Association between anti-mullerian hormone and metabolic syndrome: insights from a prospective community-based study.

BACKGROUND: Limited studies have investigated the relationship between Anti-Müllerian hormone (AMH) and metabolic syndrome (MetS), yielding inconclusive results. This study aimed to examine the relationship between AMH levels and MetS and its components in women from a general population. METHODS: This prospective study recruited 769 women. Generalized Estimating Equation (GEE) models analyzed longitudinal trends of MetS components. Cox proportional hazard models evaluated effect of age-specific AMH tertiles on MetS occurrence, adjusting for confounders. RESULTS: The GEE analysis indicated that women in the third tertile exhibited higher mean FPG compared to those in the first tertile of age-specific AMH (3 mg/dL; 95% CI: 0.40, 5.60; P = 0.024); however, this association became non-significant after adjustment. Notably, the second tertile showed a significant decrease in FPG mean changes over time (-0.69 mg/dL; 95% CI: -1.31, -0.07; P Interaction = 0.030). Women in the second and third tertiles of age-specific AMH demonstrated lower mean HDL-C compared to the first tertile (-2.96 mg/dL; 95% CI: -4.67, -1.26; P < 0.001 and -2.63 mg/dL; 95% CI: -4.31, -0.96; P = 0.002, respectively). The association between HDL-C changes and the second tertile remained significant after adjustment (-1.91 mg/dL; 95% CI: -3.68, -0.14; P = 0.034). No significant associations were observed between age-specific AMH tertiles and TG and SBP/DBP. Cox models revealed no significant differences in the hazard ratio of MetS between AMH tertiles after adjusting for confounders. CONCLUSION: Despite minor variations in MetS components, AMH levels did not affect MetS risk in women from a general population.

To what extent the weight changes impact the risk of hypertension among menopausal women: insights from Tehran lipid and glucose study.

BACKGROUND & AIM: The association between weight change and incident hypertension (HTN) in menopausal women has not been well characterized. This study aimed to determine whether weight changes after menopausal years make a difference in incidents of hypertension. MATERIALS & METHODS: This population-based study was performed using data collected from Tehran Lipid and Glucose Study cohort (1999-2018). Women who had natural and early menopause were followed up every 3 years. Data gathering was performed through the standard protocol of the study. Statistical analysis was performed using multivariable Cox hazard regression analysis. We used the 'survival' package in the R software version 3.6.0 to fit survival models. RESULTS: A total of 487 menopausal women met the inclusion criteria; 62.6% had natural menopause and remained had early menopause. Among the participants, 65.5% experienced HTN. The highest proportion of participants had > 5% weight gain, while the lowest had 3-5% weight gain. Either losing body weight (lost > 5%: HR: 0.44; CI 95%, 0.32, 0.62; p < 0.001), (lost 3-5%; HR: 0.47; CI 95%, 0.26, 0.84; p = 0.01), and weight gain > 5% (HR: 0.69; CI 95%, 0.51, 0.91; p = 0.01), were associated with decreased risk of HTN after adjustment for confounders. In this study, weight loss and gain have a protective impact on the development of HTN in subjects. For incident HTN, age (HR: 1.04 (1.01, 1.08), p = 0.004), fasting blood glucose (HR: 1.01, CI 95%:1.00, 1.01; p < 0.001), body mass index (1.02 (1.00, 1.05), p = 0.03) and smoking (1.70 (1.11, 2.58), p = 0.01) were positively associated with HTN. CONCLUSIONS: Our study indicates the significant association of weight change with hypertension risk in later life among menopausal women.

Lack of beneficiary effect of levothyroxine therapy of pregnant women with subclinical hypothyroidism in terms of neurodevelopment of their offspring.

