Artificial sweeteners affect the glucose transport rate in the Caco-2/NCI-H716 co-culture model.

BACKGROUND: Artificial sweeteners have been used widely as substitutes for sugar for several decades. In recent years they have been reported to be harmful to human health - especially to glucose absorption. However, as conclusions from previous studies using a single Caco-2 cell model were not consistent, further studies with a more suitable cell model are needed. RESULTS: We established a co-culture model with enterocyte Caco-2 and enteroendocrine NCI-H716 cell lines cultured in transwell inserts. The effects of artificial sweeteners, enhancing the glucose transport rate, lasted for 60 min and then began to diminish. Most importantly, different artificial sweeteners with the same sweetness intensity had similar effects on glucose transport. The sodium / glucose co-transporter member 1 (SGLT1) mRNA expression levels increased significantly with an initial glucose concentration of 20 mM, while glucose transporter 2 (GLUT2) mRNA expression significantly increased with initial glucose concentrations of 20 mM and 60 mM. CONCLUSION: Based on the Caco-2/NCI-H716 co-culture model, SGLT1 and GLUT2 mediated the enhancing effects of artificial sweeteners on glucose transport, depending on the sweetness intensity and initial glucose concentration.

Incidence and prevalence of diabetes and cost of illness analysis of polycystic ovary syndrome: a Bayesian modelling study.

STUDY QUESTION: What is the incidence/prevalence of type 2 diabetes in women with polycystic ovary syndrome (PCOS) and the economic burden associated with PCOS in the UK? SUMMARY ANSWER: The incidence and prevalence of type 2 diabetes in women with PCOS are 3-33 per 1000 person years and 26.5%, respectively, with an associated annual healthcare burden of at least £237 million in the UK. WHAT IS KNOWN ALREADY: Although observational studies have been designed to assess the incidence of diabetes in women with PCOS, these have been open to criticism because of short periods of follow-up, small sample sizes or invalidated diagnosis of PCOS. Only one study has estimated the healthcare-related economic burden of PCOS, reporting a cost of $4.36 billion per year in the USA. STUDY DESIGN, SIZE, DURATION: This was a modelling study using individual patient data from a UK primary care database between 2004 and 2014 and aggregate data from the literature to obtain conversion rates through disease progression of PCOS. A simulation approach was applied to model the population dynamics of PCOS over a follow-up period of 25 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 14 135 women with PCOS or symptoms indicative of PCOS were selected from the primary care database to estimate the incidence of confirmed diagnosis of PCOS and diagnosis of type 2 diabetes. A 'virtual' cohort including the entire PCOS population (size estimated from the UK census data) was simulated to model the population dynamics of PCOS. The economic and utility analyses were further conducted from a healthcare perspective. MAIN RESULTS AND THE ROLE OF CHANCE: The peak conversion rate from possible to diagnosed PCOS was 121 per 1000 person-year (PY). The maximal incidence of type 2 diabetes was 33 per 1000 PY. The estimated prevalence of diabetes in the PCOS population was 26.5% (95% interval: 25.4-27.8%) during a 25-year follow-up. The annual healthcare burden of PCOS based on our conservative estimate is at least £237 million for the follow-up period examined. LIMITATIONS, REASONS FOR CAUTION: Due to lack of data, a full economic evaluation including healthcare costs of all the comorbidities associated with PCOS was not possible. Simplification of the real-world situation represented by the model may be a concern. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that a large number of women with symptoms indicative of PCOS never receive a definitive diagnosis yet can suffer from a rapid conversion to diabetes. This significantly reduces the quality of life for individual patients and incurs high costs for healthcare providers. As the risk of diabetes in women with PCOS is similar to that seen in populations at high risks of diabetes, it is possible that including them in national screening programmes may be cost effective. STUDY FUNDING/COMPETING INTEREST(S): There was no funding for the current study. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.

A comparison of fertility preservation outcomes in patients who froze oocytes, embryos, or ovarian tissue for medically indicated circumstances: a systematic review and meta-analysis.

