A survey on functional constipation and its risk factors in older people in Shahreza, Iran.

BACKGROUND: Functional constipation is prevalent among older people. It has major effects on the quality of life of them, as well as the high costs of treatment. This study investigated functional constipation and risk factors affecting older people living in Shahreza, Iran. MATERIALS AND METHODS: This cross-sectional study was performed on 200 older people in Shahreza. They were selected by simple random sampling. We used the Rome III Criteria, the Elderly Physical Activity Questionnaire (PASE), and related questions from the SIB system (integrated health system). After completing the questionnaires, the data were analyzed using the mean and standard deviation, Chi-square test, independent-samples t-test, Fisher's exact test, and Mann-Whitney test. RESULTS: The prevalence of functional constipation was 45%. There are significant relationships between functional constipation with dental problems (P = 0.02), intake of fluid (P = 0.001), fruits (P = 0.001), and vegetables (P < 0.001), polypharmacy (P = 0.003), and antidepressants (P = 0.008), history of colon (P = 0.003) and anal (P = 0.001) diseases, stroke or mobility disabilities (P = 0.002), the level of physical activity (P = 0.002), and gender (P = 0.04) in older people living in Shahreza. CONCLUSIONS: According to the high prevalence of functional constipation in the studied older people, it is necessary to focus on controlling risk factors and planning to prevent the destructive effects of social restrictions on older people during the coronavirus disease 2019 (COVID-19) pandemic.

Nano-delivery of Silibinin Potentiate the Induction of Immunogenic Cell Death (ICD) in Melanoma Cells.

BACKGROUND: Induction of immunogenic cell death (ICD) in tumors can enhance antitumor immunity and modulate immunosuppression in the tumor microenvironment (TME). OBJECTIVE: In the current study, we investigated the effect of silibinin, a natural compound with anticancer activity, and its polymer-based nanoformulations on the induction of apoptosis and ICD in cancer cells. METHODS: Free and nanoparticulate silibinin were evaluated for their growth-inhibitory effects using an MTT assay. Annexin V/PI staining was used to analyze apoptosis. Calreticulin (CRT) expression was measured by flow cytometry. Western blotting was conducted to examine the levels of elf2α, which plays a role in the ICD pathway. The HSP90 and ATP levels were determined using specific detection kits. RESULTS: Compared to the free drug, silibinin-loaded nanocarriers significantly increased the induction of apoptosis and ICD in B16F10 cells. ICD induction was characterized by significantly increased levels of ICD biomarkers, including CRT, HSP90, and ATP. We also observed an increased expression of p-elf-2α/ elf-2α in B16F10 cells treated with silibinin-loaded micelles compared to cells that received free silibinin. CONCLUSION: Our findings showed that the encapsulation of silibinin in polymeric nanocarriers can potentiate the effects of this drug on the induction of apoptosis and ICD in B16F10 melanoma cells.

A prospective study on the relationship between polycystic ovary syndrome and age at natural menopause.

OBJECTIVE: This study aimed to determine whether polycystic ovary syndrome (PCOS) was associated with age at menopause, compared with women without PCOS, after adjusting for potential confounders. METHODS: A total of 1,696 reproductive-aged participants from the Tehran Lipid and Glucose Study were included in this population-based prospective study with a follow-up of approximately 20 years. Of these, 348 women with PCOS based on the Rotterdam criteria and 1,348 non-PCOS controls were followed to assess the age at which they reached menopause. An accelerated failure time survival regression model was used to identify the association between PCOS and the age at natural menopause (ANM), with and without adjustment for potential confounders. RESULTS: The unadjusted accelerated failure time survival model revealed a significant positive association between PCOS and ANM; PCOS women experienced time to menopause by a factor of 1.05 than non-PCOS controls (95% confidence interval, 1.02-1.06; P < 0.001). After adjusting for age at baseline, menarche age, history of hypertension, history of type 2 diabetes mellitus, parity, oral contraceptive use, body mass index, education level, physical activity, and smoking, the results remained significant (time ratio: 1.03; 95% confidence interval, 1.01-1.06; P = 0.002). CONCLUSIONS: This study indicates that ANM is significantly associated with PCOS in women. Our study findings may have implications for the fertility and reproductive health of women with PCOS. However, further large longitudinal studies on diverse populations accounting for other relevant confounders are still needed to provide data on the actual difference in age at menopause and to elucidate the underlying mechanisms of this association.

