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ObjectivesThere is considerable worldwide controversy regarding optimal screening and diagnostic approaches for GDM. This study aimed to compare the prevalence, maternal and neonatal outcomes of a One-step with a Two-step approach for the screening and diagnosis of GDM in a large community sample of pregnant women.MethodsWe conducted a secondary analysis of a randomized community non-inferiority trial of GDM screening in Iran. For the current study, all pregnant women who met the inclusion criteria were randomized into two groups for GDM screening. The first group of women (n = 14611) was screened by a One-step screening approach [75-g 2-h oral glucose tolerance test (OGTT)] and the second group (n = 14160) by a Two-step method (the 50-g glucose challenge test followed by the 100-g OGTT). All study participants were followed up until delivery, and the adverse maternal and neonatal outcomes were recorded in detail.ResultsGDM was diagnosed in 9.3% of the pregnant women who were assigned to the One-step and in 5.4% of those assigned to the Two-step approach with a statistically significant difference between them (p < 0.001). Intention-to-treat analyses showed no significant differences between the One-step and the Two-step group in the unadjusted risks of the adverse pregnancy outcomes of macrosomia, primary cesarean-section, preterm birth, hypoglycemia, hypocalcemia, hyperbilirubinemia, preeclampsia, neonatal intensive care unit admission, birth trauma, low birth weight, and intrauterine fetal death. Results remained unchanged after adjustment for potential confounder variables including gestational age at enrollment and delivery, maternal body mass index, gestational weight gain, type of delivery, treatment modality, and GDM diagnosis in the first trimester.ConclusionWe found that although the rates of GDM more than doubled with the One-step strategy, the One-step approach was similar to the Two-step approach in terms of maternal and neonatal outcomes. These findings may warn that more caution should be exercised in adopting the One-step method worldwide. Future research is needed to assess the long-term harm and benefits of those approaches to GDM screening for both mothers and their offspring.Clinical trial registrationhttps://www.irct.ir/trial/518, identifier (IRCT138707081281N1).

Background C-peptide offers potential as a marker to indicate childhood metabolic outcomes. Measuring C-peptide concentration might have better future utility in the risk stratification of neonates born to overweight or diabetic mothers. Prior research has tried to bring this matter into the light; however, the clinical significance of these associations is still far from reach. Here we sought to investigate the associations between fetomaternal metabolic variables and umbilical cord blood C-peptide concentration. Methods For the present study, 858 pregnant women were randomly selected from among a sub-group of 35,430 Iranian pregnant women who participated in a randomized community non-inferiority trial of gestational diabetes mellitus (GDM) screening. Their umbilical cord (UC) blood C-peptide concentrations were measured, and the pregnancy variables of macrosomia/large for gestational age (LGA) and primary cesarean section (CS) delivery were assessed. The variation of C-peptide concentrations among GDM and macrosomia status was plotted. Due to the skewed distribution of C-peptide concentration in the sample, median regression analysis was used to identify potential factors related to UC C-peptide concentration. Results In the univariate model, positive GDM status was associated with a 0.3 (95% CI: 0.06 − 0.54, p = 0.01) increase in the median coefficient of UC blood C-peptide concentration. Moreover, one unit (kg) increase in the birth weight was associated with a 0.25 (95% CI: 0.03 − 0.47, p = 0.03) increase in the median coefficient of UC blood C-peptide concentration. In the multivariate model, after adjusting for maternal age, maternal BMI, and macrosomia status, the positive status of GDM and macrosomia were significantly associated with an increase in the median coefficient of UC blood C-peptide concentration (Coef.= 0.27, 95% CI: 0.13 − 0.42, p Conclusion UC blood concentration of C-peptide is significantly associated with the incidence of maternal GDM and neonatal macrosomia. Using stratification for maternal BMI and gestational weight gain (GWG) and investigating molecular markers like Leptin and IGF-1 in the future might lay the ground to better understand the link between metabolic disturbances of pregnancy and UC blood C-peptide concentration.

