Association between Metal(loid)Exposure and Risk of Polycystic Ovary Syndrome Mediated by Anti-Müllerian Hormone among Women Undergoing In Vitro Fertilization and Embryo Transfer

Objective To investigate the relationship and potential pathways between metal(loid)exposure and the risk of polycystic ovary syndrome(PCOS)in women of childbearing age.Methods This case-control study included 200 patients with PCOS(cases)and 896 non-PCOS controls with the age of 25-37 years.The concentrations of 29 metal(loid)s in the follicular fluid(FF)and clinical indicators in the serum were measured in all participants.Logistic regression analysis and mediation analysis were conducted to evaluate the associations between metal(loid)exposure and PCOS risk and investigate the possible roles of clinical indicators,respectively.Results Logistic regression analysis revealed an association between high copper levels in FF and increased PCOS risk(highest vs.lowest quartile:adjusted odds ratio=2.94,95%confidence interval:1.83-4.72).A high luteinizing hormone/follicle-stimulating hormone ratio and elevated levels of testosterone and anti-Müllerian hormone(AMH)were strongly associated with increased PCOS risk induced by high copper exposure.The mediation analysis indicated a mediating effect of AMH in the association between copper exposure and PCOS risk.Conclusion Copper may affect PCOS risk through the hypothalamic-pituitary-ovarian axis,mediated by AMH.Copper exposure and internal AMH levels are important indicators for early warning of PCOS development.

Clinical Study on the Therapeutic Effect of Combined Traditional Chinese Medicine with Acupoint Injection and Herbal Paste Application in Treating Ovulatory Dysfunction in Polycystic Ovary Syndrome (PCOS)

Objective: To observe the therapeutic effect of combined traditional Chinese medicine (TCM) therapy with acupoint injection and herbal patch application on patients with ovulatory dysfunction associated with polycystic ovary syndrome (PCOS). Methods: A total of 80 PCOS patients who received treatment at the First Affiliated Hospital of Guangxi University of Chinese Medicine between October 2022 and March 2024 were enrolled in this study. They were randomly divided into a control group (n = 40) and an observation group (n = 40). The control group received conventional Western medical treatments, while the observation group was administered TCM combined with acupoint injection and herbal patch application. Pre- and post-treatment conditions were compared between the two groups. Results: After treatment, the overall effective rate was significantly higher in the observation group compared to the control group (P 0.05). Following treatment, both ovulation and pregnancy rates increased in both groups, but the increase was more evident in the observation group, showing a statistically significant difference (P < 0.01). Conclusion: For patients with oligoovulation or anovulation due to PCOS, the combined use of TCM, acupoint injection, and herbal patch application appears to be effective in improving systemic symptoms and achieving notable clinical outcomes.

Exploring the medication pattern and mechanism of action of traditional Chinese medicine in treating polycystic ovary syndrome with kidney deficiency and blood stasis based on data mining and network pharmacology

Background:Using network pharmacology to explore the potential molecular mechanism of traditional Chinese medicine in treating polycystic ovary syndrome(PCOS)with kidney deficiency and blood stasis syndrome.Method:Collect the related literature materials of PCOS with kidney deficiency and blood stasis syndrome treated by traditional Chinese medicine in four databases in recent ten years,extract the information of prescriptions and complete the frequency analysis.Traditional Chinese Medicine Systems Pharmacology Database was used to screen out the effective components.Use Online Mendelian Inheritance in Man and other databases to screen PCOS disease targets.The intersection targets obtained by clustering prescription and PCOS disease targets were submitted to STRING database for protein-protein interaction network analysis,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes pathways were analysed by Metascape.Result:There are 155 kinds of traditional Chinese medicines used in the literature.The most commonly utilized ones are Cuscutae Semen,Angelicae Sinensis Radix,and Rehmanniae Radix Praeparata.The results of the cluster analysis indicated that the plants most commonly found throughout the prescription were Leonuri Herba,Lycopi Herba,Dipsaci Radix,etc.GO results show that biological processes include cell reaction to organic nitrogen compounds and cell reaction to nitrogen compounds.The functional display of GO molecule includes cytokine receptor binding,signal receptor regulator activity and so on.Kyoto Encyclopedia of Genes and Genomes results show that the possible mechanisms of action are cancer pathway,an endocrine resistance signal pathway.Conclusion:Through data mining,the cluster prescription for PCOS with kidney deficiency and blood stasis syndrome is Leonuri Herba,Lycopi Herba,Dipsaci Radix,etc.The network pharmacology research of cluster prescription shows that the main drug components for treating PCOS with kidney deficiency and blood stasis syndrome are quercetin,kaempferol,luteolin,tanshinone IIA,etc.,which act on PTGS2,NCOA2,and other targets,and treat PCOS with kidney deficiency and blood stasis syndrome through cancer and endocrine resistance.

