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Background and objective Results of studies focusing on chronic kidney disease (CKD) among women with polycystic ovary syndrome (PCOS) are insufficient and controversial. This study aimed to evaluate the incidence rate of CKD in women with PCOS, compared to a control group of healthy women. Methods This study was a population-based cohort study conducted from among 1460 reproductive-age women including 156 women with PCOS and 1304 controls. Incidence rates per 1000 person-years of follow-up were calculated for PCOS and control groups. Cox proportional hazards regression with age as the time-scale was used to estimate hazard ratios (HR) and 95% confidence intervals for developing CKD in relation to PCOS in both univariable and multivariable models. Results During a median follow-up of 12.9 years, 330 new cases of CKD were identified, including 25 PCOS women (14.8 per 1000 person-years; 95% CI, 10-22) and 305 healthy controls (21.5 per 1000 person-years; 95% CI, 19.2-24.1). The results of the Cox model showed that the risk of CKD among women with PCOS and healthy women is comparable and women with PCOS did not have a higher risk of developing CKD compared to healthy women (unadjusted HR: 0.883; 95% CI: 0.587-1.328; P = .551). The results remained unchanged after adjustment for potential confounders of smoking status, BMI, hypertension and diabetes at baseline and follow-up of study (multiple adjusted HR: 0.911; 95% CI: 0.600-1.383; P = .661). Conclusion Our population-based study with a long-term follow-up period showed that the risk of CKD in PCOS patients was similar to the general female population. Large studies, with long-term follow-up and more diverse phenotypes, are needed to confirm the findings.

Iodine is an essential macronutrient for feto-maternal growth and development. Emerging evidence suggests that maternal iodine deficiency during pregnancy is potentially associated with both maternal and fetal adverse outcomes. The aim of this systematic review and meta-analysis was to investigate the association between maternal iodine status in euthyroid pregnant women and adverse pregnancy outcomes. A comprehensive literature search was performed in PubMed, Web of Science and Scopus up to October 2019 for retrieving related published articles in English. World Health Organization maternal median urinary iodine concentration (UIC) classification was used as follows: median UIC of less than 100, 100–149, 150–249, and more than 250 μg/L, for moderate-to-severe iodine deficiency, mild iodine deficiency, iodine adequate and more than adequate-to-excessive iodine, respectively. The primary outcomes of interest in this meta-analysis were the pooled prevalence and pooled odds ratio of the preterm birth, low birth weight (LBW), and one composite outcome of hypertensive disorders of pregnancy comprising pregnancy hypertension and preeclampsia. The secondary outcome was pooled mean of neonatal characteristics including birth weight, head circumference, Apgar score, and gestational age at birth. A total of 6 studies involving 7698 participants were included in this meta-analysis. The pooled prevalence of preterm birth, LBW, and hypertensive disorders of pregnancy were not statistically significantly different in the four groups of UIC levels. The pooled prevalence of preterm birth was 0.05, 0.04, 0.04, and 0.03 in UIC 250 μg/L, respectively. No evidence of an association was observed among the odds of preterm birth, LBW, and hypertensive disorders of pregnancy in euthyroid pregnant women with UIC between 100 and 149, 150–249, and > 250 μg/L compared with UCI

ObjectivesThe primary objective of this systemic review and meta-analysis was to investigate the risk of developing composite outcome of all cancers, regardless of the type of cancer among men with infertility diagnosis compared to fertile counterparts. The secondary objective was to compare the pooled risk of developing individual specific cancers between two groups.MethodsA systematic literature search was performed on the databases of PubMed (including Medline), Scopus, and Web of Science to retrieve observational studies published in English language from 01.01.1990 to 28. 02. 2021. They assessed cancer events in males with an infertility diagnosis compared to controls without infertility. The outcomes of interest were a composite outcome of cancers including all known cancer types, and also specific individual cancers. The fixed/random effects model was used to analyze heterogeneous and non-heterogeneous results. Publication bias was assessed using the Harbord test, Egger test, Begg test, and funnel plot. The pooled odds ratio of cancers was calculated using the DerSimonian and Laird, and inverse variance methods. Studies’ quality and risk of bias were assessed using structured standard tools.ResultsWe included eight cohort studies involving 168,327 men with the diagnosis of infertility and 2,252,806 men without it. The total number of composite outcome of cancers as well as individual cancers including prostate, testicular and melanoma were 1551, 324, 183 and 121 in the infertile men and 12164, 3875, 849, and 450 in the fertile men, respectively. The pooled OR of the composite outcome of cancers, regardless of the type of cancer, in men with infertility was 1.4 folds higher than those without infertility (pooled OR = 1.43, 95% confidence interval [CI]: 1.25-1.64). Meta-analysis of individual cancers including prostate, testicular and melanoma between two groups was carried out. The pooled ORs of testicular and prostate cancers in men with the diagnosis of infertility were significantly higher than controls without infertility (pooled OR = 1.91, 95% CI: 1.52-2.42 and pooled OR = 1.48, 95% CI: 1.05-2.08, respectively). Additionally, the pooled OR of melanoma in men with infertility was 1.3 folds higher than those without infertility (pooled OR = 1.31, 95% CI: 1.06-1.62).ConclusionA greater risk of cancers in men with male infertility was found suggesting that the history of male infertility might be an important risk factor for developing cancers in later life. Further well-designed long-term population-based prospective studies, considering all known cancers and their accompanying risk factors should be conducted to support our findings.

ObjectivesThere are controversial studies investigating whether multiple anti-Mullerian hormone (AMH) measurements can improve the individualized prediction of age at menopause in the general population. This study aimed to reexplore the additive role of the AMH decline rate in single AMH measurement for improving the prediction of age at physiological menopause, based on two common statistical models for analysis of time-to-event data, including time-dependent Cox regression and Cox proportional-hazards regression models.MethodsA total of 901 eligible women, aged 18–50 years, were recruited from the Tehran Lipid and Glucose Study (TLGS) population and followed up every 3 years for 18 years. The serum AMH level was measured at the time of recruitment and twice after recruitment within 6-year intervals using the Gen II AMH assay. The added value of repeated AMH measurements for the prediction of age at menopause was explored using two different statistical approaches. In the first approach, a time-dependent Cox model was plotted, with all three AMH measurements as time-varying predictors and the baseline age and logarithm of annual AMH decline as time-invariant predictors. In the second approach, a Cox proportional-hazards model was fitted to the baseline data, and improvement of the complex model, which included repeated AMH measurements and the logarithm of the AMH annual decline rate, was assessed using the C-statistic.ResultsThe time-dependent Cox model showed that each unit increase in the AMH level could reduce the risk of menopause by 87%. The Cox proportional-hazards model also improved the prediction of age at menopause by 3%, according to the C-statistic. The subgroup analysis for the prediction of early menopause revealed that the risk of early menopause increased by 10.8 with each unit increase in the AMH annual decline rate.ConclusionThis study confirmed that multiple AMH measurements could improve the individual predictions of the risk of at physiological menopause compared to single AMH measurements. Different alternative statistical approaches can also offer the same interpretations if the essential assumptions are met.

This study aimed to evaluate the prevalence (P)/hazard ratio (HR) of cardiovascular (CV) events among reproductive age and menopausal age women with polycystic ovary syndrome (PCOS) in comparison with healthy controls. PubMed, Scopus, ScienceDirect, Web of science, and Google scholar were searched for retrieving observational studies published up to April 2018 investigating CV events in patients with PCOS. The primary outcomes were a composite outcome of CV events [including coronary arterial disease (CAD), cardiovascular disease (CVD), myocardial infarction (MI), angina, heart failure, and ischemic heart disease] and mortality due to CV events; secondary outcomes were specific CVD events, including cerebrovascular disease, CAD, CVD, MI, angina, heart failure, ischemic heart disease, and stroke. In this meta-analysis, both fixed and random effect models were used. Potential sources of heterogeneity were explored by meta-regression and subgroup analyses. Sixteen studies including 12 population-based were analyzed for the meta-analysis. Results showed that the pooled HRs of CV events in PCOS patients of reproductive age and in menopausal/aging women were higher than healthy controls (pooled HR: 1.38, 95% CI: 1.12-1.71) and (pooled HR: 1.53, 95% CI: 1.15, 2.04), respectively. Compared to healthy controls, analysis of population-based studies revealed that the HR of CV events increased only in reproductive age PCOS patients (1.43-fold, 95% CI: 1.27, 1.61), whereas the difference was not statistically significant when comparing menopausal/aging PCOS patients to healthy controls (1.03-fold, 95% CI: 0.41, 2.59). Sufficient data were not available for comparing the HRs of mortality due to CV events between the two PCOS age groups. Mainly based on population-based study, we found a greater risk of CV events in reproductive aged but not in menopausal/aging PCOS women, suggesting that having a history of PCOS during reproductive ages may not be an important risk factor for developing events in later life. This is a preliminary assumption and needs to be reevaluated by further comprehensive cohort studies of longer duration, initiated in the reproductive period, considering all known CVD risk factors.