PURPOSE: Despite the beneficial effects of levothyroxine (LT4) therapy on pregnancy outcomes of women with subclinical hypothyroidism (SCH), its impact on the developmental status of offspring remains unclear. We aimed to assess the effects of LT4 therapy on the neurodevelopment of infants of SCH women in the first 3 years of life. METHODS: A follow-up study was conducted on children born to SCH pregnant women who had participated in a single-blind randomized clinical trial (Tehran Thyroid and Pregnancy Study). In this follow-up study, 357 children of SCH mothers were randomly assigned to SCH + LT4 (treated with LT4 after the first prenatal visit and throughout pregnancy) and SCH-LT4 groups. Children born of euthyroid TPOAb-women served as the control group (n = 737). The neurodevelopment status of children was assessed in five domains (communication, gross motor, fine motor, problem-solving, and social-personal domains) using the Ages and Stages Questionnaires (ASQ) at the age of 3 years. RESULTS: Pairwise comparisons of ASQ domains between euthyroid, SCH + LT4, and SCH-LT4 groups show no statistically significant difference between groups in the total score [median 25-75 total score: 265 (240-280); 270 (245-285); and 265 (245-285); P-value = 0.2, respectively]. The reanalyzing data using the TSH cutoff value of 4.0 mIU/L indicated no significant difference between groups in the score of ASQ in each domain or total score with TSH levels < 4.0 mIU/L, however, a statistically significant difference in the median score of the gross motor was observed between those SCH + LT4 with baseline TSH values ≥ 4.0 mIU/L and SCH-LT4 [60 (55-60) vs. 57.5 (50-60); P = 0.01]. CONCLUSIONS: Our study does not support the beneficiary effect of LT4 therapy for SCH pregnant women in terms of the neurological development of their offspring in the first three years of life.

Reduction of ovarian reserves and activation of necroptosis to in vivo air pollution exposures.

We investigated the association between air pollution and changes in ovarian follicles, anti-mullerian hormone (AMH) levels, the occurrence of necroptosis cell death by activation of receptor-interacting protein kinase 3 (RIPK3) and, the activation of mixed lineage kinase domain-like (MLKL) proteins. Forty-two female Wistar rats were divided into three groups of 14 each, which were exposed to real-ambient air, filtered air and purified air (control) in two periods of 3 and 5 months. The results showed that the number of ovarian follicles decreased in the group exposed to real-ambient air versus the control group (P < 0.0001). The trend of age-related AMH changes with respect to exposure to air pollutants was affected and its levels decreased after 3 months of exposure. The MLKL increased in the group exposed to the real-ambient air compared to the control group (P = 0.033). Apparently long-term exposure to air pollution can reduce ovarian reserves.

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.

The relationship of reproductive factors with adiposity and body shape indices changes overtime: findings from a community-based study.

BACKGROUND: Studies focusing on the relationships of adiposity and body shape indices with reproductive factors have reported conflicting results. This study aimed to investigate the influence of reproductive factors on adiposity and body shape indices changes overtime. MATERIALS AND METHODS: In this community-based prospective study, 1636 postmenopausal women were selected from Tehran Lipid and Glucose Study (TLGS). The unadjusted and adjusted Generalized Estimating Equation models (GEE) were applied to investigate secular longitudinal trends of adiposity and body shape indices. RESULTS: According to the adjusted GEE models, mean changes in body mass index (BMI) in women with early menarche was 1.18 kg/m2 higher than those with normal menarche age (P = 0.030). Moreover, the mean changes in BMI overtime were 0.11 kg/m2 higher in women with premature/early menopausal age than those with normal menopausal age (P = 0.012). Mean changes of waist circumference (WC) in women with late menopause were 2.27 cm higher than those with normal menopausal age (P = 0.036). We also observed higher mean changes in a body shape index (ABSI) in women with late menopause (P = 0.037), compared to those with normal menopausal age. We found a marginal effect of parity on BMI and WC as well. CONCLUSIONS: This study demonstrated higher BMI in females with earlier menarche age. We also showed higher values of BMI overtime in women with premature/ early menopause, whereas women with late menopausal age had higher WC and ABSI values. However, more longitudinal studies investigating body composition indices by adjusting all potential confounders are still required to confirm our study findings.

