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.

The impact of yoga on successful aging based on the selection, optimization, and compensation model in elderly women: A quasi-experimental study.

OBJECTIVE: To investigate the impact of yoga on successful aging based on the selection, optimization, and compensation model in elderly women. DESIGN: Quasi-experimental study. SAMPLE: Seniors' meeting points and parks and clubs for the old age pensioners of the ministry of education, ministry of healthcare, and the oil corporation in Shiraz, Iran. 68 elderly women within the age range of 60-86 years were divided into a yoga and a control group. MEASUREMENTS: The subjects in both groups were asked to complete the selection, optimization, and compensation model questionnaire before and after the intervention. Successful aging was measured using the selection, optimization, and compensation questionnaire. INTERVENTION: The yoga training program was implemented in 1-h sessions twice a week for eight weeks. RESULTS: After eight weeks of yoga training, the results showed a significant difference between the pretest and posttest successful aging total scores of the yoga group (P = .005). However, the difference between the yoga and control groups' posttest mean total scores was not significant (P = .601). CONCLUSION: Based on the results, it seems that yoga training can improve successful aging. Thus, yoga is recommended as an inexpensive and entertaining method.

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.

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.

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.

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.

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.

Effects of isolated maternal hypothyroxinemia on adverse pregnancy outcomes.

PURPOSE: There are conflicting results about the effects of maternal hypothyroidism (IMH) on adverse pregnancy outcomes. This study aimed to investigate the relationship between IMH identified in the first trimester of gestation and adverse pregnancy outcomes. METHODS: In this prospective cohort study, we used data from the Tehran Thyroid and Pregnancy study (TTPs). To diagnose IMH, we considered a threshold of 2.04 for FTI, which was based on the 10th percentile of this marker identified in the 1st trimesters. A generalized linear regression (GLM) model adjusted for the gravidity, urine iodine, and TPOAb status was applied to assess the effects of IMH on adverse pregnancy outcomes, compared to the controls group. RESULTS: Penalized logistic regression analysis indicated that the adjusted odds ratio (aOR) of Preterm premature rupture of the membranes (PPROM) in women with IMH was 5.43-folder higher than euthyroid group [aOR 5.43, 95% CI (1.40, 21.1), p = 0.01]. Besides, the adjusted odds ratio of low birth weight (LBW) in the IMH group was 2.53-folder higher than the healthy group [aOR 2.53, 95% CI (1.01, 6.33), p = 0.047]. Furthermore, the results of the GLM adjusted model revealed that the mean of neonatal head circumference and weight in the IMH group was around 0.43 cm (95% CI - 0.80, - 0.07, p = 0.02) and 145.4 g (95% CI - 242.6, - 48.1, p = 0.003) lower than euthyroid group, respectively. CONCLUSIONS: This study demonstrated that women with IMH identified in early pregnancy have a higher odds ratio for developing some adverse pregnancy outcomes, including PPROM and LBW compared to their euthyroid counterparts. Also, the neonatal head circumference and weight in the IMH group were lower than in the euthyroid group.

Relationship between vitamin D status in the first trimester of the pregnancy and gestational weight gain: a mediation analysis.

PURPOSE: To evaluate the total, and direct effects of vitamin D, measured by circulating 25-hydroxyvitamin D [25(OH)D] levels, on GWG after adjustment for confounding variables, and then assess the indirect effects by demonstrating the role of gestational age at birth as a mediator in this association. METHODS: Data collected in "Khuzestan Vitamin D Deficiency Screening Program in Pregnancy" were used for the present study; it included the data of 900 pregnant women referred to the health centers of Shushtar (Khuzestan Province, Iran), whose vitamin D status during the third trimester of pregnancy was available. A mediation analysis was applied to detect the causal relationship between serum level of 25(OH)D, covariates (maternal age, parity, education level, and baseline maternal weight), mediator (gestational age), and outcome (GWG). RESULTS: Of 900 pregnant women referred to the health centers, a total of 726 eligible participants were analyzed for the study. The adjusted total effect of vitamin D on GWG was estimated 0.07 (95% CI 0.06, 0.09; P = 0.000). This study also revealed adjusted direct effect of vitamin D on GWG was statistically significant 0.02 (95% CI: 0.003, 0.04; P = 0.021). In addition, the adjusted indirect effect of this micronutrient on GWG by considering gestational age as a mediator was found to be significant [0.05 (95% CI 0.04, 0.06; P = 0.000)]. This study revealed an increase in the trend of weight gain during pregnancy trimesters for women with different levels of 25(OH)D; however, women with severe vitamin D deficiency had the lowest speed as compared to moderate and normal levels. CONCLUSION: This study shows that maternal vitamin D status directly affects the gestational weight gain independent of gestational age. Therefore, the detection and treatment of women with vitamin D inadequacy can directly improve the trend of their weight gain in addition to its indirect effect on reducing the risk of preterm delivery.

