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.

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.

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.

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.

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.

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

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-age women. Significant associations between PCOS and benign breast diseases (BBD) and a possibly potential association between PCOS and breast cancer have been reported. The etiology of these events of mammary glands in PCOS remains unclear. Animal models that show BBD and breast cancer may contribute to further understanding about these diseases. We aimed to examine the spontaneous occurrence of mammary tumors, their prevalence, and type in our rat model of PCOS. Prenatal androgen-induced PCOS rats and controls were examined in later life. Benign mammary tumors were observed in 75% and 33.33% of PCOS rats and controls during the postmenopausal period, respectively (p = .0158). Mammary tumors were non-invasive, margins of excision were normal and tumors were freely movable, in both groups. After microscopic evaluations of tumors, proliferative breast lesions and adenomas with a tubular growth pattern were observed in both groups. However, in PCOS rats, of benign tumors two had a mixed pattern of fibroadenoma/fibroma and cysts. High prevalence of benign mammary tumors was observed in our rat model of PCOS during the postmenopausal period, possibly due to hormonal imbalances during their reproductive lifespan; this model may contribute to current data available regarding the events of mammary glands in PCOS.

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

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

A Comparison of Sexual Function in Women with Polycystic Ovary Syndrome (PCOS) Whose Mothers Had PCOS During Their Pregnancy Period with Those Without PCOS.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women during reproductive ages. Clinical symptoms associated with PCOS, such as hirsutism, acne, alopecia, obesity, and infertility, may lead to emotional morbidity and then impaired sexual function in those affected. During intrauterine development, the fetus may program the development of diseases during adulthood. In this study, we aimed to examine sexual function in women with PCOS, exposed to maternal androgen excess during their prenatal life compared to non-exposed PCOS patients. In this cross-sectional study, 768 married women with PCOS, aged 18-49 years, were subdivided into two groups, based on their mothers' PCOS status: women whose mothers had PCOS (N = 94) and women whose mothers did not have PCOS (N = 674). Data were collected using a questionnaire including information on demographics, anthropometric and reproductive characteristics, and the Female Sexual Function Index. Blood serum samples were collected from patients for assessment of total testosterone and sex hormone-binding globulin levels. Results revealed that sexual dysfunction was significantly higher in PCOS women whose mothers also had PCOS, compared to those whose mothers did not (38.6 vs. 25.3%, p = .01). After adjusting for confounding variables, logistic regression analysis showed that odds ratios for sexual dysfunction (total) and sexual dysfunction in the pain domain were significantly higher in the exposed PCOS women versus the non-exposed women (OR 1.81, 95% CI 1.06-3.07, p = .02 and 1.68, 95% CI 1.01-2.77, p = .04, respectively). Our study demonstrates increased sexual dysfunction in PCOS women whose mothers also had PCOS.

Alteration in follistatin gene expression detected in prenatally androgenized rats.

Impaired ovarian follicle development, the hallmark of polycystic ovarian syndrome (PCOS), is believed to be due to the changes in expression of related genes such as follistatin (FST). Expression of FST gene and methylation level of its promoter in theca cells from adult female rats, prenatally exposed to androgen excess, during different phases of the estrus cycle was determined and compared with controls. Eight pregnant Wistar rats (experimental group) were treated by subcutaneous injection of 5 mg free testosterone on day 20 of pregnancy, while controls (n = 8) received 500 ml solvent. Based on observed vaginal smear, adult female offspring of mothers were divided into three groups. Levels of serum steroidogenic sexual hormones and gonadotropins, expression and promoter methylation of the FST gene were measured using ELISA, cyber-green real-time PCR and bisulfite sequence PCR (BSP), respectively. Compared to controls, the relative expression of FST gene in the treated group decreased overall by 0.85 fold; despite significant changes in different phases, but no significant differences in methylation of FST promoter. Our results reveal that manifestation of PCOS-like phenotype following prenatal exposure to excess androgen is associated with irregularity in expression of the FST gene during the estrus cycle.

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

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

Hemodynamic properties and arterial structure in male rat offspring with fetal hypothyroidism.

