Cohort profile update: Tehran cardiometabolic genetic study.

The Tehran cardiometabolic genetic study (TCGS) is a large population-based cohort study that conducts periodic follow-ups. TCGS has created a comprehensive database comprising 20,367 participants born between 1911 and 2015 selected from four main ongoing studies in a family-based longitudinal framework. The study's primary goal is to identify the potential targets for prevention and intervention for non-communicable diseases that may develop in mid-life and late life. TCGS cohort focuses on cardiovascular, endocrine, metabolic abnormalities, cancers, and some inherited diseases. Since 2017, the TCGS cohort has augmented by encoding all health-related complications, including hospitalization outcomes and self-reports according to ICD11 coding, and verifying consanguineous marriage using genetic markers. This research provides an update on the rationale and design of the study, summarizes its findings, and outlines the objectives for precision medicine.

The effects of weight loss on health-related quality of life in obese women with PCOS and controls.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complicated endocrine disorder with widespread symptoms that reduce women's quality of life. The adverse effect of associated obesity on this reduction is unclear, therefore the impact of weight loss on health-related quality of life (HRQOL) in obese women with PCOS is unknown. This study aimed to compare the impact of weight loss following a 24-week dietary intervention on HRQOL in obese women with and without PCOS. METHODS: In a 24-week hypocaloric LGI (low glycemic index) diet intervention study, 286 women were recruited (140 PCOS, 146 controls) and 216 participants (PCOS = 105, non-PCOS = 111) completed the study. HRQOL was assessed using the SF-36 questionnaire (Short Form Health Survey). Physical activity was measured using the short form of the International Physical Activity Questionnaire (IPAQ). Anthropometric assessments, dietary intake, physical activity levels, and HRQOL scores, according to the Iranian version of SF-36, were compared at baseline and 24 weeks with intervention. RESULTS: At the end of the intervention, there was no significant difference in the percentages of weight loss between the two groups (PCOS: 6.29 ± 3.32% vs. non-PCOS: 7 ± 3.62%, p = 0.1). At baseline, women with PCOS had lower mean scores in aspects of physical function (PF), general health perception (GH), role limitation due to emotional problem (RE), vitality (VT), mental health (MH), physical (PCS) and mental component summary scales (MCS), compared to non-PCOS (P < 0.01). At 24 weeks, the percentage of improvement in HRQOL in the non-PCOS group was higher compared to the PCOS group but this difference didn't reach statistical significance except for PCS. In both groups, greater weight loss was associated with further improvement in the physical aspects of HRQOL and vitality. In the non-PCOS group, with trivial exception, greater weight loss was associated with greater improvement in the mental aspects of HRQOL. CONCLUSIONS: Both obese PCOS and non-PCOS women achieved nearly similar levels of improvement in HRQOL due to weight loss induced by a hypocaloric LGI diet. TRIAL REGISTRATION: This study is registered in the Iranian Randomized Clinical Trials Registry (IRCT, code: IRCT2016092129909N1).

Exosome engineering in cell therapy and drug delivery.

Cell-derived exosomes have opened new horizons in modern therapy for advanced drug delivery and therapeutic applications, due to their key features such as low immunogenicity, high physicochemical stability, capacity to penetrate into tissues, and the innate capacity to communicate with other cells over long distances. Exosome-based liquid biopsy has been potentially used for the diagnosis and prognosis of a range of disorders. Exosomes deliver therapeutic agents, including immunological modulators, therapeutic drugs, and antisense oligonucleotides to certain targets, and can be used as vaccines, though their clinical application is still far from reality. Producing exosomes on a large-scale is restricted to their low circulation lifetime, weak targeting capacity, and inappropriate controls, which need to be refined before being implemented in practice. Several bioengineering methods have been used for refining therapeutic applications of exosomes and promoting their effectiveness, on the one hand, and addressing the existing challenges, on the other. In the short run, new diagnostic platforms and emerging therapeutic strategies will further develop exosome engineering and therapeutic potential. This requires a thorough analysis of exosome engineering approaches along with their merits and drawbacks, as outlined in this paper. The present study is a comprehensive review of novel techniques for exosome development in terms of circulation time in the body, targeting capacity, and higher drug loading/delivery efficacies.