Effects of Qigongwan on Wnt/β-catenin Signaling Pathway in Rats with Polycystic Ovary syndrome

[Objectives] To explore the therapeutic effect and mechanism of Qigongwan on PCOS model rats by detecting the changes in sex hormone levels in rats with polycystic ovary syndrome (PCOS), and observing the effects of ovarian pathological morphological changes, apoptosis and expression of Wnt/β-β catenin signaling pathway protein. [Methods] Ten of 40 female SD rats were randomly selected as the normal group, and the other 30 rats were treated with letrozole combined with high-fat diet to establish the PCOS rat model. After successful modeling, the model group was randomly divided into Qigongwan group, positive Daying-35 (Ethinylestradiol and Cyproterone Acetate Tablets) group and model group, with 10 rats in each group. Qigongwan group was given 14.7 g/(kg·d) by gavage, Daying-35 group was given 0.21 mg/(kg·d) by oral gavage, and normal group and model group were given the same amount of distilled water, and the intervention lasted for 21 d. ELISA method was used to detect the levels of hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E 2) and progesterone (P) in serum. HE staining was used to observe the pathological morphological changes of ovarian tissues;TUNEL staining was used to observe apoptosis of ovarian tissue granule cells;the expression of Wnt, β-catenin protein in rat ovarian tissue was detected by immunohistochemistry. [Results] (i) Compared with the model group, Qigongwan group and Daying-35 group could significantly increase serum E 2 and P levels, significantly reduce serum T levels ( P <0.01), significantly reduce serum LH levels and LH/FSH ratio ( P <0.01), and increase serum FSH levels ( P <0.05) in different degrees. (ii)The results of HE staining showed that compared with the model group, Qigongwan and Daying-35 groups could improve follicular development and reduce atretic follicles in different degrees. Compared with Daying-35 group, the number of GC layers in Qigongwan group was significantly increased. (iii) The results of TUNEL staining showed that compared with the model group, the rate of TUNEL-positive cells in the Qigongwan group and Daying-35 group decreased significantly ( P <0.01). (iv) The immunohistochemical results showed that compared with the model group, the expression levels of wnt and β-catenin in the Qigongwan group and the Daying-35 group increased in different degrees ( P <0.05), and the expression range increased. [Conclusions] Qigongwan can regulate the secretion level of sex hormones such as FSH and LH, improve the pathological damage of ovarian tissue, and inhibit apoptosis of ovarian granule cells, and its mechanism may be related to the activation of Wnt/β-catenin signaling pathway.

Effect of Astragalus-hawthorn on ovarian reproductive function and inflammatory mechanism of action in rats with polycystic ovary syndrome