The association between chronic diseases and the age at natural menopause: a systematic review.

Despite several existing studies on the age at natural menopause (ANM) and its related factors, epidemiologic data on the associations between chronic diseases and ANM are scarce with conflicting and inconclusive results. The aim of this systematic review was to summarize the results of the studies investigating the association between chronic disease and ANM. PubMed, Scopus, and Web of Science were searched for retrieving and summarizing studies published up to October 2020 investigating the association between chronic medical conditions and ANM. All types of observational studies published in the English language were eligible to be included in the systematic review. Studies needed to report the effect of at least one chronic disease on ANM. Studies with other designs, studies with unreliable and incomplete results, and those that assessed none of the chronic diseases as outcomes of interest were excluded. Of the 6294 records retrieved by searching the databases, a total of 28 observational studies were included for this review. According to the Newcastle-Ottawa scale, nine studies were classified as high-quality, fifteen studies as moderate, and four as low-quality. Among the five studies investigating the association between polycystic ovary syndrome (PCOS) and ANM, three studies reported that PCOS was associated with a later ANM, whereas others found no such association. Eight studies showed that diabetes was associated with an earlier ANM, whereas eight other studies found no such association. While only one study showed a younger age at the onset of menopause in patients with a history of hypertension, five studies did not report such an effect. Only one study assessed the effect of dyslipidemia on ANM and showed no association between these variables. While three studies documented the effects of cardiovascular diseases (CVD) and heart disease on earlier ANM, one study found no association between these diseases and ANM. Most included studies showed the association of mood disorders with earlier ANM. There were no sufficient data for assessing the effects of thyroid, skin, and autoimmune diseases on ANM. Chronic diseases particularly cardio-metabolic disturbances, cardiovascular events, and psycho-emotional disorders are associated with earlier menopause, whereas other diseases such as PCOS may lead to later menopause. Accordingly, early diagnosis and managing chronic medical conditions in women can potentially prevent early or late menopause.

The risk of chronic kidney disease among women with polycystic ovary syndrome: A long-term population-based cohort study.

BACKGROUND AND OBJECTIVE: Results of studies focusing on chronic kidney disease (CKD) among women with polycystic ovary syndrome (PCOS) are insufficient and controversial. This study aimed to evaluate the incidence rate of CKD in women with PCOS, compared to a control group of healthy women. METHODS: This study was a population-based cohort study conducted from among 1460 reproductive-age women including 156 women with PCOS and 1304 controls. Incidence rates per 1000 person-years of follow-up were calculated for PCOS and control groups. Cox proportional hazards regression with age as the time-scale was used to estimate hazard ratios (HR) and 95% confidence intervals for developing CKD in relation to PCOS in both univariable and multivariable models. RESULTS: During a median follow-up of 12.9 years, 330 new cases of CKD were identified, including 25 PCOS women (14.8 per 1000 person-years; 95% CI, 10-22) and 305 healthy controls (21.5 per 1000 person-years; 95% CI, 19.2-24.1). The results of the Cox model showed that the risk of CKD among women with PCOS and healthy women is comparable and women with PCOS did not have a higher risk of developing CKD compared to healthy women (unadjusted HR: 0.883; 95% CI: 0.587-1.328; P = .551). The results remained unchanged after adjustment for potential confounders of smoking status, BMI, hypertension and diabetes at baseline and follow-up of study (multiple adjusted HR: 0.911; 95% CI: 0.600-1.383; P = .661). CONCLUSION: Our population-based study with a long-term follow-up period showed that the risk of CKD in PCOS patients was similar to the general female population. Large studies, with long-term follow-up and more diverse phenotypes, are needed to confirm the findings.

A comparison of the effects of oral contraceptives on the clinical and biochemical manifestations of polycystic ovary syndrome: a crossover randomized controlled trial.