Lactation duration and lifetime progression to metabolic syndrome in women according to their history of gestational diabetes: a prospective longitudinal community-based cohort study.

BACKGROUND: Despite the many signs of progress in pharmacotherapies, metabolic syndrome (MetS) is one of the main public-health burdens worldwide. Our study aimed to compare the effect of breastfeeding (BF) in women with and without gestational diabetes mellitus (GDM) on MetS incidence. METHODS: Of females who participated in the Tehran Lipid and glucose study, women who met our inclusion criteria were selected. The Cox proportional hazards regression model, with adjustment of potential confounders, was done to evaluate the relationship between duration of BF and incident of MetS in women with a GDM history compared to non-GDM. RESULTS: Out of 1176 women, there were 1001 non-GDM and 175 GDM. The median follow-up was 16.3 (11.9, 19.3) years. Results of the adjusted model illustrated that the total BF duration was negatively associated with MetS incidence risk (hazard ratio (HR) 0.98, 95% CI 0.98-0.99) in total participants indicating that per one-month increase of BF duration, the hazard of MetS reduced by 2%. The HR of MetS in Comparison between GDM and non-GDM women demonstrated significantly more reduced MetS incidence with a longer duration of exclusive BF (HR 0.93, 95% CI 0.88-0.98). CONCLUSIONS: Our findings illustrated the protective effect of BF, especially exclusive BF, on MetS incidence risk. BF is more effective in reducing the risk of MetS among women with a history of GDM than among women without such a history.

Adolescents' polycystic ovary syndrome health-related quality of life questionnaire (APQ-20): development and psychometric properties.

Several health-related quality of life (HRQOL) questionnaires for adults with polycystic ovary syndrome (PCOS) have been developed so far. However, an adolescent-specific HRQOL questionnaire for PCOS patients is still lacking. Hence, this study aimed to develop and validate a questionnaire to assess HRQOL in adolescents with PCOS. This mixed-method study was conducted in Tehran, Iran, from 2018 to 2020. The qualitative phase was conducted on 18 target participants, and in the quantitative phase, exploratory factor analysis (EFA) was performed on 200 adolescents with PCOS and confirmatory factor analyses (CFA) on the other 200 ones. The item-developing process was finalized with 77 questions. Concerning the optimum cutoff of content validity ratio, content validity index, kappa statistic coefficient, and item impact score, a draft with 55 items was finalized. Then, piloting scale was performed on 40 participants and considering the interitem correlation < 0.3, fifteen items were excluded. Based on the EFA, 20 items in six components (emotion and mood, loss of attractiveness due to the hirsutism, loss of attractiveness due to the acne, self-care, support, and menstrual cycle problem) that explain 60.3% of the variance were extracted. The CFA with acceptable values of goodness-of-fit statistics supports this construct validity. Results of reliability, floor, and ceiling effect were acceptable.  Conclusion: Our study showed that the short questionnaire of APQ-20 is valid and reliable for assessment of the HRQOL of adolescents with PCOS. Further studies are needed to assess the feasibility and reliability of APQ-20 for assessing the HRQOL of adolescents with PCOS. It constitutes a significant step forward in the measurement of HRQOL of adolescents with PCOS. What is Known: • There is no disease-specific questionnaire for assessment of the health-related quality of life (HRQOL) of adolescents with polycystic ovary syndrome (PCOS). What is New: • The short questionnaire of APQ-20 is easy to use, valid, and reliable for the assessment of the HRQOL of adolescents with PCOS. • APQ-20 constitutes a significant step forward in the measurement of HRQOL of adolescents with PCOS.

Parity and hypertension risk in couples: does number of parity matter: findings from Tehran Lipid and Glucose Study.