Objective:To investigate the effects of prophylactic administration of Astragalus-Hawthorn on ovarian reproductive function and inflammatory mechanism in rats with polycystic ovary syndrome(PCOS).Methods:Fifty 21-day-old female rats were randomly divided into five groups of 10 rats each:Normal group,Model group,Astragalus group,Hawthorn group and Astragalus-Hawthorn group.All groups,except the normal group,were fed a high-fat model diet.Each treatment group received astragalus,hawthorn and an astragalus-hawthorn solution orally during the molding period for an intervention period of 15 weeks.The estrous cycle of the rats in each group was observed under the microscope from week 8,the interference rate was calculated,changes in ovarian tissues were observed by HE staining and the levels of sex hormones,proinflammatory and anti-inflammatory factors in the serum of the rats were measured by ELISA.Results:Rate of estrous cycle disorders were more frequent in the model group than in the normal group.(P<0.01);ovarian tissue was polycystic,with few corpora lutea and sinusoids and numerous follicular ovarian cysts;Luteinising hormone/follicle-stimulating hormone(LH/FSH),testosterone(T),interleukin 6(IL-6),interleukin 17A(IL-17A)and tumour necrosis factor(TNF-α)levels were significantly higher in the model group than in the normal group;interleukin 10(IL-10)was significantly lower than in the normal group(P<0.05).Compared to the model group,rats in the Astragalus and hawthorn groups had a lower rate of estrous cycle disorders(P<0.01);the number of cystic follicles in the ovarian tissue decreased;the number of mature follicles and corpus luteum increased;LH/FSH,T,IL-6 and IL-17A levels were significantly lower in the Astragalus group,hawthorn group and the Astragalus and hawthorn groups;TNF-αlevels were significantly lower in the astragalus and hawthorn groups;IL-10 levels were significantly higher in the hawthorn and astragalus hawthorn groups(P<0.05).IL-10 levels were significantly higher in the astragalus and hawthorn groups(P<0.05).Compared to the astragalus group,T levels were significantly lower in the astragalus and hawthorn groups and IL-10 levels were significantly higher in the astragalus and hawthorn groups(P<0.05).Compared to the hawthorn group,levels of T and IL-17A were significantly lower in the astragalus-hawthorn group(P<0.05).Conclusion:Astragalus-Hawthorn prophylactic administration can improve ovarian reproductive function in rats with PCOS,and the mechanism of action may be related to reducing the levels of pro-inflammatory factors IL-6,IL-17A and TNF-α,increasing the levels of anti-inflammatory factor IL-10,and reducing the inflammatory state.

Effect of vitamin supplementation on polycystic ovary syndrome and key pathways implicated in its development:A Mendelian randomization study

BACKGROUND Many epidemiologic investigations have explored the relationship between viatmins and polycystic ovary syndrome(PCOS).However,the effectiveness of vitamin,vitamin-like nutrient,or mineral supplementation in reducing the risk of PCOS remains a subject of debate.AIM To investigate the impact of plasma levels of vitamins A,B12,D,E,and K on PCOS and key pathways implicated in its development,namely,insulin resistance,hyperlipidemia,and obesity,through Mendelian randomization(MR)analysis.METHODS Single nucleotide polymorphisms associated with vitamin levels were selected from genome-wide association studies.The primary analysis was performed using the random-effects inverse-variance-weighted approach.Complementary analyses were conducted using the weighted median,MR-Egger,MR-robust adjusted profile score,and MR-PRESSO approaches.RESULTS The results provided suggestive evidence of a decreased risk of PCOS with genetically predicted higher levels of vitamin E(odds ratio[OR]=0.118;95%confidence interval[CI]:0.071–0.226;P<0.001)and vitamin B12(OR=0.753,95%CI:0.568–0.998,P=0.048).An association was observed between vitamin E levels and insulin resistance(OR=0.977,95%CI:0.976–0.978,P<0.001).Additionally,genetically predicted higher concentrations of vitamins E,D,and A were suggested to be associated with a decreased risk of hyperlipidemia.Increased vitamins K and B12 levels were linked to a lower obesity risk(OR=0.917,95%CI:0.848–0.992,P=0.031).CONCLUSION The findings of this MR study suggest a causal relationship between increased vitamins A,D,E,K,and B12 levels and a reduced risk of PCOS or primary pathways implicated in its development.