STUDY QUESTION: Do oral contraceptives (OCs) containing progestins with low androgenic or antiandrogenic activities have different effects to those containing levonorgestrel (LNG) on clinical, androgenic and metabolic manifestations of polycystic ovarian syndrome (PCOS)? SUMMARY ANSWER: The three OCs tested had similar effects on clinical findings of hyperandrogenism (HA), whereas products containing LNG were less effective on androgenic profiles and had detrimental effects on lipid profiles. WHAT IS KNOWN ALREADY: Despite data available on the effects of OCs, the superiority of products with low androgenic or antiandrogenic progesterone components in comparison with older products used in women with PCOS has not been clarified. STUDY DESIGN, SIZE, DURATION: This study is a crossover randomized controlled six-arm trial, with all six arms including two 6-month treatment periods, one period with OCs containing LNG, and the other with one of three OCs containing desogestrel (DSG), cyproterone acetate (CPA) or drospirenone (DRSP). The trial was conducted between February 2016 and January 2018 and enrolled 200 patients with PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two hundred women with PCOS (ages 18-45 years) were recruited at the endocrine outpatient clinic of the Research Institute for Endocrine Sciences (RIES) of the Shahid Beheshti University of Medical Sciences, Tehran, Iran. A blocking or stratification random allocation (block size = 6) using a computer-based random number generator was prepared to assign participants to treatment groups. Both the clinical examiner and data analyst were blinded to participants during the trial. Outcomes of interest, including anthropometric and clinical manifestations and hormonal, and biochemical parameters were assessed at baseline, after 3 and 6 months of each treatment and after the washout period. MAIN RESULTS AND THE ROLE OF CHANCE: This study detected a higher decrease in free-androgen index (FAI) levels after 3 months of treatment with OCs containing DSG (95% CI: -2.3, -1.0), CPA (95% CI: -2.4, -1.1) and DRSP (95% CI: -2.6, -1.4), compared with products containing LNG (P < 0.001). Use of OCs containing DSG (95% CI: -3.6, -1.5), CPA (95% CI: -3.1, -0.8) and DRSP (95% CI: -3.4, -1.1) for 6 months was associated with more decrease in FAI, compared with products containing LNG (P < 0.001). The study showed that use of OCs containing DSG, CPA and DRSP for 3-6 months was associated with a higher increase of sex hormone-binding globulin (SHBG), compared with products containing LNG (P < 0.001). We also observed more decrease in dehydroepiandrosterone sulfate levels after use of OCs containing DSG (P = 0.003), CPA (P = 0.012) and DRSP (P < 0.001) for 6 months, compared with products containing LNG. Our results showed that the use of OCs containing DRSP for 6 months was associated with more improvement in acne, compared with products containing LNG (P = 0.007). Women treated with OCs containing CPA, and DRSP for 3 months had higher TG and HDL levels and lower LDL levels, compared with those treated with products containing LNG (P < 0.05). After 6 months of treatment, patients treated with OCs containing DRSP had a sharper decline in LDL levels and more increase in HDL levels, compared to those treated with products containing LNG (P = 0.001). LIMITATIONS, REASONS FOR CAUTION: Considering this trial was conducted in women diagnosed with Androgen Excess Society criteria, the results may not be generalizable for mild phenotypes diagnosed using Rotterdam criteria. Other limitations of the study include the high dropout rate, the lack of a gold standard androgen assay and the multiple end points. WIDER IMPLICATIONS OF THE FINDINGS: Our results support the views of clinicians, who suggest an OC with a low androgenic or antiandrogenic progestin, if available, to treat PCOS. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the RIES, Shahid Beheshti University of Medical Sciences, Tehran, Iran. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: IRCT201702071281N2. TRIAL REGISTRATION DATE: 21 February 2017. DATE OF FIRST PATIENT'S ENROLMENT: 21 March 2017.

Risk of hypertension in women with polycystic ovary syndrome: a systematic review, meta-analysis and meta-regression.

BACKGROUND: A limited number of publications have assessed the prevalence of hypertension (HTN) in polycystic ovary syndrome (PCOS) patients with inconclusive results. Since in general populations the occurrence of hypertension is related to age per se, we investigated the prevalence (P) / relative risk (RR) of HTN in pooled patients with PCOS, vs control population among reproductive age women with PCOS, compared to menopause/aging patients. METHODS: PubMed, Scopus, ScienceDirect, web of science, and Google scholar were systematically searched for retrieving observational studies published from inception to April 2019 investigating the HTN in patients with PCOS. The primary outcome of interest was pooled P and RR of HTN in reproductive and menopausal/aging women with PCOS compared to control population. RESULTS: The pooled prevalence of HTN in reproductive and menopausal/aging women with PCOS was higher than in the control population [(Pooled P: 0.15, 95% CI: 0.12-0.18 vs. Pooled P: 0.09, 95% CI: 0.08-0.10) and (Pooled P: 0.49, 95% CI: 0.28-0.70 vs. Pooled P: 0.40, 95% CI: 0.22-0.57), respectively]. Compared to the control population, pooled relative risk (RR) of HTN patients was increased only in reproductive age PCOS (1.70-fold, 95% CI: 1.43-2.07) but not in menopausal/aging patients who had PCOS during their reproductive years. The same results were obtained for subgroups of population-based studies. Meta-regression analysis of population-based studies showed that the RR of HTN in reproductive age PCOS patients was 1.76-fold than menopausal/aging PCOS patients (P = 0.262). CONCLUSION: This meta-analysis confirms a greater risk of HTN in PCOS patients but demonstrates that this risk is increased only in reproductive age women with PCOS, indicating that after menopause, having a history of PCOS may not be as an important predisposing factor for developing HTN.