Serum metabolomics study of women with different annual decline rates of anti-Müllerian hormone: an untargeted gas chromatography-mass spectrometry-based study.

STUDY QUESTION: Which metabolites are associated with varying rates of ovarian aging, measured as annual decline rates of anti-Müllerian hormone (AMH) concentrations? SUMMARY ANSWER: Higher serum concentrations of metabolites of phosphate, N-acetyl-d-glucosamine, branched chained amino acids (BCAAs), proline, urea and pyroglutamic acid were associated with higher odds of fast annual decline rate of AMH. WHAT IS KNOWN ALREADY: Age-related rate of ovarian follicular loss varies among women, and the factors underlying such inter-individual variations are mainly unknown. The rate of ovarian aging is clinically important due to its effects on both reproduction and health of women. Metabolomics, a global investigation of metabolites in biological samples, provides an opportunity to study metabolites or metabolic pathways in relation to a physiological/pathophysiological condition. To date, no metabolomics study has been conducted regarding the differences in the rates of ovarian follicular loss. STUDY DESIGN, SIZE, DURATION: This prospective study was conducted on 186 reproductive-aged women with regular menstrual cycles and history of natural fertility, randomly selected using random case selection option in SPSS from the Tehran Lipid and Glucose Study. PARTICIPANTS/MATERIALS, SETTING, METHODS: AMH concentrations were measured at baseline (1999-2001) and the fifth follow-up examination (2014-2017), after a median follow-up of 16 years, by immunoassay using Gen II kit. The annual decline rate of AMH was calculated by dividing the AMH decline rate by the follow-up duration (percent/year). The women were categorized based on the tertiles of the annual decline rates. Untargeted metabolomics analysis of the fasting-serum samples collected during the second follow-up examination cycle (2005-2008) was performed using gas chromatography-mass spectrometry. A combination of univariate and multivariate approaches was used to investigate the associations between metabolites and the annual decline rates of AMH. MAIN RESULTS AND THE ROLE OF CHANCE: After adjusting the baseline values of age, AMH and BMI, 29 metabolites were positively correlated with the annual AMH decline rates. The comparisons among the tertiles of the annual decline rate of AMH revealed an increase in the relative abundance of 15 metabolites in the women with a fast decline (tertile 3), compared to those with a slow decline (tertile 1). There was no distinct separation between women with slow and fast decline rates while considering 41 metabolites simultaneously using the principal component analysis and the partial least-squares discriminant analysis models. The odds of fast AMH decline was increased with higher serum metabolites of phosphate, N-acetyl-d-glucosamine, BCAAs, proline, urea and pyroglutamic acid. Amino sugar and nucleotide sugar metabolism, BCAAs metabolism and aminoacyl tRNA biosynthesis were among the most significant pathways associated with the fast decline rate of AMH. LIMITATIONS, REASONS FOR CAUTION: Estimating the annual decline rates of AMH using the only two measures of AMH is the main limitation of the study which assumes a linear fixed reduction in AMH during the study. Since using the two-time points did not account for the variability in the decline rate of AMH, the annual decline rates estimated in this study may not accurately show the trend of the reduction in AMH. In addition, despite the longitudinal nature of the study and statistical adjustment of the participants' ages, it is difficult to distinguish the AMH-related metabolites observed in this study can accelerate ovarian aging or they are reflections of different rates of the aging process. WIDER IMPLICATIONS OF THE FINDINGS: Some metabolite features related to the decline rates of AMH have been suggested in this study; further prospective studies with multiple measurements of AMH are needed to confirm the findings of this study and to better understand the molecular process underlying variations in ovarian aging. STUDY FUNDING/COMPETING INTEREST(S): This study, as a part of PhD thesis of Ms Nazanin Moslehi, was supported by Shahid Beheshti University of Medical Sciences (10522-4). There were no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Number of parity/live birth(s) and cardiovascular disease among Iranian women and men: results of over 15 years of follow-up.