While several studies have documented an increased risk of metabolic disorders in patients with polycystic ovary syndrome (PCOS), associations between androgenic and metabolic parameters in these patients are unclear. We aimed to investigate the relationships between biochemical markers of hyperandrogenism (HA) and metabolic parameters in women with PCOS. In this systematic review and meta-analysis, a literature search was performed in the PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science from 2000 to 2018 for assessing androgenic and metabolic parameters in PCOS patients. To assess the relationships between androgenic and metabolic parameters, meta-regression analysis was used. A total number of 33 studies involving 9905 patients with PCOS were included in this analysis. The associations of total testosterone (tT) with metabolic parameters were not significant; after adjustment for age and BMI, we detected associations of this androgen with low-density lipoproteins cholesterol (LDL-C) (β=0.006; 95% CI: 0.002, 0.01), high-density lipoproteins cholesterol (HDL-C) (β=–0.009; 95% CI: –0.02, –0.001), and systolic blood pressure (SBP) (β=–0.01; 95% CI: –0.03, –0.00). We observed a positive significant association between free testosterone (fT) and fasting insulin (β=0.49; 95% CI: 0.05, 0.91); this association remained significant after adjustment for confounders. We also detected a reverse association between fT and HDL-C (β=–0.41; 95% CI: –0.70, –0.12). There was a positive significant association between A4 and TG (β=0.02; 95% CI: 0.00, 0.04) after adjustment for PCOS diagnosis criteria. We also found significant negative associations between A4, TC, and LDL-C. Dehydroepiandrosterone sulfate (DHEAS) had a positive association with LDL-C (β=0.02; 95% CI: 0.001, 0.03) and a reverse significant association with HDL-C (β=–0.03; 95% CI: –0.06, –0.001). This meta-analysis confirmed the associations of some androgenic and metabolic parameters, indicating that measurement of these parameters may be useful for predicting metabolic risk in PCOS patients.

Objective To evaluate the incidence of hypertension, metabolic syndrome, dyslipidemia, and obesity in comparing women with polycystic ovary syndrome (PCOS) and a control group of healthy women. Design Prospective cohort study with the median and interquartile range of 12.9 (10.8–13.9) years. Setting Population-based cohort of the Tehran Lipid and Glucose Study. Patient(s) A total of 1,702 reproductive-age women including 178 women with PCOS and 1,524 controls. Intervention(s) None. Main Outcome Measure(s) Cumulative incidence of each outcome estimated using the Kaplan-Meier method and compared using the log-rank statistic; univariate and multiple extended Cox proportional hazards regression with age as the time scale to estimate the adjusted hazard ratio (HR) of developing outcomes in relation to PCOS and ages ≤40 years and >40 years with heavyside functions. Result(s) The incidence rates of hypertension, metabolic syndrome, dyslipidemia, and obesity were 13.9, 21.0, 46.1, 24.6, and 50.6, respectively, per 1,000 person-years for women with PCOS; and 13.8, 22.7, 46.0, and 24.0, respectively, per 1,000 person-years for the healthy control women. Women with PCOS aged ≤40 years had an adjusted higher risk of developing hypertension (HR 2.08; 95% confidence interval, 1.0–3.9) and the metabolic syndrome (HR 1.81; 95% confidence interval, 1.1–2.9), but the risk disappeared after age 40. The risks of central obesity and obesity had borderline statistical significance and were higher in women with PCOS aged ≤40 than in healthy controls. The risk of developing dyslipidemia showed no statistically significant difference between the two groups in the unadjusted or multiple adjusted models at any age. Conclusion(s) In this long-term population-based cohort study, the risk of developing hypertension and the metabolic syndrome in young women with PCOS was higher than in controls, but these risks were diluted in the late reproductive period.

Background: Further studies are needed to extend our knowledge about the association between male infertility and cardio-metabolic disorders. Objectives: We aimed to assess the association between male infertility and cardiometabolic disturbances using a population-based design. Methods: In total, 1611 participants of the Tehran-Lipid and Glucose-Study (phase III) were categorized into two groups of men with documented male infertility (n = 88) and those with at least one live birth and no history of primary infertility (n = 1523). Logistic regression was applied to explore the association between male infertility and cardiometabolic disturbances, including diabetes mellitus, pre-diabetes, hypertension, metabolic syndrome, dyslipidemia, obesity, central obesity, and chronic kidney disease, following adjustment for age and body mass index (BMI). Results: The unadjusted model revealed a significant association between infertility and hypertension and CKD (OR = 1.8; 95% CI: 1.2, 2.9, P-value = 0.006 and OR = 1.9; 95% CI: 1.1, 3.6, P-value = 0.033), respectively. However, after adjusting for age and BMI, as potential confounders, this association was not significant. Moreover, there was no association between infertility and other cardiometabolic disturbances, including diabetes and pre-diabetes, metabolic syndrome, dyslipidemia, obesity, and central obesity in both unadjusted and adjusted models. Conclusions: Our study revealed no association between male infertility and cardiometabolic disturbances. The findings can pave the way for further studies to extend our knowledge in this field. More population-based studies with a large sample size are warranted to confirm these findings.

Gestational diabetes mellitus (GDM) is a major public health problem and a threat to maternal and child health. There is a lack of integrated and systematically synthesized knowledge about the prevalence GDM in Norway. Therefore, this systemic review aimed to present the best available peer-reviewed published evidence from the past 20 years about the prevalence of GDM in Norway. A comprehensive literature search was performed on online databases consisting of PubMed (including Medline), Web of Science, and Scopus to retrieve original research articles published on the prevalence of GDM up to August 2020. Also, databases of Norart and SveMed+ in the Norwegian language were searched to enhance the search coverage. Data were extracted using a standardized protocol and data collection form and were presented narratively. A total of 11 studies were selected to include for data analysis and synthesis with the total sample size of 2,314,191 pregnant women. The studies included heterogenous populations and mostly reported the prevalence of GDM in healthy mothers with singleton pregnancies. The prevalence of GDM in population registered-based studies in Norway was reported to be lower than 2%, using the World Health Organization (WHO) 1999 criteria. However, studies on high-risk populations such as the non-European ethnicity reported prevalence rates ranging from 8% to 15%. Given the evidence from available literature that reported trends in the prevalence of GDM, an increase in the prevalence of GDM across most racial/ethnic groups studied in Norway was observed. Overall, the prevalence of GDM in the low risk population of Norway is fairly low, but the available literature supports the perspective that the prevalence of GDM has shown an increasing trend in recent decades. This finding is very important for health service planning and evaluation, policy development, and research in Norway. Large-scale prospective studies, using the national data, are warranted to provide firm evidence over coming years. Our review findings can help policy makers devise appropriate strategies for improving women’s reproductive health.

This systematic review and meta-analysis aimed to examine the impact of different gestational-diabetes (GDM) diagnostic-criteria on the risk of adverse-maternal-outcomes. The search process encompassed PubMed (Medline), Scopus, and Web of Science databases to retrieve original, population-based studies with the universal GDM screening approach, published in English language and with a focus on adverse-maternal-outcomes up to January 2020. According to GDM diagnostic criteria, the studies were classified into seven groups. A total of 49 population-based studies consisting of 1409018 pregnant women with GDM and 7,667,546 non-GDM counterparts were selected for data analysis and knowledge synthesis. Accordingly, the risk of adverse-maternal-outcomes including primary-cesarean, induction of labor, maternal-hemorrhage, and pregnancy-related-hypertension, overall, regardless of GDM diagnostic-criteria and in all diagnostic-criteria subgroups were significantly higher than non-GDM counterparts. However, in meta-regression, the increased risk was not influenced by the GDM diagnostic-classification and the magnitude of the risks among patients, using the IADPSG criteria-classification as the most strict-criteria, was similar to other criteria. In conclusion, a reduction in the diagnostic-threshold increased the prevalence of GDM, but the risk of adverse-maternal-outcome was not different among those women who were diagnosed through more or less intensive strategies. Our review findings can empower health-care-providers to select the most cost-effective approach for the screening of GDM among pregnant women.

