Ovary Syndrome Women Research Articles

Metformin enhances the action of insulin on porcine granulosa-lutein cells in vitro

Metformin is an oral antidiabetic drug extensively used to treat the polycystic ovary syndrome in women. Metformin increases insulin-stimulated glucose uptake and has direct effects on ovarian steroidogenesis in humans. However, the molecular mechanisms of metformin’ action on the ovary are not clear. To investigate the effects of this drug on the insulin-signaling pathway in porcine granulosa cells as an alternative model for human research, we examined the mRNA expressions of porcine insulin receptor (INSR), insulin-like growth factor-1 receptor (IGF-1R), insulin receptor substrate-1 (IRS-1), and the protein activity (activation and phosphorylation) of downstream targets including Raf, mitogen-activated protein kinase (MEK)1/2, extracellular signal regulated kinase (ERK), phosphoinositide-dependent 1 kinase (PDK1), mammalian target of rapamycin (TOR), p70, and nuclear factor-κB (NF-κB) in a primary culture system consisting of porcine granulosa-lutein cells (pGLs) incubated with 10−5M metformin and/or 100ng/ml insulin for 24h in a serum-free medium. We also investigated the luciferase activity of transcription factors activator protein-1 (AP-1) and NF-κB. Metformin with insulin significantly increased mRNA expressions of INSR, IGF-1R, and IRS-1, while metformin alone had no significant effect. And metformin with insulin had the significant effect on the protein activity (activation and phosphorylation) of downstream targets of INSR signaling pathway. Metformin with insulin significantly elicited an induction of luciferase activity in the transfection of AP-1 and NF-κBreporter, while metformin alone did not.In conclusion, we examined the activity of metformin and insulin on pGLS in vitro and metformin enhanced the action of insulin on the intracellular signaling pathways. These results suggest that metformin could change the function of ovarian granulosa cells.

Lipidomics in polycystyc ovary syndome: a novel approach for diagnosis

Lipidomics consists of qualitative profiling of follicular fluid lipids, aiming to discover possible novel biomarkers and pathways associated to Polycystic Ovary Syndrome in women who were submitted to in vitro fertilization treatment.

Variants inDENND1AAre Associated with Polycystic Ovary Syndrome in Women of European Ancestry

A genome-wide association study has identified three loci (five independent signals) that confer risk for polycystic ovary syndrome (PCOS) in Han Chinese women. Replication is necessary to determine whether the same variants confer risk for PCOS in women of European ancestry. The objective of the study was to test whether these PCOS risk variants in Han Chinese women confer risk for PCOS in women of European ancestry. This was a case-control study. The study was conducted at deCODE Genetics in Iceland and two academic medical centers in the United States. Cases were 376 Icelandic women and 565 and 203 women from Boston, MA, and Chicago, IL, respectively, all diagnosed with PCOS by the National Institutes of Health criteria. Controls were 16,947, 483, and 189 women not known to have PCOS from Iceland, Boston, and Chicago, respectively. There were no interventions. Main outcomes were allele frequencies for seven variants in PCOS cases and controls. Two strongly correlated Han Chinese PCOS risk variants on chromosome 9q33.3, rs10986105[C], and rs10818854[A], were replicated in samples of European ancestry with odds ratio of 1.68 (P = 0.00033) and odds ratio of 1.53 (P = 0.0019), respectively. Other risk variants at 2p16.3 (rs13405728), 2p21 (rs12468394, rs12478601, and rs13429458), and 9q33.3 (rs2479106), or variants correlated with them, did not associate with PCOS. The same allele of rs10986105 that increased the risk of PCOS also increased the risk of hyperandrogenism in women without PCOS from Iceland and demonstrated a stronger risk for PCOS defined by the National Institutes of Health criteria than the Rotterdam criteria. We replicated one of the five Chinese PCOS association signals, represented by rs10986105 and rs10818854 on 9q33, in individuals of European ancestry. Examination of the subjects meeting at least one of the Rotterdam criteria for PCOS suggests that the variant may be involved in the hyperandrogenism and possibly the irregular menses of PCOS.

