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Background: The mechanisms underlying ovulatory dysfunction in PCOS remain debatable. This study aimed to identify the factors affecting ovulation among PCOS patients based on a large sample-sized randomized control trial., Methods: Data were obtained from a multi-centered randomized clinical trial, the PCOSAct, which was conducted between 2011 and 2015. Univariate and multivariate analysis using binary logistic regression were used to construct a prediction model and nomogram. The accuracy of the model was assessed using receiver operating characteristic (ROC) curves and calibration curves., Results: The predictive variables included in the training dataset model were luteinizing hormone (LH), free testosterone, body mass index (BMI), period times per year, and clomiphene treatment. The ROC curve for the model in the training dataset was 0.81 (95% CI [0.77, 0.85]), while in the validation dataset, it was 0.7801 (95% CI [0.72, 0.84]). The model showed good discrimination in both the training and validation datasets. Decision curve analysis demonstrated that the nomogram designed for ovulation had clinical utility and superior discriminative ability for predicting ovulation., Conclusions: The nomogram composed of LH, free testosterone, BMI, period times per year and the application of clomiphene may predict the ovulation among PCOS patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Sexual hormone binding globulin (SHBG) is associated with the endocrine and reproductive systems. We aimed to investigate the role of SHBG in the reproductive process. Therefore, we conducted a secondary analysis of the PCOSAct (Polycystic Ovary Syndrome and Acupuncture Clinical Trial) study, which involved 21 sites in China and a total of 1000 women with PCOS. Out of these, 954 women with SHBG were included in the analysis. Through multivariate analysis of ovulation predictors, we found that age, BMI, estradiol, testosterone, and SHBG all showed a positive predictive value for ovulation ( p  = 0.0211, 0.0011, 0.0211, 0.0029, 0.0434, respectively). However, the LH to FSH ratio had a negative predictive value ( p  = 0.0539). Higher quartiles of SHBG were associated with a higher rate of ovulation, and per quartile increased was statistically significant (HR = 1.138, 95%CI [1.054,1.229]). The association remained significant even after adjusting for testosterone (HR = 1.263, 95%CI [1.059, 1.507]). On the other hand, quartiles of testosterone and estradiol did not exhibit any significant tendency toward ovulation. SHBG demonstrated predictive ability for ovulation, conception, pregnancy, and live birth ( p  < 0.05), and this correlation remained significant after adjusting intervention. Kaplan-Meier curves illustrated that increased levels of SHBG were a factor in high rates of ovulation, conception, and pregnancy. In comparison to other sexual hormones, a higher baseline level of SHBG was related to increased ovulation.

Objective: This study aims to evaluate the effect of acupuncture on the emotion domain and metabolic parameters of Chinese women with polycystic ovarian syndrome (PCOS) by secondary analysis of a randomized clinical trial, conducted from 6 July 2012 to 7 October 2015., Method: In this study, we investigated the effects of acupuncture (458 patients) and sham acupuncture (468 patients) on metabolic parameters, serum ions, and all quality-of-life scale scores related to PCOS. The quality of life of patients was evaluated using five relevant scales, operated by the research assistant, namely, PCOSQ, SF-36, and ChiQOL, as well as Zung-SAS and Zung-SDS. Metabolic parameters and serum ions were measured., Results: A reduction in acne score, AN, Hcy, and LDL-C, and an increase in the level of lipoprotein α, Apo A1, and Apo A1/Apo B were observed in the acupuncture group after 4 months' intervention after adjusting clomiphene and reproductive outcome ( p < 0.05). An increase in SF-36 total scores, RP and RE scores, ChiQOL total scores, and emotion domain scores was observed in the acupuncture group after 4 months' intervention, while PF and HT scores were decreased (adjusted p < 0.05). Those same changes were observed in sham acupuncture. Meanwhile, the serum levels of Ca, K, and Cl were elevated in the acupuncture group after the interventions (adjusted p < 0.005). There were no significant differences in HOMA-IR, MetS, FPG, FINS, HDL-C, TG, Apo B, and level of serum P, Mg, and Na. Also, no changes in BP, GH, VT, SF, physical form domain, and spirit domain were observed after treatment., Conclusion: Acupuncture can improve not only the emotional changes in SF-36 scores and ChiQOL scores, but also lipid metabolism, implying that it may have a correlation between emotional change and lipid metabolism. Furthermore, acupuncture can also regulate the changes of serum Ca, K, and Cl., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT01573858., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chang, Shi, Ge, Liu, Wang, Ma, Liu, Zhang, Zhang, Wang, Wang and Wu.)

Background: Excessive production of androgen drives oxidative stress (OS) and inflammasome activation in ovarian granulosa cells (GCs). Therefore, the induced follicular developmental disorder is the major cause of infertility in women with polycystic ovary syndrome (PCOS). Exercise-induced upregulation of irisin is capable of regulating metabolism by reducing OS and inflammation. Exercise has been shown to alleviate a range of PCOS symptoms, including maintaining a normal menstrual cycle, in several clinical trials., Methods: Female Sprague-Dawley (SD) rats and primary ovarian cells were treated with two different androgens, dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT), to simulate a hyperandrogenic environment, followed by eight weeks of exercise training and irisin intervention. The levels of reactive oxygen species (ROS), tissue inflammation and fibrosis were examined using hematoxylin and eosin (H&E) staining, western blot, quantitative real-time PCR (qRT-PCR), dichlorofluorescein diacetate (DCF-DA) probe detection, immunofluorescence staining, immunohistochemistry, and Sirius red staining., Results: Exercise for eight weeks improved polycystic ovarian morphology and decreased the levels of inflammation, OS, and fibrosis in PCOS rats. Hyperandrogen increased ROS production in ovarian cells by inducing endoplasmic reticulum stress (ERS) and activating the inositol-requiring enzyme 1α (IRE1α)-thioredoxin-interacting protein (TXNIP)/ROS-NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathway, further enhancing the levels of inflammation. Irisin suppressed the expression of IRE1α and its downstream targets, thus improving the ovarian dysfunction of PCOS rats induced by hyperandrogen., Conclusion: Exercise can alleviate various phenotypes of PCOS rats induced by DHEA, and its therapeutic effect may be mediated by secreting beneficial myokines. IRE1α may be an important target of irisin for reducing OS and inflammation, thereby improving ovarian fibrosis., (© 2023. The Author(s).)