Effect of laparoscopic sleeve gastrectomy on related variables of obesity complicated with polycystic ovary syndrome

BACKGROUND Polycystic ovary syndrome(PCOS)is closely related to obesity,and weight loss can significantly improve the metabolic,endocrine and reproductive functions of obese individuals with PCOS.However,the efficacy of laparoscopic sleeve gastrectomy(LSG)for obesity with PCOS are unclear.AIM The purpose of the study was to investigate the effect of LSG on related variables in obese patients with PCOS.METHODS A retrospective analysis was performed on 32 obese patients with PCOS who received LSG treatment at the Third Hospital of Shanxi Medical University from 2013 to 2020.The changes in anthropometric indices,insulin,testosterone,estradiol,follicle stimulating hormone(FSH),luteinizing hormone(LH),menstrual cycle and LH/FSH ratio before and 1 mo,3 mo,6 mo and 12 mo after the operation were statistically analyzed.RESULTS At 1 mo,3 mo,6 mo and 12 mo after surgery,the anthropometric indices,such as body weight and body mass index,of all patients were lower than those before the operation.The percentage excess weight loss(EWL%)at 1 mo,3 mo,6 mo and 1 year of follow-up were 25,40,46 and 65,respectively.The PCOS-related indices,such as insulin,testosterone,estradiol,follicle stimulating hormone(FSH),luteinizing hormone(LH)and menstrual cycle,were improved to varying degrees.During the 1-year follow-up,the average serum testosterone decreased from preoperative 0.72 ng/mL to 0.43 ng/mL(P<0.05),average fasting insulin level(9.0 mIU/mL,preoperative 34.2 mil,LH level,4.4 mIU/mL,preoperative 6.1 mIU/mL).The level of FSH(3.8 U/L,4.8 U/p0.05)and the ratio of LH/FSH(0.7,1.3/p0.05)were more relieved than those before surgery.During the postoperative follow-up,it was found that the menstrual cycle of 27 patients(nasty 27)returned to normal,and 6 patients(18%)who intended to become pregnant became pregnant within 1 year after surgery.CONCLUSION The weight loss effect of LSG is obvious and affirmative,and the endocrine index of obese patients with PCOS is also improved to some extent,although the mechanism is not clear.Laparoscopic sleeve gastrectomy is expected to become a backup choice for patients with polycystic ovaries in the future.

Clinical efficacy of bushen huatan huoxue recipe in combination with acupuncture in treating patients suffering from polycystic ovary syndrome with insulin resistance

Objective:To investigate the clinical efficacy and effects on sex hormone level and glucose metabolism indexes of acupuncture therapy combined with the Bushen Huatan Huoxue Recipe in patients with polycystic ovary syndrome(PCOS)with insulin resistance(IR).Methods:The patients with PCOS-IR admitted from December 2021 to December 2022 were randomly divided into two groups,30 cases in each group.The comparison one and the observation one were given the relevant treatment of metformin and traditional Chinese medicine combined with acupuncture,respectively.The evidence points,sex hormone indexes and glucose metabolism indexes were compared between the two groups before and after treatment,and the insulin resistance index(HOMA-IR),glucose area under the curve(GLU-AUC)and blood insulin area under the curve(INS-AUC)were calculated.Results:The evidence points of the observation group of patients were less than the pre-treatment and comparison groups;after treatment,the follicle-stimulating hormone(FSH)level of patients in the observation group was more than the control and pre-treatment groups(P<0.05),and the ratio of luteinizing hormone(LH)to follicle-stimulating hormone(FSH)was less than that of the comparison and pre-treatment groups(P<0.05),and the levels of LH and testosterone(T)were reduced to varying degrees in both groups around the time of treatment(P<0.05).The patients in the observation group had lower levels of 0.5hPG than those in the comparison group and pretreatment(both P<0.05),and the levels of 3hPG in both groups were lower than those before treatment(P<0.05).The oral OGIRT in each of the two groups after treatment was lower than that of pretreatment(P<0.05).HOMA-IR and INS-AUC of the observation group were lower than those of the control group and pre-treatment(P<0.05).Conclusion:The treatment of PCOS-IR patients with Bushen Huatan Huoxue Recipe combined with acupuncture can improve the sex hormone,glucose metabolism level and insulin resistance.