Thyroid hormones (THs) play a crucial role in the development of different systems during fetal life; fetal hypothyroidism (FH) is associated with reduced cardiac function and dimensions in neonates. The aim of this study is to determine whether TH deficiency during fetal life is associated with arterial structural and hemodynamic changes during adulthood. Hypothyroidism was induced by adding 0.025% 6-propyl-2-thiouracil in drinking water throughout pregnancy, while controls consumed only tap water. Hemodynamic parameters, cross-sectional area, intima-media thickness (IMT), and density of nuclei of smooth muscle cells and endothelial cells (ECs) in the aorta and mesenteric arteries were measured. Compared to controls, in the FH group, baseline systolic blood pressure (105.7 ± 3.1 vs. 87.9 ± 3.3 mm Hg, p < 0.01), diastolic blood pressure (64.4 ± 1.7 vs. 53.2 ± 2.1 mm Hg, p < 0.05), and mean arterial pressure (80.9 ± 2.1 vs. 67.1 ± 2.1 mm Hg, p < 0.01) were significantly lower. In addition, in the FH group, intensity and latency of response to phenylephrine were significantly lower and longer, respectively, as were the IMT and density of ECs in the aorta and superior mesenteric arteries. In conclusion, this study showed that TH deficiency during fetal life can have long-lasting functional and histological effects, which can compromise cardiovascular function during adulthood.

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.

Endogenous estrogen exposure and hypertension risk; a population-based cohort study with about two decades of follow-up.

CONTENT: The impact of endogenous estrogen exposure (EEE) on hypertension (HTN) incidence has not been investigated yet. OBJECTIVE: This study aimed to evaluate HTN incidence in women with different endogenous estrogen durations. METHODS: Information was gathered from the Tehran Lipid and Glucose Study (TLGS) to conduct current research. At the initiation of the study, 4463 post-menarche normotensive women, including 3599 premenopausal and 864 menopausal women, were included. EEE was calculated for each woman, and they were followed up for the HTN event. According to the EEE, the hazard ratios and 95% confidence intervals (CI) for the HTN event were presented using Cox proportional hazards regression models (unadjusted and adjusted). RESULTS: The median (interquartile range) of follow-up (between menarche and the date of HTN incidence or last follow-up) was 33.2(25.1, 42.3) years. The event of menopause occurred in 31.8% of participants. The unadjusted model's findings illustrated that the EEE z-score was inversely associated with HTN incidence in post-menarcheal women [unadjusted hazard ratio (HR) 0.47, 95% CI 0.44, 0.50], meaning that the risk of HTN decreased by 53% for every 1-SD rise in the EEE z-score. After adjusting for potential confounders, the results showed no statistically significant changes (adjusted HR 0.46, 95% CI 0.43-0.49). In participants with prehypertension at baseline, the hazard of HTN decreased by 56% per 1-SD rise in the EEE z-score. CONCLUSION: This longitudinal study demonstrated the protective effect of a longer EEE duration on HTN risk, even among those with prehypertension status.

Follicle-Stimulating Hormone and Diabetes in Postmenopausal Women: A Systematic Review and Meta-analysis.

BACKGROUND: Today, co-occurrence of hormonal changes during menopause and the risk of cardio-metabolic disorders have been well studied. We aimed to explore the association of circulating levels of follicle-stimulating hormone (FSH) with diabetes (DM) among postmenopausal women. METHOD: In this Systematic review and meta-analysis the search was performed on PubMed, Scopus, Web of sciences, Epistemonikos, and Cochrane library until the September 2023. Risk of bias was assessed by Newcastle-Ottawa Quality Assessment Scale. Pooled estimates of mean differences in FSH levels among diabetic postmenopausal women compared to those without diabetes were performed. Also, the correlation between FSH and fasting blood glucose (FBG)/Insulin/Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) as well as the pooled effect sizes with their 95% confidence intervals (CIs) for risk of DM were calculated. RESULTS: In this study, 14 articles, including 7,878 postmenopausal women, met eligibility criteria and were further analyzed. Most of the included studies had a low/moderate risk of bias. Women with DM had significantly lower FSH levels than those without DM (standardized mean difference [95% CI] -0.751, 95% CI-1.129 to -0.372, I2 = 82.46%, n = 1416). The pooled effect size (ES) for diabetes was 0.861 (95% CI: 0.740-1.001; I2 = 80.11%). The pooled risk estimate for DM based on the categorical FSH levels (high versus low) was (HR = 0.550; 95% CI, 0.356 to 0.850, I2 = 0). The significant inverse correlation was found between FSH levels and glycemic parameters [FBG (r= -0.285; 95%CI -0.441 to -0.113; n = 1229), HOMA-IR (r = -0.241; 95%CI -0.378 to -0.0924; n = 1229) and Insulin (r = -0.337; 95%CI -0.434 to -0.232; n = 959)]. There were no statistically significant differences between estradiol levels among diabetic and non-diabetic groups; however the SMD for luteinizing hormone was similar to that reported for FSH. CONCLUSION: The available data indicated an indirect association between FSH levels and glucose disturbances among postmenopausal women; notwithstanding heterogeneity among included studies, and the complexity of various influential factors needs to be considered. Further efforts should be made to clarify the underlying mechanisms.