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder affecting women at reproductive age. The therapeutic effect of electroacupuncture (EA) on PCOS has been revealed, while the anti-PCOS mechanisms of EA have not been fully explored. In this study, PCOS were induced in rats by daily injection with dehydroepiandrosterone (DHEA) for 20 days and EA treatment was performed for 5 weeks. The mRNA expression profiles in ovarian tissues from control, PCOS, and EA-treated rats were examined by high-throughput mRNA sequencing. 5'-aminolevulinate synthase 2 (Alas2), a vital rate-limiting enzyme of the heme synthesis pathway, was selected to be further studied. PCOS led to the upregulation of Alas2 mRNA, whereas EA treatment restored this change. In vitro, primary ovarian granulosa cells (GCs) were challenged with H 2 O 2 to mimic the oxidative stress (OS) state in PCOS. H 2 O 2 induced apoptosis, OS, mitochondrial dysfunction, as well as Alas2 overexpression in GCs, while lentivirus-mediated Alas2 knockdown evidently restrained the above impairments. In summary, this study highlights the crucial role of Alas2 in cell apoptosis, OS, and mitochondrial dysfunction of PCOS GCs and provides potential therapeutic candidates for further investigation on PCOS treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: We aimed to evaluate the effect of low-frequency electro-acupuncture (EA) in unmarried women with polycystic ovary syndrome (PCOS)., Design: A total of 54 women with PCOS were randomly assigned to either the acupuncture group (n=27) or the sham acupuncture group (control, n=27) for a total of 32 treatments over 16 weeks. In the acupuncture group 26 patients and in the control group 20 patients completed the trial., Outcome Measures: Main measures were androgen levels including 17-α-hydroxyprogesterone (17-α-OHP), androstenedione (A2), testosterone (T) and dehydroepiandrosterone (DHEA) at 0, 24 and 48 hours after stimulation with a dose of human chorionic gonadotropin (HCG). Other measures included body mass index, waist-to-hip ratio, sex hormone levels, etc., Results: After treatment, there was no significant difference in the main measures between the 2 groups (P > .05), except for the DHEA level at 0 h of HCG stimulation (P = .024) and acne score (P < .05). Comparison within the acupuncture group found that 17-α-OHP and A2 levels at 0 h and DHEA levels at 24 h of HCG stimulation after treatment were significantly decreased (P < .05), whereas T levels at 24 h were significantly increased (P < .05). Comparison within the control group showed 17-α-OHP level at 0 h and 17-α-OHP and A2 and DHEA levels at 24 h after treatment were significantly lower (P < .05). In addition, weight, BMI, HCG and Ferriman-Gallwey score in the acupuncture group and LH/FSH ratio was significantly reduced in the control group., Conclusion: Traditional EA is slightly more effective than sham acupuncture in reducing DHEA secretion and the acne score. Meanwhile, sham acupuncture is not completely ineffective. The specific mechanism of the two may be different.

Aim: To evaluate the association between the apolipoprotein B/A1 ratio (ApoB/ApoA1) and metabolic and endocrine parameters in women with polycystic ovary syndrome (PCOS)., Methods: This study was a secondary analysis of the Acupuncture and Clomiphene for Chinese Women with Polycystic Ovary Syndrome trial (PCOSAct), and 957 subjects with available ApoB and ApoA1 measurements were included. Tests for linear trends and linear regression were used to assess the relation between the ApoB/ApoA1 ratio and metabolic and endocrine parameters. Logistic regression was used to estimate the association between the ratio and risk of metabolic syndrome (MetS) and insulin resistance (IR). The receiver operating characteristics (ROC) curve was used to determine the predictive value of the ApoB/ApoA1 ratio for MetS and IR., Results: The results showed that the ApoB/ApoA1 ratio was positively associated with waist circumference, systolic blood pressure, total cholesterol, triglycerides, low-density lipoprotein, fasting plasma glucose, fasting insulin, homeostatic model assessment-insulin resistance, high free testosterone, high free androgen index, alanine transferase, aspartate transferase, and higher prevalence of MetS and IR, but was negatively correlated with high-density lipoprotein and sex hormone-binding globulin after adjusting for age and body mass index. Logistic regression showed that compared with the ApoB/ApoA1 ratio in first quartile, those in the fourth quartile demonstrated a higher risk of MetS (OR: 24.48, 95%CI: 8.54-70.15, P trend <0.001) and IR (OR: 1.78, 95%CI: 1.10-2.87, P trend <0.05) after adjusting for confounding factors. ROC curve results showed that the AUC MetS was 0.84 (95%CI: 0.81-0.86) and had 86.8% sensitivity and 70.3% specificity with a threshold value of 0.64, and the AUC IR was 0.68 (95%CI: 0.64-0.71) and had 74.3% sensitivity and 58.2% specificity with a threshold value of 0.56., Conclusions: Increased ApoB/ApoA1 ratio was associated with worse MetS components, IR, and elevated androgen hormones and liver enzymes. The ratio might be a useful tool to screen for MetS and IR in PCOS patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 He, Feng, Zhang, Wang, Li, Gao, Cong, Gong and Wu.)

The mechanisms that link hyperandrogenism and insulin (INS) resistance (HAIR) to the increased miscarriage rate in women with polycystic ovary syndrome (PCOS) remain elusive. Previous studies demonstrate that increased uterine and placental ferroptosis is associated with oxidative stress-induced fetal loss in a pre-clinical PCOS-like rat model. Here, we investigated the efficacy and molecular mechanism of action of the antioxidant N-acetylcysteine (NAC) in reversing gravid uterine and placental ferroptosis in pregnant rats exposed to 5α-dihydrotestosterone (DHT) and INS. Molecular and histological analyses showed that NAC attenuated DHT and INS-induced uterine ferroptosis, including dose-dependent increases in anti-ferroptosis gene content. Changes in other molecular factors after NAC treatment were also observed in the placenta exposed to DHT and INS, such as increased glutathione peroxidase 4 protein level. Furthermore, increased apoptosis-inducing factor mitochondria-associated 2 mRNA expression was seen in the placenta but not in the uterus. Additionally, NAC was not sufficient to rescue DHT + INS-induced mitochondria-morphological abnormalities in the uterus, whereas the same treatment partially reversed such abnormalities in the placenta. Finally, we demonstrated that NAC selectively normalized uterine leukemia inhibitory factor, osteopontin/secreted phosphoprotein 1, progesterone receptor, homeobox A11 mRNA expression and placental estrogen-related receptor beta and trophoblast-specific protein alpha mRNA expression. Collectively, our data provide insight into how NAC exerts beneficial effects on differentially attenuating gravid uterine and placental ferroptosis in a PCOS-like rat model with fetal loss. These results indicate that exogenous administration of NAC represents a potential therapeutic strategy in the treatment of HAIR-induced uterine and placental dysfunction., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This work sought to evaluate the effects of three androgen indexes of free testosterone (FT), total testosterone (TT), and free-androgen index (FAI) on clinical phenotype, endocrine metabolic disorders, and fertility outcomes in women with polycystic ovary syndrome. The data in this study came from a large, multicenter, randomized double-blind controlled clinical trial involving 1000 infertile PCOS patients. Baseline phenotypic, endocrine, and metabolic parameters and fertility outcomes undergoing ovulation induction were collected. FAI is superior to FT, and FT is superior to TT in terms of their correlation with anthropometric parameters and metabolic profile. FT and TT were significantly positively correlated with LH/FSH. FAI and FT were significantly correlated with the incidence of metabolic syndrome. FAI, FT, and TT were significantly positively correlated with polycystic ovary morphology and menstrual period. FAI was significantly related ovulations per cycle, pregnancy, conception, and live birth rates. After adjusting for age, the increased FT level was significantly related to the decreased rates of ovulations per cycle, conception, and pregnancy. FAI is superior to FT and FT is superior to TT in terms of their correlation with phenotypic and metabolic parameters in PCOS patients. FAI and FT are important factors related to the fertility outcomes of infertile PCOS patients. Clinical trial registration number: NCT01573858.