Research progress of natural products in treating polycystic ovary syndrome

Polycystic ovary syndrome(PCOS)is a common metabolic disorder reproductive endocrine disease in puberty and women of childbearing age.At present,metformin is mainly used in clinical to treat PCOS.From recent researches,many natural products,such as flavonoids,alkaloids,cumarins,etc,showed curing effects on PCOS.These have been attracting more and more attention.By searching the researches from database of CNKI,PubMed etc,this paper aims at providing a reference for PCOS drug research and development.

Research Progress on Mechanism of Ovulation Disorder in Polycystic Ovary Syndrome

Polycystic ovary syndrome(PCOS)is a reproductive endocrine disease characterized by ovulation disorder,hyperandrogenism and/or polycystic ovary.Follicular development disorder caused by PCOS accounts for up to 75%of anovulatory infertility,which is a common cause of infertility and affects up to 15%of reproductive aged women worldwide.Oxidative stress,chronic inflammation,endoplasmic reticulum stress and other pathological conditions coexist in the ovarian microenvironment of PCOS,which are further aggravated under the action of high levels of androgens,synergistically deteriorating the follicular microenvironment,leading to ovulation disorders in PCOS patients.This paper briefly reviewed the research on the mechanism of PCOS ovulation disorder in recent years.

Observation on Therapeutic Effects of Electroacupuncture on Polycystic Ovary Syndrome of Kidney Deficiency and Phlegm Dampness Type and Oxidative Stress Level

Objective:To observe the clinical effect of electroacupuncture on improving polycystic ovary syndrome(PCOS)of kidney deficiency and phlegm dampness type and serum oxidative stress level.Methods:There were 68 patients with polycystic ovary syndrome were randomly divided into observation group(34 cases)and the control group(34 cases),The observation group was treated by electroacupuncture,while the control group was treated by placebo electroacupuncture.Combined with the evaluation of menstrual cycle,menstrual color,quality,quantity and TCM symptom integral index,the difference of curative effect between the two groups was observed,and the levels of peripheral blood,sex hormones,insulin resistance and oxidative stress were detected before and after treatment for 3 months.Results:The total effective rate in the observation group was better than that in the control group(P<0.01);After intervention,serum LH,FSH,E_(2) and LH/FSH in the observation group were significantly different from those before intervention.The D values of serum LH,FSH,LH/FSH and E_(2) before and after intervention were significantly different between the two groups(P<0.01);Comparing the level of androgen,the serum A4 and T in the observation group were significantly different from those before intervention(P<0.01);After intervention,there was a significant difference in serum A4 and T between the two groups(P<0.01),and there was a significant difference in D value between the two groups before and after intervention;There was a difference in insulin resistance in the observation group before and after intervention(P<0.05),and there was a significant difference in D value between the two groups before and after intervention(P<0.01);After the intervention,the serum SOD,MDA,ROS in the observation group were significantly different from those before the intervention;After intervention,the results of serum SOD and ROS in the observation group were significantly different from those in the control group;There was no significant difference in serum MDA results.There were significant differences in SOD,MDA,ROS between the two groups before and after intervention.Conclusion:Electroacupuncture can improve oxidative stress injury,insulin resistance and hyperandrogenism in PCOS patients.

Polycystic Ovary Syndrome-Related Infertility Based on the Theory of“Liver and Kidney Homology”

Polycystic ovary syndrome(PCOS)is an endocrine disorder caused by hypothalamic-pituitary-ovarian(HPO)axis dysfunction.In the field of gynecology and reproduction,PCOS has emerged as both a research hot spot and a challenging area of study.According to Chinese medicine,this disease is related to kidney deficiency,phlegm and dampness obstruction,blood stasis and interconnection,Chong pulse impassability,the lack of Ren pulse,and the loss of uterine nourishment,all of which affect the normal development and maturation of eggs as well as the duration at which menstrual blood stores.In this paper,based on the theoretical basis of“liver collects blood,regulates the flow of qi,and is the master of drainage,”we explore the rationality of the treatment of this disease from the perspective of“liver and kidney have the same origin”and the development of PCOS-related infertility in relation to dysfunctional internal organs.We also explore the feasibility of treatment from the perspective of“liver and kidney homology,”expand the ideas for treatment,as well as develop and innovate the application of organ identification in PCOS in relation to infertility.