Background Determining a thyroid hormone cutoff value in pregnancy is challenging issue and several approaches have been introduced to optimize a utility function. We aimed to estimate the cutoff value of TSH using Bayesian method for prediction of preterm-birth. Methods This study was a secondary-analysis of the population-based data collected prospectively within the framework of the Tehran Thyroid and Pregnancy Study. A total of 1,538 pregnant women attending prenatal clinics. Results Using Bayesian method resulted a TSH-cutoff of (3.97mIU/L,95%CI:3.95–4.00) for distinguishing pregnant women at risk of preterm-birth. The cutoff was associated with acceptable positive predictive and negative predictive values (0.84,95% CI:0.80–0.88) and 0.92 (95%CI: 0.91–0.94), respectively). In women who were negative for thyroid peroxides antibody (TPOAb) with sufficient urinary iodine concentration (UIC), the TSH cutoff of 3.92 mIU/L(95%CI:3.70–4) had the highest predictive value; whereas in TPOAb positive women with insufficient UIC, the cutoff of 4.0 mIU/L(95%:CI 3.94–4) could better predict preterm birth. Cutoffs estimated in this study are close to the revised TSH value of 4.0mIU/L which is currently recommended by the American Thyroid Association. Conclusion Regardless of TPOAb status or iodine insufficiency, risk of preterm labor is increased in pregnant women with TSH value of > 3.92 mIU/L; these women may benefit from Levothyroxine (LT4) therapy for preventing preterm birth.

Objectives: This study aimed to investigate the risk of stillbirth, perinatal and neonatal mortality in immigrant women compared to native-origin women in host countries.Methods: A systematic literature review and meta-analysis was conducted. Relevant studies were identified using a thorough literature search and their quality was appraised. The analysis of heterogeneous data was carried out using the random effects model and publication bias was assessed using the Harbord-test. Also, the pooled odds ratio of events was calculated through the DerSimonian and Laird, and inverse variance methods.Results: In the search process 45 studies were retrieved consisting of 8,419,435 immigrant women and 40,113,869 native-origin women. The risk of stillbirth (Pooled OR = 1.35, 95% CI = 1.22–1.50), perinatal mortality (Pooled OR = 1.50, 95% CI = 1.35–1.68), and neonatal mortality (Pooled OR = 1.09, 95% CI = 1.00–1.19) in the immigrant women were significantly higher than the native-origin women in host countries. According to the sensitivity analyses, all results were highly consistent with the main data analysis results.Conclusion: The immigrant women compared to the native-origin women had the higher risks of stillbirth, perinatal and neonatal mortality. Healthcare providers and policy makers should improve the provision of maternal and neonatal healthcare for the immigrant population.

ObjectivesThere are controversies regarding the risk of adverse pregnancy outcomes among immigrants from conflict-zone countries. This systematic review and meta-analysis aimed to investigate the risk of perinatal and neonatal outcomes among immigrants from conflict-zone countries compared to native-origin women in host countries.MethodsA systematic search on the databases of PubMed/MEDLINE, Scopus, and Web of Science was carried out to retrieve studies on perinatal and neonatal outcomes among immigrants from Somalia, Iraq, Afghanistan, Yemen, Syria, Nigeria, Sudan, Ethiopia, Eritrea, Kosovo, Ukraine, and Pakistan. Only peer-reviewed articles published in the English language were included in the data analysis and research synthesis. The odds ratio and forest plots were constructed for assessing the outcomes of interests using the DerSimonian and Laird, and the inverse variance methods. The random-effects model and the Harbord test were used to account for heterogeneity between studies and assess publication bias, respectively. Further sensitivity analysis helped with the verification of the reliability and stability of our review results.ResultsThe search process led to the identification of 40 eligible studies involving 215,718 pregnant women, with an immigration background from the conflict zone, and 12,806,469 women of native origin. The adverse neonatal outcomes of the risk of small for gestational age (Pooled OR = 1.8, 95% CI = 1.6, 2.1), a 5-min Apgar score ConclusionAlthough the risk of some adverse maternal outcomes was comparable in the groups, the immigrant women from conflict-zone countries had a higher risk of neonatal mortality and morbidity, including SGA, a 5-min Apgar score

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.

