/Treg ratio, mRNA level of ROR-γt, and production of Th17-related cytokines and increased the Treg cell percentage, mRNA level of Foxp3, and secretion of Treg-related cytokines. The Th17/Treg cell imbalance favoring proinflammatory Th17 cells is involved in the pathogenesis of PCOS-AIT. Targeting the Th17/Treg cell axis may have therapeutic potential in the treatment of PCOS–AIT.

Humanin: A Potential Treatment for PCOS?

Humanin: A Potential Treatment for PCOS?

The effect of hydroalcoholic extract of Nigella Sativa seed on dehydroepiandrosterone-induced polycystic ovarian syndrome in rats: An experimental study.

BackgroundPolycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women.ObjectiveThe aim of this study was to investigate the therapeutic effect of hydroalcoholic extract of Nigella sativa (N. sativa) seed as a plant, the consumption of which has been recommended in Islam, on dehydroepiandrosterone (DHEA)-induced PCOS rats.Materials and Methods This experimental study was carried out on 36 Wistar female rats (3 wk, 60 10 gr). Then rats were divided into 6 groups (n = 6/each): control; PCOS-induced (DHEA 60 mg/kg/sc); PCOS+ Metformine (30 mg/kg); and three experimental groups receiving DHEA + hydroalcoholic extract of N. sativa seeds in doses of 50, 100 and 200 mg/kg, respectively. Blood samples were taken for the evaluation of sexual hormones, oxidative stress, glucose, and insulin after 30 days of treatment. Ovarian tissue was used for histopathological study.ResultsThe serum levels of luteinizing hormone, testosterone, glucose, insulin resistance, malondialdehyde, and insulin (p 0.001) and estrogen increased while the levels of progesterone (p = 0.01) and antioxidant enzymes in the PCOS group decreased (p 0.001).ConclusionThe administration of the N. sativa extract to the PCOS rats resulted in remarkable changes in the serumic factors relative to the PCOS group. In addition, the extract improved the structure of the ovarian tissue in the PCOS rat. The histopathological results which are in accordance with biochemical findings imply that N. sativa seed could be useful in the treatment of PCOS, the higher doses of the extract being more effective.

Addressing the role of 11β-hydroxysteroid dehydrogenase type 1 in the development of polycystic ovary syndrome and the putative therapeutic effects of its selective inhibition in a preclinical model

BackgroundPolycystic ovary syndrome (PCOS) is the most common metabolic and endocrine disorder among reproductive-age women, and the leading cause of anovulatory infertility. 11β-hydroxysteroid dehydrogenases-1 (11β-HSD1) catalysing the conversion of inactive cortisone to active cortisol plays a crucial role in various metabolic diseases. However, whether 11β-HSD1 is associated with the pathogenesis of PCOS and whether 11β-HSD1 can be a treating target of PCOS remain unknown. MethodsThis study was first designed to explore the role of 11β-HSD1 in PCOS development and the effect of selective 11β-HSD1 inhibitor administration on PCOS treatment. Follicular fluid and granulosa cells (GCs) were collected from 32 non-PCOS patients and 37 patients with PCOS to measure cortisol and 11β-HSDs levels. Female Sprague-Dawley rats (3-week-old) were injected with dehydroepiandrosterone (DHEA) to induce PCOS and their ovaries were collected to measure the abundance of corticosterone (CORT) and 11β-HSDs. To determine the role of 11β-HSD1 in PCOS development, we overexpressed 11β-HSD1 in the ovaries of female rats (5-week-old) or knocked down the expression of 11β-HSD1 in the ovaries from PCOS rats via lentivirus injection. After lentivirus infection, the body weights, ovarian weights, estrous cycles, reproductive hormones and morphology of the ovary were analysed in rats from different experimental groups. Then to figure out the translational potential of the selective 11β-HSD1 inhibitor in treating PCOS, PCOS rats were treated with BVT.2733, a selective 11β-HSD1 inhibitor and a cluster of PCOS-like traits were analysed, including insulin sensitivity, ovulatory function and fertility of rats from the Control, PCOS and PCOS+BVT groups. Rat ovarian explants and human GCs were used to explore the effect of CORT or cortisol on ovarian extracellular matrix remodelling. ResultsThe elevated expression of 11β-HSD1 contributed to the increased cortisol and corticosterone (CORT) concentrations observed in the ovaries of PCOS patients and PCOS rats respectively. Our results showed that ovarian overexpression of 11β-HSD1 induced a cluster of PCOS phenotypes in rats including irregular estrous cycles, reproductive hormone dysfunction and polycystic ovaries. While knockdown of ovarian 11β-HSD1 of PCOS rats reversed these PCOS-like changes. Additionally, the selective 11β-HSD1 inhibitor BVT.2733 alleviated PCOS symptoms such as insulin resistance (IR), irregular estrous cycles, reproductive hormone dysfunction, polycystic ovaries, ovulatory dysfunction and subfertility. Moreover, we showed that cortisol target ovarian insulin signalling pathway and ovarian extracellular matrix (ECM) remodelling in vivo, in ovarian explants and in GCs. ConclusionElevated 11β-HSD1 abundance in ovarian is involved in the pathogenesis of PCOS by impairing insulin signalling pathway and ECM remodelling. Selective inhibition of 11β-HSD1 ameliorates a cluster of PCOS phenotypes. Our study demonstrates the selective 11β-HSD1 inhibitor as a novel and promising strategy for the treatment of PCOS.