Association of thrombophilia and polycystic ovarian syndrome in women with history of recurrent pregnancy loss

Purpose: To evaluate the prevalence of thrombophilic disorders in polycystic ovarian syndrome (PCOS) women with history of recurrent pregnancy loss (RPL). Materials and methods: This study was carried out in 184 women with history of RPL, of which 92 of them were diagnosed with PCOS and 92 patients were without known PCOS. The prevalence of thrombophilic disorders was compared between the two mentioned groups. Results: According to the findings, 70.7% of PCOS women with history of RPL had thrombophilic disorders. The prevalence of protein C deficiency was significantly higher in PCOS group compared to the non-PCOS group (21.7% vs. 10.9%, p = 0.04). There was a trend toward higher prevalence of protein S deficiency in PCOS group compared to the control group, but the difference did not reach statistical significance (23.9% vs. 13%, p = 0.05). The prevalence of other thrombophilic disorders such as antithrombin III deficiency, homocysteine elevation, antiphospholipid antibody and Factor V Leiden was comparable between groups. Conclusion: The prevalence of thrombophilic disorders was more common in PCOS women than the normal group. The protein C deficiency is associated with PCOS in women with history of RPL. There was a trend toward higher prevalence of protein S deficiency in PCOS women, which needs further study.

Insulin resistance but not impaired β-cell function: a key feature in Chinese normal-weight PCOS women with normal glucose regulation

Objective: To evaluate insulin sensitivity and β-cell function in Chinese polycystic ovary syndrome (PCOS) women while taking into account the confounding variables including body mass index (BMI), blood glucose levels, ethnicity, medication history and a family history of type 2 diabetes. Study design: Cross-sectional analysis. Setting: Clinical research center in China.Subjects: 76 PCOS women and 20 age-matched healthy control women. Intervention: No. Main outcome measures: All subjects underwent botnia euglycemic-hyperinsulinemic clamp to assess their insulin sensitivity expressed as M value and β-cell function expressed as deposition index (DI). Results: Compared with age-matched controls, both DI and M (p < 0.05, respectively) value were lower in PCOS group with normal glucose regulation (NGR), and they (p < 0.05, respectively) were the lowest in PCOS group with impaired glucose regulation (IGR). The subgroup analysis showed that compared with normal-weight controls, DI (p = 0.072) was similar but M value (p < 0.05) was lower in normal-weight PCOS group with NGR, and DI (p < 0.05) and M value (p < 0.05) were lower in overweight PCOS group with NGR. DI and M value (p < 0.05, respectively) of overweight PCOS group with IGR were the lowest among all groups. Conclusions: There was insulin resistance but not impaired β-cell function in Chinese normal-weight PCOS women with NGR. Insulin resistance may be an intrinsic factor prior to impaired β-cell function of PCOS.

The Prevalence of Polycystic Ovary Syndrome in Women with Idiopathic Intracranial Hypertension

Purpose. The purpose of this study is to re-evaluate whether the prevalence of polycystic ovary syndrome (PCOS) amongst women with idiopathic intracranial hypertension (IIH) is higher than in the general population using the NIH criteria. Methods. We included all consecutive women with IIH of child-bearing age seen at a hospital-based neuro-ophthalmology clinic between the years 2000–2005. All consenting women included in this study filled-out a screening questionnaire aimed at identifying women at risk for PCOS. The endocrinologist examined each patient suspect of PCOS as well as their biochemical results and diagnosed PCOS according to NIH criteria. The prevalence of PCOS in these women with IIH was compared with the reported prevalence of PCOS in the general population. Results. Out of 58 women with IIH who completed the study, definite PCOS was diagnosed in nine women (9/58; 15.5%). We found a significantly higher prevalence of PCOS using the NIH criteria among the IHH study group (15.5%, P = 0.001) compared to the general population (8.7%). Conclusions. The prevalence of PCOS is higher among patients with IHH, compared to the general population. We suggest a novel screening questionnaire to aid in the identification of women with IIH at risk for PCOS.