BACKGROUND: Most previous studies conducted in non-Middle Eastern populations have suggested that an increase in the number of parity/live birth(s) leads to cardiovascular disease (CVD) development, although their findings were inconclusive on this issue for both sexes. Biologic and socioeconomic pathways were suggested to explain this association. We studied this issue among urban Iranian men and women. METHODS: In this population-based cohort study, which included 3929 women and 2571 men aged ≥30 years, data for the number of parity/live birth(s) were obtained by a standard questionnaire. Participants were then annually followed for CVD events. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the number of parity/live birth(s) and other traditional CVD risk factors. RESULTS: During more than 15 years of follow-up, 456 and 524 CVD events have occurred among women and men, respectively. Among women, a J-shaped association was found between the number of live births and incident CVD with the lowest risk for women with two live births. Among women in multivariable analyses, each unit increase in parity had a HR of 1.05 (CI: 1.01-1.10), and having ≥4 parity was associated with a HR of 1.86 (0.97-3.56, p-value = 0.061). Among men, in comparison with participants who had 1 child, multivariable HRs of having 2, 3, and ≥ 4 children were 1.97 (1.24-3.12), 2.08 (1.31-3.31), and 2.08 (1.30-3.34), respectively. CONCLUSION: To the best of our knowledge, the current study is the first report on this issue in the Middle East and North Africa region, a region with a high burden of CVD. It can now be suggested that the number of parity/live birth(s) is linked to CVD among the Iranian population, with this issue being more prominent among men. Further research is needed to support our results and clarify the pathways between the number of parity/live birth(s) and CVD development among Iranian populations by considering potential risk factors, especially psycho-socio-economic risk factors.

Relationship between occupational exposure to whole-body vibration and noise with sex hormone levels: An empirical assessment in an automobile parts manufacturing plant.

The present study investigated the relationship between occupational exposure to noise and whole-body vibration (WBV) with the levels of sex hormones in an automobile parts manufacturing plant. The level of workers' exposure (n = 162) to each of the mentioned stressors was measured through standard methods, and the time-weighted average of exposure was calculated for each person. In order to determine serum sex hormones (free testosterone, luteinizing hormone, and follicle-stimulating hormone), blood samples were taken from all participants after 8-10 h of fasting between 7 and 9 am and then the blood samples were analyzed by an enzyme-linked immunosorbent assay method. In general, regarding testosterone as the main male sex hormone, only 49% of the participants were in the normal range. In a total of three sections, the lowest mean testosterone levels were observed in the third exposure group (WBV > 1.93 m/s2; noise >92.69 dB) of the studied stressor; however, only the difference in testosterone levels between the three different groups of exposure to noise was statistically significant (p = 0.001). The relationship between demographic variables and levels of noise and WBV exposure with sex hormones was not linear and only the relationship between noise exposure and testosterone levels was statistically significant (R = -0.201, p = 0.013). According to the results of logistic regression, the WBV had the greatest effect on testosterone levels. However, according to the results of the correlation test, only the relationship between noise exposure and testosterone levels was statistically significant.

Iran in transition.

Being the second-largest country in the Middle East, Iran has a long history of civilisation during which several dynasties have been overthrown and established and health-related structures have been reorganised. Iran has had the replacement of traditional practices with modern medical treatments, emergence of multiple pioneer scientists and physicians with great contributions to the advancement of science, environmental and ecological changes in addition to large-scale natural disasters, epidemics of multiple communicable diseases, and the shift towards non-communicable diseases in recent decades. Given the lessons learnt from political instabilities in the past centuries and the approaches undertaken to overcome health challenges at the time, Iran has emerged as it is today. Iran is now a country with a population exceeding 80 million, mainly inhabiting urban regions, and has an increasing burden of non-communicable diseases, including cardiovascular diseases, hypertension, diabetes, malignancies, mental disorders, substance abuse, and road injuries.