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

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

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

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

Cardiovascular events among reproductive and menopausal age women with polycystic ovary syndrome: a systematic review and meta-analysis.

This study aimed to evaluate the prevalence (P)/hazard ratio (HR) of cardiovascular (CV) events among reproductive age and menopausal age women with polycystic ovary syndrome (PCOS) in comparison with healthy controls. PubMed, Scopus, ScienceDirect, Web of science, and Google scholar were searched for retrieving observational studies published up to April 2018 investigating CV events in patients with PCOS. The primary outcomes were a composite outcome of CV events [including coronary arterial disease (CAD), cardiovascular disease (CVD), myocardial infarction (MI), angina, heart failure, and ischemic heart disease] and mortality due to CV events; secondary outcomes were specific CVD events, including cerebrovascular disease, CAD, CVD, MI, angina, heart failure, ischemic heart disease, and stroke. In this meta-analysis, both fixed and random effect models were used. Potential sources of heterogeneity were explored by meta-regression and subgroup analyses. Sixteen studies including 12 population-based were analyzed for the meta-analysis. Results showed that the pooled HRs of CV events in PCOS patients of reproductive age and in menopausal/aging women were higher than healthy controls (pooled HR: 1.38, 95% CI: 1.12-1.71) and (pooled HR: 1.53, 95% CI: 1.15, 2.04), respectively. Compared to healthy controls, analysis of population-based studies revealed that the HR of CV events increased only in reproductive age PCOS patients (1.43-fold, 95% CI: 1.27, 1.61), whereas the difference was not statistically significant when comparing menopausal/aging PCOS patients to healthy controls (1.03-fold, 95% CI: 0.41, 2.59). Sufficient data were not available for comparing the HRs of mortality due to CV events between the two PCOS age groups. Mainly based on population-based study, we found a greater risk of CV events in reproductive aged but not in menopausal/aging PCOS women, suggesting that having a history of PCOS during reproductive ages may not be an important risk factor for developing events in later life. This is a preliminary assumption and needs to be reevaluated by further comprehensive cohort studies of longer duration, initiated in the reproductive period, considering all known CVD risk factors.

The relationship between clinical and biochemical characteristics and quality of life in patients with polycystic ovary syndrome.

BACKGROUND AND OBJECTIVE: While has been well demonstrated that clinical characteristics of polycystic ovary syndrome (PCOS) are associated with an impaired quality of life (QoL) in patients, it is unclear that whether the biochemical aspects of PCOS can influence their QoL. We aimed to investigate the relationship between clinical and biochemical characteristics, and various domains of QoL in patients with PCOS. DESIGN: A cross-sectional study. PATIENTS AND MEASUREMENTS: We assessed the association between clinical and biochemical characteristics and QoL domains (psychosocial-emotional, fertility, sexual function, and obesity-menstrual) in a total of 211 women with PCOS using a specific health-related quality-of-life questionnaire for PCOS patients. RESULTS: Our findings showed positive significant association of QoL with age, and its negative significant associations with BMI, hirsutism and infertility (P < 0.05). We also found a negative association between FAI and total QoL (r = -0.14; P = 0.042) and domains of hirsutism (r = -0.14; P = 0.045) and obesity-menstrual (r = -0.23; P = 0.001). DHEAS was positively associated with the sexual function aspect of QoL (r = 0.20; P = 0.043). There were no significant associations between QoL and other hormonal parameters including LH to FSH ratio and total testosterone (tT). Significant associations were found between triglycerides (TG), total cholesterol (TC), LDL and HDL cholesterol, and domain of obesity-menstrual of QoL. HOMA-IR was significantly related to all QoL domains except self-image and hirsutism. CONCLUSION: Although biochemical markers can influence QoL in patients with PCOS, clinical manifestations of this syndrome such as obesity, infertility and hirsutism seem to play roles in worsening QoL, in particular for psychosocial domains. Hence, clinicians should regularly assess the clinical and psychosocial dimensions of PCOS as well as biochemical aspects.