Background: Polycystic ovary syndrome (PCOS) is the most frequent cause of anovulatory infertility. In women with PCOS, effective ovulation induction serves as an important first-line treatment for anovulatory infertility. Individual participant data (IPD) meta-analysis is considered as the gold standard for evidence synthesis which provides accurate assessments of outcomes from primary randomised controlled trials (RCTs) and allows additional analyses for time-to-event outcomes. It also facilitates treatment-covariate interaction analyses and therefore offers an opportunity for personalised medicine., Objective and Rationale: We aimed to evaluate the effectiveness of different ovulation induction agents, in particular letrozole alone and clomiphene citrate (CC) plus metformin, as compared to CC alone, as the first-line choice for ovulation induction in women with PCOS and infertility, and to explore interactions between treatment and participant-level baseline characteristics., Search Methods: We searched electronic databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials up to 20 December 2018. We included RCTs comparing the following interventions with each other or placebo/no treatment in women with PCOS and infertility: CC, metformin, CC plus metformin, letrozole, gonadotrophin and tamoxifen. We excluded studies on treatment-resistant women. The primary outcome was live birth. We contacted the investigators of eligible RCTs to share the IPD and performed IPD meta-analyses. We assessed the risk of bias by using the Cochrane risk of bias tool for RCTs., Outcomes: IPD of 20 RCTs including 3962 women with PCOS were obtained. Six RCTs compared letrozole and CC in 1284 women. Compared with CC, letrozole improved live birth rates (3 RCTs, 1043 women, risk ratio [RR] 1.43, 95% confidence interval [CI] 1.17-1.75, moderate-certainty evidence) and clinical pregnancy rates (6 RCTs, 1284 women, RR 1.45, 95% CI 1.23-1.70, moderate-certainty evidence) and reduced time-to-pregnancy (6 RCTs, 1235 women, hazard ratio [HR] 1.72, 95% CI 1.38-2.15, moderate-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline serum total testosterone levels and treatment effects on live birth (interaction RR 1.29, 95% CI 1.01-1.65). Eight RCTs compared CC plus metformin to CC alone in 1039 women. Compared with CC alone, CC plus metformin might improve clinical pregnancy rates (8 RCTs, 1039 women, RR 1.18, 95% CI 1.00-1.39, low-certainty evidence) and might reduce time-to-pregnancy (7 RCTs, 898 women, HR 1.25, 95% CI 1.00-1.57, low-certainty evidence), but there was insufficient evidence of a difference on live birth rates (5 RCTs, 907 women, RR 1.08, 95% CI 0.87-1.35, low-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline insulin levels and treatment effects on live birth in the comparison between CC plus metformin and CC (interaction RR 1.03, 95% CI 1.01-1.06)., Wider Implications: In women with PCOS, letrozole improves live birth and clinical pregnancy rates and reduces time-to-pregnancy compared to CC and therefore can be recommended as the preferred first-line treatment for women with PCOS and infertility. CC plus metformin may increase clinical pregnancy and may reduce time-to-pregnancy compared to CC alone, while there is insufficient evidence of a difference on live birth. Treatment effects of letrozole are influenced by baseline serum levels of total testosterone, while those of CC plus metformin are affected by baseline serum levels of insulin. These interactions between treatments and biomarkers on hyperandrogenaemia and insulin resistance provide further insights into a personalised approach for the management of anovulatory infertility related to PCOS., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The aim of this study was to evaluate the effects of hyperinsulinaemia and insulin resistance (IR) on reproductive and metabolic disorders and fertility in women with polycystic ovary syndrome (PCOS)., Design, Setting, Participants and Measurements: This was a multicenter, randomized controlled trial involving a total of 1000 women diagnosed with PCOS according to the modified Rotterdam criteria at 21 sites (27 hospitals). We evaluated the effects of serum insulin levels and HOMA-IR on parameters and outcomes. The main outcome measures were anthropometric, biometric and ultrasound parameters at baseline and the clinical outcomes of ovulation, conception, pregnancy, live birth and pregnancy loss., Results: The relevant analysis between hyperinsulinaemia and IR and clinical characteristics showed that weight, waist and hip circumference, BMI, waist-to-hip ratio, acanthosis nigricans score and menstrual period were significantly correlated with fasting insulin (FIN) and HOMA-IR. There was no significant correlation between the hirsutism score or acne score with FIN or HOMA-IR. The relevant analysis between hyperinsulinaemia and IR and circulating sex steroids and gonadotrophins showed that FAI was significantly correlated with FIN and HOMA-IR (r = 0.240, P < 0.001 and r = 0.191, P < 0.001, respectively). Free testosterone was significantly correlated with FIN after adjusting for the influence of age. LH and LH/FSH were not related to FIN or HOMA-IR after statistical correction for differences in BMI. The relevant analysis between hyperinsulinaemia and IR and metabolic profile showed that FIN and HOMA-IR were positively associated with fasting glucose, cholesterol, triglycerides, low-density lipoprotein, Apo B, and the incidence of metabolic syndrome and were negatively associated with high-density lipoprotein. The predictive analysis between hyperinsulinaemia and IR with fertility showed that the levels of FIN and HOMA-IR were related to the fertility outcome (ovulation, pregnancy, conception or live birth) in patients with PCOS. After adjustments for age, total testosterone and free testosterone, increasing serum insulin levels and HOMA-IR were significantly associated with decreased cycle ovulation, conception, pregnancy and live birth rates., Conclusions: Hyperinsulinaemia and IR are associated with reproductive and metabolic disorders and can predict the fertility outcomes in PCOS patients., (© 2019 John Wiley & Sons Ltd.)

Research Question: What is the association between hyperhomocysteinaemia (HHCY), metabolic syndrome, and reproductive outcomes among women with polycystic ovary syndrome (PCOS)., Design: A secondary analysis of PCOSAct with 21 sites in China. A total of 1000 women with PCOS were enrolled; 936 women with baseline homocysteine (HCY) were analysed., Results: Higher HCY was associated with higher body mass index, free testosterone and lower FSH, fasting glucose (P < 0.001; P < 0.001; P = 0.005; P < 0.001) and ovulation rate among all participants (OR 0.59, 95% CI 0.41 to 0.86; OR 0.57, 95% CI 0.39 to 0.83 tertiles 2 and 3 versus tertile 1, respectively). The HHCY group had lower oestradiol and higher free testosterone (P = 0.04; P < 0.001) than the controls. In the metabolic syndrome group, LH, LH-FSH ratio and sex hormone-binding globulin were lowest in the metabolic syndrome group (all P < 0.001). In the HHCY group, ovulation rate decreased and the second or third trimester pregnancy loss rate increased compared with controls (OR 1.678, 95% CI 1.04 to 2.70; OR 0.03, 95% CI 0.00 to 0.42) with treatment adjustment. Compared with the controls, ovulation, conception, pregnancy, second or third trimester pregnancy loss and live birth rates were statistically lower in the metabolic syndrome group after adjusting treatment (OR 1.76, 95% CI 1.15 to 2.70; OR 1.75, 95% CI 1.15 to 2.65; OR 2.09, 95% CI 1.27 to 3.44; OR 0.02, 95% CI 0.00 to 0.33; OR 2.42 95% CI 1.42 to 4.10), and pregnancy, pregnancy loss and live birth rates remained significantly different after adjusting for treatment and sex-hormone factors (OR 1.77, 95% CI 1.05 to 2.99; OR 0.14, 95% CI 0.02 to 0.82; OR 2.02, 95% CI 1.16 to 3.50)., Conclusions: In women with PCOS, HHCY contributes to increased pregnancy loss and reduced ovulation, and metabolic syndrome was related to defects in ovulation, conception, pregnancy, pregnancy loss and live birth, indicating that the two conditions lead to defects at various reproductive stages., (Copyright © 2019. Published by Elsevier Ltd.)

