Investigation of the relationship between air pollution and gestational diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) can have negative effects on both the pregnancy and perinatal outcomes, as well as the long-term health of the mother and the child. It has been suggested that exposure to air pollution may increase the risk of developing GDM. This study investigated the relationship between exposure to air pollutants with gestational diabetes. METHODS: The present study is a retrospective cohort study. We used data from a randomised community trial conducted between September 2016 and January 2019 in Iran. During this period, data on air pollutant levels of five cities investigated in the original study, including 6090 pregnant women, were available. Concentrations of ozone (O3), nitric oxide (NO), nitrogen dioxide (NO2), nitrogen oxides (NOx), sulphur dioxide (SO2), carbon monoxide (CO), particulate matter < 2.5 (PM2.5) or <10 µm (PM10) were obtained from air pollution monitoring stations. Exposure to air pollutants during the three months preceding pregnancy and the first, second and third trimesters of pregnancy for each participant was estimated. The odds ratio was calculated based on logistic regression in three adjusted models considering different confounders. Only results that had a p < .05 were considered statistically significant. RESULTS: None of the logistic regression models showed any statistically significant relationship between the exposure to any of the pollutants and GDM at different time points (before pregnancy, in the first, second and third trimesters of pregnancy and 12 months in total) (p > .05). Also, none of the adjusted logistic regression models showed any significant association between PM10 exposure and GDM risk at all different time points after adjusting for various confounders (p > .05). CONCLUSIONS: This study found no association between GDM risk and exposure to various air pollutants before and during the different trimesters of pregnancy. This result should be interpreted cautiously due to the lack of considering all of the potential confounders.

The health of pregnant women and their children can be impacted by gestational diabetes mellitus (GDM), one of the prevalent pregnancy complications. Some of studies showed that the incidence of gestational diabetes can be influenced by genetic or environmental factors. Air pollution is an environmental stimulus that may predispose pregnant women to GDM. This research explored whether air pollution could increase the risk of developing gestational diabetes. Over 6000 pregnant women in five cities of Iran participated in the study and were screened for gestational diabetes. Their exposure to the various air pollutants during the three months preceding pregnancy and total pregnancy period was measured. In this study, we found no clear association between air pollution and gestational diabetes. However, this finding needs to be interpreted cautiously since all the influential factors were not assessed.

Prediction of adverse pregnancy outcomes by first-trimester components of metabolic syndrome: a prospective longitudinal study.

PURPOSE: This study aimed to identify the optimal cutoff values of each component of metabolic syndrome (MetS) in the first trimester of pregnancy for predicting adverse pregnancy outcomes. METHODS: A total of 1076 pregnant women in the first trimester of gestation were recruited in this prospective longitudinal cohort study. Specifically, 993 pregnant women at 11-13 weeks of gestation who were followed up until the end of pregnancy were included in the final analysis. The cutoff values of each component of MetS in the occurrence of adverse pregnancy outcomes including gestational diabetes (GDM), gestational hypertensive disorders, and preterm birth were obtained via receiver operating characteristic (ROC) curve analysis using the Youden's index. RESULTS: Among the 993 pregnant women studied, the significant associations between the first trimester MetS components and adverse pregnancy outcomes were as follows: triglyceride (TG) and body mass index (BMI) with preterm birth; mean arterial pressure (MAP), TG, and high-density lipoprotein cholesterol (HDL-C) with gestational hypertensive disorders; BMI, fasting plasma glucose (FPG), and TG with GDM (all p values < 0.05). The cutoff point values for the above-mentioned MetS components were: TG > 138 mg/dl and BMI < 21 kg/m2 for the occurrence of preterm birth; TG > 148 mg/dL, MAP > 84, and HDL-C < 84 mg/dl for gestational hypertensive disorders; BMI > 25 kg/m2, FPG > 84 mg/dl, and TG > 161 mg/dl for GDM. CONCLUSION: The study findings imply the importance of early management of metabolic syndrome in pregnancy to improve maternal-fetal outcomes.

Umbilical cord blood concentration of connecting peptide (C-peptide) and pregnancy outcomes.

