The Hidden Link between Polycystic Ovary Syndrome and Kidney Stones: Finding from the Tehran Lipid and Glucose Study (TLGS).

BACKGROUND: We aimed to investigate the association between kidney stones and polycystic ovarian syndrome (PCOS). MATERIALS AND METHODS: In a cross-sectional study, data from the Tehran Lipid and Glucose Study (TLGS) were used to investigate the risk of kidney stones in women with Polycystic Ovary Syndrome (PCOS). Four distinct phenotypes of PCOS, as defined by the Rotterdam criteria, were examined in a sample of 520 women and compared to a control group of 1638 eumenorrheic non-hirsute healthy women. Univariate and multivariable logistic regression models were employed for analysis. The four PCOS phenotypes were classified as follows: Phenotype A, characterized by the presence of all three PCOS features (anovulation (OA), hyperandrogenism (HA), and polycystic ovarian morphology on ultrasound (PCOM)); Phenotype B, characterized by the presence of anovulation and hyperandrogenism; Phenotype C, characterized by the presence of hyperandrogenism and polycystic ovarian morphology on ultrasound; and Phenotype D, characterized by the presence of anovulation and polycystic ovarian morphology on ultrasound. RESULTS: The prevalence of a history of kidney stones was found to be significantly higher in women with Polycystic Ovary Syndrome (PCOS) compared to healthy controls (12.5% vs. 7.7%, p = 0.001). This increased prevalence was observed across all PCOS phenotypes (p < 0.001). After adjusting for potential risk factors, including age, family history of kidney stones, waist-to-height ratio, total cholesterol, and low-density lipoprotein, the odds ratio for kidney stones in women with PCOS was found to be 1.59 [95% CI: 1.12-2.25, p = 0.01], indicating a 59% increase in risk compared to healthy women. Women with PCOS Phenotype A [OR: 1.97, 95% CI: 1.09-3.55, p = 0.02] and Phenotype D [OR: 3.03, 95% CI: 1.24-7.41, p = 0.01] were found to be at a higher risk for kidney stones. CONCLUSION: Women with Polycystic Ovary Syndrome (PCOS), particularly those exhibiting menstrual irregularities and polycystic ovarian morphology on ultrasound (PCOM), have been found to be two to three times more likely to develop kidney stones. This increased prevalence should be taken into consideration when providing preventive care and counseling to these individuals.

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.

Induction of a rat model of premature ovarian insufficiency using D-galactose feeding during the critical periods of development: A pilot study.

Background: Premature ovarian insufficiency (POI) affects about 1% of women of reproductive ages (15-45 yr), with no curative treatment. Objective: We aimed to present a rat model of POI using a D-galactose enriched diet. Materials and Methods: In a pilot study, 4 pregnant Wistar rats were divided into 4 groups; 3 groups were fed galactose-enriched diets at days 3-15 of pregnancy (G1); on the 3 rd day of pregnancy to parturition (G2), and the 3 rd day of pregnancy until the end of the weaning period (G3). Also, group 4, as the control group (G0), was fed standard pellets during the study. After confirming the lack of adverse effects of dieting with galactose in terms of offsprings' birth weight, we performed our study designed the same as the pilot study. A total of 40 pregnant Wistar rats were randomly divided into 4 groups. Ovarian histology, reproductive hormones, and immunological characteristics of the female offspring were examined in all experimental groups and compared. Results: The pilot study revealed no significant differences in the birth weight of the offspring of the 4 study groups (p = 0.96). The ovarian index in the female offspring of those with a gal-exposed diet was significantly lower than that of the control group offspring (p < 0.01). Conclusion: As the birth weights of the offspring of our experimental and control groups were similar, it can be concluded that the reduction of ovarian follicles after prenatal exposure to D-galactose is due to the ovotoxicity of galactose. The results of our final study will provide more information about the rat POI model induced by prenatal exposure to D-galactose.