ObjectivesIt is uncertain whether the treatment of mild gestational diabetes mellitus (GDM) improves pregnancy outcomes. The aim of this systemic review and meta-analysis was to investigate the effect of mild GDM treatment on adverse pregnancy outcomes.MethodsA comprehensive literature search was conducted on the databases of PubMed, Scopus, and Google Scholar to retrieve studies that compared interventions for the treatment of mild GDM with usual antenatal care. The fixed/random effects models were used for the analysis of heterogeneous and non-heterogeneous results. Publication bias was assessed using the Harbord test. Also, the DerSimonian and Laird, and inverse variance methods were used to calculate the pooled odds ratio of events. The quality assessment of the included studies was performed using the Modified Newcastle–Ottawa Quality Assessment scale and the CONSORT checklist. In addition, the risk of bias was evaluated using the Cochrane Collaboration’s tool for assessing risk of bias.ResultsThe systematic review and meta-analysis involved ten studies consisting of 3317 pregnant women who received treatment for mild GDM and 4407 untreated counterparts. Accordingly, the treatment of mild GDM significantly reduced the risk of macrosomia (OR = 0.3; 95%CI = 0.3–0.4), large for gestational age (OR = 0.4; 95%CI = 0.3–0.5), shoulder dystocia (OR = 0.3; 95%CI = 0.2–0.6), caesarean-section (OR = 0.8; 95%CI = 0.7–0.9), preeclampsia (OR = 0.4; 95%CI = 0.3–0.6), elevated cord C-peptide (OR = 0.7; 95%CI = 0.6–0.9), and respiratory distress syndrome (OR = 0.7; 95%CI = 0.5–0.9) compared to untreated counterparts. Moreover, the risk of induced labor significantly increased in the treated group compared to the untreated group (OR = 1.3; 95%CI = 1.0–1.6). However, no statistically significant difference was observed between the groups in terms of small for gestational age, hypoglycemia, hyperbilirubinemia, birth trauma, admission to the neonatal intensive care unit, and preterm birth. Sensitivity analysis based on the exclusion of secondary analysis data was all highly consistent with the main data analysis.ConclusionTreatment of mild GDM reduced the risk of selected important maternal outcomes including preeclampsia, macrosomia, large for gestational age, cesarean section, and shoulder dystocia without increasing the risk of small for gestational age. Nevertheless, the treatment could not reduce the risk of neonatal metabolic abnormalities or several complications in newborn.

Background and Objectives: Mild gestational diabetes (GDM) refers to the gestational hyperglycemia, which does not fulfill the diagnostic criteria for GDM. The results of studies on adverse pregnancy outcomes among women with mild GDM are controversial. Therefore, the aim of this systematic review and meta-analysis was to investigate the impact of mild GDM on the risk of adverse maternal and neonatal outcomes.Methods: A thorough literature search was performed to retrieve articles that investigated adverse maternal and neonatal outcomes in women with mild GDM in comparison with non-GDM counterparts. All populations were classified to three groups based on their diagnostic criteria for mild GDM. Heterogeneous and non-heterogeneous results were analyzed using the fixed/random effects models. Publication bias was assessed using the Harbord test. DerSimonian and Laird, and inverse variance methods were used to calculate the pooled relative risk of events. Subgroup analysis was performed based on mild GDM diagnostic criteria. Quality and risk of bias assessment were performed using standard questionnaires.Results: Seventeen studies involving 11,623 pregnant women with mild GDM and 53,057 non-GDM counterparts contributed to the meta-analysis. For adverse maternal outcomes, the results of meta-analysis showed that the women with mild GDM had a significantly higher risk of cesarean section (pooled RR: 1.3, 95% CI 1.2–1.5), pregnancy-induced hypertension (pooled RR: 1.4, 95% CI 1.1–1.7), preeclampsia (pooled RR: 1.3, 95% CI 1.1–1.5) and shoulder dystocia (pooled RR: 2.7, 95% CI 1.5–5.1) in comparison with the non-GDM population. For adverse neonatal outcomes, the pooled relative risk of macrosomia (pooled RR = 0.4, 95% CI: 1.1–1.7), large for gestational age (pooled RR = 1.7, 95% CI: 1.3–2.3), hypoglycemia (pooled RR = 1.6, 95% CI: 1.1–2.3), hyperbilirubinemia (pooled RR = 1.1, 95% CI: 1–1.3), 5 min Apgar Conclusion: The risks of sever adverse neonatal outcomes including small for gestational age and neonatal mortality are not increased with mild GDM. However, the increased risks of most adverse maternal and neonatal outcomes are observed. The risks have similar magnitudes for all mild GDM diagnostic classifications.

Background: The actions of adipocytokines may be a connective factor between obesity and polycystic ovary syndrome (PCOS). It is suggested that irisin, as recently described cytokine secreted by skeletal muscles and glucose-dependent insulinotropic polypeptide (GIP) as an incretin hormone that induces cytokine expression, may play key roles in favoring obesity in these women. Objectives: We aimed to evaluate the association between body mass index (BMI) and serum concentrations of irisin/GIP in women with and without PCOS in the linear and non-linear models. Methods: This cross-sectional study was conducted among 159 PCOS and 82 healthy eumenorrheic non-hirsute women aged 20 - 50 years. The fractional-polynomial model was used to develop a model of continuous risk factors, which evaluates non-linear associations between irisin/GIP and BMI among women with and without PCOS. Results: Women with PCOS were significantly younger (28.2 ± 5.8 vs. 33.0 ± 7.8 years, P < 0.001) and had a greater BMI (26.6 ± 5.2 vs. 25.2 ± 4.8 kg/m2, P = 0.04) than the healthy counterparts. There were no significant linear and non-linear associations between serum concentration of irisin/GIP and BMI in both groups. The analysis of pair-wise age and BMI matching of women with PCOS and controls confirmed these findings. Conclusions: This study showed that irisin and GIP have no association with BMI in women with or without PCOS. This finding could help to better understand the underlying pathophysiological status of PCOS, insulin resistance, and obesity-related disorders. Further large cohort studies are needed to confirm these findings.

Aims/Introduction Despite there being several meta‐analyses on the effects of antidiabetic agents in patients with gestational diabetes mellitus, the reliability of their findings is a concern, mainly due to undetermined methodological quality of these studies. This study aimed to assess the methodological quality of available meta‐analyses and provide a summary estimation of the effectiveness of treatments modalities. Materials and Methods PubMed, Web of Science and Scopus databases were comprehensively searched for retrieving relevant meta‐analyses published in English up to May 2020. A Measurement Tool to Assess Systematic Reviews (AMSTAR‐2) was applied to evaluate methodological quality of eligible meta‐analyses. A network meta‐analysis was used to calculate the pooled odds ratio of maternal and neonatal outcomes in gestational diabetes mellitus patients treated with metformin or glyburide compared with those treated with insulin. The rank network analysis was carried out for ranking of the treatments and reporting the most efficient treatment. Results A total of 27 and 17 studies were included for qualitative and quantitative syntheses, respectively; of these, just four studies were classified as high quality. The results showed that metformin had the highest probability of being the best treatment, compared with insulin and glyburide, for the majority of adverse neonatal outcomes, whereas glyburide was the best treatment in reducing the risk of adverse maternal outcomes. The results were not significantly changed after excluding low‐quality studies. Conclusions This review study of available literature shows that metformin can be a superior option in most neonatal and maternal adverse pregnancy outcomes in women with gestational diabetes mellitus; the results need to be further updated by including future more qualified studies., Despite there being several meta‐analyses on the effects of the antidiabetic agents in patients with gestational diabetes mellitus, the reliability of their findings is a concern, mainly due to undetermined methodological quality of these studies. This study aimed to assess the methodological quality of available meta‐analyses and provide a summary estimation of the effectiveness of treatments modalities.

The aim of this meta-analysis was to evaluate the prevalence of acne among women with PCOS worldwide, and in subgroups of patients with different age, geographical-region, and PCOS definition-criteria, compared to healthy non-PCOS counterparts. A comprehensive literature search was performed in PubMed (including Medline), Web of Science, and Scopus databases for retrieving articles in English investigating the prevalence of PCOS. ‘Meta-prop’ method was applied to estimate pooled prevalence of acne in both groups. Meta-regression was conducted to find the association between acne in women with and without PCOS. We used 60 studies, included data of 240,213 women with PCOS and 1,902,022 healthy-controls for the meta-analysis. The overall pooled prevalence of acne among women with and without PCOS, was 43% (95% CI: 41–45%) and 21% (95% CI: 19–22%), respectively, which was 1.6-fold significantly higher than among healthy-controls. The pooled prevalence of acne in adults, and in adolescents PCOS patients were 42 and 59%, respectively, which were significantly higher than non-PCOS counterparts. The pooled estimated prevalence of acne in adult PCOS women was 76% using the NIH definition and 36% by Rotterdam-criteria; both were significantly higher than non-PCOS counterparts, respectively. In subgroups of adults, who used Rotterdam-definition, the highest prevalence of acne in PCOS patients was reported in East Asia and was 3.5-fold higher than non-PCOS counterparts. Despite the presence of heterogeneity and publication bias among available literature, it may be concluded that acne is one of the common dermatological manifestations in PCOS. In addition, results highlight geographical differences among PCOS patients.