OBJECTIVE: To compare obstetric outcomes in patients cryopreserving reproductive cells or tissues before gonadotoxic therapy. DESIGN: A literature search was conducted following PRISMA guidelines on Embase, Medline, and Web of Science. Studies reporting obstetric outcomes in cancer patients who completed cryopreservation of oocyte, embryo, or ovarian tissue were included. SETTING: Not applicable. PATIENT(S): Cancer patients attempting pregnancy using cryopreserved cells or tissues frozen before cancer therapy. INTERVENTION(S): Oocyte, embryo, or ovarian tissue cryopreservation for fertility preservation in cancer. MAIN OUTCOME MEASURE(S): The total numbers of clinical pregnancies, live births, and miscarriages in women attempting pregnancy using cryopreserved reproductive cells or tissues were calculated. A meta-analysis determined the effect size of each intervention. RESULT(S): The search returned 4,038 unique entries. Thirty-eight eligible studies were analyzed. The clinical pregnancy rates were 34.9%, 49.0%, and 43.8% for oocyte, embryo, and ovarian tissue cryopreservation, respectively. No significant differences were found among groups. The live birth rates were 25.8%, 35.3%, and 32.3% for oocyte, embryo, and ovarian tissue cryopreservation, respectively, with no significant differences among groups. The miscarriage rates were 9.2%, 16.9%, and 7.5% for oocyte, embryo, and ovarian tissue cryopreservation, respectively. Significantly fewer miscarriages occurred with ovarian tissue cryopreservation than with embryo cryopreservation. CONCLUSION(S): This enquiry is required to counsel cancer patients wishing to preserve fertility. Although the limitations of this study include heterogeneity, lack of quality studies, and low utilization rates, it serves as a starting point for comparison of reproductive and obstetric outcomes in patients returning for family-planning after gonadotoxic therapy.

The impact of eating behavior on psychological symptoms typical of reactive hypoglycemia. A pilot study comparing women with polycystic ovary syndrome to controls.

The idea that diet can affect mood and behavior in women with polycystic ovary syndrome (PCOS) by altering blood glucose levels has become popular in recent years. This paper describes an online survey (N=462) of 24 women with PCOS, 299 healthy control women, 47 women who possibly had undiagnosed PCOS, and 92 men. The groups were compared for symptoms of mood and behavioral symptoms typical of reactive (postprandial) hypoglycemia. The outcome measures were two questionnaires that measure states associated with hypoglycemia: the Hypoglycemia Symptom Checklist-7 (HSC-7), which measures behavioral symptoms and the Mood Adjective Checklist (MACL), which measures emotional states. Controlling for age and body mass index (BMI) using between-groups analysis of covariance (ANCOVA), the women with PCOS scored significantly higher than the other three groups (p<0.001) on the outcome measures. These differences remained statistically significant in a subset of twelve women with PCOS compared to twelve healthy control women closely matched for age, BMI, and eating behavior. The findings are suggestive of hypoglycemia-related mood and behavioral problems in PCOS. Future research should test whether blood glucose levels correlate with these symptoms in PCOS, and whether a low glycemic index ('low-GI') diet improves the symptoms.

Development of 1-2 years Offspring Born to Mothers with Polycystic Ovary Syndrome.

OBJECTIVE: To evaluate the body mass index and neurologic development of 1-2 years offspring born to mothers with polycystic ovary syndrome. STUDY DESIGN: A case-control study. PLACE AND DURATION OF STUDY: Dongyang Women and Children's Hospital, Zhejiang Province, China, between June 2018 and January 2019. METHODOLOGY: A total of 145 children were included in the final analysis, including 16 daughters of mothers with PCOS, 13 sons of mothers with PCOS, 55 daughters of mothers without PCOS and 61 sons of mothers without PCOS. Developmental assessments for each child were conducted, including anthropometric measurements and ability developments using the Denver developmental screening test. RESULTS: The body mass index of children was significantly lower in polycystic ovary syndrome group than control group (p=0.022). Children of mothers with polycystic ovary syndrome and control group had no significant differences in the outcomes of the Denver developmental screening test (all p >0.05). CONCLUSION: Maternal polycystic ovary syndrome may affect body mass index of offspring aged 1-2 years and had no negative effects on neurologic development. However, this conclusion may be limited due to the small sample size. Key Words: Neurologic development, Polycystic ovary syndrome, Offspring, Denver development screening test, Body mass index.