Objective: To evaluate the efficacy of electroacupuncture (EA) for the treatment of anxiety and depression in unmarried patients with polycystic ovarian syndrome (PCOS) by secondary analysis of a randomised controlled trial., Methods: A prospective pilot randomised controlled trial of unmarried women with PCOS was conducted from November 2012 to March 2016. Participants were assigned to the acupuncture group (receiving EA for 16 weeks) or the control group (receiving sham acupuncture for 16 weeks), with 27 patients in each group. The pre-specified primary outcomes and all secondary outcomes, with the exception of serum levels of neurotransmitters including norepinephrine (NE), epinephrine (AD), serotonin (5-HT) and γ-aminobutyric acid (GABA), will be reported separately. Additional outcome measures selected for this secondary analysis included anxiety and depression scale scores (Zung-SAS and Zung-SDS), 36-Item Short Form (SF-36) scale scores, PCOS Quality of Life (PCOSQOL) scale scores and Chinese Quality of Life (CHQOL) scale scores., Results: After the16-week intervention, an increase in serum NE and reduction in 5-HT were observed in the acupuncture group (P=0.028 and P=0.023, respectively). The serum level of GABA decreased in both groups after the interventions (both P<0.001). However, there were no significant differences between the two groups in the levels of any neurotransmitters (p>0.05). After EA treatment, SAS and SDS scores were decreased in the acupuncture group (P=0.007 and P=0.027, respectively) and were lower than those of the control group (P=0.003 and P=0.004, respectively). The SF-36 domain scores for mental health, vitality, social functioning, general health and health transition, the total CHQOL scores, and the infertility problems and body hair domains of the PCOSQOL improved significantly after EA (P<0.05)., Conclusion: EA appears to improve symptoms of anxiety/depression and quality of life in PCOS patients and may influence serum levels of NE and 5-HT. These findings should be interpreted with caution, given the secondary nature of the outcome measures reported herein., Trial Registration Number: NCT01812161; ChiCTR-TRC-12002529.

The design of research protocol and quality control are the key to ensure the quality of clinical trial. A randomized clinical trial regarding the effects of medication combined with acupuncture on live birth rate in polycystic ovary syndrome (PCOS), which was initially designed as a comparative effectiveness research, then added with an acupuncture control group and finally became a factorial analysis, is taken as an example to explain the protocol design and optimization process, demonstrating the high level of methodology design and international recognization. By a series of measurements, such as unified purchase of acupuncture equipment, multiple trainings and assessments for acupuncturists' knowledge and operation standardization, in-site supervision of local center experts, the standard operation of acupuncture could be ensured and the credibility and scientificity of research results could be improved.

Objective: To evaluate the effects of berberine on the menstrual pattern, ovulation rate, hormonal and metabolic profiles in anovulatory Chinese women with polycystic ovary syndrome., Methods: Berberine 0.4 g three times per day was given for four months to 102 anovulatory Chinese women with polycystic ovary syndrome. The menstrual pattern, ovulation rate, hormonal and metabolic profiles were compared before and after the berberine treatment. Ovulation was confirmed by serum progesterone level ≥10 ng/ml., Results: A total of 98 of 102 subjects (96.1%) completed the four month treatment, including 69 (70.4%, 69/98) normal weight and 29 (29.6%, 29/98) overweight/obese. Fourteen women (14.3%, 14/98) had regained regular menses after berberine treatment and there was no significant difference between normal weight and overweight/obese groups. The ovulation rate was 25.0% over four months in the whole group, 22.5% in the normal weight group and 31.0% in the overweight/obese group. Sex hormone binding globulin, insulin resistance, total cholesterol, total triglyceride and low-density lipoprotein cholesterol decreased after berberine treatment in the normal weight group only., Conclusions: Our study found that administration of berberine alone may improve the menstrual pattern and ovulation rate in anovulatory Chinese women with polycystic ovary syndrome. Berberine can also decrease sex hormone binding globulin, insulin resistance, total cholesterol, triglycerides and low-density lipoprotein cholesterol in normal weight polycystic ovary syndrome women., Trial Registration: Chictr.org ChiCTR-OO-13003943.

Introduction: Hyperinsulinaemia and insulin resistance (IR) are key features of polycystic ovary syndrome (PCOS) and metabolic syndrome. The effect of 5 weeks of acupuncture treatment has been investigated in a completed prospective pilot trial (Clinicaltrials.gov: NCT01457209), and acupuncture with electrical stimulation applied to insulin-resistant rats with dihydrotestosterone-induced PCOS was shown to improve insulin sensitivity. Therefore, we now aim to conduct a prospective pilot study to evaluate whether using the same acupuncture treatment protocol given over a longer period of time (6 months) than in the previous pilot trial will improve insulin sensitivity in women with PCOS and IR. Our hypothesis is that acupuncture with combined manual and low-frequency electrical stimulation of the needles will improve insulin sensitivity in women with PCOS and IR., Methods/analysis: This is a prospective pilot trial. A total of 112 women with PCOS and IR will be recruited and categorised according to their body mass index (BMI) as normal weight (BMI=18.5-23 kg/m(2)) or as overweight/obese (BMI>23 kg/m(2)). Acupuncture will be applied three times per week for 6 months at 30 min per treatment. The primary outcome will be the change in insulin sensitivity before and after 6 months of acupuncture treatment, as measured by an oral glucose tolerance test., Ethics/dissemination: Ethical approval of this study has been granted from the ethics committee of the First Affiliated Hospital of Guangzhou Medical University (No. 2013039). Written and informed consent will be obtained from each patient before any study procedure is performed, according to good clinical practice. The results of this trial will be disseminated in a peer-reviewed journal and presented at international congresses., Trial Registration Numbers: NCT02026323 and ChiCTR-OCH-13003921., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: This study aimed to investigate the effect of polycystic ovary syndrome (PCOS) on the association of aromatase activity assessed by estradiol-to-testosterone ratio (E2/T) with body mass index (BMI) in women., Methods: This was a cohort study in five centers for reproductive medicine in China. Data were collected from July 2012 to December 2013. PCOS patients (n = 785) and non PCOS, healthy, age-matched controls (n = 297) were included. Plasma sex hormones including estradiol (E2), testosterone (T), follicle stimulating hormone (FSH), and luteinizing hormone (LH) were measured by ELISA, together with BMI and E2/T being calculated, on the third day of the menstrual cycle. Aromatase activity in PCOS patients with different BMI, T and E2 levels were compared., Results: E2/T was significantly lower (P < 0.05) while BMI was significantly increased (P < 0.05) in PCOS than non-PCOS. No significant difference was observed in E2/T among different BMI subgroups of either PCOS or control. Ovarian aromatase activity was decreased in PCOS patients which was independent of BMI. Hyperestrogen promoted ovarian aromatase activity, while hyperandrogen inhibited such activity, both in a dose-dependent, biphasic manner., Conclusions: Ovarian aromatase activity was lower in PCOS, which was independent of BMI. New therapeutic strategies can be developed by targeting aromatase activity for treating PCOS women, especially those with obesity.