Background Maternal thyroid hormones are vital for a normal pregnancy and the development of fetus and childhood; inadequate availability of thyroid hormones during pregnancy is associated with adverse pregnancy outcomes. This systematic review aimed to investigate the association between Isolated Maternal hypothyroxinemia (IMH) and adverse pregnancy outcomes. Method: PubMed, Scopus and Web of science were searched for retrieving observational studies published up to September 2019, investigating the association of IMH with adverse pregnancy outcomes. From a total of 267 articles, 15 met our eligibility criteria and were used for the purpose of the present study. Results Definition of IMH varied in different studies. While some studies reported no adverse pregnancy outcomes for IMH, other studies found a positive association between first trimester IMH and feto-maternal outcomes including gestational hypertension, gestational diabetes, preterm delivery, fetal distress, small for gestational age, musculoskeletal malformations, spontaneous abortion, placental abruption and macrosomia. IMH, identified in the second trimester was associated with an increase in the risk of gestational diabetes, and hypertensive disorders of pregnancy in one study. Conclusions There is no consensus on the adverse effects of IMH on pregnancy outcomes. Further comprehensive cohort studies using one standard definition for IMH, with large sample size and control of important confounders such as iodine status and maternal Thyroid peroxidase antibody (TPOAb) are needed for precise assessment of this association.

Background A limited number of publications have assessed the prevalence of hypertension (HTN) in polycystic ovary syndrome (PCOS) patients with inconclusive results. Since in general populations the occurrence of hypertension is related to age per se, we investigated the prevalence (P) / relative risk (RR) of HTN in pooled patients with PCOS, vs control population among reproductive age women with PCOS, compared to menopause/aging patients. Methods PubMed, Scopus, ScienceDirect, web of science, and Google scholar were systematically searched for retrieving observational studies published from inception to April 2019 investigating the HTN in patients with PCOS. The primary outcome of interest was pooled P and RR of HTN in reproductive and menopausal/aging women with PCOS compared to control population. Results The pooled prevalence of HTN in reproductive and menopausal/aging women with PCOS was higher than in the control population [(Pooled P: 0.15, 95% CI: 0.12–0.18 vs. Pooled P: 0.09, 95% CI: 0.08–0.10) and (Pooled P: 0.49, 95% CI: 0.28–0.70 vs. Pooled P: 0.40, 95% CI: 0.22–0.57), respectively]. Compared to the control population, pooled relative risk (RR) of HTN patients was increased only in reproductive age PCOS (1.70-fold, 95% CI: 1.43–2.07) but not in menopausal/aging patients who had PCOS during their reproductive years. The same results were obtained for subgroups of population-based studies. Meta-regression analysis of population-based studies showed that the RR of HTN in reproductive age PCOS patients was 1.76-fold than menopausal/aging PCOS patients (P = 0.262). Conclusion This meta-analysis confirms a greater risk of HTN in PCOS patients but demonstrates that this risk is increased only in reproductive age women with PCOS, indicating that after menopause, having a history of PCOS may not be as an important predisposing factor for developing HTN.

Background There is lack of ideal and comprehensive economic evaluations of various GDM strategies. The aim of this study is to the compare efficacy and cost-effectiveness of five different methods of screening for gestational diabetes mellitus (GDM). Methods This study is a randomized community non-inferiority trial among 30,000 pregnant women in five different geographic regions of Iran, who were randomly assigned to one of the five GDM screening methods. All first trimester pregnant women, seeking prenatal care in governmental health care systems, who met our eligibility criteria were enrolled. The criteria suggested by the International-Association-of-Diabetes-in-Pregnancy-Study-Group, the most intensive approach, were used as reference. We used the non-inferiority approach to compare less intensive strategies to the reference one. Along with routine prenatal standard care, all participants were scheduled to have two phases of GDM screening in first and second-trimester of pregnancy, based on five different pre-specified protocols. The screening protocol included fasting plasma glucose in the first trimester and either a one step or a two-step screening method in the second trimester of pregnancy. Pregnant women were classified in three groups based on the results: diagnosed with preexisting pre-gestational overt diabetes; gestational diabetes and non-GDM women. Each group received packages for standard-care and all participants were followed till delivery; pregnancy outcomes, quality of life and cost of health care were recorded in detail using specific standardized questionnaires. Primary outcomes were defined as % birth-weight > 90th percentile and primary cesarean section. In addition, we assessed the direct health care direct and indirect costs. Results This study will enable us to compare the cost effectiveness of different GDM screening protocols and intervention intensity (low versus high). Conclusion Results which if needed, will also enable policy makers to optimize the national GMD strategy as a resource for enhancing GDM guidelines. Trial registration Name of the registry: Iranian Registry of Clinical Trials. Trial registration number: IRCT138707081281N1. Date of registration: 2017-02-15. URL of trial registry record: https://www.irct.ir/trial/518

Objectives This study aimed to examine the trends of contraception use among married reproductive age women in Tehran Lipid and Glucose study between 2002 and 2011. Methods This analysis investigated a proportion of women users and non-users of family planning, using data from 10 year population-based Tehran Lipid Glucose Study from surveys conducted in 2002, 2005, 2008, and 2011. Of the 6813, 6993, 7077, and 6789 women in the four phases mentioned, 34.1%, 33.9%, 33.5% and 35% of participants in each phase preferred to use contraception. Number of participants studied were 2506 women in 2002, 2529 women in 2005, 2594 women in 2008 and 2525 women in 2011. Results Types of methods and patterns of change in contraception differed across time. The percentage of women using traditional methods increased significantly from 25.7% in 2002 to 34.6% in 2011 (p value for trend = 0.001). Accordingly, modern contraception use showed a reverse trend. From 2002 to 2011, 61.4%, 61%, 57.7%, and 51% of married women reported currently using various modern contraceptives, respectively (p value for trend = 0.001). The proportion of users relying on condoms showed a significant increase during this decade, being 10.9% in 2002, 15.2% in 2005, 20% in 2008 and 21.9% in 2011. The prevalence of non-users for contraception was generally low; 12.7%, 8.2%, 8% and 14.3%, respectively from 2002 to 2011, but increased significantly across time (p = 0.005) Conclusion Relying on less effective contraceptive methods has increased rapidly among women in the Tehran Lipid and Glucose cohort study, a trend that could be a warning to policy makers about the possibility of higher unsafe abortion and maternal mortality/morbidity rates in the near future.

Aim The purpose of study was to assess the effect of zinc sulfate (ZS) supplementation on premenstrual syndrome (PMS) and health-related quality of life (QoL). Methods This was a double-blind randomized and placebo-controlled trial using the parallel technique conducted between June 2013 and May 2014. A total of 142 women (age, 20–35 years) with PMS were allocated to either the ZS or placebo group. The women in the intervention group received ZS 220-mg capsules (containing 50 mg elemental zinc) from the 16th day of the menstrual cycle to the second day of the next cycle. Data were collected using the Premenstrual Symptoms Screening Tool (PSST) and 12-item Short-Form Health Survey Questionnaire. Result The prevalence of moderate to severe PMS in the ZS group significantly decreased throughout the study period (9.5% in the first, 6% in the second and 2.6% in the third month of the study, P < 0.001), but in the control placebo group this reduction was seen only in the first month of the study (14.2% in the first, 13.7% in the second and 13.5% in the third month, P = 0.08). Also, ZS improved the PSST component scores throughout the study period. The mean scores of QoL in physical and mental components were significantly improved in the ZS intervention group. However, the differences were statistically significant only 3 months after the intervention. Conclusion Zinc sulfate, as a simple and inexpensive treatment, was associated with improvement of PMS symptoms and health-related QoL. Additional studies are warranted to confirm these findings.

Background: Although preeclampsia (PE), as an endothelial disorder can lead to renal dysfunction during pregnancy, results of studies focusing on the potential long-term potential effects of PE on renal function are insufficient and those available are controversial. This study investigated the incidence rate and risk of chronic kidney disease (CKD) among women with prior history of PE compared with healthy controls in a long-term population-based study. Methods: This was a prospective population-based cohort study. Subjects were 1,851 eligible women, aged 20–50 years, with at least 1 pregnancy (177 women with prior-PE and 1,674 non-PE controls) selected from among the Tehran-Lipid and Glucose-Study-participants. A pooled-logistic-regression-model and Cox’s-proportional-hazards-models were utilized to estimate the risk of CKD in women of both PE and without PE groups, after further adjustment for confounders. Results: Median and interquartile ranges for follow-up durations of the PE and non-PE groups were 7.78 (5.19–10.40) and 7.32 (4.73–11.00) years, respectively. Total cumulative incidence rates of CKD at the median follow-up time of each group were 35/100,000 (95% CI 25/100,000–50/100,000) and 36/100,000 (95% CI 32/100,000–39/100,000) in PE and non-PE women, respectively (p value = 0.90). Based on pooled-logistic-regression-analysis, OR of CKD progression (adjusted for age, body mass index [BMI], systolic blood pressure [SBP], and diastolic blood pressure [DBP]) for the PE group did not differ, compared to their non-PE counterparts (OR 1.04; p value = 0.80; 95% CI 0.77–1.40). Compared to non-PE women, women with prior PE did not have higher hazard ratios (HRs) of developing CKD in the unadjusted model (unadjusted HR 1.1, 95% CI 0.83–1.69, p = 0.35), results which remained unchanged after adjustment for age, BMI, baseline SBP, and DBP. Conclusion: PE was not found to be a risk factor for CKD. More studies using a prospective cohort design with long-term follow-ups are needed to investigate the relationship between preeclamsia and CKD.