Association between circadian rhythm disruption and polycystic ovary syndrome.

OBJECTIVE: To explore the association of circadian rhythm disruption with polycystic ovary syndrome (PCOS) and the potential underlying mechanism in ovarian granulosa cells (GCs). DESIGN: Multicenter questionnaire-based survey, in vivo and ex vivo studies. SETTING: Twelve hospitals in China, animal research center, and research laboratory of a women's hospital. PATIENTS/ANIMALS: A total of 436 PCOS case subjects and 715 control subjects were recruited for the survey. In vivo and ex vivo studies were conducted in PCOS-model rats and on ovarian GCs collected from women with PCOS and control subjects. INTERVENTION(S): The PCOS rat model was established with the use of testosterone propionate. MAIN OUTCOME MEASURE(S): Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), RNA sequencing, rhythmicity analysis, functional enrichment analysis. RESULT(S): There was a significant correlation between night shift work and PCOS. PCOS-model rats presented distinct differences in the circadian variation of corticotropin-releasing hormone, adrenocorticotropic hormone, prolactin, and a 4-h phase delay in thyrotropic hormone levels. The motif enrichment analysis of ATAC-seq revealed the absence of clock-related transcription factors in specific peaks of PCOS group, and RNA sequencing ex vivo at various time points over 24 hours demonstrated the differential rhythmic expression patterns of women with PCOS. Kyoto Encyclopedia of Genes and Genomes analysis further highlighted metabolic dysfunction, including both carbohydrate and amino acid metabolism and the tricarboxylic acid cycle. CONCLUSION(S): There is a significant association of night shift work with PCOS, and genome-wide chronodisruption exists in ovarian GCs.

Molecular mechanisms underlying altered neurobehavioural development of female offspring of mothers with polycystic ovary syndrome: FOS-mediated regulation of neurotrophins in placenta.

BACKGROUND: This study explored the mechanisms underlying altered neurobehavioural development of female offspring born to mothers with polycystic ovary syndrome (PCOS). METHODS: In total, 20 women with PCOS and 32 healthy women who underwent caesarean deliveries with a single female foetus were recruited. Infants were assessed with Dubowitz scoring. Swan71 cell line with stable FOS overexpression was used to verify the regulatory effects of FOS on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) expression. Learning and memory in female first-generation (F1) and second-generation (F2) offspring in a rat model of PCOS was tested using the Morris water maze at puberty and adulthood. Transcriptome analysis of pubertal hippocampi and hypothalami of female F1 offspring was conducted. FINDINGS: Total score and behaviour subscales of Dubowitz scoring were significantly lower in female infants of women with PCOS. FOS and NGF protein levels were downregulated in placental villi of the PCOS group. FOS played a key role in BDNF inhibition and enhancing NGF in Swan71 cells. PCOS female F1 rats exhibited lower target crossing times during puberty when compared to controls. Transcriptome analysis revealed significant changes in hippocampal and hypothalamic neuronal pathways in female F1 rats at puberty. INTERPRETATION: FOS regulation of neurotrophins in the placenta negatively affects neurobehavioural development of female offspring of PCOS mothers. FUNDING: This study was funded by the National Key R&D Program of China (2018YFC1004900 to F.Q. and F.W.) and the National Natural Science Foundation of China (81874480 to F.Q.; 81873837 to F.W.).