Effect of Mitochondrial Function of Ovarian Granulosa Cells on In Vitro Fertilization and Embryo Transfer Outcomes in Obese Polycystic Ovary Syndrome Patients

Objective:To investigate the effect of abnormal ovarian granulosa cell metabolism on in vitro fertilization and embryo transfer(IVF-ET)outcomes in obese polycystic ovary syndrome(PCOS)patients.Methods:Patients with PCOS who met the study criteria were screened according to the inclusion criteria.A total of 32 patients with obese PCOS were recruited into the study group,and 39 patients with non-obese PCOS were recruited into the control group.The general data(age,body mass index,and years of infertility),insulin resistance index(HOMA-IR),follicle-stimulating hormone(FSH),luteinizing hormone(LH),granulosa cell mitochondrial function,and IVF-ET outcome of patients in the study group and control group were retrospectively analyzed.Results:The differences in age and years of infertility between the study group and the control group were insignificant(P>0.05),and the body mass index(BMI)of the study group and control group was 30.5±1.24 kg/m2 and 22.3±1.12 kg/m2,respectively,in which the difference was statistically significant(P<0.05);the HOMA-IR of the study group was significantly higher than that of the control group(P<0.05);the reactive oxygen species(ROS)in the study group was significantly higher than that in the control group(P<0.05),and the ATP content in the study group was significantly lower than that in the control group(P<0.05);comparing the FSH and LH levels between the two groups,the difference was not statistically significant(P>0.05);the rate of IVF-ET failure was significantly higher in the study group than in the control group.Conclusion:PCOS is a complex endocrine disorder,and obesity is one of the independent risk factors for the development of PCOS.

Nonalcoholic fatty liver disease and polycystic ovary syndrome

Nonalcoholic fatty liver disease(NAFLD)is the most common cause of chronic liver disease in the Western world comprising a spectrum of liver damage from fatty liver infiltration to end-stage liver disease,in patients without significant alcohol consumption.Increased prevalence of NAFLD has been reported in patients with polycystic ovary syndrome(PCOS),one of the most common endocrinopathies in premenopausal women,which has been redefined as a reproductive and metabolic disorder after the recognition of the important role of insulin resistance in the pathophysiology of the syndrome.Obesity,in particular central adiposity and insulin resistance are considered as the main factors related to NAFLD in PCOS.Moreover,existing data support that androgen excess,which is the main feature of PCOS and is interrelated to insulin resistance,may be an additional contributing factor to the development of NAFLD.Although the natural history of NAFLD remains unclear and hepatic steatosis seems to be a relatively benign condition in most patients,limited data imply that advanced stage of liver disease is possibly more frequent in obese PCOS patients with NAFLD.PCOS patients,particularly obese patients with features of the metabolic syndrome,should be submitted to screening for NAFLD comprising assessment of serum aminotransferase levels and of hepatic steatosis by abdominal ultrasound.Lifestyle modifications including diet,weight loss and exercise are the most appropriate initial therapeutic interventions for PCOS patients with NAFLD.When pharmacologic therapy is considered,metformin may be used,although currently there is no medical therapy of proven benefit for NAFLD.Long-term follow up studies are needed to clarify clinical implications and guide appropriate diagnostic evaluation,follow-up protocol and optimal treatment for PCOS patients with NAFLD.

Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome

Polycystic ovary syndrome(PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequently have metabolic complications including insulin resistance(IR), early diabetes, hypertension and dyslipidemia. Recent studies have demonstrated an association between PCOS and another metabolic complication: nonalcoholic fatty liver disease(NAFLD). NAFLD occurs as a result of abnormal lipid handling by the liver, which sensitizes the liver to injury and inflammation. It can progress to nonalcoholic steatohepatitis(NASH), which is characterized by hepatocyte injury and apoptosis. With time and further inflammation, NASH can progress to cirrhosis. Thus, given the young age at which NAFLD may occur in PCOS, these women may be at significant risk for progressive hepatic injury over the course of their lives. Many potential links between PCOS and NAFLD have been proposed, most notably IR and hyperandrogenemia. Further studies are needed to clarify the association between PCOS and NAFLD. In the interim, clinicians should be aware of this connection and consider screening for NAFLD in PCOS patients who have other metabolic risk factors. The optimal method of screening is unknown. However, measuring alanine aminotransferase and/or obtaining ultrasound on high-risk patients can be considered. First line treatment consists of lifestyle interventions and weight loss, with possible pharmacologic interventions in some cases.