The Association Between Male Infertility and Cardiometabolic Disturbances: A Population-Based Study.

BACKGROUND: Further studies are needed to extend our knowledge about the association between male infertility and cardio-metabolic disorders. OBJECTIVES: We aimed to assess the association between male infertility and cardiometabolic disturbances using a population-based design. METHODS: In total, 1611 participants of the Tehran-Lipid and Glucose-Study (phase III) were categorized into two groups of men with documented male infertility (n = 88) and those with at least one live birth and no history of primary infertility (n = 1523). Logistic regression was applied to explore the association between male infertility and cardiometabolic disturbances, including diabetes mellitus, pre-diabetes, hypertension, metabolic syndrome, dyslipidemia, obesity, central obesity, and chronic kidney disease, following adjustment for age and body mass index (BMI). RESULTS: The unadjusted model revealed a significant association between infertility and hypertension and CKD (OR = 1.8; 95% CI: 1.2, 2.9, P-value = 0.006 and OR = 1.9; 95% CI: 1.1, 3.6, P-value = 0.033), respectively. However, after adjusting for age and BMI, as potential confounders, this association was not significant. Moreover, there was no association between infertility and other cardiometabolic disturbances, including diabetes and pre-diabetes, metabolic syndrome, dyslipidemia, obesity, and central obesity in both unadjusted and adjusted models. CONCLUSIONS: Our study revealed no association between male infertility and cardiometabolic disturbances. The findings can pave the way for further studies to extend our knowledge in this field. More population-based studies with a large sample size are warranted to confirm these findings.

Prevalence of premature ovarian insufficiency and its determinants in Iranian populations: Tehran lipid and glucose study.

BACKGROUND: Premature ovarian insufficiency (POI) considered as a concerning health issue for women of reproductive age. In this study we aim to estimate the prevalence of POI and assessing the influential factors. METHODS: Data was obtained from Tehran lipid and glucose study (TLGS). All eligible post-menarcheal female participants of the TLGS, ages 20-65, were recruited (n = 6521). Participants were followed for the event of menopause, and age at menopause was recorded. Kaplan Meier analysis was applied to estimate mean and median for age at menopause. Weibull accelerated failure time survival regression model (AFT), was applied to assess influential determinants of POI. Conditional probability approach was used to provide estimation for prevalence of POI. RESULTS: In this population-based study, the prevalence of POI (menopause age < 40 years) and early menopause (menopause age < 45 years) were estimated 3.5% and 24.6%, respectively. AFT model showed that in comparison to normal weight women, time to menopause was decreased by - 0.09 year (95% CI - 0.27, - 0.01, p = 0.023) and - 0.03 year (95% CI - 0.05, - 0.02, p = 0.000) in underweight and overweight women, respectively. Moreover, time to natural menopause was increased by 0.12 year (95% CI 0.07 to 0.17, p = 0.000) in women used oral contraceptives for > 6 months. CONCLUSION: About one quartile of Iranian women experienced menopause at an age less than 45, especially the non-normal weight ones; this high prevalence is a critical public health concerns that needs to be addressed by health policy makers.

The Menstrual Disturbances in Endocrine Disorders: A Narrative Review.

CONTEXT: Menstrual cycle is considered the fifth vital sign among women. This study aimed to summarize the menstrual disturbances in different endocrine disorders. EVIDENCE ACQUISITION: In this narrative review, relevant studies (up to December 2019) were searched based on the MeSH keywords diabetes, polycystic ovary syndrome, Cushing's syndrome, thyroid dysfunction, hyperprolactinemia, menstrual cycle, uterine bleeding, and menstruation. Databases used for searching articles included Google Scholar, Scopus, PubMed, and Web of science for observational, experimental, and review studies. RESULTS: Endocrine disorders trigger the onset of menstrual disturbance across the reproductive lifespan of women. Endocrine glands (pituitary, thyroid, pancreas, adrenal, and ovaries) have a functional role in endocrine regulation of the menstrual cycle. According to available evidence, oligomenorrhea (cycles longer than 35 days) is the most common menstrual disturbance among endocrine disorders (thyrotoxicosis, hypothyroidism, polycystic ovary syndrome, Cushing's syndrome, and diabetes). Complex endocrine pathways play an essential role in a women's menstrual calendar. CONCLUSIONS: The menstrual cycle length and amount of bleeding can be indicative of endocrine disorders. Further studies are needed to identify the unknowns about the association between endocrine disorders and the menstrual cycle.