Effects of oral contraceptives on the quality of life of women with polycystic ovary syndrome: a crossover randomized controlled trial.

BACKGROUND AND OBJECTIVE: A limited number of studies have evaluated the effects of oral contraceptives (OCs) on the quality of life (QOL) of polycystic ovary syndrome (PCOS) patients. This study aimed to compare the effects of using OCs containing levonorgestrel (LNG) and those containing desogestrel (DSG), cyproterone acetate (CPA) or drospirenone (DRSP) for 6 months on the QOL with PCOS. METHODS: In this crossover randomized controlled 6-arm trial, 200 eligible patients with PCOS scheduled for OC therapy were randomly assigned to one of the 6 study arms. All 6 arms include two 6-month treatment periods, one period with OCs containing LNG, and the other with each of the 3 OCs containing DSG, CPA, or DRSP. Outcomes of interest were the total score of QOL and its domains, which were assessed using a specific and valid health-related quality of life questionnaire for PCOS, which is consisted of six domains, including psychosocial-emotional, self-image, fertility, sexual function, hirsutism, and obesity- menstrual disorders. RESULTS: Finally, a total of 88 patients were analyzed for this study. The results showed that use of OCs containing DSG, CPA, and DRSP for 3 months was not associated with significant differences in the total scores of QOL compared to those OCs containing LNG, whereas, after 6 months of treatment, patients treated with OCs containing CPA had more improvements in their total scores of QOL, in comparison to OCs containing LNG (P < 0.042). We found no significant differences in QoL domains, including psychosocial-emotional, self-image, fertility, sexual function, hirsutism, and obesity-menstrual disorders after 3-6 months of treatment with DSG, CPA, or DRSP, compared to LNG. The sequence and period effects were not significant in any of the analyses at 3 and 6 months of treatment. The carry-over effect was not significant for most outcomes assessed. CONCLUSIONS: This crossover study demonstrated non-inferiority of OCs with newer generation progestins on different domains of QOL, in comparison with older compounds, although usage of products containing CPA was significantly associated with more improvement in total QOL of PCOS patients, compared to those containing LNG after 6-month of treatment. TRIAL REGISTRATION: IRCT201702071281N2 .

Effect of lifestyle modifications on anthropometric, clinical, and biochemical parameters in adolescent girls with polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age. This study aimed to compare the effects of lifestyle interventions on anthropometric, clinical, and biochemical parameters in adolescent girls with PCOS. METHODS: PubMed, Scopus, and Web of Science was systematically searched to retrieve studies investigating the effects of lifestyle modifications in adolescent girls with PCOS, which were published up to December 2019. The primary outcome was Body Mass Index (BMI) and secondary outcomes were all manifestations of PCOS, including clinical, metabolic, and hormonal parameters. Random effect meta-analysis was applied for significant results. Publication bias was assessed using the Egger test. RESULTS: This study showed significant improvements in luteinizing hormone (LH) (Pooled SMD = - 0.1.23; 95% CI, - 2.44 to - 0.03), and Free Androgen Index (FAI) levels (Pooled SMD = - 0.78 95% CI, - 0.1.42 to - 0.13) in adolescent girls receiving lifestyle intervention compared to baseline. This study also revealed that diet modifications alone were associated with a significant decrease in Body Mass Index (BMI) (Pooled SMD = - 0.45; 95% CI, - 0.76 to - 0.13), and FG score (Pooled SMD = - 0.81; 95% CI, - 1.33 to - 0.28). Exercise interventions were associated with significant changes in the menstrual cycles (Pooled SMD = 1.16; 95% CI, 0.72 to 1.61), Ferriman-Gallwey (FG) score (Pooled SMD = - 0.57; 95% CI, - 0.99 to - 0.15), LH (Pooled SMD = - 056; 95% CI, - 0.98 to - 0.14), Anti-Müllerian Hormone (AMH) (Pooled SMD = - 0.81; 95% CI, - 0.1.24 to - 0.38), and Triglyceride (TG) levels (Pooled SMD = - 0.32; 95% CI, - 0.62 to - 0.02). CONCLUSION: This meta-analysis concluded lifestyle interventions, such as diet and exercise, can improve some clinical, metabolic, and hormonal parameters in adolescent girls with PCOS.