Polycystic ovary syndrome patients with high BMI tend to have functional disorders of androgen excess:a prospective study

Biochemical or clinical changes of hyperandrogenism are important elements of polycystic ovary syndrome （PCOS）. There is currently no consensus on the definition and diagnostic criteria of hyperandrogenism in PCOS. The aim of this study was to investigate the complex symptoms of hyperandrogenic disorders and the correlations between metabolism and hyperandrogenism in patients with PCOS from an outpatient reproductive medicine clinic in China. We conducted a case control study of 125 PCOS patients and 130 controls to evaluate differences in body mass index （BMI）, total testosterone （TT）, modified Ferriman-Gallwey hirsutism score, sex hormone binding globulin （SHBG）, homeostasis model assessment-estimated insulin resistance （HOMA-IR） and free androgen index （FAI） between PCOS patients and controls and subgroups of PCOS. The prevalence of acne and hirsutism did not differ significantly between the hyperandrogenic and non-hyperandrogenic subgroup. Patients with signs of hyper- androgenism had significantly higher BMI （P 〈 0.05）, but differences in TT, SHBG, FAI and waist/hip ratio were insignificant. The odds ratio of overweight was calculated for all PCOS patients. Our results suggest that PCOS patients with high BMI tend to have functional disorders of androgen excess; therefore, BMI may be a strong pre-dictor of hyperandrogenism in PCOS.

Expression of Leptin Long-form Receptor mRNA in Luteinized Granulosa Cells of Obese Women with Polycystic Ovary Syndrome

To investigate the expression of mRNA of leptin long-form receptor （OB-Rb） in luteinized granulosa ceils of obese women with polycystic ovary syndrome （PCOS）, and to determine the role of leptin in the physiopathology of PCOS, luteinized granulosa cells were collected from the follicle fluid of 10 obese women who met the diagnostic criteria for PCOS and their BMI was equal to or greater than 25 kg/m^2, and at the same time, granulosa cells were collected from 10 normal women undergoing IVF-ET who served as the control group. Some luteinized granulosa cells were taken from normal women for in-vitro culture, into which human leptin of different concentrations was added （0, 10, 100 and 1000 ng/mL）. After stimulation with leptin for 48 h, RT-PCR was employed for the detection of the expression of OB-RLInRNA in the luteinized granulosa cells. Our results showed that the level of OB-RLmRNA in luteinized granulosa cells of obese PCOS women was higher than those in the control （P〈0.05）. In luteinized granulosa cells cultured in vitro and stimulated by human leptin for 48 h, the level of OB-RLmRNA was higher than those without leptin stimulation （P〈0.01）, and when leptin concentration was at 100 ng/mL, and the level of OB-RLmRNA reached a peak, It is concluded that in obese PCOS women, the level of serum leptin is increased, which promotes the expression of OB-RL in luteinized granulosa cells and increases the sensitivity of the granulosa cells to leptin. Leptin may contribute to anovulation in obese women with PCOS.

Exploring new treatment options for polycystic ovary syndrome: Review of a novel antidiabetic agent SGLT2 inhibitor