Induced premature ovarian insufficiency by using D galactose and its effects on reproductive profiles in small laboratory animals: a systematic review.

BACKGROUND: Development of a hyper-gonadotropic hypoestrogenism condition in women < 40 years, defined as premature ovarian insufficiency (POI), is the most common long-term complication in female survivors of galactosemia. In this systematic review, summarize the galactose (GAL) induced POI in rat and mice models. METHODS: For this systematic review, we conducted a search of case control studies published from 1990 until August 2018 in PubMed/Medline, and Web of science, using the descriptors in the title/abstract field. A 'pearl growing' strategy was employed whereby, after obtaining the full text articles, reference lists of all included studies (n = 14) were reviewed for additional publications that could be used. RESULTS: We selected and categorized 14 studies according to the time of exposure to GAL into two groups of prenatal (n = 4) and postnatal (n = 10). Findings of these studies showed that the different stages of follicular development are targeted differently by galactose exposure during the prenatal and postnatal periods: The small follicles (primordial and primary follicles) are targeted by galactose toxicity during prenatal exposure and the pre-antral and antral follicles are targeted by galactose toxicity during postnatal exposure. CONCLUSIONS: This systematic review shows that galactose has an ovotoxicity effect that can be used to induce appropriate POI animal models only if sufficient doses, proper onset time, and duration of prenatal exposure are taken into account. An optimized model of POI induction should manifest all the required ovarian morphological, hormonal, and estrus cycle changes.

Habitual dietary lactose and galactose intakes in association with age at menopause in non-galactosemic women.

INTRODUCTION: Rodent models and studies on women with galactosemia suggest the ovo-toxicity effect of galactose. However, the association between galactose intake from dietary sources and the ovarian function in women without galactosemia has not yet been described. Therefore, this study aimed to investigate the associations between both dietary galactose and lactose intake, and ovarian dysfunction as the odds of early menopause in women without galactosemia. MATERIALS AND METHODS: This cross-sectional study was conducted on 821 women without galactosemia, participants of the Tehran Lipid and Glucose Study (TLGS), who experienced natural menopause. Habitual dietary intakes of lactose and galactose during the past 12 month were assessed, using a food-frequency questionnaire (FFQ). In this study, early menopause was defined as natural menopause before the age of 45 years. RESULTS: Mean- and menopausal age of women were reported as 59.3±7.94 and 48.6±4.81 years, respectively. No statistically significant linear association was observed between the daily intakes of lactose and galactose and the odds of early menopause. After adjusting for age, energy intake, and age at menarche, women in the middle tertiles of lactose (62%, 95%CI: 1.07, 2.46) and galactose (58%, 95% CI: 1.05, 2.39) intake had significantly higher odds of early menopause, than those in the first tertile. When the daily intake of lactose and galactose were expressed as the percentage of energy intake, the higher odds of early menopause among women in the middle tertile compared to those with the first tertile were reduced and became non-significant. CONCLUSION: No statistically significant linear associations were reported between the intake of lactose and galactose and age of menopause. However, the odds of early menopause in those women with the middle tertile of lactose and galactose intake were significantly higher than those women in the first tertile.

Reproductive Assessment: Findings from 20 Years of the Tehran Lipid and Glucose Study.