Understanding the Role of Gui-Zhi-Fu-Ling-Capsules (Chinese Medicine) for Treatment of Endometriosis in the Rat Model: Using NMR Based Metabolomics.

The objective of this study is to identify the changes of metabolites in the rat endometriosis models treated with Gui-Zhi-Fu-Ling-capsules (GZFLC), a classic Chinese medicinal formula, and to explore the effects of GZFLC on the serum levels of transforming growth factor-ß1 (TGF-ß1) and the mRNA expression levels of vascular endothelial growth factor (VEGF) and glucose transporter 4 (GLUT-4) in the endometriotic tissues. Forty female Wistar rats were randomly divided into the sham-operation group (Normal group), Model group, Danazol group, and GZFLC group. The serum levels of TGF-ß1 were measured using enzyme-linked immune-sorbent assay (ELISA). The mRNA expression levels of VEGF and GLUT-4 in the endometriotic tissue of the rat endometriosis models were measured using real-time quantitative PCR. The metabolites in urine were detected by 1H NMR method. Eight identified metabolites of the NMR resonance were involved in the glycolysis metabolism. Among the 8 metabolites, Lactate, Acetate, TMA, and Formate were downregulated with GZFLC. Citrate, TMAO, Taurine, and Hippurate were unregulated with GZFLC. The serum levels of TGF-ß1 in the Danazol and GZFLC groups were significantly higher than those of Normal group and significantly lower than the Model group. GZFLC treatment significantly decreased the GLUT-4 and VEGF mRNA expression levels in the endometriotic tissues of the endometriosis rats (P < 0.05). GZFLC significantly decreased the GLUT-4 mRNA expression levels in rats of GZFLC group compared with Danazol group. It is through regulating the metabolites changes of glycolysis or gluconeogenesis that GZFLC significantly affected the expression levels of TGF-ß1, GLUT-4, and VEGF of the model rats with endometriosis.

American, European, and Chinese practice guidelines or consensuses of polycystic ovary syndrome: a comparative analysis.

Polycystic ovary syndrome (PCOS) is the most common metabolic and endocrine disorder in women. However, there is no agreement concerning how to diagnose and treat PCOS worldwide. Three practice guidelines or consensuses, including consensus from the European Society of Human Reproduction and Embryology (ESHRE)/the American Society for Reproductive Medicine (ASRM) in Rotterdam, diagnosis criteria and consensus in China, and clinical practice guideline from the Endocrine Society (ES) in the United States are widely recognized. The present paper may provide some guidance for clinical practice based on a comparative analysis of the above three practice guidelines or consensuses.

Women's health and Chinese integrative medicine.

Researchers in the fields of obstetrics, gynecology, and Chinese integrative medicine (CIM) were invited to share their perspectives on the most recent studies.

The prevalence of polycystic ovary syndrome in reproductive-aged women of different ethnicity: a systematic review and meta-analysis.

The prevalence of PCOS was investigated in many studies in different continents. However, there is no established prevalence of PCOS for distinct ethnic groups. In the current analysis, we conducted searches in PubMed, The Cochrane Library, EMBASE, CINAHL up to Jan. 2017 to identify studies reporting prevalence of PCOS in the general female population. Forty-two studies were identified, with 13 eligible for evidence synthesis. The prevalence among different ethnicity was estimated using random effect modelling. Our results suggested the lowest prevalence in Chinese women(2003 Rotterdam criterion: 5.6% 95% interval: 4.4-7.3%), and then in an ascending order for Caucasians (1990 NIH criterion: 5.5% 95% interval: 4.8-6.3%), Middle Eastern (1990 NIH 6.1% 95% interval: 5.3-7.1%; 2003 Rotterdam 16.0% 95% interval: 13.8-18.6%; 2006 AES 12.6% 95% interval: 11.3-14.2%), and Black women (1990 NIH: 6.1% 95% interval: 5.3-7.1%).There is variation in prevalence of PCOS under different diagnostic criteria and across ethnic groups. This emphasises the need for ethnicity-specific guidelines for PCOS to prevent under- or over-diagnosis of the condition given that under-diagnosis may lead to rapid conversion of metabolic disorders for patients whereas over-diagnosis may exert negative psychological effects on patients which worsens the major symptoms of PCOS.