Stimulators of immunogenic cell death for cancer therapy: focusing on natural compounds.

A growing body of evidence indicates that the anticancer effect of the immune system can be activated by the immunogenic modulation of dying cancer cells. Cancer cell death, as a result of the activation of an immunomodulatory response, is called immunogenic cell death (ICD). This regulated cell death occurs because of increased immunogenicity of cancer cells undergoing ICD. ICD plays a crucial role in stimulating immune system activity in cancer therapy. ICD can therefore be an innovative route to improve anticancer immune responses associated with releasing damage-associated molecular patterns (DAMPs). Several conventional and chemotherapeutics, as well as preclinically investigated compounds from natural sources, possess immunostimulatory properties by ICD induction. Natural compounds have gained much interest in cancer therapy owing to their low toxicity, low cost, and inhibiting cancer cells by interfering with different mechanisms, which are critical in cancer progression. Therefore, identifying natural compounds with ICD-inducing potency presents agents with promising potential in cancer immunotherapy. Naturally derived compounds are believed to act as immunoadjuvants because they elicit cancer stress responses and DAMPs. Acute exposure to DAMP molecules can activate antigen-presenting cells (APCs), such as dendritic cells (DCs), which leads to downstream events by cytotoxic T lymphocytes (CTLs) and natural killer cells (NKs). Natural compounds as inducers of ICD may be an interesting approach to ICD induction; however, parameters that determine whether a compound can be used as an ICD inducer should be elucidated. Here, we aimed to discuss the impact of multiple ICD inducers, mainly focusing on natural agents, including plant-derived, marine molecules, and bacterial-based compounds, on the release of DAMP molecules and the activation of the corresponding signaling cascades triggering immune responses. In addition, the potential of synthetic agents for triggering ICD is also discussed.

Predictors of decline in kidney function in the general population: a decade of follow-up from the Tehran Lipid and Glucose Study.

BACKGROUND AND AIMS: We aimed to assess the potential socio-demographic, clinical, and lifestyle-related risk factors for kidney function decline (KFD), defined as ≥30% estimated glomerular filtration rate (eGFR) decline, in an Iranian cohort study. METHODS: 7190 participants (4049 women) aged 20-90 years with 2-5 eGFR data from examinations (2001-2005 to 2015-2018) were included. Cox proportional hazard models were used to examine the association between potential risk factors and eGFR decline. RESULTS: During 11.5 years of follow-up, 1471 (889 women) participants had incident KFD with a crude incidence rate of 192.1 (182.6-202.2) per 10,000 person-year. Among the total population, older age, female gender, prehypertension, hypertension, diabetes, widowed/divorced states, higher triglycerides (TG), prevalent cardiovascular diseases (CVD), and higher baseline eGFR were significantly associated with higher, while moderate physical activity and a positive family history of diabetes were associated with lower risk of KFD (all p values <.05). Prevalent CVD in women but not men, diabetes, and hypertension among postmenopausal than premenopausal women were significant risk factors of KFD. According to the presence of chronic kidney disease (CKD) at baseline, higher eGFR decreased the risk of KFD in patients with CKD and increased KFD risk in those without CKD (all p for interactions <.05). CONCLUSION: KFD is associated with multiple modifiable risk factors among the Iranian urban population that is affected by gender, menopausal status, and initial kidney function. Interventions targeting these factors might potentially help reduce the burden of KFD.Key messages:Menopausal status may influence the relationship between cardiometabolic risk factors and KFD;The impact of higher baseline eGFR on the risk of KFD differed between subjects with preserved kidney function and CKD patients.The interaction between gender, menopausal status, and baseline kidney function with different risk factors on KFD may help to make renal risk prediction scores to identify those in the general population at risk who may benefit from early prevention.

Anti-Mullerian hormone and cardiometabolic status: a systematic review.