Increased prevalence of diabetes and polycystic ovary syndrome in women with a history of preterm birth: a case-control study

To test the hypothesis that endocrine and metabolic factors predispose to preterm birth. A cross-sectional, case-control study. Namsos Hospital district (Namsos, Norway). Women from the Namsos Hospital district with previous preterm births (n = 114) were compared with matched controls with term births (n = 127). A clinical examination including transvaginal ultrasound was performed. Fasting blood samples were collected and an oral glucose tolerance test was performed. The prevalence of polycystic ovary syndrome (PCOS) diagnosis (Rotterdam criteria) and serum levels of androgens, glucose and insulin. Twenty-nine of 114 women (25.4%) met the PCOS criteria among women with preterm birth, compared with 18 of 127 (14.2%) among controls (P = 0.03). Eight (7.1%) women with preterm birth were diagnosed with diabetes compared with none in the control group (P < 0.01). Hirsutism was present in 34 (29.8%) women with preterm birth versus 12 (9.4%) in the control group (P < 0.01). The prevalences of PCOS, diabetes and hirsutism are increased among women with a history of preterm birth. This indicates that endocrine and/or metabolic factors may be involved in the pathogenesis of preterm birth. Women experiencing preterm delivery may have an increased risk of developing diabetes and PCOS later in life.

A comparative study on the impact of fresh variables on the success of frozen-thawed embryo transfer cycles using 2PN sibling embryos in women with/without polycystic ovary syndrome

Aims: The aim of the present study was to identify the fresh variables that influence the frozen-thawed embryo transfer (FET) outcome using sibling two pronuclei (2PN) embryos in women with polycystic ovary syndrome (PCOS) and non-PCOS women. Material & methods: Fifty-five FET cycles were performed using sibling embryos randomly cryopreserved at 2PN states and basal/cycle characteristics of fresh variables were compared between PCOS and non-PCOS groups according to the success in FET pregnancy: group A (pregnant PCOS); group B (not pregnant PCOS); group C (pregnant non-PCOS); group D (not pregnant non-PCOS). Results: In PCOS patients, higher progesterone level on human chorionic gonadotropin (hCG) day was observed in group A than in group B (0.9 ± 0.0 vs. 0.5 ± 0.3, p = 0.004). In non-PCOS patients who achieved a pregnancy in the fresh cycle, a subsequent FET cycle using sibling 2PN embryos conferred a thirteen times increased chance of achieving pregnancy (OR 13.0; 95% CI, 2.3–74.1). Embryo quality and endometrial maturation were comparable between A and B or C and D. Conclusions: The success of the fresh embryo transfer (ET)was the most important predictor of pregnancy in FET cycles in the non-PCOS group. The relationship between serum progesterone on hCG day in the fresh cycle and the outcome of subsequent FET would benefit further evaluation in PCOS group.

Effect of androgen treatment during foetal and/or neonatal life on ovarian function in prepubertal and adult rats.

We investigated the effects of different windows of testosterone propionate (TP) treatment during foetal and neonatal life in female rats to determine whether and when excess androgen exposure would cause disruption of adult reproductive function. Animals were killed prepubertally at d25 and as adults at d90. Plasma samples were taken for hormone analysis and ovaries serial sectioned for morphometric analyses. In prepubertal animals, only foetal+postnatal and late postnatal TP resulted in increased body weights, and an increase in transitory, but reduced antral follicle numbers without affecting total follicle populations. Treatment with TP during both foetal+postnatal life resulted in the development of streak ovaries with activated follicles containing oocytes that only progressed to a small antral (smA) stage and inactive uteri. TP exposure during foetal or late postnatal life had no effect upon adult reproductive function or the total follicle population, although there was a reduction in the primordial follicle pool. In contrast, TP treatment during full postnatal life (d1–25) resulted in anovulation in adults (d90). These animals were heavier, had a greater ovarian stromal compartment, no differences in follicle thecal cell area, but reduced numbers of anti-Mullerian hormone-positive smA follicles when compared with controls. Significantly reduced uterine weights lead reduced follicle oestradiol production. These results support the concept that androgen programming of adult female reproductive function occurs only during specific time windows in foetal and neonatal life with implications for the development of polycystic ovary syndrome in women.