Context Although it is well-acknowledged that gestational diabetes mellitus (GDM) is associated with the increased risks of adverse pregnancy outcomes, the optimal strategy for screening and diagnosis of GDM is still a matter of debate. Objective This study was conducted to demonstrate the noninferiority of less strict GDM screening criteria compared with the strict International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria with respect to maternal and neonatal outcomes. Methods A cluster randomized noninferiority field trial was conducted on 35 528 pregnant women; they were scheduled to have 2 phases of GDM screening based on 5 different prespecified protocols including fasting plasma glucose in the first trimester with threshold of 5.1 mmol/L (92 mg/dL) (protocols A, D) or 5.6 mmol/L (100 mg/dL) (protocols B, C, E) and either a 1-step (GDM is defined if one of the plasma glucose values is exceeded [protocol A and C] or 2 or more exceeded values are needed [protocol B]) or 2-step approach (protocols D, E) in the second trimester. Guidelines for treatment of GDM were consistent with all protocols. Primary outcomes of the study were the prevalence of macrosomia and primary cesarean section (CS). The null hypothesis that less strict protocols are inferior to protocol A (IADPSG) was tested with a noninferiority margin effect (odds ratio) of 1.7. Results The percentages of pregnant women diagnosed with GDM and assigned to protocols A, B, C, D, and E were 21.9%, 10.5%, 12.1%, 19.4%, and 8.1%, respectively. Intention-to-treat analyses satisfying the noninferiority of the less strict protocols of B, C, D, and E compared with protocol A. However, noninferiority was not shown for primary CS comparing protocol E with A. The odds ratios (95% CI) for macrosomia and CS were: B (1.01 [0.95-1.08]; 0.85 [0.56-1.28], C (1.03 [0.73-1.47]; 1.16 [0.88-1.51]), D (0.89 [0.68-1.17]; 0.94 [0.61-1.44]), and E (1.05 [0.65-1.69]; 1.33 [0.82-2.00]) vs A. There were no statistically significant differences in the adjusted odds of adverse pregnancy outcomes in the 2-step compared with the 1-step screening approaches, considering multiplicity adjustment. Conclusions The IADPSG GDM definition significantly increased the prevalence of GDM diagnosis. However, the less strict approaches were not inferior to other criteria in terms of adverse maternal and neonatal outcomes.

Author's accepted version (postprint). This is an Accepted Manuscript of a book chapter published by Springer on 22/06/2022. Available online: https://link.springer.com/chapter/10.1007/978-3-030-98777-0_17

Disparities in health outcomes between immigrant and native-origin populations, particularly pregnant women, pose significant challenges to healthcare systems. The aim of this systematic-review and meta-analysis was to investigate the risk of adverse pregnancy outcomes among immigrant-women compared to native-origin women in the host country.PubMed (including MEDLINE), Scopus, and Web of Science were searched to retrieve studies published in English language up to September 2020. All observational studies examining the prevalence of at least one of the short-term single pregnancy outcomes for immigrants who crossed international borders compared to native-origin pregnant population were included. The meta-prop method was used for the pooled-estimation of adverse pregnancy-outcomes' prevalence. For pool-effect estimates, the association between the immigration-status and outcomes of interest, the random-effects model was applied using the model described by DerSimonian and Laird. IThis review involved 11 320 674 pregnant women with an immigration-background and 56 102 698 pregnant women as the native-origin population. The risk of emergency cesarean section (Pooled-OR = 1.1, 95%CI = 1.0-1.2), shoulder dystocia (Pooled-OR = 1.1, 95%CI = 1.0-1.3), gestational diabetes mellites (Pooled-OR = 1.4, 95%CI = 1.2-1.6), small for gestational age (Pooled-OR=1.3, 95%CI = 1.1-0.4), 5-min Apgar less than 7 (Pooled-OR = 1.2, 95%CI = 1.0-1.3) and oligohydramnios (Pooled-OR = 1.8, 95%CI = 1.0-3.3) in the immigrant women were significantly higher than those with the native origin background. The immigrant women had a lower risk of labor induction (Pooled-OR = 0.8, 95%CI = 0.7-0.8), pregnancy induced hypertension (Pooled-OR = 0.6, 95%CI = 0.5-0.7) preeclampsia (Pooled-OR = 0.7, 95%CI = 0.6-0.8), macrosomia (Pooled-OR = 0.8, 95%CI = 0.7-0.9) and large for gestational age (Pooled-OR = 0.8, 95%CI = 0.7-0.8). Also, the risk of total and primary cesarean section, instrumental-delivery, preterm-birth, and birth-trauma were similar in both groups. According to meta-regression analyses, the reported ORs were not influenced by the country of origin.The relationship between the immigration status and adverse perinatal outcomes indicated a heterogenous pattern, but the immigrant women were at an increased risk of some important adverse pregnancy outcomes. Population-based studies with a focus on the various aspects of this phenomena are required to explain the source of these heterogenicities.