Comparison of Body Compositions Evaluated with Bioelectrical Impedance Analysis (BIA) with Metabolic, Hormonal and Anthropometric Measurements in PCOS Patients

Aim: In this study, it was aimed to compare the body composition parameters measured by BIA(Bioelectrical Impedance Analysis) and the metabolic, anthropometric and hormonal parameters of the PCOS patients with the healthy control group and to examine the effect of PCOS on body composition parameters. It is aimed to give a better direction to PCOS follow-up and treatment. Material and Method: 23 non-obese PCOS patients were involved to this prospective study. PCOS diagnosis was made according to the Rotterdam Consensus. Antropometric, metabolic and hormonal parameters were measured. Body compositions were measured by BIA. Results: When the relationship between body composition parameters and metabolic and hormonal values were examined, significant correlations were found. There was a negative correlation between AUC-insulin levels and SHBG while a significant positive correlation between free testosterone in hirsute women with PCOS. There was a significant negative correlation between free testosterone level increase and body fat ratio while a significant positive correlation between SHBG and body fat ratio. There was a significant negative correlation between DHEAS and BMI and the hip circumference. When the relationship between body composition and antropometric parameters were examined, a significant positive correlation was found between BMI and body fat ratio, total body water and basal metabolic rate in women with PCOS. Conclusion: In this study, significant correlations were found between body compositions and hormonal, metabolic and anthropometric parameters in patients with PCOS. Based on these findings, we believe that BIA can play an important role in outpatient follow-up of patients with PCOS.

Effects of Cangfu Daotan Decoction on obese polycystic ovary syndrome and its mechanism

BackgroundPolycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women of reproductive age. Cangfu Daotan Decoction (CFDTT) is one of the prescriptions in the stagnation of obesity-type PCOS. Our previous study showed that CFDTT treatment of obese PCOS was correlated with organic anion transporting polypeptides (OATPs). MethodsHere, we studied the effects of CFDTT on obese PCOS and its underlying mechanism. We built an obese PCOS rat model and treated the rats with CFDTT. Then, we detected the serum levels of TCHO, TG, LDL-c, HDL-c, luteinizing hormone (LH), follicle stimulating growth hormone (FSH), testosterone (T), estradiol (E2), IL-1β, IL-6, and TNF-α in each group and adopted RT-PCR, western blotting and immunohistochemical staining to investigate the effects of CFDTT treatment on the expression of OATP2B1 and OATP3A1 in ovarian and uterine tissues. In addition, we compared the pregnancy outcomes of each group. ResultsWe found that CFDTT decreased the serum levels of TCHO, TG, LDL-c, LH, T, IL-1β, IL-6, and TNF-α and increased the levels of HDL-c, FSH and E2 in a dose-dependent manner. CFDTT could induce the expression of OATP2B1 and OATP3A1 in ovarian and uterine tissues. Moreover, CFDTT could improve pregnancy outcomes. ConclusionThese data suggested that the therapeutic mechanism of Cangfu Daotan Decoction on PCOS may be correlated with regulating lipid metabolism, sex hormone secretion and the inflammatory response and increasing OATP2B1 and OATP3A1 expression. Cangfu Daotan Decoction can be developed as a PCOS treatment drug.

Article Review: The Women with PCOS Syndrome and Probiotic Supplements Effects

PCOS syndrome is major compatible female problem there for this mini review was focus on the research which are tested the effect of probiotic supplement on PCOS. Methods: In this mini review the was key word such as (PCOS, obesity, lipid profile, testosterone) and used Google scholar and pub med. the study was used 7 article published between (2015-2019). Results: The study was positive result about effect of probiotic on the body weight, lipid profile, sex hormone and oxidative factors. the study was showed more relationship between the 7 articles which are used in this study. Conclusion: This review was showed probiotic positive function on PCOS treatment in the women.

ROLE OF SATVAVAJAYA CIKITSA IN STRESS, QUALITY OF LIFE, PSYCHOSO-CIAL WELL-BEING AND SEXUAL SATISFACTION IN WOMEN WITH POLYCYS-TIC OVARY SYNDROME

Polycystic ovary syndrome is a multisystem disorder having a great impact on psychological and social functioning. It may attribute poor QOL and reduced sexual satisfaction. A non-randomized controlled clin-ical trial to evaluate the add-on effect of Satvavajya Cikitsa in stress, QOL and Psychosocial wellbeing in 30 eligible women in the age group of 18-40 receiving treatment for PCOS from a tertiary care Ayurvedic hospital was tried. 30 participants were consecutively divided into trial group receiving counseling along with conventional treatment for PCOS symptoms and the control group receiving conventional treatment alone. The trial group underwent three sessions of supportive counseling incorporating Ayurvedic princi-ples, each of one-hour duration with 15 days gap. Main outcome measures included psychological stress, PCOS related QOL and general QOL in psycho-social domains and sexual satisfaction. Changes were sig-nificantly different in two groups in stress scores (p<0.001), PCOS related QOL (p<0.001) and general QOL in the Psychological (p<0.01) and social (p<0.05) domains and sexual satisfaction (p<0.05) after the intervention. Better clinical efficacy was also noticed in the trial group.

The Effect of Metformin on Polycystic Ovary Syndrome in Overweight Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objective Metformin is an important component of PCOS treatment. At present, the effect of metformin in overweight women with PCOS has not been evaluated. Therefore, we conducted a systematic review to assess the effects of metformin in overweight women with PCOS and to analyze the effects of metformin in overweight women with PCOS. Methods We searched the PubMed, Cochrane Library, Embase, CNKI, VIP, and Wanfang databases for studies published before March 2020. Randomized controlled trials were identified to study the effects of metformin in overweight women with PCOS. Data from studies including body mass index (BMI), waist circumference (WC), follicle-stimulating hormone (FSH), homeostasis model assessment of insulin resistance (HOMA-IR), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol (TC), triglycerides (TG), fasting blood glucose (FBG), fasting insulin, testosterone, and androstenedione were pooled. Qualified trials were selected, and methodological quality was strictly assessed. Two reviewers chose the studies independently of each other. Results Twelve trials were included. The intervention group and the control group had significant differences in the changes in body mass index (BMI) (WMD = −1.25, 95% CI (−1.60, −0.91), p < 0.00001) and waist circumference (WC) (WMD = −1.41, 95% CI (−2.46, −0.37), p=0.008) after metformin. The comprehensive results show that, in all studies, overweight women with polycystic ovary syndrome treated with metformin had significantly improved endocrine and metabolic indicators, including testosterone, follicle-stimulating hormone, luteinizing hormone, and low-density lipoprotein cholesterol. However, metformin did not regulate the secretion indexes of fasting insulin, homeostasis model assessment of insulin resistance, sex hormone-binding globulin, high-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting blood glucose, and androstenedione. Conclusions Compared with control interventions, metformin appears to be an effective intervention for overweight women with PCOS.