BACKGROUND AND AIMS: As reported, hypertension (HTN) plays a leading role in explaining mortality worldwide, but it still has many confounding factors. This study explored whether the number of parity and age matters for HTN among couples from the Tehran Lipid and Glucose Study (TLGS). METHODS: This study was conducted on 2851 couples from TLGS. All the variables were collected based on the standard protocol. The participants were categorized into four and five categories according to the number of parity (childless, one, two, three, or more parities) and age (18-30y, 30-40y, 40-50y, 50-60y, and 60-70y), respectively. Spline regression models via log link function for the binary outcome and linear link function for continuous outcomes were applied to evaluate the effect of interaction term age and parity categories on the desired outcome. RESULTS: Among the total of 2851 pairs, 2.3% had no child, 9.5% had 1 child, 38.4% had 2 children, and 49.8% had ≥ 3 children. The adjusted risk (95% CI) of HTN in females aged 40-50y with 1 child, 2 and ≥ 3 children compared to no child were 1.14(1.04, 1.26), 1.05(1.01, 1.10), 1.12(1.07, 1.17), respectively (p < 0.05). Moreover, in those aged 50-60y with 2 and ≥ 3 children, the risk of HTN significantly increased by 4%. In females aged 60-70y with ≥ 3 children compared to those without children, the risk of HTN increased by 2%. For males aged 30-40y with 2 children compared to the no child group, the adjusted risk of HTN increased by 17%, while for those with ≥ 3 children in the same age group, this risk significantly decreased by 13%. Moreover, in males aged 30-40y with 2 children, risk ratio of HTN increased by 17%, but in males with ≥ 3 children, it decreased by 13% and in those in the same groups but aged 40-50y the risk increased by 6% and 11%, respectively. CONCLUSION: Our findings suggest that gender, childlessness, having one child, and multi-parity had different impacts on HTN. Further research is needed to confirm our findings.

Maternal androgen excess increases the risk of metabolic syndrome in female offspring in their later life: A long-term population-based follow-up study.

PURPOSE: Hyperandrogenic intrauterine environment may lead to the development of metabolic disorders in offspring in their later life. In this study, we aimed to determine the impact of maternal hyperandrogenism (MHA) on metabolic syndrome (MetS) risk in female offspring in their later life. METHODS: In this cohort study conducted in Tehran, Iran, female offspring with MHA (n = 323) and without MHA (controls) (n = 1125) were selected. Both groups of female offspring were followed from the baseline to the date of the incidence of events, censoring, or end of the study period, whichever came first. We used age-scaled unadjusted and adjusted Cox regression models to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MHA and MetS in female offspring. The software package STATA was used for statistical analysis, and the significance level was set at P < 0.05. RESULTS: We observed a higher risk of MetS (unadjusted HR (95% CI), 1.36 (1.05-1.77)), (P = 0.02) and (adjusted HR (95% CI), 1.34 (1.00-1.80)), (P = 0.05, borderline)), in female offspring with MHA, compared to controls. The results were adjusted for the potential confounders including body mass index (BMI) at baseline, net changes of BMI, physical activity, education status, and birth weight. CONCLUSION: Our results suggest that MHA increases the risk of developing MetS in female offspring in their later life. Screening of these female offspring for MetS may be recommended.

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.

Health-related quality of life in women with various levels of spiritual health.

This study investigates for the first time the relationship between spiritual health (SH) and health-related quality of life (HRQoL) in different periods of life in healthy women, which could be important in the current critical post-pandemic situation. We recruited data from 2238 healthy women in the Tehran Lipid and Glucose Study (TLGS) framework, performed a cross-sectional study, and divided them into four age groups: 1) 20-34, 2) 35-44, 3) 45-54, and 4) 55≤ years. HRQoL and SH were measured using Short-Form 12-Item Health Survey version 2 and spiritual health inventory in Muslim adults (SHIMA-48). We defined low and high SH as the first and third tertile of SHIMA-48 scores. Most participants were in the first age group (39 percent), were married (74.7 percent), and were housewives (74.7 percent). The mean mental component summary score and its domains were directly associated with age. This subscale was significantly higher in individuals with high SH scores in all age groups. However, except for general health, other physical subscales did not differ significantly between the two levels of SH among the age groups studied. Results indicate higher HRQoL, especially mental health, in healthy women with increased spiritual well-being. This finding can be used in programs to improve psychological health in women.