The results of studies that assessed the impact of metformin treatments on gestational diabetes mellitus (GDM) in patients with polycystic ovary syndrome (PCOS) are inconclusive. In addition, the impact of time and duration of metformin therapy for an optimum reduction of GDM has not been reported in these studies. This study aimed to summarize current knowledge regarding the effect of metformin-therapy before conception versus throughout pregnancy on the risk of GDM in women with PCOS. PubMed, Scopus, Google Scholar and ScienceDirect databases were searched to identify relevant studies. Both fixed and random effect models were used. Subgroup analyses were performed based on the on the study methodology. The association between the PCOS status and GDM was assessed using the univariate and multiple meta-regression analysis adjusted by the BMI and metformin therapy. Forty-eight of 1397 identified studies were included involving 5711 PCOS patients and 20,296 controls. Regardless of metformin therapy, the prevalence of GDM diagnosed in the second trimester among women with PCOS was significantly higher than healthy controls that was independent of obesity. Including all studies, the increased risk of GDM among women with PCOS, compared to healthy controls, disappeared after the adjustment of metformin-therapy (β = 0.08, 95% CI 0.04, 0.2; p = 0.624). By excluding observational studies as a source of bias, the prevalence of GDM among women with PCOS treated using metformin before conception till the end of pregnancy did not differ from treated just before conception (β = − 0.09, 95% CI − 0.2, 0.02; p = 0.092) or those without metformin therapy (β = − 0.05, 95% CI − 0.07, 0.04; p = 0.301). The results remained unchanged after the subgroup analysis based on the methodology of RCTs and non-RCTs studies. The main body of literature in the current meta-analysis was observational, which may be mixed with some sources of bias. Also, a lack of well-designed and high quality interventional studies means that the findings should be interpreted with cautious. In this respect, decisions regarding the continuation or discontinuation of metformin therapy in women with PCOS are somewhat arbitrary and can be made individually based on the patient’s condition given the presence or absence of other GDM risk factors. Additional well-designed RCTs still need for precise recommendation. Electronic supplementary material The online version of this article (10.1186/s13098-019-0453-7) contains supplementary material, which is available to authorized users.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-age women. Significant associations between PCOS and benign breast diseases (BBD) and a possibly potential association between PCOS and breast cancer have been reported. The etiology of these events of mammary glands in PCOS remains unclear. Animal models that show BBD and breast cancer may contribute to further understanding about these diseases. We aimed to examine the spontaneous occurrence of mammary tumors, their prevalence, and type in our rat model of PCOS. Prenatal androgen-induced PCOS rats and controls were examined in later life. Benign mammary tumors were observed in 75% and 33.33% of PCOS rats and controls during the postmenopausal period, respectively (p = .0158). Mammary tumors were non-invasive, margins of excision were normal and tumors were freely movable, in both groups. After microscopic evaluations of tumors, proliferative breast lesions and adenomas with a tubular growth pattern were observed in both groups. However, in PCOS rats, of benign tumors two had a mixed pattern of fibroadenoma/fibroma and cysts. High prevalence of benign mammary tumors was observed in our rat model of PCOS during the postmenopausal period, possibly due to hormonal imbalances during their reproductive lifespan; this model may contribute to current data available regarding the events of mammary glands in PCOS.

Background Data of studies focusing on the trends of adiposity indices among women with prior gestational diabetes mellitus (GDM), are limited and controversial. The aim of this study was to compare overtime trends of adiposity indices in women with and without history of GDM, using data of the long term longitudinal population-based Tehran-Lipid and Glucose-Study (TLGS). Methods A total of 3395 eligible women aged (20–50 years), including 801 women with prior history of GDM and 2594 non-GDM controls were recruited from among Tehran-Lipid and Glucose-Study participants. Generalized estimating equations were applied to assess the time trend of adiposity indices including obesity, central obesity, body mass index (BMI), lipid accumulation product index (LAP), visceral adiposity index (VAI) and a body shape index (ABSI) in women with prior GDM and the non-GDM groups after further adjustment for age and BMI. Results Median follow-up years for the GDM and non-GDM groups were 12.12 and 11.62 years, respectively. Women with GDM at initiation had worse adiposity indices than their healthy counterparts. While overall odds of obesity in women with prior GDM were significantly higher those of the non-GDM groups (OR: 1.35; 95% CI, 1.03–1.7; P = 0.03), both these groups overtime revealed a positive trend in obesity (P trend

Background The absence of universal gold standards for screening of gestational diabetes (GDM) has led to heterogeneity in the identification of GDM, thereby impacting the accurate estimation of the prevalence of GDM. We aimed to evaluate the effect of different diagnostic criteria for GDM on its prevalence among general populations of pregnant women worldwide, and also to investigate the prevalence of GDM based on various geographic regions. Methods A comprehensive literature search was performed in PubMed, Scopus and Google-scholar databases for retrieving articles in English investigating the prevalence of GDM. All populations were classified to seven groups based-on their diagnostic criteria for GDM. Heterogeneous and non-heterogeneous results were analyzed using the fixed effect and random-effects inverse variance model for calculating the pooled effect. Publication bias was assessed by Begg’s test. The Meta-prop method was used for the pooled estimation of the prevalence of GDM. Meta-regression was conducted to explore the association between prevalence of GDM and its diagnostic criteria. Modified Newcastle–Ottawa Quality Assessment Scale for nonrandomized studies was used for quality assessment of the studies included; the ROBINS and the Cochrane Collaboration’s risk of bias assessment tools were used to evaluate the risk of bias. Results We used data from 51 population-based studies, i.e. a study population of 5,349,476 pregnant women. Worldwide, the pooled overall-prevalence of GDM, regardless of type of screening threshold categories was 4.4%, (95% CI 4.3–4.4%). The pooled overall prevalence of GDM in the diagnostic threshold used in IADPSG criteria was 10.6% (95% CI 10.5–10.6%), which was the highest pooled prevalence of GDM among studies included. Meta-regression showed that the prevalence of GDM among studies that used the IADPSG criteria was significantly higher (6–11 fold) than other subgroups. The highest and lowest prevalence of GDM, regardless of screening criteria were reported in East-Asia and Australia (Pooled-P = 11.4%, 95% CI 11.1–11.7%) and (Pooled-P = 3.6%, 95% CI 3.6–3.7%), respectively. Conclusion Over the past quarter century, the diagnosis of gestational diabetes has been changed several times; along with worldwide increasing trend of obesity and diabetes, reducing the threshold of GDM is associated with a significant increase in the incidence of GDM. The harm and benefit of reducing the threshold of diagnostic criteria on pregnancy outcomes, women’s psychological aspects, and health costs should be evaluated precisely. Electronic supplementary material The online version of this article (10.1186/s13098-019-0406-1) contains supplementary material, which is available to authorized users.

BACKGROUND Despite existing evidence regarding the role of testosterone as a protective factor for the kidney function in male adults, there are conflicting and inconclusive results on the influence of testosterone deficiency on developing chronic kidney disease (CKD). OBJECTIVE This study aimed to investigate the incidence and hazard ratio of CKD among male adults with low testosterone levels compared to controls with normal testosterone levels. MATERIALS AND METHODS During a 15-year follow-up study, a total of 1277 eligible male adults aged 20-80 year consisting of 605 males with low testosterone levels (< 350 ng/dL) and 672 controls with normal levels participating in the Tehran Lipid and Glucose Study were recruited. Cox's proportional hazards models were applied to estimate hazard ratios of CKD between the groups after adjusting for confounders. RESULTS The total cumulative incidence rate of CKD at the median follow-up time of approximately 11.2 years was 21/1000 (95% CI: 18/1000, 25/1000) and 18/1000 (95% CI: 16/1000, 22/1000) in the low and normal testosterone groups, respectively (P = .2). The multivariate Cox model adjusted for age, body mass index, dyslipidemia, hypertension, diabetes, and smoking showed that HR of developing CKD in the male adults with low testosterone levels was significantly higher than those with normal levels (HR = 1.38; 95% CI: 1.05, 1.80). DISCUSSION AND CONCLUSION This study shows a higher hazard ratio of CKD progression in male adults with hypogonadism compared to those with normal levels in their later life. Therefore, timely diagnosis and treatment of kidney diseases in hypogonadal men can prevent the morbidity and mortality from CKD.