CHARACTERISTICS OF WOMEN WITH PCOS WHO UNDERGO ENDOMETRIAL BIOPSIES

In 2018, the International Evidence-Based Guidelines for the Assessment and Management of PCOS were released to integrate best practices for the diagnosis and treatment of PCOS. These guidelines do not include recommendations about endometrial biopsies for women with PCOS. Although patients with PCOS are at increased risk of endometrial hyperplasia and carcinoma due to unopposed estrogen and oligomenorrhea, no clear guidelines for endometrial biopsy for women with PCOS exist. The objective of this study is to assess characteristics of patients with PCOS who undergo endometrial biopsies. Retrospective chart review A retrospective chart review of women ages 12-65 who were seen at a university hospital system in 2017 with an ICD code for PCOS were identified and demographic, clinical, laboratory, and ultrasound data were collected in REDCap Database. Patient characteristics were compared for women who did and did not undergo endometrial biopsy, and results of endometrial biopsies were analyzed. Statistical analysis was performed with SAS 9.4 (Cary, NC) software with data analysis performed via t-test and Chi-square test, as appropriate, and a p-value <0.05 was considered significant. Of the 450 patients with PCOS identified, 51 patients had endometrial biopsies. Factors associated with having an endometrial biopsy performed were older age, diabetes, and irregular menses which were significantly different between the groups. Ethnicity, BMI, PCOS by updated guidelines, previous hormone treatment, and metformin use were not different between groups. Of the endometrial biopsies performed, 76% were benign, 20% had hyperplasia, and 2% had malignancy. Having diabetes, irregular menses, or older age increased the chance of endometrial biopsy being performed. As expected, a high percentage (22%) of patients with PCOS had endometrial hyperplasia or cancer on endometrial biopsy. Although most endometrial biopsies performed in our study were benign, future research is needed to establish clear guidelines for performing endometrial biopsies for women with PCOS since this group is at increased risk for endometrial hyperplasia and malignancy.

METFORMIN SHOULD BE RECOMMENDED FOR MORE PATIENTS WITH PCOS BASED ON UPDATED GUIDELINES

In 2018, the International Evidence-Based Guidelines for the Assessment and Management of PCOS were released to integrate best practices for the diagnosis and treatment of PCOS. Among these guidelines are updated recommendations for the use of metformin in patients with PCOS. These recommendations advise that patients with PCOS and BMI≥25, impaired glucose tolerance, and/or adolescents age <18 should take metformin to prevent metabolic sequelae of PCOS (1). Previously, metformin use was recommended for patients with PCOS who displayed evidence of glucose intolerance and/or hyperinsulinemia (2,3). The objective of this study was to evaluate patients with PCOS who are and should be taking metformin based on these updated recommendations. Retrospective chart review. A retrospective chart review of women ages 12-65 who were seen at a university system in 2017 with an ICD code for PCOS were identified and demographic, clinical, laboratory, and ultrasound data were collected in REDCap database. Forty-two women with a self-reported history of diabetes were eliminated to assess patients who were on metformin for PCOS. Patients with PCOS based on updated guidelines were identified with 2 out of 3 of the following criteria met 1) oligo or amenorrhea, 2) clinical and/or laboratory hyperandrogenism, 3) either ovary displaying ≥20 follicles between 2-9mm and/or volume > 10mL (1). It was determined whether the patients with PCOS based on new guidelines were currently taking metformin, and if they should be taking metformin based on updated recommendations as above. Patients with previously diagnosed PCOS were similarly analyzed, and it was determined if they should be taking metformin based on evidence of glucose intolerance and/or hyperinsulinemia. Statistical analysis was performed with SAS 9.4 (Cary, NC) software using Chi-square, and p-value <0.05 was considered significant. Significantly more women with PCOS by updated guidelines should be taking metformin than women with PCOS by previous guidelines. Using the old guidelines 12% of patients should be taking metformin which increased to 91% using the new guidelines (p<0.0001). Ninety-nine percent of patients who should be taking metformin by new guidelines meet criteria by BMI (Table 1). Based on updated guidelines, practitioners should prescribe metformin to more patients with PCOS, particularly those patients who are overweight and obese. Tabled 1PCOS, should be taking metformin (n=144)BMI ≥25142 (98.6%)Impaired glucose tolerance (A1c >5.7)22 (15.3%)Adolescence (age <18)17 (11.8%) Open table in a new tab