Effects of Rosa damascena on reproductive improvement, metabolic parameters, liver function and insulin-like growth factor-1 gene expression in estradiol valerate induced polycystic ovarian syndrome in Wistar rats.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-age women. The present study aimed to evaluate the effects of Rosa damascena (RD) extract in estradiol valerate (EV) induced polycystic ovary syndrome rats. METHODS: Adult female Wistar rats were divided into control (n = 12) and PCOS groups (n = 36). The PCOS model was induced using EV (4 mg/kg/day), which was confirmed in 6 rats in each control and PCOS group by observation of irregular estrous cycles in vaginal smears and ovarian multiple cystic. Then, the rest of the control group (n = 6) and PCOS rats (n = 30 in 5 divided groups) were treated orally for 28 days with metformin (MET) as a positive control (200 mg/kg/day) and RD extract (400, 800, and 1200 mg/kg/day, respectively). Body and ovary weights, biochemical and histological parameters, and expression of the IGF-1 gene were measured. RESULTS: Compared to the PCOS group, metformin and higher doses of RD extract (800 and 1200 mg/kg/day) significantly reduced BW, HOMA-IR, FBS, FINS, TG, LDL, TT, E2, LH, TC, and liver enzymes, and increased HDL and FSH levels. In addition, ovarian weight and CFs decreased, and the findings showed an increment in PFs, CLs, PAFs, AFs, and GFs. IGF-1 gene expression levels were significantly decreased (p < 0.001). CONCLUSION: RD extract seems to have the potential therapeutic effect of alleviating PCOS complications, and IGF-1 signaling may be involved in the beneficial effects of RD on PCOS.

Reduced expression of Il10, Stat3, Hoxa10, and Itgb3 in the embryo implantation site of rat model with prenatal androgen-induced polycystic ovary syndrome.

AIMS: Impaired implantation due to the reduced endometrial receptivity considers an etiology for infertility in polycystic ovary syndrome (PCOS). In this context, we aimed to compare the expression of interleukin 10 (Il10), homeobox A10 (Hoxa10), signal transducer and activator of transcription 3 (Stat3), and ß3-integrin (Itgb3) in the embryo implantation site of a prenatally-androgenized rat model of PCOS before and during gestation. MATERIALS AND METHODS: PCOS rat model was created by the injection of testosterone prenatally. The uterine tissues were collected before pregnancy (day 0) and on days 0.5, 4.5, 5.5, and 8.5 of gestation in the PCOS rat model and controls (n = 6; each group). RNA was extracted from the uterine samples and reverse transcribed to cDNA. Expression levels of Il10, Stat3, Hoxa10, and Itgb3 were measured using SYBR Green real-time RT-PCR and compared between the two groups. FINDINGS: PCOS rats showed decreased expression levels of the Il10 on day 8.5 compared to control rats. The mRNA levels of Hoxa10, Itgb3, and Stat3 were significantly decreased in the PCOS group on day 0 as well as on days 0.5, 4.5, 5.5, and 8.5 for Hoxa10, Itgb3, and Stat3. SIGNIFICANCE: The decreased gene expression of Il10, Hoxa10, Stat3, and Itgb3 in the PCOS rat model indicates the importance of the Il10 signaling axis as one of the possible disrupted mechanisms of endometrial receptivity in PCOS.

Various screening and diagnosis approaches for gestational diabetes mellitus and adverse pregnancy outcomes: a secondary analysis of a randomized non-inferiority field trial.