Aim: To compare the effect of a single session of acupuncture with either low-frequency electrical or manual stimulation on insulin sensitivity and molecular pathways in the insulin-resistant dihydrotestosterone-induced rat polycystic ovary syndrome (PCOS) model. Both stimulations cause activation of afferent nerve fibers. In addition, electrical stimulation causes muscle contractions, enabling us to differentiate changes induced by activation of sensory afferents from contraction-induced changes., Materials and Methods: Control and PCOS rats were divided into no-stimulation, manual-, and electrical stimulation groups and insulin sensitivity was measured by euglycemic hyperinsulinemic clamp. Manually stimulated needles were rotated 180° ten times every 5 min, or low-frequency electrical stimulation was applied to evoke muscle twitches for 45 min. Gene and protein expression were analyzed by real-time PCR and Western blot., Results: The glucose infusion rate (GIR) was lower in PCOS rats than in controls. Electrical stimulation was superior to manual stimulation during treatment but both methods increased GIR to the same extent in the post-stimulation period. Electrical stimulation decreased mRNA expression of Adipor2, Adrb1, Fndc5, Erk2, and Tfam in soleus muscle and increased ovarian Adrb2 and Pdf. Manual stimulation decreased ovarian mRNA expression of Erk2 and Sdnd. Electrical stimulation increased phosphorylated ERK levels in soleus muscle., Conclusions: One acupuncture session with electrical stimulation improves insulin sensitivity and modulates skeletal muscle gene and protein expression more than manual stimulation. Although electrical stimulation is superior to manual in enhancing insulin sensitivity during stimulation, they are equally effective after stimulation indicating that it is activation of sensory afferents rather than muscle contraction per se leading to the observed changes.

Objective: To identify aberrantly methylated candidate genes that are involved in the development of polycystic ovary syndrome (PCOS)., Design: Animal model., Setting: University-affiliated laboratory., Animal(s): Sprague-Dawley rats., Intervention(s): The prenatally androgenized (PNA) rat model was established. Pregnant rats were treated with daily SC injections of T propionate during late gestation, and their female offspring were studied as adults., Main Outcome Measure(s): Serum glucose and hormone levels, ovary morphology and cell apoptosis, genome-wide CpG methylation, and expression of caspase-3 protein were measured., Result(s): In the PNA group, the levels of serum glucose, 17-hydroxyprogesterone, and T were significantly higher when compared with the control group. Ovarian morphology showed increased atretic follicles and cystic follicles. Using the MeDIP-chip approach, we identified 528 genes that were hypermethylated in PNA ovaries. Gene ontology analyses revealed that these genes are involved in a variety of reproductive development and biological processes. The methylation enrichments of Bcl2l1 and Scr5a1 observed in the PNA group by MeDIP-quantitative polymerase chain reaction assay were significantly higher than those obtained from the control group. Furthermore, the mRNA level of the Bcl2l1 gene was significantly decreased in the PNA group. The percentage of caspase-3-positive cells in the PNA group was obviously higher compared with the control group, by terminal deoxynucleotidyl transferase dUTP nick end labeling detection as well., Conclusion(s): DNA methylation alteration may be an important factor affecting the genes involved in the pathophysiological processes that result in the phenotype of PCOS., (Copyright © 2014. Published by Elsevier Inc.)

Background: Polycystic ovary syndrome (PCOS) is a common condition estimated to affect 5.61% of Chinese women of reproductive age, but little is known about the prevalence and predictors in Chinese PCOS patients. This study aimed to determine the prevalence and predictors of the metabolic abnormalities in Chinese women with and without PCOS., Methods: A large-scale national epidemiological investigation was conducted in reproductive age women (19 to 45 years) across China. 833 reproductive aged PCOS women, who participated in the healthcare screening, were recruited from ten provinces in China. Clinical history, ultrasonographic exam (ovarian follicle), hormonal and metabolic parameters were the main outcome measures., Results: The prevalence of metabolic syndrome (MetS) as compared in PCOS and non-PCOS women from community were 18.2% vs 14.7%, and IR (insulin resistance) were 14.2% vs 9.3% (p < 0.001) respectively. After adjusting for age, the indicators (central obesity, hypertension, fasting insulin, SHBG, dyslipinaemia) for metabolic disturbances were significantly higher in PCOS than in non-PCOS groups. Using multivariate logistic regression, central obesity and FAI were risk factors, while SHBG was a protective factor on the occurrence of Mets and IR in PCOS women (OR: 1.132, 1.105 and 0.995)., Conclusions: The risk factors of the metabolic syndrome and insulin resistance were BMI and FAI for PCOS women, respectively. The decrease of SHBG level was also a risk factor for insulin resistance in both PCOS and metabolic disturbance.

Objective: This article aims to introduce the benefits of qualitative research and to discuss how such research can be applied to the study of polycystic ovary syndrome (PCOS)., Data Sources: Relevant articles were published in English as of May 2013 from Pubmed. Terms "polycystic ovary syndrome/PCOS, qualitative research and methodology" were used for searching., Study Selection: Articles studying PCOS with qualitative methods were reviewed. Articles associated with the use of qualitative research in clinical research were cited., Results: Six qualitative studies related to PCOS were found in the literature search. These studies addressed different aspects in PCOS women including their womanhood, lived experience, information need, and experience of treatment with acupuncture. Five of these six studies used phenomenology as guiding theory., Conclusion: Quantitative research has been the dominant approach in the field so far, qualitative research is relevant to the advancement of PCOS.

Study Question: What is the prevalence of polycystic ovary syndrome (PCOS) in Han Chinese women from different communities?, Summary Answer: The prevalence of PCOS in Chinese women aged 19-45 years is 5.6%., What Is Known Already: The prevalence of PCOS is reported to range from 5 to 10% but to the best of our knowledge the Han Chinese population has not been studied., Study Design, Size, Duration: A large-scale epidemiological study was carried out between October 2007 and September 2011 in 15 924 Han Chinese women of reproductive age (19-45 years) from the 10 provinces and municipalities in China., Participants/materials, Setting, Methods: A total of 16 886 women from 152 cities and 112 villages were involved in the study. All study participants received a questionnaire and underwent a physical and transvaginal ultrasound examination. Blood samples were collected from a subsample of women (n = 3565) for analysis of metabolic markers and hormones. Based on the Rotterdam PCOS criteria, we assessed hyperandrogenism (H), chronic anovulation (O) and polycystic ovaries (P). Following diagnosis, women with PCOS were assigned to one of four different phenotypes. Finally, the prevalence and related risks of PCOS among Chinese women were estimated based on all the data sources., Main Results and the Role of Chance: A total of 16 886 women were initially involved in the study and 15 924 eligible participants then completed the study; the overall response rate was 94.3% (15 924/16 886). The prevalence of PCOS in the Chinese community population was 5.6% (894/15 924). Blood samples were analyzed from 833 of these women who were assigned to the four PCOS phenotypes as follows: 19% H + O, 37% H + P, 15% O + P and 29% H + O + P. Comparing the 833 women with PCOS to 2732 women without PCOS indicated that PCOS occurs in younger women (P < 0.05) and these women were prone not only to menstrual problems, hyperandrogenism, PCO and infertility but also metabolic syndrome (MS) and insulin resistance (IR). However, there was no significant difference in the rate of hypertension or hyperlipemia between the two groups. Obese patients with PCOS had a higher rate of MS (16 versus 48%), IR (7 versus 28%), hypertension (8 versus 30%) and hyperlipemia (48 versus 73%) compared with non-obese patients (all P < 0.05), respectively. The rates of metabolic complications in patients with PCOS increased with age., Limitations, Reasons for Caution: Age and ethnic origin contribute to the differing manifestations of PCOS; therefore, sampling is one of the most important issues in epidemiological research into PCOS. Owing to the mobility of the Chinese population, the survey among resident populations caused a certain deviation in the age distribution., Wider Implications of the Findings: The prevention and treatment of PCOS, particularly in those who are obese, are essential in Chinese women of reproductive age.