Background Reduction of the body iron stores can improve hyperandrogenemia and insulin resistance. This study aimed to compare clinical and para-clinical responses to the treatment of phlebotomy using oral contraceptive pills (OCs) containing cyproterone acetate in women with PCOS. Methods In this randomized clinical trial, 64 patients with PCOS were randomly assigned to the phlebotomy and OCs groups (n = 32 in each group). The intervention group, using a single treatment procedure, underwent venesection of 450 mL of whole blood at the early follicular phase of the spontaneous or progesterone-induced menstrual cycle. The control group received OCs pills for 3 months from the 1th day of spontaneous or progesterone-induced menstrual cycle onwards for 3 weeks, followed by a pill-free interval of 7 days. The women were evaluated after the 3-month intervention. The primary outcome measure was a change in the HOMA-IR and free androgen index (FAI). Secondary outcomes were changes in the Ferriman-Gallwey (FG) score and other clinical, biochemical and hormonal changes from the baseline (pre-treatment) to week 12. Results In the phlebotomy group, 27 (84.3%) and in the OCs group 30 (93.7%) of the women completed the 3-month follow-up. The median HOMA-IR significantly decreased from 3.5 to 2.7 in the phlebotomy, and from 3.1 to 2.8 in the OCs group, and the changes were comparable between the groups. Median changes in the FAI significantly decreased in both groups, but the differences were not statistically significant between the groups (P = 0.061). With regard to secondary outcomes, mean FG scores in both groups significantly decreased [from 16.8 (6) to 13.3 (7.4), P

Objective To investigate whether a body shape index (ABSI) and waist to height ratio (WHtR) could predict insulin resistance (IR) and metabolic syndrome (MetS) in women with polycystic ovary syndrome (PCOS) compared to healthy women. Study design In a population-based study a cohort of 754 reproductive-aged women including 704 eumenorrheic non-hirsute subjects and 50 PCOS women selected according to the national institutes of health’s (NIH) criteria. The ability of ABSI and WHtR for the prediction of IR was estimated by the homeostasis model and metabolic syndrome according to the joint interim statement criteria. Results Age and BMI adjusted prevalence of IR and MetS in PCOS women vs. healthy controls were 34% vs. 26%, P = 0.041 and 15% vs. 14%, P = 0.917, respectively. Mean (SD) of ABSI in PCOS women and healthy women were 0.76 (0.05) and 0.76 (0.053), respectively ( P = 0.363). The area under curve (CI 95%) of WHtR for predicting IR and MetS among PCOS women vs. healthy women were 0.751 (0.60–0.89) vs. 0.69 (0.65–0.73) and 0.902 (0.81–0.98) vs. 0.802 (0.76–0.83), respectively. As such, the area under curve (CI 95%) of ABSI for ROC curve analysis for predicting IR and MetS among PCOS women vs. healthy women were 0.482 (0.31–0.64) vs. 0.537 (0.49–0.58) and 0.538 (0.35–0.72) vs. 0.584 (0.60–0.69), respectively. Conclusions These findings suggested that WHtR but not ABSI were a good predictor of IR and MetS among PCOS and healthy women. WHtR may be proposed as a screening tool for IR and MetS risk assessment among PCOS women as a sensitive, inexpensive, noninvasive, simple to assess and easy to calculate measurement tools.

Aim The aim of this study was to examine the association between maternal inherited bleeding disorders and neonatal complications. Material and Methods This was a historical cohort study. The rare inherited bleeding disorders (RIBD) group consisted of a total of 100 women suffering from inherited bleeding disorders, aged 20–45 years who experienced pregnancy. In the healthy control group, 200 age- and body mass index-matched women were selected. Details of demographic and obstetric characteristics of the samples in both groups were collected using their medical records. Results The mean ages of the women in the RIBD and healthy control groups were 32.6 (7.07) and 32.4 (7.3) years, respectively. No statistically significant differences were found in terms of age and other demographic characteristics of the women between the groups. The mean neonatal birthweight in the RIBD group was statistically lower than that in the healthy control group, 3018.2 (546.9) g vs 3299.4 (456.8) g, respectively (P = 0.021). The prevalence of low birthweight in the RIBD group was statistically higher in comparison to that in the healthy control group (P = 0.041). After adjustment for potential confounders, it was found that maternal bleeding disorder had significant negative effects on birthweight in newborns (odds ratio, 1.05; 95% confidence interval, 1.01–3.43, P = 0.001). Those infants were statistically more likely to experience head bleeding, early hyperbilirubinemia and hospitalization than the healthy group (P = 0.001). Conclusions Maternal rare inherited bleeding disorders may have a devastating consequence for neonates.

Background: Delayed childbearing is a growing trend in Iran. Purpose: This study explores the perspectives of women on delayed childbearing. Methods: A qualitative study using a content analysis approach was conducted on data acquired using private semistructured interviews with 23 women aged Q30 years who were childless or pregnant for the first time in an urban area of Iran. Results: Three main themes were developed using conventional content analysis: ＂personal inclination,＂ ＂perceived beliefs about delayed childbearing,＂ and ＂social support.＂ Conclusions: Although women in Iran hold favorable attitudes toward childbearing, a wide range of sociocultural and economic factors encourage these women to postpone their first pregnancy. The findings of this study are relevant and important for nursing and midwifery policymaking in countries with cultural and contextual backgrounds similar to Iran.

To estimate the incidence of hypertension and the trend of systolic and diastolic blood pressure changes and relating factors influencing women with and without prior preeclampsia (PE).This prospective population based study included a total of 3022 eligible women (355 with PE and 2667 non-PE) recruited from participants of the Tehran Lipid and Glucose Study (TLGS) who were assessed for progression to subsequent hypertension over 15-year follow up. Pooled logistic regression model was utilized to estimate odds ratio (OR) of hypertension. The generalized estimating equation (GEE) was used to evaluate the trend of changes in hypertension parameters over time.At the end of follow-ups, 109 women (30.7%) in the PE group and 575 (21.5%) in the non-PE group had hypertension. The total cumulative incident rate of hypertension was 34/1000 person-years for PE groups and 22/1000 person years for non-PE groups (P 0.001). Pooled logistic regression analysis showed that compared to non-PE women, OR of hypertension progression in women with PE was 3.70 after adjustment for age, body mass index (BMI), parity, triglycerides (TG) and high-density lipoprotein (HDL-C) (P-value 0.001). Based on GEE analysis, mean changes of systolic and diastolic blood pressure in PE women increased by 4.66 and 2.55 mmHg, respectively, compared to the non-PE group, after adjustment for age, and BMI at baseline (P 0.001), although the interaction term (follow-up year × PE) was not statistically significant.This study demonstrated increased chances of developing hypertension among women with prior PE, particularly in those who develop additional risk factors in their later life, compared to the non-PE women. While the trajectory of blood pressure change over time is similar between women with and without preeclampsia, women with a history of preeclampsia consistently have higher levels of blood pressure.

Context: Reproductive domains of the Tehran lipid and glucose study (TLGS) are unique in that they provide reliable information on reproduction of an urban population of West Asia. The aim of this review is to present the most important reproductive findings of TLGS. Evidence Acquisition: This review is summarizing all articles published in the context of reproductive aspects of TLGS results over the 20-year follow-up. A comprehensive databases search was conducted in PubMed (including Medline), Web of Science and Scopus for retrieving articles on the reproductive histories in context of the TLGS. Results: The mean (SD) age at menarche and menopause was 13 (1.2) and 49.6 (4.5) years respectively. While pills were the most commonly used modern methods at the initiation of TLGS, the prevalence of condoms rose sharply and significantly over the follow up duration. Among women with history of gestational diabetes, the risk of diabetes and dyslipidemia progression were 2.44 and 1.2 fold higher than others. Prevalences of PCOS and idiopathic hirsutism among reproductive age participants of TLGS were 8.5% (95% CI: 6.8% - 10.2%) and 13.0% (95% CI: 10.9% - 15.1%), respectively. Trend of cardio-metabolic risk factors among women with PCOS showed that there were no statistically significant differences between mean changes of each cardio metabolic variables between PCOS and healthy women; PCOS status also significantly associated with increased hazard of diabetes and prediabetes among women aged younger than 40 years (HR: 4.9; 95% CI: 2.5 - 9.3, P value < 0.001)) and (HR: 1.7; 95% CI: 1.1 - 2.6), P value < 0.005), respectively. Conclusions: The population based nature of TLGS provides a unique opportunity for valid assessment of reproductive issues, the results of which could provide new information for modification of existing guidelines.