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.

Overtime trend of thyroid hormones and thyroid autoimmunity and ovarian reserve: a longitudinal population study with a 12-year follow up.

BACKGROUND: Ovarian reserve, vital for reproductive function, can be adversely affected by thyroid diseases. Despite alternations of thyroid hormones with ageing, data on interactions between the overtime trend of thyroid functions and ovarian reserve status has rarely been reported. We aimed to examine the overtime trend of thyroid hormones, thyroid peroxidase antibody (TPO Ab) and their associations with ovarian reserve status, identified by levels of age specific anti-mullerian hormone (AMH) in reproductive aged women, who participated in 12-year cohort of Tehran Thyroid Study (TTS). METHODS: Reproductive age women(n = 775) without any thyroid disease or ovarian dysfunction were selected from the Tehran Thyroid Study cohort. Participants were divided into four age specific AMH quartiles (Q1-Q4), Q1, the lowest and Q4, the highest. AMH was measured at the initiation of study and thyroid stimulating hormone (TSH), free T4 (FT4), and TPO Ab were measured at baseline and at three follow up visits. RESULTS: At baseline, there was no statistically significant difference in thyroid hormones between women of the four quartiles, although TPO Ab levels were higher in women of Q1. During the follow ups, FT4 was decreased in all quartiles (p < 0.05), whereas TPO Ab increased in Q1 (p = 0.02). Odds ratio of overall TPO Ab positivity in women of Q1 was 2.08 fold higher than those in Q4. (OR: 2.08, 95%CI: 1.16, 3.72; p = 0.01). CONCLUSION: Women with the lowest ovarian reserves had higher levels of TPO Ab, with a positive trend of this antibody overtime in comparison to other quartiles, indicating that this group may be at a higher risk of hypothyroidism over time.

Do dietary intakes influence the rate of decline in anti-Mullerian hormone among eumenorrheic women? A population-based prospective investigation.

BACKGROUND: Dietary intakes are suggested to affect age at menopause but associations between dietary factors and ovarian reserve reduction have not yet been investigated. We aimed to examine dietary intakes in relation to the rate of decline in anti-Mullerian hormone (AMH), an indicator of ovarian reserve, in a generally healthy cohort of women. METHODS: This prospective investigation was conducted among 227 eumenorrheic women, aged 20-50 years, from the Tehran Lipid and Glucose study, who were followed over a mean of 16 years. AMH was measured twice, at baseline and the 5th follow-up examination cycle, and yearly rate of decline in AMH was calculated. Rapid decline in AMH was defined as the annual percent change AMH > 5.9%/year based on tertile 3 of the variable. Average usual dietary intakes were estimated using the food frequency questionnaires administered at the second, third, and the fourth follow-up examinations. After adjusting for potential covariates, the association between dietary factors and both risk of rapid decline in AMH and also annual percent decline of AMH (as a continuous variable) were examined using logistic regression and the Spearman correlation, respectively. RESULTS: The baseline age of the participants and the median rate of decline in AMH were 37.2 years and was 5.7% yearly, respectively. The odds of rapid decline in AMH was reduced by 47% for dairy products (95% CIs = 0.36, 0.79; p = 0.002), 38% for milk (95% CIs = 0.41, 0.93; p = 0.020), and 36% for fermented dairy (95% CIs = 0.45, 0.93, p = 0.018) per one standard deviation (SD) increase in their dietary intakes. The odds of rapid decline in AMH was significantly reduced with higher intakes of fat, carbohydrate, protein, and calcium intakes from dairy sources, lactose and galactose. Annual rate of AMH decline was inversely correlated with dairy products, milk, fermented dairy, fruits, dairy carbohydrate, dairy fat, dairy protein, total calcium and dairy calcium, lactose and galactose, and positively correlated with organ meats. CONCLUSION: Dairy foods consumption may reduce the rate of AMH decline in regularly menstruating women. Life style modification in terms of dietary advice may be considered as a preventive strategy for reduction in the rate of ovarian reserve loss.