Background: Insulin resistance and hyperinsulinemia play a key role in the pathogenesis of polycystic ovary syndrome (PCOS), which is characterized by hyperandrogenism, ovulatory dysfunction, and presence of polycystic ovaries on pelvic scanning. Insulin resistance is significantly associated with the long-term risks of metabolic syndrome and cardiovascular disease. Berberine has effects on insulin resistance but its use in women with PCOS has not been fully investigated. In this paper, we present a research design evaluating the effects of berberine on insulin resistance in women with PCOS., Methods/design: This is a multicenter, randomized, placebo-controlled and double-blind trial. A total of 120 patients will be enrolled in this study and will be randomized into two groups. Berberine or placebo will be taken orally for 12 weeks. The primary outcome is the whole body insulin action assessed with the hyperinsulinemic-euglycemic clamp., Discussion: We postulate that women with PCOS will have improved insulin resistance following berberine administration., Trial Registration: This study is registered at ClinicalTrials.gov, NCT01138930.

Human androgen receptor (AR) contains a highly polymorphic polyglutamine tract encoded by CAG repeats [(CAG)n] in exon 1 of the AR gene. The CAG repeats, ranging from 11 to 38, have been reported to be inversely correlated with AR activity. A case-control study involving 261 polycystic ovary syndrome (PCOS) patients and 278 healthy controls was conducted. Fluorescently labeled DNA fragments containing (CAG)n were obtained by PCR and genotyped via capillary electrophoresis. AR (CAG)n ranges were 6, 12-28 in PCOS cases and 9, 10, 12-32 in controls. In the PCOS group, a higher frequency of short (CAG)n alleles was found compared with that of controls (P=0.007). Similarly, CAG biallelic mean distributions also showed statistical difference between the two groups (P=0.025). In conclusion, shorter alleles of the (CAG)n in exon 1 of the AR gene enhanced the susceptibility to PCOS, either by upregulating AR activity or by causing hyperandrogenism.

Objective: To systematically review the literature to identify the impact of polycystic ovary syndrome (PCOS) on specific health-related quality of life domains., Design: Meta-analysis., Setting: N/A., Patient(s): The outcomes of 423 patients and 285 controls from 5 articles that used the Short Form 36 (SF-36) questionnaire were used for meta-analysis., Intervention(s): N/A., Main Outcome Measure(s): The SF-36 dimensions including physical function, physical role function, body pain, general health, vitality, social function, emotional role function, and mental health were evaluated., Result(s): Compared with controls, women with PCOS had lower scores in all SF-36 dimensions: physical function (mean differences [MD], -5.46; 95% confidence intervals [CI], -8.52, -2.41), physical role function (MD, -5.76; 95% CI, -8.49, -3.03), body pain (MD, -4.55; 95% CI, -7.99, -1.11), general health (MD, -11.34; 95% CI, -19.53, -3.15), vitality (MD, -15.14; 95% CI, -17.43, -12.84), social function (MD, -15.95, 95% CI, -18.57, -13.33), emotional role function (MD, -23.86; 95% CI, -27.51, -20.21), and mental health (MD, -13.83; 95% CI, -16.13, -11.53)., Conclusion(s): The meta-analysis showed that women with PCOS score lower in each dimension of the SF-36, mostly in the emotional role function., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is characterized by chronic hyperandrogenic anovulation leading to symptoms of hirsutism, acne, irregular menses, and infertility. Multiple metabolic and cardiovascular risk factors are associated with PCOS, including insulin resistance, obesity, type 2 diabetes, hypertension, inflammation, and subclinical atherosclerosis. However, current treatments for PCOS are only moderately effective at controlling symptoms and preventing complications. This article describes how the physiological effects of major complementary and alternative medicine (CAM) treatments could reduce the severity of PCOS and its complications. Acupuncture reduces hyperandrogenism and improves menstrual frequency in PCOS. Acupuncture's clinical effects are mediated via activation of somatic afferent nerves innervating the skin and muscle, which, via modulation of the activity in the somatic and autonomic nervous system, may modulate endocrine and metabolic functions in PCOS. Chinese herbal medicines and dietary supplements may also exert beneficial physiological effects in PCOS, but there is minimal evidence that these CAM treatments are safe and effective. Mindfulness has not been investigated in PCOS, but it has been shown to reduce psychological distress and exert positive effects on the central and autonomic nervous systems, hypothalamic-pituitary-adrenal axis, and immune system, leading to reductions in blood pressure, glucose, and inflammation. In conclusion, CAM treatments may have beneficial endocrine, cardiometabolic, and reproductive effects in PCOS. However, most studies of CAM treatments for PCOS are small, nonrandomized, or uncontrolled. Future well-designed studies are needed to further evaluate the safety, effectiveness, and mechanisms of CAM treatments for PCOS.

Theca cells with dexamethasone-induced insulin resistance showed defective glucose uptake and excessive testosterone production, both of which were effectively antagonized by berberine. Therefore, insulin-resistant theca cells may contribute to the pathogenesis of hyperandrogenism in polycystic ovary syndrome., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

In traditional Chinese medicine, polycystic ovary syndrome (PCOS) is considered an anovulation disorder related to ovarian insulin resistance. The three phenotypes of PCOS, according to the Rotterdam criteria, are differently steroidogenic but similarly insulin resistant, suggesting a similar involvement of insulin resistance/hyperinsulinemia in different compartments of the PCOS ovary, namely, overactive theca and/or granulosa cells., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: This study was to evaluate whether polymorphisms of TCF7L2 (rs7903146) and HHEX (rs1111875) genes responsible for insulin secretion are associated with the polycystic ovary syndrome (PCOS) in Chinese people., Methods: 326 PCOS patients and 290 healthy individuals as controls were studied. Blood samples were obtained for DNA analyses and hormone measurements. Genotyping of the TCF7L2 (rs7903146) and HHEX (rs1111875) genes was carried out by the polymerase chain reaction-restriction fragment length polymorphism method., Results: We did not find statistically significant differences in the distribution of the TCF7L2 rs7903146 and HHEX rs1111875 polymorphisms between the Chinese women with PCOS and the controls. Levels of hormones such as insulin, FSH, LH, LH/FSH, P, T and E2 were also similar between the different genotypes of the genes TCF7L2 and HHEX, respectively, which was confirmed within either the PCOS subjects or controls., Conclusions: There was no association of either of the two variants, rs7903146 of TCF7L2 and rs1111875 of HHEX, with the occurrence of PCOS in the Chinese population.