Morphological Changes in Ovaries in Rats with Experimental Polycystic Ovary

Polycystic ovary syndrome is one of the important causes of infertility, metabolic syndrome. Complications of PCOS are a serious health hazard. The relevance of the study of morphological changes in the ovaries in rats is justified by the need to improve the treatment of PCOS. The experiment consisted in the fact that rats from the experimental group received testosterone for 7 days and were in constant artificial daylight for 60 days. As a result of histological examination of the ovaries in this group, multiple cysts, foci of fibrosis were found. Vaginal smears in rats from the experimental and control groups were collected and compared. The extracted ovaries of rats of the experimental and control groups were compared, the differences in colour according to Van Gieson X 100, haematoxylin-eosin X 40, haematoxylin-eosin X 100, B-G X 100 were analysed. Studies indicated oestrous cycle disturbance, hormonal changes in rats with experimental polycystic. The work can serve as material for further studies aimed at identifying fast and easily accessible methods for the diagnosis of metabolic syndrome predictors.

MON-033 Androgen Increases the Accumulation of Advanced Glycation End Products in Granulosa Cells by Activating ER Stress in PCOS

Polycystic ovarian syndrome (PCOS) is associated with hyperandrogenism. Previously we found that androgen activated endoplasmic reticulum (ER) stress in granulosa cells of antral follicles in PCOS, contributing to ovarian fibrosis (1) and growth arrest of antral follicles (2). In addition, recent studies demonstrated the accumulation of advanced glycation end products (AGEs) in granulosa cells from PCOS patients, which contribute to its pathology. Based on these findings, we hypothesized that androgen upregulates the expression of the receptor for AGEs (RAGE) in granulosa cells of antral follicles by activating ER stress. This in turn, increases the accumulation of AGEs in these cells. In the present study, we found that testosterone induced the expression of RAGE and accumulation of AGE in cultured human granulosa-lutein cells (GLCs). These effects were inhibited with the treatment of tauroursodeoxycholic acid (TUDCA), a clinically available ER stress inhibitor agent. Knockdown of the transcription factor C/EBP homologous protein (CHOP), an unfolded protein response (UPR) factor activated by ER stress, inhibited the testosterone-induced RAGE expression and AGE accumulation. Pretreatment with flutamide, as well as knockdown of androgen receptor decreased the testosterone-induced RAGE expression. Expression of RAGE was increased in GLCs obtained from patients with PCOS. Concomitantly, the expression of RAGE and the accumulation of AGE was increased in granulosa cells of antral follicles from PCOS patients and dehydroepiandrosterone (DHEA)-induced PCOS mice. Administration of the RAGE inhibitor, FPS-ZM1 or TUDCA to PCOS mice, reduced the expression of RAGE and the accumulation of AGE in granulosa cells of antral follicles, accompanied by a reduction of atretic follicles and improvement in the estrous cycle. In summary, our findings indicate that hyperandrogenism in PCOS increases the expression of RAGE and accumulation of AGEs in the ovary by activating ER stress. The potential therapeutic benefit of targeting the AGE-RAGE system, either with a RAGE inhibitor or an ER stress inhibitor agents, may serve as a novel approach for the treatment of PCOS. (1) Takahashi et al. Sci Rep. 2017;7(1):10824. (2) Azhary et al. Endocrinol. 2019;160(1):119–132