Beneficial effects of pelvic floor muscle exercises on sexual function among postmenopausal women: a randomised clinical trial.

Background The adverse effects of menopause on sexual function could be mitigated by pelvic floor muscle (PFM) training. This study aimed to investigate the effects of PFM exercises on sexual function in postmenopausal women. METHODS: A randomised clinical trial was conducted among 97 Iranian postmenopausal women, aged 40 to 60 years. The participants' baseline sexual functions were assessed using the Female Sexual Function Index (FSFI) questionnaire. They were then randomly designated to two groups: (1) the intervention group, which received specific instructions on PFM exercises and was followed up on a weekly basis; and (2) the control group, which received general information on menopause. After 12 weeks, the sexual functions of the participants were reassessed. RESULTS: No significant difference was initially observed between the two groups in terms of demographic and socioeconomic characteristics and total scores of FSFI. After the intervention, however, the scores of arousal, orgasm and satisfaction were significantly higher in the intervention group (3.10, 4.36, and 4.84 vs 2.75, 3.89, and 4.36 respectively; P<0.05). CONCLUSION: PFM exercises have the potential to improve the sexual function of postmenopausal women and are thus suggested to be included in healthcare packages designed for postmenopausal women.

The relationship between menopausal symptoms and sexual function.

Sexual function could be affected by several factors in postmenopausal women. This cross-sectional study aimed to investigate the relationship between the severity of menopausal symptoms and sexual function. The study was conducted among 405 postmenopausal women aged 40-65 years, in Chalous and Noshahr, Iran, from October 2013 to May 2014. The participants were selected using a multistage sampling method. The instruments used for data collection were the Female Sexual Function Index (FSFI), the Menopause Rating Scale (MRS), and a demographics questionnaire. The relationship between the severity of menopausal symptoms and sexual function was examined using Pearson's correlation coefficient and multiple linear and logistic regressions. The mean unadjusted FSFI and MRS scores were 24.11 and 12.45, respectively; and 61.0 percent of the participants had female sexual dysfunction (FSD) (FSFI ≤26.55). A significant negative correlation was observed between the MRS scores (total and all subscales) and the total scores for FSFI (p < 0.001). The results of the logistic regression analysis showed that with every unit increase in the total score of MRS, the likelihood of sexual dysfunction was 9.6 percent greater. We conclude that menopausal symptoms need to be considered in the design of health initiatives aimed at postmenopausal women's sexual function.

Effects of recruiting midwives into family physician program on the percentage of low birth weight (LBW) infants in rural areas of Kurdistan.