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 < 0.001; and Coef.= 0.34, 95% CI: 0.06 - 0.63, p = 0.02, respectively). 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.

Prevalence of acne vulgaris among women with polycystic ovary syndrome: a systemic review and meta-analysis.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The risk of chronic kidney disease among women with polycystic ovary syndrome: A long-term population-based cohort study.

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.

Risk of hypertension in women with polycystic ovary syndrome: a systematic review, meta-analysis and meta-regression.

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.

Cardiovascular events among reproductive and menopausal age women with polycystic ovary syndrome: a systematic review and meta-analysis.

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.

Relationships Between Biochemical Markers of Hyperandrogenism and Metabolic Parameters in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

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) (ß=0.006; 95% CI: 0.002, 0.01), high-density lipoproteins cholesterol (HDL-C) (ß=-0.009; 95% CI: -0.02, -0.001), and systolic blood pressure (SBP) (ß=-0.01; 95% CI: -0.03, -0.00). We observed a positive significant association between free testosterone (fT) and fasting insulin (ß=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 (ß=-0.41; 95% CI: -0.70, -0.12). There was a positive significant association between A4 and TG (ß=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 (ß=0.02; 95% CI: 0.001, 0.03) and a reverse significant association with HDL-C (ß=-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.

Trend of various adiposity indices in women with and without history of gestational diabetes: a population-based cohort study.

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 < 0.001), an incremental trend which was less pronounced in GDM women (OR: 0.87; 95% CI, 0.80, 0.95; P interaction = 0.001). Women with prior GDM had higher odds of central obesity, compared to non-GDM groups (OR: 1.44; 95% CI, 1.06-1.96; P = 0.02) and showed a significant an incremental trend overtime for both groups (P trend < 0.001 for both) without statistically significant interaction in terms of their GDM status (P interaction = 0.134). Mean VAI in women with prior GDM was significantly higher than the non-GDM group (19.7, 95%CI: 6.24, 33.15, P = 0.004), although both groups overtime experienced a negative trend (- 10.9, 95%CI: -13.1, - 2.1, P < 0.001); the GDM group showed a higher decrease in VAI (mean changes: -6.62; 95% CI, - 11,-2.1; P interaction = 0.001). However overtime there was a positive trend in LAP and ABSI among both women with and without prior-GDM, though the mean changes were less obvious in women with prior GDM. CONCLUSION: Women with prior GDM gained better control of their adiposity than non-GDM women. Nevertheless the increasing numbers of individuals with GDM and uncontrolled adiposity indices, require prompt attention be paid to the issue.

High prevalence of benign mammary tumors in a rat model of polycystic ovary syndrome during postmenopausal period.

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.

The risk of metabolic syndrome in polycystic ovary syndrome: A systematic review and meta-analysis.

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

Association between biochemical hyperandrogenism parameters and Ferriman-Gallwey score in patients with polycystic ovary syndrome: A systematic review and meta-regression analysis.

BACKGROUND AND OBJECTIVE: A limited number of studies have evaluated the relationship between clinical and biochemical hyperandrogenism (HA). This study aimed to evaluate the association between biochemical hyperandrogenism parameters (BHPs) and Ferriman-Gallwey (FG) score in patients with polycystic ovary syndrome (PCOS). METHODS: We searched PubMed, Scopus, Google Scholar, ScienceDirect and Web of Sciences databases (2000-2015) to identify studies investigating clinical and biochemical parameters of HA in PCOS patients. In this meta-analysis, both fixed and random effect models were applied to estimate pooled effect size. To assess the relationships between BHPs and FG score, meta-regression analysis was used. RESULTS: Fifty-five study groups with a total of 6593 PCOS patients were analysed. Meta-regression analysis of pooled data from all eligible studies showed significant positive relationships of FG score with androstenedione (A4) (P=.034) and dehydroepiandrosterone sulphate (DHEAS) (P=.012), whereas it showed no association with total testosterone (tT), free testosterone (fT), sex hormone bonding globulin (SHBG) and free androgen index (FAI). The results did not change after adjusting for quality assessment or method of assay. Nor did the associations between A4 and FG score remain after adjusting for age and BMI, diagnostic criteria for PCOS and study design or the association between DHEAS and FG score remain after adjusting for ethnicity. CONCLUSION: This meta-analysis confirmed the associations of some BHPs, including A4 and DHEAS with FG score, indicating that measurement of these parameters can be useful for managing PCOS patients with hirsutism.