MON-029 Polycystic Ovary Syndrome (PCOS) in Adolescent Girls:Toward a Simple On-Treatment Predictor of Post-Treatment Ovulation Rate

There is no approved treatment for adolescent girls with PCOS. The vast majority of these patients are guided into a trajectory that starts with oral contraceptive (OC) treatment, leads into oligo-anovulatory subfertility, then into the use of assisted reproductive techniques, and ultimately into pregnancies with a double-to-triple risk for complications (such as gestational diabetes, preeclampsia and preterm birth) potentially with lifelong sequelae in the offspring.Evidence is converging into the insight that adolescent PCOS is frequently driven by hepato-visceral fat excess (“central obesity”) ensuing from a mismatch between (rather restrictive) prenatal and (rather abundant) postnatal nutrition, on a background of genetic susceptibility (Trends Endocrinol Metab 2018;29:815). This insight has prompted the exploration of an alternative PCOS treatment that aims at reducing the central-fat excess (without causing weight loss in non-obese girls) in order to normalize the entire phenotype, including ovulation rate.So far, this alternative approach has been tested in two randomized controlled pilot studies that were performed in non-obese girls with PCOS and with no need for contraception (total N=62; age 16 yr; BMI 24 Kg/m2; treatment for 1 year; ovulation assessment during the post-treatment year). In these studies, the effects of an OC were compared to those of SPIOMET, which is a low-dose combination of spironolactone (= a mixed anti-androgen and -mineralocorticoid, also activating brown adipose tissue; Diab Ob Metab 2019;21:509), pioglitazone and metformin (= two insulin sensitizers acting through different mechanisms).Pooled results of the pilot studies confirm the first report (J Adolesc Health 2017;61:446) that SPIOMET has more normalizing effects than OC; there were approximately 3-fold more ovulations post-SPIOMET than post-OC; normovulation occurred only post-SPIOMET; anovulation was >10-fold more frequent post-OC.Pooled results also disclosed two new features of adolescent PCOS: low concentrations of circulating CXCL14 (= a brown adipokine, signaling activity in brown adipose tissue; Cell Metab 2018;28:750) and miR-451a (= an inhibitor of THRSP-mediated hepatic lipogenesis; Mol Cell Endocrinol 2018;474:260), both of which remain abnormally low on OC, but normalize on SPIOMET treatment. The on-treatment Z-scores of fasting insulin and miR-451a explained together approximately 50% of the variation in post-treatment ovulation rates. This simple duo, if validated in larger and more diverse PCOS populations, may become a first on-treatment predictor of post-treatment ovulation rate.

Measures of Patient Dissatisfaction With Health Care in Polycystic Ovary Syndrome: Retrospective Analysis.

BackgroundPolycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder in women; however, many clinicians may not be well versed in scientific advances that aid understanding of the associated reproductive, metabolic, and psychological abnormalities. Women with PCOS are dissatisfied with health care providers, the diagnostic process, and the initial treatment of PCOS and seek information through alternative sources. This has affected the patient-physician relationship by allowing medical information acquired through the internet, whether correct or not, to become accessible to patients and reshape their health care perspective. Patient dissatisfaction with health care providers regarding PCOS raises questions about the responsibilities of academic institutions to adequately train and maintain the competence of clinicians and government agencies to sufficiently support scientific investigation in this field.ObjectiveThe primary aim was to examine internet searching behaviors of the public regarding PCOS vs another highly prevalent gynecologic disorder. The secondary aim was to explore satisfaction with health care among patients with PCOS and their internet use. The tertiary aim was to examine medical education in reproductive endocrinology and infertility (REI) during obstetrics and gynecology (Ob/Gyn) residency as a proxy for physician knowledge in this field.MethodsGoogle search trends and StoryBase quantified monthly Google absolute search volumes for search terms related to PCOS and fibroids (January 2004 to December 2017; United States). The reproductive disorder, fibroids, was selected as a comparison group because of its high prevalence among women. Between female groups, monthly absolute search volumes and their trends were compared. A Web-based questionnaire (June 2015 to March 2018) explored health care experiences and the internet use of women with PCOS. REI rotation information during Ob/Gyn residency in the United States was obtained from the Association of Professors of Gynecology and Obstetrics website.ResultsFor PCOS (R=0.89; P<.01), but not fibroids (R=0.09; P=.25), monthly absolute search volumes increased significantly. PCOS-related monthly absolute search volumes (mean 384,423 searches, SD 88,756) were significantly greater than fibroid-related monthly absolute search volumes (mean 348,502 searches, SD 37,317; P<.05). PCOS was diagnosed by an Ob/Gyn in 60.9% (462/759) of patients, and 57.3% (435/759) of patients were dissatisfied with overall care. Among patients with PCOS, 98.2% (716/729) searched for PCOS on the Web but only 18.8% (143/729) of patients joined an online PCOS support group or forum. On average, Ob/Gyn residencies dedicated only 4% (2/43) of total block time to REI, whereas 5.5% (11/200) of such residencies did not offer any REI rotations.ConclusionsOver time, PCOS has been increasingly searched on the Web compared with another highly prevalent gynecologic disorder. Patients with PCOS are dissatisfied with their health care providers, who would benefit from an improved understanding of PCOS during Ob/Gyn residency training.

Effects of a ketogenic diet in overweight women with polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is the most common endocrine disorder in women during reproductive age. It is characterised clinically by oligo-ovulation or anovulation, hyper-androgenism, and the presence of polycystic ovaries. It is associated with an increased prevalence of metabolic syndrome, cardiovascular disease and type 2 diabetes. The onset of PCOS has been associated to several hereditary and environmental factors, but insulin resistance plays a key pathogenetic role. We sought to investigate the effects of a ketogenic diet (KD) on women of childbearing age with a diagnosis of PCOS.MethodsFourteen overweight women with diagnosis of PCOS underwent to a ketogenic Mediterranean diet with phyoextracts (KEMEPHY) for 12 week. Changes in body weight, body mass index (BMI), fat body mass (FBM), lean body mass (LBM), visceral adipose tissue (VAT), insulin, glucose, HOMA-IR, total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides (TGs), total and free testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH); dehydroepiandrosterone sulfate (DHEAs), estradiol, progesterone, sex hormone binding globulin (SHBG) and Ferriman Gallwey score were evaluated.ResultsAfter 12 weeks, anthropometric and body composition measurements revealed a significant reduction of body weight (− 9.43 kg), BMI (− 3.35), FBM (8.29 kg) and VAT. There was a significant, slightly decrease of LBM. A significant decrease in glucose and insulin blood levels were observed, together with a significant improvement of HOMA-IR. A significant decrease of triglycerides, total cholesterol and LDL were observed along with a rise in HDL levels. The LH/FSH ratio, LH total and free testosterone, and DHEAS blood levels were also significantly reduced. Estradiol, progesterone and SHBG increased. The Ferriman Gallwey Score was slightly, although not significantly, reduced.ConclusionsOur results suggest that a KD may be considered as a valuable non pharmacological treatment for PCOS. Longer treatment periods should be tested to verify the effect of a KD on the dermatological aspects of PCOS.Trial registration Clinicaltrial.gov, NCT04163120, registrered 10 November 2019, retrospectively registered, https://clinicaltrials.gov.