BACKGROUND: To summarise the relationship between Anti-mullerian hormone (AMH) levels and cardiometabolic status in different populations. METHODS: PubMed, Scopus, and Embase were searched for retrieving observational studies published up to February 2022 investigating the relationship between AMH level and cardiometabolic status. RESULTS: Of 3,643 studies retrieved from databases, a total of 37 observational studies were included in this review. The majority of the included studies revealed an inverse association between AMH and lipid profiles, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), and a positive correlation with high-density lipoprotein (HDL). While some studies have revealed a significant inverse association between AMH and glycemic parameters, including fasting plasma glucose (FPG), fasting insulin, and HOMA-IR, others found no such relationships. There is also an inconsistency among studies regarding the association of AMH with adiposity indices and blood pressure. Evidence indicates a significant association between AMH and some vascular markers, such as intima-media thickness and coronary artery calcification. Of 3 studies evaluating the relationship between AMH and cardiovascular events, two studies showed an inverse relationship between AMH levels and cardiovascular (CVD), whereas another study showed no significant association. CONCLUSIONS: The results of this systematic review suggest that serum AMH levels can be associated with CVD risk. This may provide new insight into the use of AMH concentrations as a predictive marker for assessing the risk of cardiovascular disease, although more well-design longitudinal studies are still necessary for this area. Future studies on this topic will hopefully provide an opportunity to run a meta-analysis; it will increase the persuasiveness of this interpretation.

Adipose Tissue Dysfunction in Polycystic Ovary Syndrome.

PURPOSE: Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women globally, with associated cardiometabolic dysfunction. Adipose tissue (AT) dysfunction appears to play an important role in the pathophysiology of PCOS even in patients who do not have excess adiposity. METHODS: We undertook a systematic review concerning AT dysfunction in PCOS, and prioritized studies that assessed AT function directly. We also explored therapies that targeted AT dysfunction for the treatment of PCOS. RESULTS: Various mechanisms of AT dysfunction in PCOS were identified including dysregulation in storage capacity, hypoxia, and hyperplasia; impaired adipogenesis; impaired insulin signaling and glucose transport; dysregulated lipolysis and nonesterified free fatty acids (NEFAs) kinetics; adipokine and cytokine dysregulation and subacute inflammation; epigenetic dysregulation; and mitochondrial dysfunction and endoplasmic reticulum and oxidative stress. Decreased glucose transporter-4 expression and content in adipocytes, leading to decreased insulin-mediated glucose transport in AT, was a consistent abnormality despite no alterations in insulin binding or in IRS/PI3K/Akt signaling. Adiponectin secretion in response to cytokines/chemokines is affected in PCOS compared to controls. Interestingly, epigenetic modulation via DNA methylation and microRNA regulation appears to be important mechanisms underlying AT dysfunction in PCOS. CONCLUSION: AT dysfunction, more than AT distribution and excess adiposity, contributes to the metabolic and inflammation abnormalities of PCOS. Nonetheless, many studies provided contradictory, unclear, or limited data, highlighting the urgent need for additional research in this important field.

Does fasting plasma glucose values 5.1-5.6 mmol/l in the first trimester of gestation a matter?

Objectives: The aim of the study was to investigate the effect of treatment on pregnancy outcomes among women who had fasting plasma glucose (FPG) 5.1-5.6 mmol/l in the first trimester of pregnancy. Methods: We performed a secondary-analysis of a randomized community non-inferiority trial of gestational diabetes mellitus (GDM) screening. All pregnant women with FPG values range 5.1-5.6 mmol/l in the first trimester of gestation were included in the present study (n=3297) and classified to either the (i) intervention group who received treatment for GDM along with usual prenatal care (n=1,198), (ii) control group who received usual-prenatal-care (n=2,099). Macrosomia/large for gestational age (LGA) and primary cesarean-section (C-S) were considered as primary-outcomes. A modified-Poisson-regression for binary outcome data with a log link function and robust error variance was used to RR (95%CI) for the associations between GDM status and incidence of pregnancy outcomes. Results: The mean maternal age and BMI of pregnant women in both study groups were similar. There were no statistically significant differences in the adjusted risks of adverse pregnancy outcomes, including macrosomia, primary C-S, preterm birth, hyperbilirubinemia, preeclampsia, NICU-admission, birth trauma, and LBW both groups. Conclusions: It is found that treating women with first-trimester FPG values of 5.1-5.6 mmol/l could not improve adverse pregnancy outcomes including macrosomia, Primary C-S, Preterm birth, hypoglycemia, hypocalcemia, preeclampsia, NICU admission, Birth trauma and LBW. Therefore, extrapolating the FPG cut-off point of the second trimester to the first -which has been proposed by the IADPSG, might therefore not be appropriate. Clinical Trial Registration: https://www.irct.ir/trial/518, identifier IRCT138707081281N1.