Polycystic ovary syndrome(PCOS)is the most common endocrinopathy in women of reproductive age associated with long-term metabolic and cardiovascular consequences.A plethora of symptoms and their severity differentiate on an individual level,giving the syndrome numerous phenotypes.Due to menstrual cycle abnormalities,women suffer from irregular menstrual bleeding,difficulty in conception,and infertility.Furthermore,the risk of pregnancy complications such as gestational diabetes mellitus,hypertensive disorders of pregnancy,and preterm birth are higher in women with PCOS than in the general population.Often,women with PCOS have comorbidities such as dyslipidemia,obesity,glucose intolerance or diabetes type 2,non-alcoholic fatty liver disease,and metabolic syndrome,which all influence the treatment plan.Historic insulinsensitizing agents,although good for some of the metabolic derangements,do not offer long-term cardiovascular benefits;therefore,new treatment options are of paramount importance.Sodium-glucose co-transporter-2(SGLT-2)inhibitors,a new class of antidiabetic agents with beneficial cardiovascular,bodyweight,and antihyperglycemic effects,although not approved for the treatment of PCOS,might be an attractive therapeutic addition in the PCOS armamentarium.Namely,recent studies with SGLT-2 inhibitors showed promising improvements in anthropometric parameters and body composition in patients with PCOS.It is important to further explore the SGLT-2 inhibitors potential as an early therapeutic option because of the PCOS-related risk of metabolic,reproductive,and psychological consequences.

Markers of insulin resistance in Polycystic ovary syndrome women:An update

Polycystic ovary syndrome(PCOS)is one of the most common endocrine disorders,affecting 5%-10%of women of reproductive age.The importance of this syndrome lies in the magnitude of associated comorbidities:infertility,metabolic dysfunction,cardiovascular disease(CVD),plus psychological and oncological complications.Insulin resistance(IR)is a prominent feature of PCOS with a prevalence of 35%-80%.Without adequate management,IR with compensatory hyperinsulinemia contributes directly to reproductive dysfunction in women with PCOS.Furthermore,epidemiological data shows compelling evidence that PCOS is associated with an increased risk of impaired glucose tolerance,gestational diabetes mellitus and type 2 diabetes.In addition,metabolic dysfunction leads to a risk for CVD that increases with aging in women with PCOS.Indeed,the severity of IR in women with PCOS is associated with the amount of abdominal obesity,even in lean women with PCOS.Given these drastic implications,it is important to diagnose and treat insulin resistance as early as possible.Many markers have been proposed.However,quantitative assessment of IR in clinical practice remains a major challenge.The gold standard method for assessing insulin sensitivity is the hyperinsulinemic euglycemic glucose clamp.However,it is not used routinely because of the complexity of its procedure.Consequently,there has been an urgent need for surrogate markers of IR that are more applicable in large population-based epidemiological investigations.Despite this,many of them are either difficult to apply in routine clinical practice or useless for women with PCOS.Considering this difficulty,there is still a need for an accurate marker for easy,early detection and assessment of IR in women with PCOS.This review highlights markers of IR already used in women with PCOS,including new markers recently reported in literature,and it establishes a new classification for these markers.

Polycystic ovary syndrome and type 2 diabetes mellitus:A state-ofthe-art review

Polycystic ovary syndrome(PCOS)often coexists with a wide spectrum of dysglycemic conditions,ranging from impaired glucose tolerance to type 2 diabetes mellitus(T2D),which occur to a greater extent compared to healthy body mass index-matched women.This concurrence of disorders is mainly attributed to common pathogenetic pathways linking the two entities,such as insulin resistance.However,due to methodological flaws in the available studies and the multifaceted nature of the syndrome,there has been substantial controversy as to the exact association between T2D and PCOS which has not yet been elucidated.The aim of this review is to present the best available evidence regarding the epidemiology of dysglycemia in PCOS,the unique pathophysiological mechanisms underlying the progression of dysglycemia,the most appropriate methods for assessing glycemic status and the risk factors for T2D development in this population,as well as T2D risk after transition to menopause.Proposals for application of a holistic approach to enable optimal management of T2D risk in PCOS are also provided.Specifically,adoption of a healthy lifestyle with adherence to improved dietary patterns,such the Mediterranean diet,avoidance of consumption of endocrine-disrupting foods and beverages,regular exercise,and the effect of certain medications,such as metformin and glucagon-like peptide 1 receptor agonists,are discussed.Furthermore,the maintenance of a healthy weight is highlighted as a key factor in achievement of a significant reduction of T2D risk in women with PCOS.