Clinical and biochemical presentation of polycystic ovary syndrome in women between the ages of 20 and 40

The clinical features and metabolic complications of polycystic ovary syndrome (PCOS) may change with age. This study was designed to investigate the clinical and biochemical characteristics of PCOS patients between the ages of 20 and 40. The study included 781 Taiwanese women, of whom 453 were diagnosed with PCOS and 328 were non-PCOS controls. Anthropometric components, androgens, endocrine, insulin resistance, and metabolic components were measured and correlated with age. Above parameters were compared between younger and elder women with PCOS. Age had significant negative correlations with androgens (total testosterone and dehydroepiandrosterone sulfate), the modified Ferriman-Gallwey score and the prevalence of acne and hirsutism. Age had significant positive correlations with fasting glucose, cholesterol, triglycerides and low-density lipoprotein. The 453 women who fulfilled diagnostic criteria for PCOS were classified by age into two groups: Group A (20-29 years old, n= 294) and Group B (30-40 years old, n= 159). Group A had significantly higher total testosterone levels than Group B. Group B had higher fasting insulin and glucose levels, triglycerides, body mass index and waist measurements and a higher incidence of obesity than Group A. The average ovarian volume was not significantly different among the two groups. Increased age is accompanied by a decrease in the prevalence of both clinical and biochemical hyperandrogenism in women. Hyperandrogenism is the important factor for young women with PCOS; however, abdominal obesity and certain metabolic disturbances became major concerns for older women with PCOS.

A meta-analysis of polycystic ovary syndrome in women taking valproate for epilepsy

To conduct a meta-analysis to quantify whether valproate (VPA) is associated with an increased risk of polycystic ovary syndrome (PCOS) in women with epilepsy. A comprehensive literature search for all published studies of MEDLINE and EMBASE was performed for English language studies published from 1st January 1990 to 4th February 2011. The studies included should be prospective and controlled. We then performed a meta-analysis to identify polycystic ovary syndrome in women with epilepsy treated with VPA. The meta-analysis included 11 studies that met inclusion/exclusion criteria, involving 556 women with epilepsy treated with VPA, 593 women treated with other antiepileptic drugs (AEDs), 120 women with untreated epilepsy and 329 healthy controls. The calculated incidence of PCOS in women treated with VPA was higher than that in women treated without VPA (10 studies included, P<0.05, OR 3.04, 95% CI 2.09-4.43). According to different definitions or diagnostic criteria of PCOS, the results were different. VPA's treatment was associated with higher incidence of PCOS in the criteria of hyperandrogenism and/or hyperandrogenemia, oligoovulation (4 studies included, P<0.05, OR 3.22, 95% CI 1.79-5.80), and in the criteria of two of the three following fulfilled: appearance of polycystic ovary (PCO) on the ultrasonogram, elevated serum testosterone levels and irregular (oligo-/amenorrhea) menstrual cycles (1 post hoc reanalysis study included, P<0.05, OR 5.01, 95% CI 2.40-10.49. Another prospective and crosssectional included, P<0.05, OR 3.50, 95% CI 1.30-9.40). However, in the criteria of PCO with ovulatory dysfunction (polymenorrhea, amenorrhea, or oligomenorrhea), clinical and/or biochemical evidence of hyperandrogenism according to National Institutes of Child Health and Human Development (NICHHD) and The National Institutes of Health (NIH) Consensus Conference, VPA did not increase the PCOS incidence compared with other AEDs (4 studies included, P>0.05, OR 1.37, 95% CI 0.59-3.19). Data on PCOS's components were pooled. PCO was higher in women treated with VPA than in those without VPA (6 studies included, P<0.05, OR 1.94, 95% CI 1.28-2.95) or in healthy controls (4 studies included, P<0.05, OR 4.99, 95% CI 2.97-8.37). VPA treated women were more subject to hyperandrogenism than non-VPA treated women (5 studies included, P<0.05, OR 2.35, 95% CI 1.57-3.53). There is significant difference of menstrual disorders between VPA treated women and non-VPA treated women (7 studies included, P<0.05, OR 1.64, 95% CI 1.19-2.25). Results of this meta-analysis suggest that the raw incidence of PCOS in VPA treated women with epilepsy is approximately 1.95 folds that in other AEDs treated women. PCOS and its components may be associated with VPA treated women with epilepsy. We recommend monitoring PCOS and its components in women with VPA mono-/polytherapy. In light of limitations and heterogenicity, there is surely the need for more prospective studies to identify VPA and PCOS.