Mode of delivery and maternal vitamin D deficiency: an optimized intelligent Bayesian network algorithm analysis of a stratified randomized controlled field trial.

This study aimed to elucidate the algorithm of various influential factors relating to the association between 25-hydroxyvitamin D (25(OH)D) concentration at delivery and mode of delivery. The investigation constituted a secondary analysis using data collected as part of the Khuzestan Vitamin D Deficiency Screening Program in Pregnancy, which is a stratified randomized vitamin D supplementation-controlled trial comprising 1649 eligible pregnant women. The Bayesian Network (BN) method was utilized to determine the association algorithm between diverse influential factors associated with maternal vitamin D and mode of delivery. The optimized intelligent BN algorithm revealed that women presenting with moderate (35.67%; 95% CI: 33.36-37.96) and severe vitamin D deficiency (47.22%; 95% CI: 44.81-49.63) at delivery were more likely to undergo cesarean section than those presenting with normal concentrations of this nutritional hormone (18.62%; 95% CI: 16.74-20.5). The occurrence probabilities of preeclampsia in mothers with normal, moderate, and severe vitamin D deficiency at delivery were (1.5%; 95% CI: 0.92-2.09), (14.01%; 95% CI: 12.33-15.68), and (26.81%; 95% CI: 24.67-28.95), respectively. Additionally, mothers with moderate (11.81%; 95% CI: 10.25-13.36) and severe (27.86%; 95% CI: 25.69-30.02) vitamin D deficiency exhibited a higher probability of preterm delivery in comparison to those presenting with normal concentrations (1.12%; 95% CI: 0.62-1.63). This study demonstrated that the vitamin D status of pregnant women at delivery could directly affect the mode of delivery and indirectly through maternal complications, such as preeclampsia and preterm delivery, leading to a higher occurrence probability of cesarean section.

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.

Idiopathic hirsutism and dyslipidemia: A systematic review, meta-analysis, and meta-regressions.

BACKGROUND: Despite existing several kinds of studies on idiopathic hirsutism (IH) and its association with metabolic disturbances, a limited number of studies have assessed lipid profiles in patients with IH with conflicting and inconclusive results. This study aimed to evaluate the lipid profiles in women with IH, compared to those of polycystic ovary syndrome (PCOS) and healthy controls. MATERIALS AND METHODS: For this systematic review and meta-analysis, PubMed, Scopus, and EMBASE databases were searched to obtain studies published from inception to July 2021 investigating the lipid parameters, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in women with IH, compared to control groups. A meta-regression and subgroup analysis were conducted to explore heterogeneity sources. Publication bias was assessed by the Egger test. RESULTS: Of 209 studies retrieved through searching databases and other sources, a total of 12 studies including 3913 participants were included for the meta-analysis. This meta-analysis showed higher standardized mean difference (SMD) of TC (SMD: 0.09 mg/dl; 95% CI: 0.001, 0.18) and lower SMD of HDL-C (SMD: -0.10 mg/dl; 95% CI: -0.18, -0.02) in women with IH, compared to those of the healthy controls, whereas there were no significant differences in the SMDs of TG and LDL-C between the study groups. This study also revealed no difference in the levels of lipid profiles of women with IH in comparison with PCOS patients, except for TG (SMD: -0.24 mg/dl; 95% CI: -0.46, -0.02). The results of subgroup analysis based on the study design revealed no significant differences in the SMD of lipid parameters between women with IH and healthy controls. We also found no significant difference in the levels of lipid profiles of women with IH versus PCOS patients, except for HDL-C in the subgroup of case-control studies (SMD: 0.18 mg/dl; 95% CI: 0.01, 0.34). CONCLUSION: This study demonstrated that the majority of lipid parameters were not significantly different in women with IH, compared to those of healthy and PCOS controls.