Effect of zinc sulfate supplementation on premenstrual syndrome and health-related quality of life: Clinical randomized controlled trial.

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.

Insulin resistance in obesity and polycystic ovary syndrome: systematic review and meta-analysis of observational studies.

We aimed at investigating whether insulin resistance (IR)/sensitivity are impaired in obese/non-obese polycystic ovary syndrome (PCOS) and obese/non-obese healthy controls. A comprehensive literature search was performed for observational, English language studies. Meta-analysis was performed with the random effects model according to the heterogeneity. Eligible studies, involving 3037 women in four groups of: 1-obese, PCOS; 2-non-obese, PCOS, 3-obese, non-PCOS and 4-Non-obese, non-PCOS were included. Based on the insulin resistance index (HOMA-IR) analysis, the pooled mean (95% Conf. Interval) of HOMA IR in groups 1-4 were 4.38 (3.84, 4.92), 2.68 (2.16, 3.20), 2.44 (2.06, 2.82) and 1.34 (1.06, 1.63), respectively. Meta-analysis showed that group 1 (obese, PCOS patients) statistically have the highest IR and group 4 (non-obese, non-PCOS women) have the highest insulin sensitivity. Group 2 (non-obese, PCOS patients) and group 3 (obese, non-PCOS women) were between this range and they had lower IR than group 1 (obese, PCOS) and lower insulin sensitivity than group 4 (non-obese, non-PCOS). So, there were statistical differences between all groups except between groups 2 and 3. Insulin sensitivity indexes (quickie and ISI), also confirm the IR index (HOMA-IR) results. Based on different IR/sensitivity indexes, we found no evidence of any different effects of BMI ≥ 30 kg/m(2) on IR/sensitivity. In conclusion, PCOS status intensifies the adverse effects of obesity on IR, it has to be appropriately addressed in primary and secondary preventive cares and treatments provided for these women.

Maternal rare inherited bleeding disorders and neonatal complications.

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.

Association between serum concentrations of nitric oxide and transition to menopause.

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.

Menopause status as the main factor explaining the gender differences of serum nitric oxide concentrations in middle-aged population.

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

Anti-hemorrhagic activity of Punica granatum L. flower (Persian Golnar) against heavy menstrual bleeding of endometrial origin: a double-blind, randomized controlled trial.

BACKGROUND: Heavy menstrual bleeding of endometrial origin (HMB) is a major healthcare problem in premenopausal women and affects several aspects of women's health and quality of life (QoL). The aim of this study was to compare the efficacy of Persian Golnar (PG) and tranexamic acid (TA) on heavy menstrual bleeding of endometrial origin (HMB) and patients' QoL. METHODS: A double-blind randomized controlled trial with parallel design and block randomization technique was conducted. A total of 94 women with HMB were randomly assigned to take either PG or TA for 5 days from day 1 of menses for three consecutive menstrual cycles. Blood loss was measured by the pictorial blood loss assessment chart (PBAC). Hematological assessments were made before the intervention and after treatment. QoL as a secondary outcome was evaluated using SF-36 and the menorrhagia questionnaire (MQ). Statistical analysis was performed using t-test, paired ttest, χ2 test, Mann-Whitney test, and Wilcoxon signed-rank test. RESULTS: In each group, 38 women (80.8%) completed the 3-month follow-up. Both PG and TA reduced blood loss. PBAC mean (SD) score was reduced from 304.92 (176.17) and 304.44 (192.72) to 164.60 (100.24) and 143.13 (96.07) after the third treatment cycle, respectively (p< 0.001). Furthermore, mean hemoglobin, Hb (SD) concentrations in the PG and TA groups increased significantly from 12.06 (0.86) and 11.53 (0.86)mg/dl to 13.02 (0.82) and 12.72 (0.88) mg/dl (p< 0.001). QoL was significantly improved in both groups (p< 0.001). However, there were no significant differences between the groups after the intervention. CONCLUSION: The results of the present study demonstrate the efficacy of PG in treating HMB in terms of clinical and QoL indicators.