24. The incidence of polycystic ovary syndrome in women with epilepsy treated with valproate versus lamotrigine

24. The incidence of polycystic ovary syndrome in women with epilepsy treated with valproate versus lamotrigine

Prognostic value of total testosterone for pregnancy during treatment in patients with clomiphene-citrate-resistant polycystic ovary syndrome: a pilot study

Reduction of serum total testosterone (TT) is associated with pregnancy rate in polycystic ovary syndrome (PCOS) women receiving metformin, but most of the studies focus on the changes of basal levels of TT. The aim of this study was to evaluate whether the TT level around the ovulation period is related to the outcome of pregnancy in women with PCOS. In total, 30 non-obese PCOS women with clomiphene citrate (CC) resistance from the Medical College's Reproductive Health Center were enrolled and randomly assigned to be treated with placebo (Group 1) or metformin (850 mg) (Group 2) twice daily for 3 months as the pre-treatment. Then, metformin alone was administered with CC, human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG) to induce ovulation for 3 months in Group 1. In Group 2, CC/HMG/HCG was used to induce ovulation for 3 months without metformin. Follicle-stimulating hormone, luteinizing hormone, estradiol and TT levels before and after ovulation in pregnant cycles and non-pregnant cycles were evaluated over the course of treatment. A total of 26 subjects completed 65 cycles. The TT levels after ovulation in the pregnant cycles were significantly lower than in the non-pregnant cycles in both groups (P = 0.001 and P < 0.001, respectively). The level of TT after ovulation may be of prognostic value for pregnancy in non-obese women with PCOS and CC resistance during treatment.

Personality types of Korean reproductive women with polycystic ovary syndrome

Objective The aim of this study was to compare personality types between polycystic ovary syndrome (PCOS) patients and women with normal menstrual cycle. Methods A total of 2,311 Korean women aged 15-39 was recruited. After initial screening, 131 women were excluded who had polarity index under 45. The study subjects were divided into PCOS patients (n=833) and women with normal menstrual cycle (n=1,347). Selfadministered questionnaire surveys, somatometry, blood test and transvaginal or transrectal ultrasound test were performed. By using Myers-Briggs Types Indicator (MBTI) personality types including characteristic index, function and temperament were also assessed. Results There was no signifi cant difference in the frequency of personality types between the patient and control groups. Among 16 MBTI subtypes, the extraversion-sensing-thinking-judgement type was the most common in both groups, 25.69% in PCOS patients and 24.51% in control group. In analysis of the judgement-perception index, the p
erceiving type was predominant in PCOS patients (30.73%) than control group (25.09%) with a statistical signifi cance ( P=0.013). The average testosterone level in women with the extroversion type was 53.43 ± 20.13 ng/dL, which was signifi cantly higher than women with the introversion type (51.58 ± 18.60 ng/dL). Conclusion Higher frequency of the perception type is typical feature in PCOS patients. Hyperandrogenism is closely related to the extroversion type of personality.