The association between psychological stress and miscarriage: A systematic review and meta-analysis.

This systematic review and meta-analysis was designed to investigate whether maternal psychological stress and recent life events are associated with an increased risk of miscarriage. A literature search was conducted to identify studies reporting miscarriage in women with and without history of exposure to psychological stress (the only exposure considered). The search produced 1978 studies; 8 studies were suitable for analysis. A meta-analysis was performed using a random-effects model with effect sizes weighted by the sampling variance. The risk of miscarriage was significantly higher in women with a history of exposure to psychological stress (OR 1.42, 95% CI 1.19-1.70). These findings remained after controlling for study type (cohort and nested case-control study OR 1.33 95% CI 1.14-1.54), exposure types (work stress OR 1.27, 95% CI 1.10-1.47), types of controls included (live birth OR 2.82 95% CI: 1.64-4.86). We found no evidence that publication bias or study heterogeneity significantly influenced the results. Our finding provides the most robust evidence to date, that prior psychological stress is harmful to women in early pregnancy.

Transcutaneous Electrical Acupoint Stimulation Improves the Outcomes of In Vitro Fertilization: A Prospective, Randomized and Controlled Study.

OBJECTIVES: To explore whether transcutaneous electrical acupoint stimulation (TEAS) can improve the outcomes of in vitro fertilization (IVF). DESIGN: A prospective, randomized, and controlled study. SETTING: IVF center in a university hospital. PARTICIPANTS: Four hundred and eighty-one infertile patients with bilateral tubal blockage who were referred for IVF. Patients were randomized into four groups. INTERVENTION: TEAS was administered for 30min, respectively, at 24h before TVOR and two hours before ET. The acupoints included SP10 (Xuehai, bilateral), SP8 (Diji, bilateral), LR3 (Taichong, bilateral), ST36 (Zusanli, bilateral), EX-CA1 (Zigong, bilateral), RN4 (Guanyuan), PC6 (Neiguan, bilateral), and RN12 (Zhongwan). Based on different frequencies of TEAS, patients were grouped into a TEAS-2Hz group, a TEAS-100Hz group and a TEAS-2/100Hz group. Patients in the control group only received routine IVF treatment and no TEAS was applied on them. PRIMARY AND SECONDARY OUTCOME MEASURES: The number of mature oocytes, normally fertilized oocytes and good-quality embryos were used to evaluate oocyte developmental competence of the patients. Data of clinical pregnancy rate (CPR), implantation rate (IR), and live birth rate (LBR) were also obtained. The levels of neuropeptide Y (NPY), transforming growth factor alpha and granulocyte colony-stimulating factor in the follicular fluids were measured with enzyme-linked immunosorbent assay (ELISA). RESULTS: No significant differences were found between the control, TEAS-2Hz, TEAS-100Hz and TEAS-2/100Hz groups on the numbers of metaphase II oocytes, normally fertilized zygotes, early cleavage embryos or good quality embryos (P > .05). However, the CPR, IR and LBR of the TEAS-2/100Hz group were significantly higher than those of the other groups, respectively (P < .05). The NPY levels in the follicular fluids of TEAS-2/100Hz group were significantly higher than those of the other groups (P < .05). CONCLUSION: TEAS using a frequency of 2/100Hz could help to improve the IVF outcomes partly by increasing NPY levels in the follicular fluids.

Diagnosis and management of polycystic ovary syndrome in the UK (2004-2014): a retrospective cohort study.