Polycystic ovary syndrome and body image concerns during adolescence.

PURPOSE: This study aimed to compare body image concerns in adolescents with and without PCOS. DESIGN AND METHODS: This cross-sectional study included 1076 adolescents, including 344 with PCOS and 732 without PCOS. The participants were asked to complete a comprehensive questionnaire that included demographic and reproductive parameters and the body image concerns inventory (BICI) which comprised two factors (1-dissatisfaction and embarrassment about one's appearance and 2-social function due to appearance concerns). Linear regression analysis was conducted to evaluate the effect of hyperandrogenism and/or abnormal uterine bleeding (AUB) and/or obesity on BICI and its domains both before and after adjustment for potential confounders. RESULTS: The result showed that adolescents with PCOS had a worse total BICI score and its domains (p < 0.05). In multivariable-adjusted regression models, adolescents with PCOS were more likely to have a high body image concern (ß = 0.05, P < 0.001), while those with high household income were less likely to have body image concern (ß = -0.08, P = 0.004). Considering hyperandrogenism status, those with high household income were also less likely to have high body image concern (ß = -0.08, P = 0.004), and age of menarche (ß = -0.01, P = 0.013) were also inversely associated with total BICI score. Likewise, considering obese status, only high household income (ß = -0.08, P = 0.004) was inversely associated with total BICI score. Also, considering menstrual irregularity status, high household income (ß = -0.08, P = 0.005), and age of menarche (ß = -0.01, P = 0.01) were inversely associated with the total BICI score. CONCLUSION: Adolescents with PCOS had higher body image concerns. Apart from the being PCOS label, abnormal uterine bleeding was also a predictor of body image concern. PRACTICAL IMPLICATIONS: Clinicians should pay attention to the greater influence of the PCOS label on altered body image in adolescents.

Altered expression of leukemia inhibitory factor (LIF), LIFR, gp130, and IL11 in the embryo implantation site of rat model with prenatal androgen-induced polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that represents infertility in many reproductive-age women. Reduced implantation of blastocyst was proposed as an etiology for infertility in this syndrome. In this regard, many candidate genes such as leukemia inhibitory factor (LIF), LIF receptor (LIFR), glycoprotein 130 (gp130), and interleukin 11 (IL11) were proposed to be disrupted. Investigation of these genes is not ethically approved in pregnant women with PCOS. In this study, we aimed to compare the expression of LIF, LIFR, gp130, and IL11 before and during different gestational days in uterine tissues of prenatally-androgenized rat models of PCOS with control rats. The rat model of polycystic ovary syndrome was created by the injection of testosterone during prenatal life. RNA extraction and cDNA synthesis from uterine tissues were performed in both prenatal induced PCOS and control rats. Expression of LIF, LIFR, gp130, and IL11 genes was compared before pregnancy (GD0) and during pregnancy on GD0.5, GD4.5, GD5.5, and GD8.5 between two study groups (n = 6 each group) using SYBR Green real-time PCR. The expression of the LIF mRNAs significantly decreased on GD4.5, 5.5, and 8.5 in the PCOS rats compared to the controls (P-values: 0.0483, 0.0152, and 0.0043). Additionally, decreased expression of LIFR and gp130 was observed on GD0.5 to 8.5 in PCOS rats compared to controls (P-values: 0.022, 0.0480, 0.0043, 0.0022 for LIFR and 0.0189, 0.0022, 0.0087, 0.0022 for gp130). Moreover, IL-11 mRNA levels decreased in the PCOS group compared to their controls both before (P-value:0.0362) and during the gestational period (P-values:0.0085, 0.0043, 0.0389, 0.0087). Reduced expression of LIF, LIFR, gp130, and IL11 in the rats with PCOS indicates a possible disruption in the implantation and decidualization stages in this syndrome.

Pregnancy loss and subsequent risk of prediabetes, diabetes and metabolic syndrome in couples: Tehran lipid and glucose study.