Does the addition of serum antimüllerian hormone concentrations to the Framingham Risk Score and Pooled Cohort Equations improve the prediction of cardiovascular disease?

The current study aimed to examine the added value of serum antimüllerian hormone (AMH) concentration to the Framingham Risk Score (FRS) and Pooled Cohort Equations (PCE) in predicting the risk of cardiovascular disease (CVD) in women of reproductive age. Women 30 years and older were considered eligible for this population-based prospective study. The univariate and multivariate Cox proportional hazard models were used to evaluate the association between the serum concentrations of AMH and the risk of CVD. In the enhanced model, which integrated AMH into FRS and PCE and was adjusted for family history of premature CVD, AMH showed a significant association with the risk of CVD during a 19-year follow-up of 800 women (hazard ratio, 0.77 [95% CI, 0.60-0.99] and hazard ratio, 0.64 [95% CI, 0.48-0.84], respectively). According to the likelihood-ratio test, the addition of AMH measurements to FRS and PCE could significantly improve the risk prediction of CVD ( P = 0.02 and P < 0.001, respectively); however, the integration of this biomarker did not improve the classification of risk categories. The present findings revealed that the addition of serum AMH concentrations to FRS and PCE could potentially improve the risk prediction of CVD.

Maternal Subclinical Hyperthyroidism and Adverse Pregnancy Outcomes: A Systematic Review and Meta-analysis of Observational Studies.

Context: Findings from studies evaluating adverse pregnancy outcomes in pregnant women with subclinical hyperthyroidism are conflicting and inconclusive. Objectives: In this systematic review and meta-analysis, our aim was to evaluate the pooled odds ratio (OR) of adverse pregnancy outcomes in women with subclinical hyperthyroidism, compared to euthyroid women. Data Sources: Scopus, PubMed (including Medline), and Web of Science databases were systemically searched for regaining published studies to January 2022 examining adverse pregnancy outcomes in women with subclinical hyperthyroidism. Study Selection: Outcomes of interest were classified into seven composite outcomes, including hypertensive disorders, preterm delivery, macrosomia/large for gestational age (LGA), pregnancy loss, adverse maternal outcomes, adverse neonatal outcomes, and adverse fetal outcomes. Data Extraction: In this meta-analysis, both fixed and random effect models were used. Publication bias was also evaluated by Egger test and the funnel plot, and the trim and fill method was conducted in case of a significant result, to adjust the bias. Results: Of 202 records retrieved through searching databases, 11 studies were selected for the final analyses. There were no significant differences in pooled ORs of hypertensive disorders, preterm delivery, macrosomia/LGA, and pregnancy loss in pregnant women with subclinical hyperthyroidism, compared to the euthyroid controls. The pooled OR of adverse maternal, neonatal, and fetal outcomes in pregnant women with subclinical hyperthyroidism was not statistically significantly different from that of the euthyroid control group. Conclusions: The current meta-analysis demonstrated that subclinical hyperthyroidism in pregnancy is not related with adverse maternal and fetal outcomes. Therefore, clinicians should be avoided unnecessary treatments for pregnant women with subclinical hyperthyroidism.

Estrogen as a key regulator of energy homeostasis and metabolic health.

Over the last two decades, it has become evident that estrogens preserve the integrity of energy homeostasis at central and peripheral levels. Estrogen deficiency, such as that caused by menopause or ovariectomy, has been linked to obesity and metabolic disorders that can be resolved or reversed by estrogen therapy. 17ß-estradiol (E2), as the major estrogen in the body, primarily regulates energy balance via estrogen receptor alpha (ERα). At the central level, E2 plays its catabolic role predominantly by interacting with hypothalamic arcuate neurons and sending signals via ventromedial hypothalamic neurons to control brown adipose tissue-mediated thermogenesis. In peripheral tissues, several organs, particularly the liver, brown and white adipose tissues, and pancreatic ß cells, have attracted considerable attention. In this review, we focused on the current state of knowledge of "central and peripheral" estrogen signaling in regulating energy balance via "nuclear and extranuclear pathways" in both "females and males". In this context, according to an exploratory approach, we tried to determine the principal estrogen receptor subtype/isoform in each section, the importance of extranuclear-initiated estrogen signaling on metabolic functions, and how sex differences related to ER signaling affect the prevalence of some of the metabolic disorders. Moreover, we discussed the data from a third viewpoint, understanding the clinical significance of estrogen signaling in abnormal metabolic conditions such as obesity or being on a high-fat diet. Collectively, this review exposes novel and important research gaps in our current understanding of dysmetabolic diseases and can facilitate finding more effective treatment options for these disorders.