Effect of finasteride on ovulation induction in nonresponder (hyperandrogenic) polycystic ovary syndrome (PCOS) women

Effect of finasteride on ovulation induction in nonresponder (hyperandrogenic) polycystic ovary syndrome (PCOS) women

High prevalence of polycystic ovary syndrome in women born small for gestational age

There is evidence that intrauterine growth restriction, resulting in newborn girls that are small for gestational age (SGA), may be related to the onset of polycystic ovary syndrome (PCOS). Thus, we studied whether women born SGA have a higher prevalence of PCOS than women born appropriate for gestational age (AGA). This was a prospective birth cohort study of 384 women born at term between June 1, 1978, and May 31, 1979, in Ribeirão Preto, Brazil. After exclusion, 165 women effectively participated in this study, of whom 43 were SGA and 122 were AGA. The prevalence of PCOS was analysed. At a mean age of 29 years, the women agreed to follow the study protocol, which included: anamnesis, physical examination, serum tests [follicle stimulating hormone, luteinizing hormone, total and free testosterone, dehydroepiandrostenedione sulphate, 17-OH-progesterone, fasting insulin, sex steroid-binding globulin (SHBG) and fasting glucose] and pelvic ultrasound. Data regarding gestational age, birthweight, age at menarche and maternal data were obtained from the files of the cohort. The adjusted relative risk (RR) values of the SGA, insulin resistance, body mass index, maternal smoking and parity variables were analysed using Poisson regression with robust adjustment of variance for the prediction of PCOS. The prevalence of PCOS was higher in the SGA group than in the AGA group [adjusted RR = 2.44, 95% CI (1.39-4.28)]. Hyperandrogenism was more prevalent in the SGA women than in the AGA women (P = 0.011). Circulating SHBG was lower in the SGA women than in the AGA women (P = 0.041), but fasting insulinemia was similar in both groups. The prevalence of PCOS in SGA women was twice as high as in AGA women in our study population.

Serum and follicular fluid levels of IGF-II, IGF-binding protein-4 and pregnancy-associated plasma protein-A in controlled ovarian hyperstimulation cycle between polycystic ovarian syndrome (PCOS) and non-PCOS women

Objective. To investigate the difference of serum and follicular expression patterns for IGFα, IGFBP4 and PAPP-A in COH cycle between PCOS and non-PCOS women.Methods. COH was performed for total 30 sterile women (20 with PCOS and 10 with normal ovarian function). The serum and follicular fluid (FF)from dominant follicles levels of IGFα, IGFBP4 and PAPP-A before COH, day of hCG, and were measured using an ELISA.Results. The PCOS women had significantly higher day 3 serum PAPP-A, day of hCG serum IGFBP-4, and ff IGF-II levels compared to the normoovulatory subjects. Serum levels of IGF-II and IGFBP-4 in PCOS women had increased after gonadotropins stimulation, and yet PAPP-A was decreased. Within the PCOS women, day of hCG serum IGFBP-4 was strongly correlated with BMI (r = 0.777; P = 0.000), day of hCG IGF II (r = −0.573, p = 0.008), ff IGF II (r = −0.573, p = 0.008) and ff PAPP-A (r = −0.461, p = 0.041) was inversely related to diameter >16 mm follicle number and day 3 PAPP-A correlated to diameter >16 mm follicle number (r = 0.474; p = 0.035).Conclusions. Ovarian IGF system on the gonadotropin response to differences in the PCOS and non-PCOS women in COH cycle, and may indicate a inordinate IGF system that might disturb folliculogenesis in PCOS women.