BACKGROUND: There is limited evidence regarding the impact of pregnancy loss on the subsequent risk of metabolic disorders. We aimed to investigate whether history of pregnancy loss is associated with the subsequent risk of prediabetes (pre-DM), diabetes (DM), and metabolic syndrome (METs) among couples. METHOD: In this population-based cohort study, 2765 couples with and without history of pregnancy loss and free of DM, pre-DM, and METs at baseline were included and followed for incidents of DM, pre-DM, and METs by 3-year intervals visits from 1999 to 2018. Detailed data of variables was collected using standard questionnaires, interviews, clinical and laboratory assessments. A modified Poisson regression for binary outcome data with a log link function and robust error variance was used to estimate relative risks (RRs) in couples with and without history of pregnancy loss. Both unadjusted and adjusted models were fitted, and effect measures were calculated. RESULT: During a median follow-up of 15 years, females with history of pregnancy loss were experienced more pre-DM (50% vs. 45.5%), DM (28.9% vs. 21.3%), and METs (70% vs. 60.1%) than females without such history. Moreover, history of pregnancy loss increased the risk of METs by 8% among females. The incidence of DM in males with history of pregnancy loss in their spouses was higher than in males without it (28.8% vs. 23.5%). Among males, having a spouse with history of pregnancy loss was positively associated with the risk of pre-DM (RR = 1.12; 95%CI: 1.02, 1.23, p = 0.02); furthermore, they were more prone to the risk of METs than females with a history of pregnancy loss (RR = 1.13; 95%CI: 1.07, 1.20, p < 0.001). CONCLUSION: Although pregnancy loss is a female-specific factor, may foreshadow the subsequent METs, our study identified a higher risk of subsequent pre-DM and METs in males with history of pregnancy loss in their spouses. Pregnancy loss could be considered a possible future risk factor for metabolic disorders in couples.

Ovarian expression of follicle stimulating hormone and activin receptors genes in a prenatally-androgenized rat model of polycystic ovary syndrome in adulthood.

BACKGROUND: The expression of genes involved in basic pathways, such as folliculogenesis and steroidogenesis may be affected following prenatal androgen exposure. Besides, exposure to androgens during prenatal life plays a central role in developing polycystic ovary syndrome (PCOS) in females in later life. In the present study, we aimed to examine the expression of the follicle stimulating hormone receptor (FSHR) and activin receptor (actR) genes in ovarian granulosa cells (GCs) of a prenatally-androgenized rat model of PCOS in adulthood. METHODS AND RESULTS: In the adult rat model of PCOS and their controls (n = 8 in each group), different phases of the estrous cycle were determined by vaginal smear. Total RNA was extracted from the ovarian GCs using the TRIzol protocol, a reverse transcription kit was used for complementary DNA (cDNA) synthesis, and the expression of FSHR and actR genes was measured by SYBR-Green Real-Time PCR. GraphPad Prism was used for statistical analysis of data, and the t-Student's test was used to compare the results between the two groups. PCOS rats had longer and irregular estrous cycles compared to controls. The expression of FSHR and actR genes were significantly decreased in the rat model of PCOS compared to control rats. In PCOS rats, genes expression ratios for FSHR and actR were 0.91 ± 0.11 times (P = 0.008) and 0.42 ± 0.13 times (P = 0.048) less than controls, respectively. CONCLUSION: Reduced expression of the FSHR and actR genes in ovarian GCs may be one of the mechanisms mediating PCOS-related disorders, especially abnormal ovarian folliculogenesis and ovulation dysfunction, following exposure to androgens during fetal life.

Is there any association between migraine headache and polycystic ovary syndrome (PCOS)? A review article.