ObjectivesThe aim of the present study was to evaluate the prevalence of polycystic ovary syndrome (PCOS), its phenotypical and cardio-metabolic features in a community sample of the Iranian population in comparison to healthy eumenorrheic, non-hirsute women without polycystic ovaries. The second aim was to assess the cardio-metabolic characteristics of women who suffered from one criteria of PCOS compared to those healthy eumenorrheic, non-hirsute women.MethodsIn this cross-sectional population-based study, a total of 1,960 eligible women, aged (18–45 years) were recruited from the Tehran-Lipid and Glucose-Study participants and were classified as the three groups of (i) women with PCOS by the Rotterdam criteria, (ii) non-PCOS women with one criteria of PCOS and (iii) healthy eumenorrheic, non-hirsute women without polycystic ovaries morphology (PCOM) as the control group. Further PCOS women were extended to four phenotypes of hyperandrogenism, oligo-anovulation, polycystic ovaries (phenotype A), hyperandrogenism, oligo/anovulation (phenotype B), hyperandrogenism, polycystic ovaries (phenotype C) and oligo-anovulation, polycystic ovaries (phenotype D). Cardio-metabolic profiles and the prevalence of comorbidities of metabolic syndrome (MetS) and lipid abnormalities were compared among these groups linear, and the median regression models adjusted for age and body mass index.ResultsThe prevalence of PCOS according to the diagnostic criteria of the NIH, Rotterdam and AE-PCOS Society were 13.6, 19.4, and 17.8, respectively. Among those who met the Rotterdam criteria, 23.9, 46.3, 21.6, and 8.2% had phenotypes A, B, C, and D, respectively. Among the remaining 1,580 women who did not fulfil the PCOS criteria, 108 (6.8%) suffered from only oligo/anovulation, 332 (21%) only hyperandrogenism/hyperandrogenemia, 159 (16.2%) only PCOM in ultrasound and 981 (62%) were healthy eumenorrheic, non-hirsute women without PCOM. The study revealed that some adiposity indices and lipid abnormalities in PCOS phenotypes with hyperandrogenism (A, B, and C) were worse than in healthy women. By contrast, women with phenotype D did not differ from the healthy ones in terms of adiposity and lipid abnormalities. However, the respective values for other cardio-metabolic profiles and MetS rates in different phenotypes of PCOS were similar to the healthy women. Only the prevalence of MetS in phenotype A was significantly higher than in the healthy women. There were no statistically significant differences between participants with one criteria of PCOS and healthy counterparts in terms of most adiposity indexes, cardio-metabolic factors, and comorbidity of MetS and its components. However, women with hyperandrogenism had a significantly higher level of the waist to height ratio (WHtR) and hypertriglyceridemia than their healthy counterparts.ConclusionPCOS, mainly classical phenotypes A and B, are common among Iranian women of reproductive age. Women with PCOS who had androgen excess exhibited the worst lipid profile, and those who had full three criteria of the syndrome exhibited the higher rate of MetS. However, women with only ovulatory dysfunction and only PCOM had similar cardio-metabolic characteristics, compared to healthy subjects. These data suggest that routine screening for metabolic disturbances may be needed in the prevention of cardio-metabolic disorders in patients with more serious phenotypes of PCOS.

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.

Context Although it is well documented that estrogen hormone is positively associated with bone mineral density and lower risk of fracture, there are limited studies on the association between duration of endogenous estrogen exposure (EEE) and fracture, especially by longitudinal design. Objective This study aimed to investigate the relationship between EEE with fracture incidence by longitudinal design in a community-based study. Methods A total of 5269 eligible postmenarcheal women, including 2411 premenopausal and 2858 menopausal women, were recruited from among the Tehran Lipid and Glucose Study. Cox proportional hazards regression model with adjustment of potential confounders was performed to assess the relationship between duration of EEE and incident of any hospitalized fractures. Results A total of 26.7% (1409/5269) women were menopausal at the baseline, and 2858 of the remaining participants reached menopause at the end of follow-up. Results of the unadjusted model demonstrated that the EEE z-score was negatively associated with fracture incidence [unadjusted hazard ratio (HR) 0.81, 95% CI 0.68-0.96] in postmenarchal women, indicating that per 1-SD increase of EEE z-score, the hazard of fracture reduced by 19%. Results remained statistically unchanged after adjustment for potential confounders (adjusted HR 0.70, 95% CI 0.58-0.86). Conclusion The findings of this cohort study suggest that a longer duration of EEE has a protective effect on fracture incidence; a point that needs to be considered in fracture risk assessment.