Maternal subclinical hyperthyroidism and adverse pregnancy outcomes considering the iodine status: Tehran thyroid and pregnancy study.

BACKGROUND: Unlike overt thyroid diseases, the impacts of subclinical thyroid dysfunction, especially subclinical hyperthyroidism (SH), on adverse pregnancy outcomes are inconclusive. OBJECTIVE: We aimed to investigate the effect of maternal SH on adverse maternal and neonatal outcomes based on urinary iodine concentration (UIC). METHODS: A secondary analysis was run on data collected in the Tehran Thyroid and Pregnancy study (TTPs). We used the data of 131 women with SH and 1650 cases of euthyroid. Serum levels of thyroid-stimulating hormone (TSH), thyroxine (T4), free thyroxine index (FT4I), and thyroid peroxidase antibody (TPOAb) were assessed at the first prenatal visit. A generalized linear regression model was applied to identify the effect of SH on the pregnancy outcomes based on UIC, and the effects were estimated with a 95% confidence interval. RESULTS: Preterm delivery was observed in 12.3% of women with SH and 6.7% of those with euthyroid (P = 0.03). Women with TSH< 0.3 mIU/L had a higher odds of preterm delivery than those with TSH≥ 0.3 regardless of urine iodine cut-off [OR= 2.27; 95% CI: (1.15, 4.48), p = 0.02]. Among those with UIC levels≥ 150 µg/L, the odds ratio of preterm delivery was 4.61 folds higher in the SH group compared to those with euthyroid [95%CI: (1.36, 15.71), p = 0.01)]. No significant difference between these two study groups was found in Neonatal Intensive Care Unit admission. Moreover, the results revealed no statistically significant difference in the means of neonatal anthropometric parameters in the SH and euthyroid groups in none of the subgroups of UIC (<150 or ≥150 µg/l). CONCLUSIONS: According to our results, maternal SH appears to be a risk factor for preterm delivery. This effect is more pronounced in women with higher UIC than those with lower UIC.

Idiopathic Hirsutism and Metabolic Status: A Population-based Prospective Cohort Study.

BACKGROUND: A limited number of studies have investigated the impact of idiopathic hirsutism (IH) on cardiometabolic parameters with contradictory and inconclusive results. This study aimed to explore the effect of IH on metabolic outcomes. METHOD: In this population-based prospective study, 334 women with IH and 1226 women as healthy controls were selected from Tehran Lipid and Glucose Study. The generalized estimation equations method was applied to investigate the secular longitudinal trends of metabolic indices, including fasting blood sugar (FBS), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL), non-HDL, triglyceride (TG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and waist circumference (WC) in both groups. Unadjusted and adjusted Cox regression models were applied to assess the hazard ratios (HR) and 95% CIs for the association between IH and metabolic disorders. Potential confounding factors such as age, body mass index, smoking, physical activity, history of hypertension (HTN), and family history of diabetes were included in the adjusted model. RESULTS: This study showed that compared with healthy controls, women with IH had lower SHBG and higher total testosterone (median [interquartile ratio; IQR]: 0.37 [0.16-0.70] vs 0.33 [0.14-0.58]; P = 0.01), free androgen index (median [IQR]: 0.85 [0.38-1.54] vs 0.54 [0.26-0.97]; P = 0.001), androstenedione (median [IQR]: 1.60 [1.00-2.25] vs 1.10 [0.90-1.70]; P = 0.001), and dehydroepiandrosterone sulfate (median [IQR]: 168.5 [91.1-227.8] vs 125.2 [66.3-181]; P = 0.001). Over time, mean changes of FBS, HDL-C, LDL-C, non-HDL-C, TG, SBP, DBP, and WC were not significantly different in women with IH, compared with healthy controls. According to the unadjusted Cox regression model, except for type 2 diabetes mellitus (T2DM) (HR [95% CI]: 1.45 [1.00-2.11]) P = 0.05; there was no statistically significant difference in hazard of metabolic disorders (ie, HTN, pre-HTN, pre-T2DM, and metabolic syndrome) in IH, compared with healthy controls. Besides, the adjusted Cox regression model showed no significant differences in the hazard of these outcomes. CONCLUSION: This study showed no significant difference in overtime mean changes of metabolic risk factors and cardiometabolic outcomes in women with IH, compared with the healthy control group, except marginally significant difference on T2DM, which disappeared after further adjustment for potential confounders. Accordingly, routine screening of women for these metabolic outcomes should not recommend.