Objective Menopausal status may increase cardiovascular disease (CVD) risk. Nitric oxide plays a role in the protection against CVD onset and progression but has not been studied around the time of menopause. We investigated associations between serum nitric-oxide metabolite (NOx) concentrations and menopausal status. Design Comparative case-control cross-sectional study. Setting Tehran Lipid and Glucose Study, university center. Sample Sub-groups from a cohort of 2137 women, of whom 213 met enrollment criteria. Methods We studied four sub-groups in a 1.2 ratio: (1) post-menopausal women (n = 29) with natural amenorrhea for 13–24 months, (2) age- and BMI-matched controls (n = 58) with regular menstrual cycles; (3) peri-menopausal women (n = 42) with natural amenorrhea for 1–12 months, and (4) age- and BMI-matched women as controls for the last group of women (n = 84). Main outcome measure Serum nitric oxide concentrations. Results Medians (inter-quartile ranges) of NOx in post-menopausal women and their controls were 31 (21.7–40.2) and 23.5 (17.2–31) μmol/L, respectively (p = 0.012). In peri-menopausal women and their controls the medians (inter-quartile ranges) were 28 μmol/L (18.5–50.5) and 25 (20–31.25) μmol/L, respectively (p = 0.035), but were not significantly different between peri- and postmenopausal women and were unchanged after adjustment for lipids. In a conditional fixed-effect logistic regression model, the risk of “transition to menopause” and “menopause” rose respectively 2.44- and 2.27-fold for a one-score increase in the NOx standard deviation. Conclusion Menopausal status, by itself and not as a consequence of aging, is associated with increased serum nitric oxide concentrations. Identification of variables associated with menopausal cardiovascular consequences may be used to improve women's health after menopause.

Background: Primary infertility is a health issue among women over the world. The aim of this study was to investigate the prevalence and causes of primary infertility based on a population-based study in an urban area of Iran. Materials and Methods: In a cross-sectional study, a total of 1067 married women who participated in the Tehran Lipid and Glucose Study were randomly selected using systematic random sampling. Unmarried women, those with unwilling pregnancy and duration of marriage below one year were excluded from the study. Data was collected by using validated ad-hoc questionnaires. Descriptive and inferential statistics were used for data analysis. Results: The mean (SD) of age and marriage age of the studied women were 40.3 (9.3) and 20.6 (4.49) years, respectively; the overall prevalence of lifetime primary infertility among couples was 17.3% (185/1067). Ovulatory disorder (39.7%) and male factors (29.1%) were the main causes of primary infertility. In addition, 31 (17%) of the women were diagnosed with more than one cause. According to the logistic regression analysis, primary infertility was independently related to the old age of women (OR: 1.37; 95% CI: 1.14–13.63, P.value: 0.001), higher BMI (OR: 1.95; 95% CI: 1.87–4.14, P.value: 0.003), active smoking (OR: 1.47; 95% CI: 1.38–3.53, P.value: 0.012) and higher educational level (OR: 2.23; 95% CI: 1.12–5.53, P.value: 0.03). Conclusion: The prevalence of primary infertility in Iran was higher than the worldwide trends of infertility, indicating that understanding such risks help healthcare providers and policy makers to design and implement interventions to slow down this trend.

Objectives To assess the prevalence of anemia and VulvoVaginal Candidiasis (VVC) in women before and 3 months after copper Intra Uterine Device (IUD) insertion. Methods Longitudinal prospective study was performed with 101 women aged 15–45 year who wanted to use the IUD at six health centers in Tehran, Iran from November 2011 to August 2012. The pattern of bleeding, Hemoglobin and Hematocirt levels, and Candida colony count/cultures in the women were assessed before and after 3 months of IUD insertion. Data analysis was performed by descriptive and analytical statistics using the SPSS software for Windows. Results At the end of 3 months, a significant increase in menstrual blood loss and a significant decrease of Hb and HCT ( P = 0.047 and 0.001, respectively) were reported. Moreover, no difference in the prevalence of anemia before and after IUD insertion was observed. The mean ± SD Candida colony counts significantly increased ( P = 0.001), but positive Candida cultures were not significantly different before and 3 months after IUD insertion. Also, no clinical VVC was reported 3 months after IUD insertion. While BMI ≥ 29 had a positive relationship with Candida colony counts, the results remained unchanged after adjusting for potential risk factors. Conclusions Despite an increase in bleeding and Candida colony counts in copper IUD users in this study, clinical VVC or anemia cases were not increased, which indicates relative safety of this contraception method. The study findings can be helpful to healthcare professionals and midwives to counsel women who want to start using IUD and also current users who are contemplating IUD removal due to its complications.

Most reproductive aged women suffer from somatic and mental disorders prior to menstruation. This study investigated whether omega-3 supplement improved premenstrual symptoms and health-related quality of life among reproductive aged women.A multi-center, balanced (1:1), placebo-controlled, parallel-group randomized clinical trial was conducted in an urban academic institution. A sample consisting of 95 Iranian women aged 20-35 years who were suffering from premenstrual symptoms were randomly allocated into two groups. The treatment consisted of omega-3 supplement containing 1 g fish oil. Placebo was free of oil. The premenstrual symptoms' screening tool and 12-item short form health survey questionnaire were used for data collection.No statistically significant differences in the baseline characteristics of the groups were reported. Most premenstrual symptoms and their interference with daily activities were significantly reduced over the follow-up period. The mean score of overeating in the omega-3 supplement group and insomnia in the placebo group showed no difference between the groups. The longer use of omega-3 supplement provides improvement of premenstrual symptoms and activities. The mean scores of physical and mental components of quality of life were significantly improved in the omega-3 supplement and placebo groups.The treatment of premenstrual symptoms using omega-3 supplement reduced symptoms and ameliorated women's quality of life.

Despite polycystic ovary syndrome (PCOS) being one of the most common endocrine disorders affecting reproductive-aged women, the etiopathogenesis and mechanisms of this syndrome remain unclear. Considering the ethical limitations in human studies, animal models that reflect many features of PCOS are crucial resources to investigate this syndrome. We aimed to introduce the most suitable rat model of PCOS that closely mimics the endocrine, ovarian and metabolic disturbances of human PCOS phenotype, while maintaining normal reproductive system morphology in adulthood, in order to further more detailed investigations about PCOS. We searched Pubmed, Science direct, and Web of science between 1990 and 2016, for relevant English manuscripts, using keywords including the "Polycystic Ovary Syndrome AND Rat Model" to generate a subset of citations relevant to our research. Included were those articles that compared at least both ovarian histology or estrous cycle and reproductive hormonal profiles in hormone-induced rat model of PCOS and controls. Differences in the findings between hormone-induced PCOS rats appear to be a result of the degree of transplacental transfer of the steroid administered into the fetus, dose and type of hormone, route of administration and timing and duration of exposure. We conclude that prenatal hormone-induced rat model with a lower dose and shorter time of exposure during the critical period of fetal development that exhibits endocrine, ovarian and metabolic disturbances similar to PCOS in women, while maintaining normal reproductive system morphology in adulthood is more suitable than postnatal hormone-induced rat model to facilitate studies regarding PCOS.

Objective To study the incidence rate and hazard ratios of diabetes and prediabetes between women with PCOS and healthy subjects. Design Prospective population-based study. Setting Not applicable. Patient(s) Women with PCOS (n = 178) and eumenorrheic, nonhirsute, healthy women as controls (n = 1,524), all followed for a median time of 12.9 years. Intervention(s) None. Main Outcome Measure(s) Incidence rate and hazard ratios of diabetes and prediabetes between women with PCOS and healthy controls. Result(s) We analyzed the participants on two pathways. First, for detecting new diabetes mellitus (DM) events, we selected participants who were free of DM at baseline (n = 39). Second, for detecting new pre-DM events, we selected participants who were free of pre-DM and DM at baseline (n = 222) from the baseline population. The rest of the population were included for final analysis to calculate the incidence rates and hazard ratio of diabetes and prediabetes events. The incidence rates of diabetes were 12.9 and 4.9 per 1,000 person-years for PCOS and controls, respectively. This incidence rate in women younger than 40 with and without PCOS was 13.4 and 4.2, respectively. The adjusted hazard ratio (HR) for women ≤40 was 4.9 (95% confidence interval [CI], 2.5–9.3). There were no statistically significant differences between the two groups studied after age 40. The incidence rates of prediabetes were 29.7 and 25.9 per 1,000 person-years for PCOS and healthy women, respectively. The incidence rate in women younger than 40 with and without PCOS was 30.3 and 23.9, respectively. The adjusted HR for women ≤40 years, 1.7 (95% CI, 1.1–2.6), disappeared after age 40. Conclusion(s) These data suggest that routine screening for diabetes in prevention strategies does not need to be emphasized for PCOS patients at late reproductive ages if they have not been affected by glucose intolerance up to that point.