Background: LBW is an important factor that can affect infant mortality and represents an index of economic and social development. It is expected that an increase in the density of midwives attending family physician programs will lead to a decrease in LBW in health centers. This study aimed to compare the percentage of LBW infants before and after the implementation of the family physician program in health centers with and without an increase in midwives density. Methods: This cross-sectional study compared the percentage of LBW infants before and after the implementation of family physician programs in rural health centers with and without changes in midwives density in Kurdistan. In this study, we included 668 mothers of 2-month-old children and administered structured interviews in 2005 and 2013. Data were analyzed using the difference-indifferences and the Matchit statistical models. Results: The Matchit model showed a significant average percentage increase 0.08 (0.006-0.17) in LBW infants born between 2005 and 2013 in health centers where the density of midwives increased compared with those where it remained unchanged. The difference-in-differences model showed that the odds ratio of LBW infants is increased by more than twice among participants who had a history of caesarean section. Conclusion: The results of this study showed that an increase in the density of midwives in a family physician program did not have an impact on reducing the percentage of LBW infants born between 2005 and 2013, in health centers where the density of midwives augmented compared to those where it remained unaltered; it indicated that the increase in the density of midwives alone was not efficient. On the other hand, the results of our study show an increase in the risk of infants born at a LBW due to caesarean section. It is recommended that obstetricians and gynecologists must strictly control pregnancies and avoid unnecessary termination of pregnancy.

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.

Lipid profiles and ovarian reserve status: a longitudinal study.

STUDY QUESTION: Is there any association between ovarian reserve status and lipid profile changes? SUMMARY ANSWER: Women with lower ovarian reserve might be susceptible to higher cardiovascular risks, especially lipid disturbances, even during their reproductive life span. WHAT IS KNOWN ALREADY: The risk of developing cardiovascular disease (CVD) in women increases after menopause, but the association between ovarian reserve status and CVD is not known. STUDY DESIGN, SIZE AND DURATION: This longitudinal study was conducted on 1015 participants of Tehran Lipid and Glucose Study, an ongoing population based cohort study with 12 years follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: There were 1015 women who were aged 20-50 years and met our eligibility criteria. Their ovarian reserve status was identified according to their age-specific AMH levels, calculated using the exponential-normal 3-parameter model. At the time of recruitment, 268, 233, 256 and 258 subjects were in the first, second, third and fourth quartiles of age-specific AMH, respectively. The cardiovascular risk factors of these groups were compared. MAIN RESULTS AND THE ROLE OF CHANCE: Anthropometric measurements, lipid profiles and mean systolic and diastolic blood pressures in the first and fourth AMH quartiles did not differ at the initiation of the study. Total cholesterol (TC) net changes per year were incremental in the first AMH quartile but not in the fourth quartile (P < 0.001). According to the generalized estimating equation (GEE), after adjustment for age, BMI, time interaction and menopause status, the changes across time in TC, LDL and HDL were varied according to the age-specific AMH status. LIMITATIONS, REASONS FOR CAUTION: A potential limitation is that development of cardiovascular risk is a major long-term event that needs decades of follow-up from birth to death; hence further studies with longer follow-up times are needed. WIDER IMPLICATIONS OF THE FINDINGS: We provide the insight that women with lower ovarian reserve might be susceptible to developing cardiovascular risk factors, particularly lipid disturbances, even during their reproductive life span. STUDY FUNDING/COMPETING INTERESTS: This study was funded by Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER: Not applicable.

The prevalence of metabolic disorders in various phenotypes of polycystic ovary syndrome: a community based study in Southwest of Iran.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrinopathy, associated with metabolic abnormalities. Metabolic features of various phenotypes of this syndrome are still debatable. The aim of present study hence was to evaluate the metabolic and hormonal features of PCOS phenotypes in comparison to a group of healthy control. METHODS: A total of 646 reproductive-aged women were randomly selected using the stratified, multistage probability cluster sampling method. The subjects were divided into five phenotypes: A (oligo/anovulation + hyperandrogenism + polycystic ovaries), B (oligo/anovulation + hyperandrogenism), C (hyperandrogenism + polycystic ovaries) and D (oligo/anovulation + polycystic ovaries). Hormonal and metabolic profiles and the prevalence of metabolic syndrome among these groups were compared using ANCOVA adjusted for age and body mass index. RESULTS: Among women with PCOS (n = 85), those of groups A and C had higher serum levels of insulin and homeostatic model assessment for insulin resistance (HOMA-IR), compared to PCOS women of group D. Serum concentrations of cholesterol, low density lipoprotein, triglycerides and glucose in group A were higher than in other phenotypes, whereas the metabolic syndrome was more prevalent among group B. CONCLUSIONS: Women who had all three components of the syndrome showed the highest level of metabolic disturbances indicating that metabolic screening of the severest phenotype of PCOS may be necessary.