CONTEXT: Reproductive domains of the Tehran lipid and glucose study (TLGS) are unique in that they provide reliable information on reproduction of an urban population of West Asia. The aim of this review is to present the most important reproductive findings of TLGS. EVIDENCE ACQUISITION: This review is summarizing all articles published in the context of reproductive aspects of TLGS results over the 20-year follow-up. A comprehensive databases search was conducted in PubMed (including Medline), Web of Science and Scopus for retrieving articles on the reproductive histories in context of the TLGS. RESULTS: The mean (SD) age at menarche and menopause was 13 (1.2) and 49.6 (4.5) years respectively. While pills were the most commonly used modern methods at the initiation of TLGS, the prevalence of condoms rose sharply and significantly over the follow up duration. Among women with history of gestational diabetes, the risk of diabetes and dyslipidemia progression were 2.44 and 1.2 fold higher than others. Prevalences of PCOS and idiopathic hirsutism among reproductive age participants of TLGS were 8.5% (95% CI: 6.8% - 10.2%) and 13.0% (95% CI: 10.9% - 15.1%), respectively. Trend of cardio-metabolic risk factors among women with PCOS showed that there were no statistically significant differences between mean changes of each cardio metabolic variables between PCOS and healthy women; PCOS status also significantly associated with increased hazard of diabetes and prediabetes among women aged younger than 40 years (HR: 4.9; 95% CI: 2.5 - 9.3, P value < 0.001)) and (HR: 1.7; 95% CI: 1.1 - 2.6), P value < 0.005), respectively. CONCLUSIONS: The population based nature of TLGS provides a unique opportunity for valid assessment of reproductive issues, the results of which could provide new information for modification of existing guidelines.

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.

Menstrual Cycle Irregularity and Metabolic Disorders: A Population-Based Prospective Study.

The regularity of menstrual cycles is considered an indicator of women's reproductive health. Previous studies with a cross-sectional design have documented the relationship between menstrual cycle irregularities, insulin-resistance and the future risks for metabolic disorders. Limited data documented by prospective studies can lead to premature conclusions regarding the relationship between menstrual cycle irregularities and other conditions influencing women's health. The present study therefore, using a prospective design aimed to assess the risk of metabolic disorders in women with a history of irregular menstrual cycles, was based on the data gathered from the Tehran Lipid and Glucose study (TLGS) an ongoing prospective cohort study initiated in 1999. Participants of the current study were 2128 women, aged between 18-49 years, followed for 15 years. Based on their menstrual cycles, the women were divided into two groups: (i) women with regular menstrual cycles (n = 1749), and (ii) those with irregular menstrual cycles (n = 379). The proportional COX regression model was used to compare hazard ratios (HRs) between the groups for the proposed events, including diabetes mellitus (DM), pre-diabetes (pre-DM), hypertension (HTN), pre-hypertension (pre-HTN) and dyslipidemia. It was found that during a 15-year follow up, there were 123 cases of DM, 456 cases of pre-DM, 290 cases of HTN, 481 cases of pre-HTN, and 402 cases of dyslipidemia. Compared to those with regular cycles, women with irregular menstrual cycles were found to have an increased risk for DM2 (age adjusted Hazard Ratios (HRs), 2.01; 95% confidence intervals (CI:1.59-3.50), the increased risk for DM, associated with irregular cycles remained significant after the adjustment for Body Mass Index (BMI), fasting blood sugar (FBS), family history of diabetes, and parity (HRS, 1.73; 95% CI: 1.14-2.64). There was no significant difference in the increased risk for pre-DM between the groups (age adjusted HRs, 1.33, 95% CI: 1.05-1.69). However, after the adjustment of BMI, FBS and family history of pre-DM, compared to those with regular menstrual cycles, irregular menstrual cycles showed an increased risk for pre-DM (HRs, 1.33; 95% CI: 1.05-1.69). No statistically significant difference was found in the increasing risk for other proposed events between the groups demonstrating that menstrual cycle irregularities could be considered a marker of metabolic disorders and a predisposing factor of the increased risk for diabetes mellitus and pre-diabetes in women with irregular menstrual cycles.