SummaryBackground and Objective Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder associated with metabolic syndrome (MetS). The aim of this systematic review and meta-analysis was to provide the most reliable estimate risk of MetS in women with PCOS, compared to healthy controls. Methods A comprehensive literature search was performed in PubMed [including Medline], Web of Science and Scopus databases for retrieving articles in English language on the prevalence/incidence and odds of MetS in women with PCOS compared to healthy controls. Mantel-Haenszel methods of meta-analysis were used to present results in terms of the pooled odds ratio (OR) (95% confidence interval [CI]) using fixed/random-effects models with/without the publication bias correction, based on the various subgroups of age and study methods. Newcastle-Ottawa Scaling and The Cochrane Collaboration's risk of bias assessment tool were used to evaluate the quality of studies included. Results The search strategy yielded 2759 potentially relevant articles of which 44 articles were included for meta-analysis. Results of the meta-analysis demonstrated that the patients with PCOS regardless of age, BMI and recruitment sources of samples had higher odds of MetS compared to healthy controls (OR 2.5, 95% CI 2.0-3.2). However, adolescents with PCOS had an increased odds of MetS compared to healthy adolescent controls in population- and nonpopulation-based studies (OR 4.7, 95% CI 1.8-11.9; OR 6.1, 95% CI 6.0- 6.1, respectively). However, the odds of MetS had no differences between adults with PCOS compared to healthy controls in population-based studies. These results were confirmed by the subgroup meta-analysis of some studies using age and BMI adjustment/matching. In addition, subgroup analysis based on diagnostic criteria of PCOS showed that the OR of MetS in PCOS using NIH criteria was higher than AES and Rotterdam criteria (Pooled Overall OR based on NIH criteria = 6.05, 95% CIL: 6.0-6.04). Conclusion These findings provide some information on the real features and a broader view of this syndrome that also helps clarify conflicting results documented in the literature. Accordingly, in prevention strategies, routine screening for metabolic syndrome is suggested for adolescents with PCOS.

Background and Objective A limited number of studies have evaluated the relationship between clinical and biochemical hyperandrogenism (HA). This study aimed to evaluate the association between biochemical hyperandrogenism parameters (BHPs) and Ferriman–Gallwey (FG) score in patients with polycystic ovary syndrome (PCOS). Methods We searched PubMed, Scopus, Google Scholar, ScienceDirect and Web of Sciences databases (2000 to 2015) to identify studies investigating clinical and biochemical parameters of HA in PCOS patients. In this meta-analysis, both fixed and random effect models were applied to estimate pooled effect size. To assess the relationships between BHPs and FG score, meta-regression analysis was used. Results Fifty-five study groups with a total of 6593 PCOS patients were analyzed. Meta-regression analysis of pooled data from all eligible studies showed significant positive relationships of FG score with androstenedione (A4) (p= 0.034) and dehydroepiandrosterone sulfate (DHEAS) (p=0.012), whereas it showed no association with total testosterone (tT), free testosterone (fT), sex hormone bonding globulin (SHBG) and free androgen index (FAI). The results did not change after adjusting for quality assessment or method of assay. Nor did the associations between A4 and FG score remain after adjusting for age and BMI, diagnostic criteria for PCOS and study design or the association between DHEAS and FG score remain after adjusting for ethnicity. Conclusion This meta-analysis confirmed the associations of some BHPs, including A4 and DHEAS with FG score, indicating that measurement of these parameters can be useful for managing PCOS patients with hirsutism. This article is protected by copyright. All rights reserved.

The aim of this study was to investigate whether the observed differences between serum NOx levels of men and women were influenced by the menopausal status of women. A total of 1,209 eligible subjects, aged 40–60 years, were recruited from among participants of the Tehran lipid and glucose study, and subdivided into three groups: men (n = 457), women with regular cycles (n = 288) and postmenopausal women (n = 464). Serum concentrations of NOx were compared between these groups using Kruskal Wallis–Mann–Whitney U test, followed by Bonferroni correction. ANCOVA was applied for comparison of log-transformed NOx values between groups after adjustment for confounder variables. The mean (SD) of age and BMI did not differ between studied groups. There were statistically significant differences between the medians (inter-quartile ranges) of serum NOx levels in men, women with regular cycles and the postmenopausal women [26 (20–37), 25.5 (19–39) and 29 (21–43) μmol/L], respectively (P = 0.012). Post hoc pair-wised comparison, adjusted with Bonferroni correction, demonstrated that women with postmenopausal status had higher serum levels of NOx values than those women with regular cycle or men (P = 0.011). The results remained unchanged after further adjustment for potential confounders. These results provide evidence that differences observed between serum NOx values of middle-aged women and men are more related to menopausal status rather than gender.

This study aimed to investigate the interactive effect of polycystic ovary syndrome (PCOS) status and obesity status on the serum levels of adipokines. In this comparative case–control cross-sectional study, 58 women with PCOS and 104 eumenorrheic non-hirsute women as the control group were recruited. They were further divided into two subgroups of overweight/obese and normal weight. The interactive effect of the PCOS status and obesity status on the circulating levels of adipokines was assessed using general linear model with the adjustment of age. A statistically significant negative interaction was reported between obesity status and PCOS status in the determination of serum adiponectin and resistin concentrations (effect size = −0.14, interaction P = 0.001, effect size = −0.15, P = 0.016). It indicated that adiponectin and resistin were significantly decreased in overweight/obese patients with PCOS compared with other subgroups. Statistically significant positive interactive effects were found between PCOS status obesity status and leptin (effect size = 0.321, interaction P = 0.036), indicating that the overweight/obese women with PCOS had the higher levels of leptin compared with the control group. Also, no interaction was reported between PCOS status and obesity status with regard to the serum levels of other adipokines. While no sufficient evidence is available with regard to the causal association between adipokines and PCOS, they may contribute to the development of PCOS and regarded as the novel biomarkers of PCOS.

Objectives To explore older (35 years ) primigravid women ' s knowledge of the risks of delayed childbearing and to identify the characteristics of those with limited knowledge. Methods A cross-sectional survey involving 675 primigravid women in Tehran, Iran, using a cluster random sampling method at the fi rst prenatal visit. A validated questionnaire assessed the women ' s awareness of delayed-childbearing risks. Results Women variously identifi ed conception diffi culties, gestational diabetes, hyperten- sion, multiple birth, caesarean section, preterm delivery, stillbirth, Down ' s syndrome, con- genital abnormality, and low birth weight, as associated with delayed childbearing. Awareness of infant risks ranged between 10 and 72%. Awareness of maternal risks were independently related to the women's educational levels (odds ratio (OR): 1.95; 95% confi dence interval (CI): 1.12 - 3.38), planned pregnancy (OR: 1.87; 95% CI: 1.25 - 2.78) and maternal age 40 (OR: 1.24; 95% CI: 1.14 - 2.53). Women aware of infant risks were signifi cantly likely to be aged 40 (OR: 1.87; 95% CI: 0.01 - 5.12), have post-graduate education (OR: 2; 95% CI: 1.90 - 4.42), and have a planned pregnancy (OR: 1.99; 95% CI: 1.03 - 5.12). Conclusion Women are largely unaware of the potential complications of delayed child- birth. Understanding the risks is important for reproductive healthcare providers and policy makers in providing appropriate information to enable women to make informed decisions on the timing of conception.

This study aimed at comparing the efficacy of medroxyprogesterone acetate (MPA) and tranexamic acid (TA) for treating heavy menstrual bleeding of endometrial origin (HMB). A randomized controlled trial was carried out in three gynecology clinics in Tehran, Iran. Ninety women with the HMB of endometrial origin were randomized into the study: 44 patients took MPA for 21 days from day 5 and 46 patients took tranexamic acid for 5 days from day 1 of menses for three consecutive menstrual cycles. Blood loss was measured using the pictorial blood loss assessment chart (PBAC); hematological assessments were made before intervention and after treatment. SF-36 and HMB Questionnaire (MQ) were given to assess quality of life. Statistical analysis was performed using t test, Paired t test, χ2, Mann–Whitney, Wilcoxon signed-rank test, and repeated measure analysis. PBLC mean score, duration of bleeding and Hb values as well as quality of life were significantly improved in both groups (P

The aim of this prospective study was to determine the relationship between anaemia during pregnancy and postpartum depression. Two hundred eighty-one non-anaemic mothers with singleton and low-risk pregnancy and no history of antidepressant-use were studied. Demographic and reproductive data at week 20 were obtained. Mothers were followed up and haemoglobin (Hb) was checked at delivery. Iranian version of Edinburgh Postpartum Depression Scale (EPDS) was completed 4-6 weeks after delivery. Mean age of the mothers was 26.6±4 years. The prevalence of postpartum depression according to EPDS was 5.5%. Binary logistic regression analysis showed that Hb