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.

Background and Objectives:The global trend of healthcare is to improve the quality and safety of care for older people with cognitive disorders in their own home. There is a need to identify how medicines management for these older people who are cared by their family caregivers can be safeguarded. This integrative systematic review aimed to perform the needs assessment of medicines management for older people with cognitive disorders who receive care from their family caregivers in their own home.Methods:An integrative systematic review of the international literature was conducted to retrieve all original qualitative and quantitative studies that involved the family caregivers of older people with cognitive disorders in medicines management in their own home. MeSH terms and relevant keywords were used to search four online databases of PubMed (including Medline), Scopus, CINAHL, and Web of Science and to retrieve studies published up to March 2021. Data were extracted by two independent researchers, and the review process was informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Given that selected studies were heterogeneous in terms of the methodological structure and research outcomes, a meta-analysis could not be performed. Therefore, narrative data analysis and knowledge synthesis were performed to report the review results.Results:The search process led to retrieving 1,241 studies, of which 12 studies were selected for data analysis and knowledge synthesis. They involved 3,890 older people with cognitive disorders and 3,465 family caregivers. Their methodologies varied and included cohort, randomised controlled trial, cross-sectional studies, grounded theory, qualitative framework analysis, and thematic analysis. The pillars that supported safe medicines management with the participation of family caregivers in home care consisted of the interconnection between older people's needs, family caregivers' role, and collaboration of multidisciplinary healthcare professionals.Conclusion:Medicines management for older people with cognitive disorders is complex and multidimensional. This systematic review provides a comprehensive image of the interconnection between factors influencing the safety of medicines management in home care. Considering that home-based medicines management is accompanied with stress and burden in family caregivers, multidisciplinary collaboration between healthcare professionals is essential along with the empowerment of family caregivers through education and support.

Background: Evidence supporting various diagnostic criteria for diagnose gestational diabetes mellitus (GDM) are consensus-based, needs for additional evidence related to outcomes. Therefore, the aim of this systematic-review and meta-analysis was to assess the impact of different GDM diagnostic-criteria on the risk of adverse-neonatal-outcomes.Methods: Electronic databases including Scopus, PubMed, and Web of Sciences were searched to retrieve English original, population-based studies with the universal GDM screening approach, up to January-2020. GDM diagnostic criteria were classified in seven groups and International Association of the Diabetes and Pregnancy Study Groups (IADPSG) was considered as reference one. We used the Mantel–Haenszel method to calculate the pooled odds of events. The possibility of publication bias was examined by Begg’s test.Results: A total of 55 population-based studies consisting of 1,604,391 pregnant women with GDM and 7,770,855 non-GDM counterparts were included. Results showed that in all diagnostic-criteria subgroups, the risk of adverse neonatal outcomes including macrosomia, hyperbilirubinemia, respiratory distress syndrome, neonatal hypoglycemia, neonatal intensive care unit admission, preterm birth, and birth-trauma were significantly higher than the non-GDM counterparts were significantly higher than non-GDM counterparts. Meta-regression analysis revealed that the magnitude of neonatal risks in all diagnostic-criteria subgroups are similar.Conclusion: Our results showed that the risk of adverse-neonatal-outcome increased among women with GDM, but the magnitude of risk was not different among those women who were diagnosed through more or less intensive strategies. These findings may help health-care-providers and policy-makers to select the most cost-effective approach for the screening of GDM among pregnant women.

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.

Low ovarian reserve is a serious condition, leading to sterility in up to 10% of women in their mid-thirties. According to current knowledge, serum anti-Müllerian hormone (AMH) levels for age are the best available marker for the screening the quantity of a woman's functional ovarian reserve, better than age alone or other reproductive markers. This review summarizes recent findings, clinical utility and limitations in the application of serum AMH testing as an accurate marker for the screening of functional ovarian reserves and predicting age at menopause. AMH assessment hold promise in helping women make informed decisions about their future fertility and desired family size. However, screening of the functional ovarian reserve could be offered to all women at 26 years of age or older who seek to assess future fertility or in case of personal request, ovarian reserve screening may be considered beyond 30 years; however, it has never been advocated beyond 35 years, since it is not advisable to delay childbearing beyond this age. In this respect, an age-specific serum AMH levels lower than the 10th percentile may be used as a threshold for the identification of a low functional ovarian reserve in an individual woman. Its level should be interpreted with caution in the adolescent and young women aged below 25 years (since AMH levels peak at this age); recent users of hormonal contraceptives (since AMH levels transiently decrease until two months after discontinuation); and women with PCOS (which dramatically increases AMH levels). However, the ability of AMH levels to predict the time to menopause is promising but requires further investigation and routine AMH testing for the purposes of predicting the time to menopause is not recommended.