INTRODUCTION: We evaluate which screening and diagnostic approach resulted in the greatest reduction in adverse pregnancy outcomes due to increased treatment. RESEARCH DESIGN AND METHODS: This study presents a secondary analysis of a randomized community non-inferiority trial conducted among pregnant women participating in the GULF Study in Iran. A total of 35 430 pregnant women were randomly assigned to one of the five prespecified gestational diabetes mellitus (GDM) screening protocols. The screening methods included fasting plasma glucose (FPG) in the first trimester and either a one-step or a two-step screening method in the second trimester of pregnancy. According to the results, participants were classified into 6 groups (1) First-trimester FPG: 100-126 mg/dL, GDM diagnosed at first trimester; (2) First trimester FPG: 92-99.9 mg/dL, GDM diagnosed at first trimester; (3) First trimester FPG: 92-99.9 mg/dL, GDM diagnosed at second trimester; (4) First trimester FPG: 92-99.9 mg/dL, healthy at second trimester; (5) First trimester FPG<92 mg/dL, GDM diagnosed at second trimester; (6) First trimester FPG<92 mg/dL, healthy at second trimester. For our analysis, we initially used group 6, as the reference and repeated the analysis using group 2, as the reference group. The main outcome of the study was major adverse maternal and neonatal outcomes. RESULTS: Macrosomia and primary caesarean section occurred in 9.8% and 21.0% in group 1, 7.8% and 19.8% in group 2, 5.4% and 18.6% in group 3, 6.6% and 21.5% in group 4, 8.3% and 24.0% in group 5, and 5.4% and 20.0% in group 6, respectively. Compared with group 6 as the reference, there was a significant increase in the adjusted risk of neonatal intensive care unit (NICU) admission in groups 1, 3, and 5 and an increased risk of macrosomia in groups 1, 2, and 5. Compared with group 2 as the reference, there was a significant decrease in the adjusted risk of macrosomia in group 3, a decreased risk of NICU admission in group 6, and an increased risk of hyperglycemia in group 3. CONCLUSIONS: We conclude that screening approaches for GDM reduced the risk of adverse pregnancy outcomes to the same or near the same risk level of healthy pregnant women, except for the risk of NICU admission that increased significantly in groups diagnosed with GDM compared with healthy pregnant women. Individuals with slight increase in FPG (92-100 mg/dL) at first trimester, who were diagnosed as GDM, had an even increased risk of macrosomia in comparison to those group of women with FPG 92-100 mg/dL in the first trimester, who were not diagnosed with GDM, and developed GDM in second trimester TRIAL REGISTRATION: IRCT138707081281N1 (registered: February 15, 2017).

Maternal Exposure to D-galactose Reduces Ovarian Reserve in Female Rat Offspring Later in Life.

Background: Embryonic life is critical for the formation of ovaries in mammals, and the intrauterine environment may affect ovarian reserve. Objectives: The present study aimed to investigate the impact of prenatal D-galactose exposure on ovarian reserve in female rat offspring in their later lives. Methods: Ten pregnant Wistar rats were randomly divided into two groups. In one group, rats were fed with 35% D-galactose-enriched food from the third day to the end of pregnancy, and in the other group, rats were fed with a standard diet throughout pregnancy. Female offspring (prenatally galactose-exposed rats and non-exposed control rats) were examined in terms of hormonal levels [anti-Mullerian hormones (AMH), follicle-stimulating hormone (FSH), and estradiol (E2)] and ovarian histology at 45 - 50, 105 - 110, and 180 - 185 days of their age. Results: The number of primordial follicles significantly decreased time-dependently in prenatally galactose-exposed rats compared to controls (P-value = 0.002). In addition, decreases in AMH (3.25 vs. 7.5 ng/mL; P = 0.000) and E2 (7.9 vs. 19.5 pg/mL; P = 0.000) and increases in FSH (6.5 vs. 0.8 mIU/mL; P < 0.007) were observed in galactose-exposed rats compared to controls at 45 - 50 days of age. Conclusions: Prenatal exposure to D-galactose negatively affects ovarian reserve in female rats in their later lives. However, further investigation is needed to confirm our findings and explore underlying mechanisms.