Comparison of Metabolic and Hormonal Profiles of Women With and Without Premenstrual Syndrome: A Community Based Cross-Sectional Study.

BACKGROUND: Premenstrual syndrome (PMS) is reported by up to 85% of women of reproductive age. Although several studies have focused on the hormone and lipid profiles of females with PMS, the results are controversial. OBJECTIVES: This study was designed to investigate the association of hormonal and metabolic factors with PMS among Iranian women of reproductive age. MATERIALS AND METHODS: This study was a community based cross-sectional study. Anthropometric measurements, biochemical parameters, and metabolic disorders were compared between 354 women with PMS and 302 healthy controls selected from among 1126 women of reproductive age who participated in the Iranian PCOS prevalence study. P values < 0.05 were considered significant. RESULTS: Prolactin (PRL) and triglycerides (TG) were significantly elevated in women with PMS, whereas their testosterone (TES), high density lipoprotein (HDL) and 17-hydroxyprogesterone (17-OHP) levels were significantly less than they were in women without the syndrome (P < 0.05). After adjusting for age and body mass index (BMI), linear regression analysis demonstrated that for every one unit increase in PMS score there was 12% rise in the probability of having metabolic syndrome (P = 0.033). CONCLUSIONS: There was a significant association between PMS scores and the prevalence of metabolic syndrome. Further studies are needed to confirm and validate the relationships between lipid profile abnormalities and metabolic disorders with PMS.

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.

A population-based study on infertility and its influencing factors in four selected provinces in Iran (2008-2010).

BACKGROUND: Infertility has a varied impact on multiple dimensions of health and functioning of women. OBJECTIVE: We aimed to identify the burden of infertility and its influencing factors based on a population based study conducted in four provinces of Iran. MATERIALS AND METHODS: A sample of 1126 women, aged 18-45 years, was selected using the multi stage, stratified probability sampling procedure; those met the eligibility criteria were invited for further comprehensive interview. This study used the definition of infertility proposed by World Health Organization "the woman has never conceived despite cohabitation and exposure to pregnancy for a period of 1 year". Results : The overall prevalence of lifetime infertility and current primary infertility were 21.1% (95% CI: 18.4- 23.8) and 6.4% (95% CI: 4.8-8) respectively. The probability of first pregnancy at the end of 2 years of marriage was 94% for all ever-married women. Infertility were observed as significantly higher among women age 31-35 (OR: 4.6; 95% CI: 1.9-11.5; p=0.001) and women with more than 9 years of education (OR: 2.8; 95% CI: 1.5-3.3; p<0.0001). CONCLUSION: The necessities of modern living have compelled many women to postpone childbearing to their late reproductive years; however they must be informed of being at risk of infertility with ageing.

Main facilitators of smoking among young males in tehran: tehran lipid and glucose study.

BACKGROUND: Smoking is the most preventable risk factor for non-communicable diseases and its alarming trend. OBJECTIVES: The aim of this study was to explore and determine facilitating factors for smoking in young males, who participated in the Tehran Lipid and Glucose Study (TLGS), from their own perspective. PATIENTS AND METHODS: This qualitative study was conducted within the framework of the TLGS. Participants were young males with 15 to 25 years of age and various levels of education. The inductive content analysis approach was used to analyze data on the participants' perceptions with regard to smoking facilitators. Data collection was conducted through discussions by six semi-structured focus groups consisted of five to seven people. All the interviews were transcribed after being recorded and analyzed through constant comparative analysis. RESULTS: Two main categories derived from the analysis of the data: I) personal needs and features; and II) environmental facilitators. The former concept included three subcategories: 1) fulfilling essential needs; 2) search for identity; and 3) lack of life skills. Environmental facilitators were also divided into two subcategories: 1) social patterns; and 2) ease of access. CONCLUSIONS: Tendency towards smoking is influenced by different factors. Clarifying these influential factors for smoking from the perspective of young males can be important in designing effective preventive programs.