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.

Aim: Studies focusing of male infertility and cardio-metabolic disorders is insufficient and controversial. The aim of this study was to evaluate the association between male infertility and cardiometabolic disturbances in a population based Tehran lipid and glucose study. Material and methods: For the purpose of the present study, we used data collected in 3rd follow up visit of Tehran Lipid and Glucose Study, which included comprehensive data on reproductive status of participants. All those who were never married, were unwillingness to have a child, had documented female infertility were excluded from the study. A total of 1611 remaining participants were further classified as two groups: men who had documented male infertility as infertile group (n = 88) and those had at least one live birth and did not have a history of primary infertility as the fertile group (n = 1523). Generalized Linear Regression model (GLM) with logit link were applied to assess the 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 after further adjustment for age and BMI.Results: Compared to fertile controls, infertile men were more likely to be older, [58 (13.3) versus 53 (10.2) years (P = 0.003)]. The results of unadjusted model revealed that infertility were significantly associated with 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, the significant association, which were found in crude analyses, were disappeared after adjusting for potential confounders of age and BMI. Moreover, infertility did not have any association with other cardiometabolic disturbances including diabetes and pre-diabetes, metabolic syndrome, dyslipidemia, obesity and central obesity in unadjusted and adjusted analysis. Conclusion: Our study revealed that there were not any association between male infertility and cardiometabolic disturbances in a population based setting. This study is an incentive to initiate more explicit surveys concerning this topic in order to provide more accurate data on male infertility. More population-based studies with large sample size are still warranted to confirm these findings.

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.

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 100, 100-149, 150-249, and 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 100 μg/L. Likewise, there were not any statistical significant differences between the neonatal characteristics in different UIC groups. The results remained unchanged after subgroup analysis based on UIC less than 150 μg/L as abnormal UIC level. The present meta-analysis showed that the UIC of euthyroid pregnant women is not generally associated with the pregnancy outcomes and it per se is an insufficient indicator for prediction of pregnancy complications. The results of this study are important for reproductive healthcare providers and policymakers in providing appropriate healthcare service for pregnant women. However, further studies are needed to confirm these findings.

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.

There is controversial data available regarding the impact of age at menarche on cardio-metabolic parameters. This community-based study aimed to assess this association among Iranian women.We recruited 5,344 eligible women out of 7718, aged 10-50 years who participated in the Tehran lipid and glucose study (TLGS), conducted in 1999-2000. Based on their age at menarche, these women were subdivided into five groups:11 years, 11-12 years, 13-14 years, 15-16 years and ≥17 years. The status of metabolic syndrome (MetS) and its components were compared among study subgroups.The crude prevalence of MetS was 11.9, 95% CI: 11.0-13.0. Prevalence values for MetS components were 20.1 for central obesity (95% CI: 19.0-21.3), 15.7 for high fasting blood sugar (FBS), (95% CI: 14.5-17.1), 15.1 for high triglycerides, (95% CI: 14.1-16.3), 53.5 for low high density lipoproteins (HDL) (95% CI: 51.9-55.0) and 9.5 for high blood pressure (BP) (95% CI: 8.5-10.4). After adjustment for covariates, menarche age11 years, compared to 13-14 years, was significantly associated with higher risk of Mets (odds ratio [OR] = 2.3, 95% CI: 1.1-5.4) and its components; i.e. central obesity (OR = 2.5, 95% CI: 1.5-4.2), BP (OR = 2.9, 95% CI: 1.4-6.0) and FBS (OR = 3.0, 95% CI: 1.4-6.0). To compare our results with other studies, we calculated the standardized prevalence of MetS which was based on the WHO standardized population 11.5, 95%CI: 10.7-12.5 and the standardized prevalence of MetS by the population in Tehran was 11.7, 95% CI: 10.7-12.6.Early menarche can be associated with an increase in metabolic disturbances later in life.

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.