Adiposity trajectories and cardiovascular disease risk in women: a population-based cohort study with a focus on menopausal status.

Objectives: A single measurement of adiposity indices could predict the incidence of cardiovascular disease (CVD); nonetheless their long-term pattern and its association with incident CVD are rarely studied. This study aimed to determine distinct trajectories of adiposity indices among participants of Tehran Lipid and Glucose Study (TLGS) and their association with incident CVD. Furthermore, this study aimed to investigate whether this association differed among individuals according to their menopausal status. Method: A total of 6840 women participated in TLGS, aged 20 years and older were included in this study; they were followed for a median of 16 years. Body mass index (BMI), waist circumference (WC), conicity index (CI) and body roundness index (BRI) were included in the analysis as adiposity indices. The cohort outcome panel of medical specialists identified the CVD outcomes. Trajectory analyses were used to identify homogeneous distinct clusters of adiposity indices trajectories. The association between the trajectory group membership and incident CVD were explored by Cox proportional hazard models, with unadjusted and adjusted model for baseline age, physical activity, smoking status, menopause and family history of CVD. Results: Three BMI trajectory groups of low, medium, and high and two trajectories for WC, BRI and CI were identified. Adjusted cox proportional hazard models revealed significant associations between the hazard of CVD experience and the high trajectory group of the BMI (HR: 2.06, 95% CI: 1.38-3.07), WC (HR: 2.71, 95% CI: 1.98-3.70), CI (HR: 1.87, 95% CI: 1.26-2.77) and BRI (HR: 1.55-95% CI: 1.12-2.15), compared to the low trajectory group. Subgroup analysis based on the menopausal status of participants showed that the HR of CVD incidences for all of trajectories adiposity indices, except BMI, was statistically significant. Adjusted cox proportional hazard models, in those women not reached menopause during study, revealed that the HR (95% CI) of CVD incidences for high trajectory of BMI, WC, CI and BRI were 2.80 (1.86-7.05); 2.09 (1.40-6.16); 1.72 (1.42-5.61), and 3.09 (1.06-9.01), respectively. These values for those were menopause at the initiation of the study were 1.40 (1.11, 2.53); 1.65 (1.04-2.75); 1.69 (1.01-2.87), and 1.61 (0.98-2.65), respectively. Conclusion: Our findings suggest that adiposity trajectories, particularly central adiposity index of CI, could precisely predict the CVD risk. Consequently, preventive strategies should be tailored accordingly.

Prevalence of depression, stress and suicide tendency among individuals with long COVID and determinants: a protocol of a systematic review and meta-analysis.

BACKGROUND: It is well known that the COVID-19 pandemic has had a devastating impact on mental health, especially among individuals with long COVID. This systematic review and meta-analysis aims to investigate the prevalence of depression, stress and suicide tendencies among individuals with long COVID, as well as to explore the factors that contribute to these conditions. METHODS AND ANALYSIS: A comprehensive review of literature will be conducted in various databases of including PubMed, including Medline, Embase, PsycINFO, CINAHL and Cochrane Library. The studies to be included in this review will be published in the English language, and the time frame of included studies will be from the date of inception of COVID-19 until 30 December 2023. Two independent reviewers will identify studies for inclusion based on a screening questionnaire, and the JBI standardised critical appraisal checklist for studies reporting prevalence data will be used to assess the methodological quality. The strength of the body of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. To analyse the data, a robust Bayesian approach will be applied using the STATA software package (V.14; STATA) and JASP software. The findings of this systematic review and meta-analysis will provide valuable insights into the prevalence of depression, stress and suicide tendencies among individuals with long COVID, as well as the factors that contribute to these conditions. ETHICS AND DISSEMINATION: There is no research ethics board approval required. The dissemination plan is to publish results in a peer-reviewed academic journal. PROSPERO REGISTRATION NUMBER: CRD42022346858.