How Do Iranian Men Perceive Their Sexual and Reproductive Health Situation? A Qualitative Content Analysis.

Background: Males' viewpoint about sexual and reproductive health (SRH) and their situation are essential components of men's and women's health in the community. Men have been overlooked in reproduction health, especially with reproductive issues such as contraception, sexually transmitted infections (STIs), infertility, and sexual function. This study aimed to investigate the males' perceptions of their SRH situation in Iran. Methods: A qualitative study was conducted from May 2016 to April 2017 on data retrieved through semi-structured interviews with 19 adult males aged 18 to 59 years. The participants were purposefully recruited from among populations of health centers in Alborz province, Iran. Conventional content analysis in OneNote software version 2016 was used for data analysis. Results: Three main themes and nine categories emerged including 1) Perceived SRH needs, including "need to increase men's awareness about SRH", "need to have an accessibility to SRH services", and "need to have a high-quality sexual relationship"; 2) perceived SRH responsibilities, including "health-seeking behaviors", "sexual skills", "childbearing responsibilities", and "ethical commitment", and 3) Men' perception of trends of social and cultural norms, including "changing SRH priorities" and "changing marital prototype". Conclusion: In this study, men perceived SRH as an important issue due to the changes in social and cultural trends, and many of their SRH needs have not yet been addressed. Hence, along with socio-economic changes, the policymakers of the health system should develop strategies and interventions to meet these needs.

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.

Insulin resistance and idiopathic hirsutism: A systematic review, meta-analysis, and meta-regression.

OBJECTIVES: This study aimed to evaluate the Standardized Mean Difference (SMD) of insulin resistance parameters in women with IH, compared to healthy and polycystic ovary syndrome (PCOS) controls. MATERIALS AND METHODS: PubMed, Scopus, Web of Sciences, and Embase were searched for retrieving studies published up to November 2021 investigating the insulin resistance parameters in women with IH, compared to control groups. Meta-regression and subgroup analysis were conducted to evaluate the effect of potential confounders, such as age, BMI, and study design. RESULTS: A meta-analysis of 20 studies revealed that higher SMDs of fasting insulin (SMD: 0.58; 95% CI: 0.10, 1.06), HOMA-IR (SMD: 0.53; 95% CI: 0.09, 0.97), and FBS levels (SMD: 0.11; 95% CI: 0.03, 0.19) in women with IH than healthy. It also showed that the SMD of HOMA-IR was significantly lower in women with IH than PCOS patients (SMD: -0.49; 95% CI: -0.88, -0.09). A subgroup analysis of cross-sectional studies showed higher SMDs of fasting insulin (SMD: 0.86; 95% CI: 0.05, 1.68), HOMA-IR (SMD: 0.83; 95% CI: 0.01, 1.64), and FBS levels (SMD: 0.14; 95% CI: 0.00, 0.28) in women with IH than healthy, whereas there was no difference in the SMD of these metabolic parameters between IH and PCOS groups, except for SMD of HOMA-IR (SMD: -0.22; 95% CI: -0.42, -0.02). CONCLUSIONS: The results of the study demonstrate that insulin resistance parameters are related to IH, although insulin resistance values in women with IH are not as high as in patients with PCOS. According to the results of the study, measuring these metabolic parameters can be beneficial to evaluate all hirsute women with IH.

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.