OBJECTIVE: To estimate the incidence and prevalence of polycystic ovary syndrome (PCOS) in UK primary care and investigate prescribing patterns before and after a PCOS diagnosis. DESIGN: Retrospective cohort study. SETTING: UK primary care (2004-2014). PARTICIPANTS: Women aged 15-45 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The incidence and prevalence of diagnosed PCOS and probable PCOS (ie, those without a confirmed diagnosis but with at least 2 PCOS features recorded within 3 years). Among women with diagnosed or probable PCOS, the prevalence of prescribing of drugs typically used to treat PCOS was calculated prior to and in the 24 months after the diagnosis of PCOS. RESULTS: We identified 7233 women with PCOS diagnoses and 7057 women with records suggestive of probable PCOS, corresponding to incidence rates of 0.93 and 0.91 per 1000 person-years at risk (PYAR) and an overall rate of 1.84 per 1000 PYAR. Women aged 20-24 years and women living in deprived areas had the highest incidence of PCOS. The prevalence of PCOS in 2014 was ∼2%. The proportion of women with a prescription in the 24 months after their PCOS index date varied by drug type: 10.2% metformin, 15.2% combined oral contraceptives, 18.8% acne-related treatments, 1.93% clomiphene, 1.0% spironolactone, 0.28% cyproterone and 3.11% eflornithine. Acne-related treatments were more commonly used to treat probable (28.3%) than diagnosed (12.3%) cases, while metformin was prescribed much more commonly in diagnosed cases. CONCLUSIONS: In conclusion, compared to rates estimated in community samples, the incidence and prevalence of women presenting in primary care with PCOS diagnoses and features are low, indicating that PCOS is an under-recognised condition. Although considerable variation is observed in treatments prescribed to women with PCOS, the treatments initiated following a confirmed diagnosis generally reflect the long-term prognostic concerns raised in PCOS consensuses.

Acupuncture for treating polycystic ovary syndrome: guidance for future randomized controlled trials.

OBJECTIVE: To provide guidance for future randomized controlled trials (RCTs) based on a review concerning acupuncture for treating polycystic ovary syndrome (PCOS). METHODS: A comprehensive literature search was conducted in October 2015 using MEDLINE, EMBASE, SCISEARCH, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Menstrual Disorders and Subfertility Group trials register, Allied and Complementary Medicine (AMED), China National Knowledge Infrastructure (CNKI), and the Wanfang databases. RCTs comparing either acupuncture with no/sham/pharmacological intervention or a combination of acupuncture and conventional therapy with conventional therapy in the treatment of PCOS were included in this review. A quality evaluation was performed for each of the included studies. RESULTS: Thirty-one RCTs were included in the review and were divided into four categories according to the type of intervention used in the comparator or control group. Menstrual frequency, hormones, anthropometrics, insulin sensitivity, blood lipids, and fertility were used as the main measurements to assess the effects of acupuncture on the patients with PCOS. Thirty trials, except for one, showed an improvement in at least one of the indicators of PCOS after acupuncture treatment. However, normalizing the methodological and reporting format remains an issue. CONCLUSIONS: Based upon this review of current clinical trials concerning acupuncture for treating PCOS, we provide guidelines for better clinical trial design in the future.

Androgens as double-edged swords: Induction and suppression of follicular development.

Androgens, which are mediated via the androgen receptor (AR), play important roles in normal follicular development and female fertility. However, just like a double-edged sword, besides the positive effects of androgen on follicular development, abnormal androgen levels, especially as in hyperandrogenism, seriously suppress normal follicular development. A crucial balance exists between the importance of androgens in follicular development and their negative effects when in excess. As the first meiotic division and epigenetic reprogramming are two critical events in oogenesis, abnormal androgen levels or deficiency in androgen/AR signaling in the ovary may affect these vital events. Oocytes have a tendency to develop genomic instability, thus resulting in an increasing incidence of unpredictable adult diseases. Although many studies have explored the effects of androgens and AR on follicular development, the conclusions are controversial and there has been no thorough review of this topic. This review focuses on the roles of androgens in the physiological process of follicular development, summarizes new insights into the roles of androgens in the arrested development of follicles, and discusses the potential risk of adult diseases originating from abnormal follicular androgen levels or androgen receptor signals, which may determine areas for future studies.

Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common condition affecting ∼8% of women. The objective of the present study was to quantify separately the risk of endometrial cancer, ovarian cancer and breast cancer in women with PCOS compared with non-PCOS controls, and quantify separately the risk to women of all ages as well as the risk to premenopausal women. METHODS: We conducted a systematic review and meta-analysis of observational studies. Studies were eligible for inclusion if they compared women with PCOS to non-PCOS groups for fatal or non-fatal gynaecological cancers. Studies listed in MEDLINE and EMBASE published up to 7 October 2013 in any language were identified, and relevant papers were also searched by hand. Relevant data (for example, study design, source of control data, diagnostic criteria) were extracted and tabulated. RESULTS: From 698 references, 11 studies (5 of endometrial cancer and 3 each of ovarian and breast cancer) met the inclusion criteria for the meta-analysis (919 women with PCOS and 72054 non-PCOS controls). Using the Mantel-Haenszel method, with fixed or random effects model as appropriate, women with PCOS were at a significantly increased risk of endometrial cancer (odds ratio (OR), 2.79; 95% confidence interval (CI), 1.31-5.95, P < 0.008), but the risk of ovarian and breast cancers was not significantly increased (OR, 1.41; 95% CI, 0.93-2.15, P < 0.11 and OR, 0.95; 95% CI, 0.64-1.39, P < 0.78, respectively). However when studies which included women aged over 54 years were excluded from the analysis, the risk for women with PCOS increased further for endometrial cancer (OR, 4.05; 95% CI, 2.42-6.76, P < 0.00001), became significantly increased for ovarian cancer (OR, 2.52; 95% CI, 1.08-5.89, P < 0.03), but remained non-significant for breast cancer (OR, 0.78; 95% CI, 0.46-1.32, P < 0.35). CONCLUSIONS: This is the first meta-analysis to examine gynaecological cancers in women with PCOS younger than 54 years of age compared with controls of similar age. Current data suggest that women of all ages with PCOS are at an increased risk of endometrial cancer but the risk of ovarian and breast cancer was not significantly increased overall. These results highlight the potential risk of gynaecological cancer morbidities associated with PCOS. However, the available evidence is far from robust and variation in diagnostic criteria for PCOS, associated risk factors (particularly obesity), and selection bias in the studies may have resulted in an exaggeration of the increased risk. Furthermore, women who have PCOS should also be made aware that any increased risk for endometrial cancer must be judged in the context of its relatively low incidence in the general population. A large well-controlled prospective study is required in order to gain a more accurate estimate of the risk of gynaecological cancers in women with PCOS. PROSPERO CRD REGISTRATION NUMBER: CRD42012003500.

Testosterone and mood dysfunction in women with polycystic ovarian syndrome compared to subfertile controls.

Women with polycystic ovarian syndrome (PCOS) have been found to suffer from fertility problems and mood dysfunction. To control for any effect of fertility problems, the present study compared mood dysfunction in women with PCOS to non-PCOS women with fertility problems. Seventy-six women with PCOS and 49 subfertile controls reported their anxiety, depression and aggression levels, and the relationship between mood and testosterone (T) was assessed. Controlling for age and BMI using MANCOVA, women with PCOS were significantly more neurotic (had difficulty coping with stress) than controls, had more anger symptoms, were significantly more likely to withhold feelings of anger and had more quality of life problems related to the symptoms of their condition (acne, hirsutism, menstrual problems and emotions). In a subgroup of 30 women matched on age, BMI and ethnicity, it was found that women with PCOS were significantly more anxious and depressed than controls. T was not generally correlated with mood states. This is the first study to identify problems with neuroticism and withholding anger in women with PCOS. These mood problems appear to be mainly attributable to PCOS symptoms, though other factors, such as hypoglycaemia, cannot be ruled out.