Background: I/D polymorphisms of ACE are associated with the plasma ACE concentration. The ACE is associated with the angiogenesis of ovarian endothelium in vitro as well as steroidogenesis and follicular growth in cattle. Since ACE induces a high blood supply and hypersteroidogenesis in the ovary, it may be associated with polycystic ovary syndrome (PCOS) which exhibits hyperplasia, hypervascularity of the ovarian theca interna and stroma, as well as disorderd steroidogenesis. Therefore, we hypothesized that the ACE plays some roles in the human ovary. To investigate whether the ACE I/D polymorphisms are associated with the steroidogenesis disorder in PCOS and contribute to the susceptibility of PCOS in Chinese women, we designed a case-controlled association study in 582 individuals., Methods: The ACE I/D polymorphisms were assessed in 582 reproductive-age women. Genotyping and frequency of ACE I/D polymorphisms were obtained by PCR amplification that was performed on genomic DNA isolated from blood leucocytes. Results were analyzed in respect to clinical test results., Results: The frequencies of the D allele and the genotypic distributions (DD, ID and II) in the women with PCOS did not differ from those in controls (P = 0.458). However, there were significant differences in the concentrations of testosterone among three genotypes both in the PCOS patients and controls (P = 0.0045, P = 0.0052, respectively). Differences were also found between these groups with distinct genotypes: DD versus II and DI versus II in the PCOS patients as well as DD versus DI and DD versus II in the controls. There were significant differences in the ratio of LH/FSH among three genotypes in the patients (P = 0.01). However, there were no statistical differences in the BMI, AAM, E2 concentrations and other serum hormone concentrations among the three genotypes both in the PCOS patients and controls., Conclusion: The ACE I/D polymorphisms were not associated with the pathogenesis of PCOS. However, the polymorphisms were associated with the steroidogenesis in the ovary. The observation indicated that the ACE I/D polymorphisms were not the key etiological factor, which in stead may be associated with the aggravated clinical manifestations of PCOS.

A (tttta)n microsatellite polymorphism in the promoter of CYP11a gene was investigated in 201 Chinese Han women with polycystic ovary syndrome (PCOS) and 147 control women. The 6/6 genotype was defined with significant difference of CYP11a polymorphism between women with PCOS and control women, and associated with greater BMI in PCOS patients, suggesting a certain role of the six-repeat allele variant in the pathogenesis of Chinese women with PCOS.

The polymorphisms of the peroxisome proliferator-activated receptor-gamma (Pro12Ala) and its coactivator-1 (Gly482Ser) genes were investigated among 201 Chinese Han women with polycystic ovary syndrome (PCOS) and among 147 regularly cycling women as control subjects. We did not find statistically significant differences with peroxisome proliferator-activated receptor-gamma2 Pro12Ala and peroxisome proliferator-activated receptor-gamma-1alpha Gly482Ser polymorphism distributions between Chinese women with PCOS and controls, or with body mass index and reproductive hormones among various genotypic groups of PCOS, suggesting that these genetic mutants did not have an effect on the susceptibility to PCOS.

Background In recent years, women with polycystic ovary syndrome (PCOS) have had a higher prevalence of lipid metabolism disorders, which are strongly associated with obesity and insulin resistance (IR) . Higher levels of lipid metabolism have been also found in PCOS women with normal body mass index (BMI) , but there are fewer studies on dyslipidemia in this population. Objective To investigate the factors influencing the development of hyperlipidemia in PCOS women with normal BMI. Methods Based on the data of the clinical trial Effect of Acupuncture and Clomiphene on Live Birth Rate in Women with Polycystic Ovary Syndrome (PCOSAct) , a total of 428 subjects with complete baseline data and meeting the study criteria were selected. The evaluation criteria for determining hyperlipidemia included total cholesterol (TC) 6.22 mmol/L and/or triglycerides (TG) 2.26 mmol/L and/or low-density lipoprotein (LDL) 4.14 mmol/L and/or high-density lipoprotein (HDL)

Background The incidence of insulin resistance (IR) is higher in patients with polycystic ovary syndrome (PCOS) regardless of whether they are obese, which seriously affects their reproductive and metabolic health. At present, there are few studies on the influencing factors of IR in PCOS patients with normal body mass index (BMI) . Objective To explore the influencing factors of IR in PCOS patients with normal BMI. Methods This study was a secondary analysis based on the clinical trial of the Effect of Acupuncture and Clomiphene Citrate on Live Birth in Infertile Women with PCOS (PCOSAct) , which was a multicenter, large-sample randomized controlled trial conducted in Chinese from 2011 to 2015, involving 1 000 PCOS infertile participants with fertility demand from 27 hospitals in the sub-centers, among whom 453 with normal BMI (18.5 kg/m2

Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women. Moderate aerobic exercise intervention is considered an initial treatment strategy for managing PCOS. Brain-derived neurotrophic factor (BDNF) is an important molecular mediator and a beneficial response to exercise. We aimed to investigate the expression pattern and underlying molecular mechanisms of this neurotrophic factor during follicle development in ovarian tissues. The PCOS model was established by subcutaneous injection of 60 mg/kg dehydroepiandrosterone (DHEA) into the neck of Sprague Dawley rats for 35 consecutive days. PCOS rats then received aerobic exercise for 8 weeks. Body/ovarian weight and peripheral serum hormone levels were observed. Immunohistochemistry combined with Western blot analysis and fluorescence quantitative polymerase chain reaction were used to detect the changes in BDNF-TrkB/p75NTR pathway, apoptosis, and inflammatory factors. We show that moderate aerobic exercise not only reverses the PCOS phenotype but also activates the BDNF-TrkB pathway and initiates downstream targets. p-TrkB upregulates and phosphorylates phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) to inhibit apoptosis. In addition, aerobic exercise therapy reduces the high expression of p75NTR in the ovarian tissue of PCOS rats and initiates the anti-apoptotic effect from the downstream pathway of NF-κB/JNK. Our in vitro results state that treatment with BDNF ameliorated dihydrotestosterone (DHT)-induced granulosa cells (GCs) apoptosis by provoking p-TrkB activation and upregulating the PI3K/AKT pathway. The present study suggests that moderate aerobic exercise regulates follicular dysfunction in PCOS-like rats. One possible mechanism is to initiate the BDNF-mediated anti-apoptotic signaling pathway. [ABSTRACT FROM AUTHOR]

As a highly dynamic tissue, the endometrium is periodically shed in response to the secretion of estrogen and progesterone. After menarche, the endometrium of healthy women proliferates and differentiates under the action of steroid hormones (e.g., 17β-estradiol and progesterone) that are secreted by the ovaries to provide appropriate conditions for embryo implantation. Polycystic ovary syndrome (PCOS), a prevalent endocrine and metabolic disorder in reproductive-aged women, is usually associated with multiple cysts within the ovaries and excess levels of androgen and is characterized by hirsutism, acne, menstrual irregularity, infertility, and increased risk of insulin resistance. Multiple factors, such as anovulation, endocrine-metabolic abnormalities, and inflammation, can disrupt the endometrium in PCOS patients and can lead to endometrial hyperplasia, pregnancy complications, or even cancer. Despite many recent studies, the relationship between PCOS and abnormal endometrial function is still not fully understood. In this review, we investigate the correlation of PCOS patient endometrium with anovulation, hyperandrogenemia, insulin resistance, progesterone resistance, and inflammatory cytokines, aiming to provide a theoretical basis for the treatment of disorders caused by endometrial dysfunction in PCOS patients. [ABSTRACT FROM AUTHOR]