Introducing a rat model of prenatal androgen-induced polycystic ovary syndrome in adulthood.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women, with a prevalence of 8-12% during the reproductive years. In the present study, using prenatal exposure to a single dose of testosterone during the critical period of fetal development, we aimed to introduce an enhanced rat model that would exhibit both endocrine and ovarian disturbances similar to PCOS, while maintaining normal reproductive system morphology in adulthood. Ten pregnant rats were injected s.c. with 5 mg free testosterone on gestational day 20, while control rats received only solvent. The development and function of the reproductive system in female offspring were examined in adulthood. Prenatally androgenized offspring had irregular oestrous cycles compared with control animals, and their anogenital and anovaginal distances were increased compared with control rats (P < 0.001). No significant differences were observed in the lengths of the vagina and clitoris or the number of nipples between the two groups. Levels of testosterone and luteinizing hormone and the luteinizing hormone/follicle-stimulating hormone ratio were increased in prenatally androgenized offspring compared with control animals (P < 0.05). The numbers of preantral and antral follicles in the ovaries of prenatally androgenized offspring were also increased compared with control rats (P = 0.07 and P < 0.01, respectively). The number of corpora lutea was decreased in prenatally androgenized offspring compared with control rats. Cystic follicles were observed in the ovaries of prenatally androgenized offspring. Prenatal exposure to a single dose of testosterone during the critical period of fetal development could facilitate the development a functional rat model of PCOS in adulthood, with minimal morphological disorders in the reproductive system.

2023 International Evidence-Based Polycystic Ovary Syndrome Guideline Update: Insights From a Systematic Review and Meta-Analysis on Elevated Clinical Cardiovascular Disease in Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most prevalent female endocrinopathy. Although increased cardiovascular risk factors are well established for the syndrome, PCOS remains overlooked within the realm of cardiology. We conducted a systematic review and meta-analysis on the risk of clinical cardiovascular disease (CVD) events in women with PCOS to inform the 2023 International Evidence-Based PCOS Guideline. METHODS AND RESULTS: A systematic review and meta-analysis was conducted comparing the risk of clinical CVD events in women with and without PCOS. Medline (Ovid), PsycInfo (Ovid), EMBASE, All EBM (Ovid), and CINAHL were searched from January 1, 2017, until March 1, 2023, to update the 2018 PCOS Guideline. Pooled odds ratios (ORs), incidence rate ratios (IRRs), and hazard ratios (HRs) were calculated. Twenty studies involving 1.06 million women (369 317 with PCOS and 692 963 without PCOS) were included. PCOS was associated with higher risk of composite CVD (OR, 1.68 [95% CI, 1.26-2.23]; I2 = 71.0%), composite ischemic heart disease (OR, 1.48 [95% CI, 1.07-2.05]; I2 = 81.0%), myocardial infarction (OR, 2.50 [95% CI, 1.43-4.38]; I2 = 83.3%), and stroke (OR, 1.71 [95% CI, 1.20-2.44]; I2 = 81.4%). The relationship with cardiovascular mortality was less clear (OR, 1.19 [95% CI, 0.53-2.69]; I2 = 0%). Meta-analyses of IRRs support these findings. Results from pooled HRs were limited by the small number of studies and significant heterogeneity. CONCLUSIONS: This review provides evidence and highlights the importance of recognizing PCOS as a significant risk factor for CVD morbidity. The 2023 International Evidence-Based PCOS Guideline now recommends awareness of increased CVD risk and comprehensive risk assessment in PCOS to help mitigate the burden of CVD in this common and high-risk condition.