Assessment of pulmonary functions and anthropometric measurements in women with polycystic ovary syndrome

Objectives. The aims of this study were to compare pulmonary function tests of patients with polycystic ovary syndrome (PCOS) versus healthy women, and to investigate correlations between pulmonary function tests and anthropometric measurements of them.Materials and Methods. A total of 31 women with PCOS and 29 controls matched for age and body mass index (BMI) were enrolled into the study. Pulmonary function tests were performed with spirometer. Body fat percentage was calculated from the skinfold thicknesses using the formula. Biacromial, chest antero-posterior and lateral diameter measurements were carried out with anthropometric set.Results. There were no significant differences between patients with PCOS and healthy controls in the pulmonary function tests, body fat %, chest and abdomen region anthropometric measurements. There were moderate negative correlations only between forced expiratory volume per 1 s and BMI, abdomen circumference, body fat percentage in patients with PCOS. In the control group, however, there were moderate or strong negative correlations between anthropometric measurements (BMI, body fat percentage, abdominal circumference, chest lateral diameter) and at least three different pulmonary function tests.Conclusion. These results suggest that the upper body anthropometry and respiratory function relations might have impaired in patients with PCOS. We think that this situation might support the increased tendency for poor health status in patients with PCOS.

1201 New fluorine-18 radiolabeled Cdk4/6 inhibitors: potential radiotracers for tumour imaging by positron emission tomography

Metformin is an oral antidiabetic drug extensively used to treat the polycystic ovary syndrome in women. Metformin increases insulin-stimulated glucose uptake and has direct effects on ovarian steroidogenesis in humans. However, the molecular mechanisms of metformin’ action on the ovary are not clear. To investigate the effects of this drug on the insulin-signaling pathway in porcine granulosa cells as an alternative model for human research, we examined the mRNA expressions of porcine insulin receptor (INSR), insulin-like growth factor-1 receptor (IGF-1R), insulin receptor substrate-1 (IRS-1), and the protein activity (activation and phosphorylation) of downstream targets including Raf, mitogen-activated protein kinase (MEK)1/2, extracellular signal regulated kinase (ERK), phosphoinositide-dependent 1 kinase (PDK1), mammalian target of rapamycin (TOR), p70, and nuclear factor-κB (NF-κB) in a primary culture system consisting of porcine granulosa-lutein cells (pGLs) incubated with 10−5 M metformin and/or 100 ng/ml insulin for 24 h in a serum-free medium. We also investigated the luciferase activity of transcription factors activator protein-1 (AP-1) and NF-κB. Metformin with insulin significantly increased mRNA expressions of INSR, IGF-1R, and IRS-1, while metformin alone had no significant effect. And metformin with insulin had the significant effect on the protein activity (activation and phosphorylation) of downstream targets of INSR signaling pathway. Metformin with insulin significantly elicited an induction of luciferase activity in the transfection of AP-1 and NF-κBreporter, while metformin alone did not.In conclusion, we examined the activity of metformin and insulin on pGLS in vitro and metformin enhanced the action of insulin on the intracellular signaling pathways. These results suggest that metformin could change the function of ovarian granulosa cells.

Prevalence of Polycystic Ovary Syndrome in Women from Opposite-Sex Twin Pairs

Intrauterine androgens of a male fetus may influence the female fetus in opposite-sex twin pairs. Because female intrauterine overexposure to androgens could lead to polycystic ovary syndrome (PCOS), the prevalence of PCOS should be higher in women from opposite-sex twin pairs. Therefore, the aim of the current study was to evaluate the prevalence of PCOS in women from opposite-sex twin pairs compared to women from same-sex twin pairs, sisters, and female spouses of twins. Data from 1325 monozygotic twins, 1191 dizygotic twins (711 women from same-sex twin pairs and 480 women from opposite-sex twin pairs), 745 sisters of twins, and 218 spouses of male twins were evaluated. PCOS was defined as less than nine natural menstrual cycles a year combined with either hirsutism or acne. The prevalence of PCOS was compared using a chi2 test. Binary logistic regression analyses were conducted to test for confounding effects of smoking, age, and body mass index. No significant differences in PCOS prevalence were found between women from same-sex twin pairs (either monozygotic or dizygotic), opposite-sex twin pairs, sisters, and spouses. The prevalence of PCOS is not different in women from opposite-sex and same-sex twin pairs, singleton sisters, or spouses. This indicates that possible androgen exposure of the female fetus, caused by a shared intrauterine environment with a male fetus, does not result in PCOS-like traits.