BACKGROUND: Polycystic ovary syndrome (PCOS) and migraine headaches are considered to be common health problems that may share some risk factors. This study aimed to discuss the possible association between migraine headache and polycystic ovary syndrome. METHODS AND RESULTS: In this narrative review, PubMed, Scopus, Web of Science, and Google Scholar were systematically searched for retrieving and summarizing published studies up to January 2021 to explore the possible interplay between migraine headache and PCOS. We discuss the possible pathways that may explain the association between migraine headaches and PCOS signs/symptoms and complications. While genetic factors have profound effects on the pathogenesis of migraine headaches, sex hormones, including estrogen and progesterone may also play an important role in inducing migraine headaches. Some disorders, such as sleep apnea, amenorrhea, and vascular disease that are more likely to occur in women with PCOS, may cause or exacerbate migraine headaches in women with PCOS. CONCLUSIONS: Future comprehensive studies are needed to investigate the exact underlining mechanisms related to the association between PCOS and migraine headaches.

The effects of different physiologic concentrations of prolactin in association with reproductive hormones on the incidence of type 2 diabetes mellitus in men: Tehran Lipid and Glucose Study.

BACKGROUND: Data is inconsistent and, for the most part, not sufficient to demonstrate the association between serum Prolactin (PRL) concentration within the physiologic range and the incidence rate of type 2 Diabetes Mellitus (DM) among men. Moreover, since both PRL and type 2 DM are associated with reproductive hormones, investigating these hormones might improve our understanding of how PRL might impose its effect on the incidence rate of type 2 DM. METHODS: For the present study, 652 eligible men aged 29-70 with a normal baseline PRL concentration were selected from the Tehran Lipid and Glucose Study (TLGS). Participants were sub-classified into three groups (tertiles) according to the serum concentration of PRL and were followed for 15.8 years. The incidence of type 2 DM and PRL, LH, FSH, testosterone, and AMH concentrations were measured. The effect of hormonal variables on the incidence of type 2 DM was estimated using the log-binomial model, adjusted for major confounding factors. The correlations between PRL and the indicators of glucose and lipid metabolism and other hormonal variables were also explored. RESULTS: In the unadjusted model, PRL was not significantly associated with the incidence rate of type 2 DM (RR = 0.98, 95% CI: 0.94 - 1.03). After adjusting for potential confounders, the inverse effect of AMH on the incidence rate of type 2 DM was the only significant association. The analyses also indicated a significant positive association between PRL and LH/FSH ratio (r = 0.1, P = 0.01). CONCLUSION: No significant association was found between serum PRL concentrations within the physiologic range and the incidence rate of type 2 diabetes mellitus among middle-aged men. Men with higher concentrations of PRL within the physiologic range tended to show higher levels of LH and LH/FSH. AMH was the only variable significantly linked to the incidence rate of type 2 DM in men.

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.

Bone Health in Women With Polycystic Ovary Syndrome: A Narrative Review.

Bone as an active connective and endocrine tissue is influenced by hormones, physical activity, inflammatory factors, minerals, dietary components, and body weight. Bone fractures are a major cause of decreased quality of life and mortality in humans. Polycystic ovary syndrome (PCOS), is one of the most common endocrine disorders in women of reproductive age worldwide. PCOS is associated with disturbances in androgen and estrogen levels, insulin resistance (IR), obesity, as well as low-grade chronic inflammation, and gut microbiota (GM) dysbiosis, all of which may negatively or positively affect bone metabolism. However, it has not yet been well clarified whether PCOS is bone-protective or bone-destructive. This study aimed to review the association between bone health and PCOS, and summarize its related factors. PubMed, Scopus, and Web of Science databases were searched to retrieve relevant English publications investigating the relationship between bone health and PCOS. Several disorders associated with PCOS can negatively or positively affect bone metabolism. Despite some positive effects of insulin, androgens, estrogens, and obesity on bone, IR, estrogen deficiency, low-grade chronic inflammation, and GM dysbiosis may adversely affect the bone metabolism in PCOS women. Studies comparing bone mineral density or bone metabolism and the risk of bone fractures in women with PCOS have controversial results. Further studies are required to understand the mechanisms underlying bone metabolism in PCOS subjects. Moreover, prospective studies are needed to estimate the risk of bone fractures and osteoporosis in PCOS subjects.