Aim: This work sought to evaluate the correlation between the five domains of the Polycystic Ovary Syndrome Questionnaire (PCOSQ) and anxiety and depression scales and the clinical phenotype and fertility outcomes in infertile polycystic ovary syndrome (PCOS) patients and to determine the effect of quality of life (QOL) on the clinical, biochemical and fertility disorders in these patients. Methods: The data in this study came from a large‐scale hospital‐based cohort survey of infertile PCOS patients across mainland China. A total of 1000 infertile PCOS subjects diagnosed according to the modified Rotterdam criteria ranging in age from 20 to 40 years in 21 sub‐centers (27 hospitals) were enrolled. Baseline anthropometric parameters, endocrine indexes, metabolic panel, QOL questionnaires and the fertility outcomes of ovulation, conception, pregnancy, pregnancy loss and live birth were collected. Results: PCOSQ scores were significantly correlated with most of the baseline parameters. PCOSQ‐weight domain scores of National Institute of Health‐PCOS group were significantly lower compared with non‐National Institute of Health‐PCOS group. The five domains scores of PCOSQ were significantly negatively correlated with the body mass index levels of PCOS patients. The serum testosterone levels (total testosterone, free testosterone and free androgen index) were significantly negatively correlated to the scores for the weight, body hair, infertility and emotion domains of PCOSQ. Scores on the anxiety and depression scales were significantly and positively correlated with luteinizing hormone, luteinizing hormone/follicle‐stimulating hormone levels. In the low‐score group of infertility domain, the rates of conception, pregnancy and live birth decreased significantly. Conclusions: QOL appears to have an impact on the physical symptoms of PCOS, and the emotional stress of infertility affects fertility outcomes. [ABSTRACT FROM AUTHOR]

Purpose. To assess the efficacy and safety of berberine on reproductive endocrine and metabolic outcomes in women with polycystic ovary syndrome (PCOS). Methods. PubMed (from 1950), the Cochrane Library, the CNKI (from 1979), the VIP (from 1989), and the Wanfang Data (from 1990) and the reference lists of the retrieved articles were searched for randomized controlled trials in human beings with the search terms including "polycystic ovary syndrome/PCOS" and "berberine/BBR/Huangliansu (in Chinese)/Xiao bojian (in Chinese)" till 30 May 2019. Relevant indicators were collected and the data were analyzed by using RevMan 5.3 software. Results. Eventually, a total of 12 randomized controlled trials were included in this systematic review. Our study suggested that berberine had similar live birth rates compared with placebo or metformin and lower live birth rates (RR: 0.61, 95% CI: 0.44 to 0.82) compared with letrozole. There was a significant difference between berberine and placebo and between berberine and no treatment in terms of decreasing total testosterone and luteinizing hormone to follicle-stimulating hormone (LH/FSH) ratio (8 RCTs, 577 participants, MD: −0.34, 95% CI: −0.47 to −0.20; 3 RCTs, 179 participants, MD: −0.44, 95% CI: −0.68 to −0.21, respectively). Berberine was associated with decreasing total cholesterol (3 RCTs, 201 participants; MD: −0.44, 95% CI: −0.60 to −0.29), waist circumference (3 RCTs, 197 participants, MD: −2.74, 95% CI: −4.55 to −0.93), and waist-to-hip ratio (4 RCTs, 258 participants, MD: −0.04, 95% CI: −0.05 to −0.03) compared with metformin, but not with improved BMI (4 RCTs, 262 participants, MD: −0.03, 95% CI: −0.46 to 0.39). Berberine did not increase the incidence of gastrointestinal adverse events (3 RCTs, 567 participants, RR: 1.01, 95% CI: 0.76 to 1.35) or serious events during pregnancy (RR: 0.98, 95% CI: 0.70 to 1.37) compared with placebo. Conclusion. This review found no solid evidence that berberine could improve live birth or other clinical outcomes in women with PCOS. However, berberine appeared to be more efficacious for improving insulin resistance and dyslipidemia and decreasing androgen levels and LH/FSH ratio in women with PCOS when compared with metformin. [ABSTRACT FROM AUTHOR]

Abstract: The use of acupuncture to treat reproductive dysfunction has not been well investigated. Only a few clinical studies have been reported, most of which are flawed by poor design and a lack of valid outcome measures and diagnostic criteria, making the results difficult to interpret. Experimental studies, however, show that acupuncture has substantial effects on reproductive function. Here we review the possible mechanisms of action of acupuncture on the reproductive system and its effects on reproductive dysfunction, focusing in particular on polycystic ovary syndrome, the most common endocrine and metabolic disorder in women. Clinical and experimental evidence demonstrates that acupuncture is a suitable alternative or complement to pharmacological induction of ovulation, without adverse side effects. Clearly, acupuncture modulates endogenous regulatory systems, including the sympathetic nervous system, the endocrine system, and the neuroendocrine system. Randomized clinical trials are warranted to further evaluate the clinical effects of acupuncture in reproductive disorders. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether insulin resistance (IR) within theca cells may directly contribute to their hyperandrogenism, a heritable trait of polycystic ovary syndrome (PCOS).Design: In vitro cell model.Setting: University-affiliated laboratory.Animal(s): Porcine ovaries.Intervention(s): Ovarian theca cells from porcine follicles were isolated and cultured. Insulin resistance was induced in theca cells without (Con) or with dexamethasone (Dex); cells were further treated by troglitazone (Tro) and metformin (Met) in IR cells or by vehicle only in IR and Con cells.Main Outcome Measure(s): Medium glucose and T levels; reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot for insulin signal molecules and androgenic enzyme.Result(s): As compared with Con cells, Dex-treated cells had significantly lower [(3)H]-glucose uptake (565 +/- 58 cpm/10(6) vs. 1077 +/- 78 cpm/10(6)) but higher medium glucose levels (16.31 +/- 0.39 nmol/L vs. 10.62 +/- 1.02 nmol/L) and had approximately twofold T levels (0.82 +/- 0.20 microg/L vs. 0.38+/-0.08 microg/L). Troglitazone and Met significantly reduced the medium glucose and testosterone concentrations to levels comparable to those in Con cells. The RT-PCR and Western blot showed that the two sensitizers in different ways reversed the altered messenger RNA and protein expression of insulin receptor substrate-1, glucose transporter-4, peroxisome proliferator-activated receptor-gamma, and 17 alpha-hydroxylase in Dex-induced IR cells.Conclusion(s): Insulin resistance induced by Dex could directly exaggerate androgenic potential within theca cells, suggesting the possible involvement of this ovarian metabolic phenotype in PCOS hyperandrogenism. [ABSTRACT FROM AUTHOR]

This study aimed to determine whether glucocorticoid receptor (GR) signaling, mitochondrial function, and local inflammation in the ovary and uterus are intrinsically different in rats with hyperandrogenism and insulin resistance compared to controls. Female Sprague Dawley rats were exposed to daily injections of human chorionic gonadotropin and/or insulin. In both the ovary and the uterus, decreased expression of the two GR isoforms was concurrent with increased expression of Fkbp51 but not Fkbp52 mRNA in hCG + insulin-treated rats. However, these rats exhibited contrasting regulation of Hsd11b1 and Hsd11b2 mRNAs in the two tissues. Further, the expression of several oxidative phosphorylation-related proteins decreased in the ovary and uterus following hCG and insulin stimulation, in contrast to increased expression of many genes involved in mitochondrial function and homeostasis. Additionally, hCG + insulin-treated rats showed increased expression of ovarian and uterine NFκB signaling proteins and Tnfaip3 mRNA. The mRNA expression of Il1b , Il6 , and Mmp2 was decreased in both tissues, while the mRNA expression of Tnfa , Ccl2 , Ccl5 , and Mmp3 was increased in the uterus. Ovaries and uteri from animals co-treated with hCG and insulin showed increased collagen deposition compared to controls. Our observations suggest that hyperandrogenism and insulin resistance disrupt ovarian and uterine GR activation and trigger compensatory or adaptive effects for mitochondrial homeostasis, allowing tissue-level maintenance of mitochondrial function in order to limit ovarian and uterine dysfunction. Our study also suggests that hyperandrogenism and insulin resistance activate NFκB signaling resulting in aberrant regulation of inflammation-related gene expression. [ABSTRACT FROM AUTHOR]