Interictal coupling of HFOs and slow oscillations predicts the seizure-onset pattern in mesiotemporal lobe epilepsy.

OBJECTIVE: Low-voltage fast activity (LVF) and low-frequency high-amplitude periodic spiking (PS) are the two most common seizure-onset patterns in mesiotemporal lobe epilepsy, with different underlying mechanisms, pathology, and postsurgical outcome. The present work aims to investigate whether specific coupling patterns of high-frequency oscillations (HFOs >80 Hz) and low-frequency waves in the interictal period may distinguish these two patterns, and also seizure-onset zone (SOZ) from non-SOZ as a secondary aim. METHODS: We used intracranial electroencephalography (iEEG) data (during non-rapid eye movement [NREM] sleep) of 18 patients with either LVF or PS seizure-onset patterns. We investigated the interaction between HFOs (ripples: 80-250 Hz and fast ripples: >250 Hz) and slow oscillations (slow-delta, delta, and theta waves). We compared classic features (amplitude, duration, frequency, and power) and phase of coupling between HFOs and slower oscillations inside and outside the SOZ. We then used these features to classify HFOs and subsequently patients into LVF and PS groups. RESULTS: Ripples in the LVF group had significantly longer duration, lower frequency, and higher amplitude than in the PS group. The phase of slow oscillations at which HFOs occur is different between the LVF and PS HFOs (LVF, mostly at the peak or the transition of peak to trough; PS, mostly during the transition of trough to peak). HFOs associated with theta waves best discriminate seizure-onset patterns. The coupling phase improves the classification of HFOs and patients to either LVF or PS groups, and also the classification of HFOs in SOZ and non-SOZ. SIGNIFICANCE: The phase of coupling of HFOs and low-frequency waves may help to not only identify the SOZ, but also to classify patients with different types of seizure-onset patterns. It likely reflects that different disease processes are involved in these patterns during the interictal period.

Relationships Between Biochemical Markers of Hyperandrogenism and Metabolic Parameters in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

While several studies have documented an increased risk of metabolic disorders in patients with polycystic ovary syndrome (PCOS), associations between androgenic and metabolic parameters in these patients are unclear. We aimed to investigate the relationships between biochemical markers of hyperandrogenism (HA) and metabolic parameters in women with PCOS. In this systematic review and meta-analysis, a literature search was performed in the PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science from 2000 to 2018 for assessing androgenic and metabolic parameters in PCOS patients. To assess the relationships between androgenic and metabolic parameters, meta-regression analysis was used. A total number of 33 studies involving 9905 patients with PCOS were included in this analysis. The associations of total testosterone (tT) with metabolic parameters were not significant; after adjustment for age and BMI, we detected associations of this androgen with low-density lipoproteins cholesterol (LDL-C) (ß=0.006; 95% CI: 0.002, 0.01), high-density lipoproteins cholesterol (HDL-C) (ß=-0.009; 95% CI: -0.02, -0.001), and systolic blood pressure (SBP) (ß=-0.01; 95% CI: -0.03, -0.00). We observed a positive significant association between free testosterone (fT) and fasting insulin (ß=0.49; 95% CI: 0.05, 0.91); this association remained significant after adjustment for confounders. We also detected a reverse association between fT and HDL-C (ß=-0.41; 95% CI: -0.70, -0.12). There was a positive significant association between A4 and TG (ß=0.02; 95% CI: 0.00, 0.04) after adjustment for PCOS diagnosis criteria. We also found significant negative associations between A4, TC, and LDL-C. Dehydroepiandrosterone sulfate (DHEAS) had a positive association with LDL-C (ß=0.02; 95% CI: 0.001, 0.03) and a reverse significant association with HDL-C (ß=-0.03; 95% CI: -0.06, -0.001). This meta-analysis confirmed the associations of some androgenic and metabolic parameters, indicating that measurement of these parameters may be useful for predicting metabolic risk in PCOS patients.

Trend of various adiposity indices in women with and without history of gestational diabetes: a population-based cohort study.

BACKGROUND: Data of studies focusing on the trends of adiposity indices among women with prior gestational diabetes mellitus (GDM), are limited and controversial. The aim of this study was to compare overtime trends of adiposity indices in women with and without history of GDM, using data of the long term longitudinal population-based Tehran-Lipid and Glucose-Study (TLGS). METHODS: A total of 3395 eligible women aged (20-50 years), including 801 women with prior history of GDM and 2594 non-GDM controls were recruited from among Tehran-Lipid and Glucose-Study participants. Generalized estimating equations were applied to assess the time trend of adiposity indices including obesity, central obesity, body mass index (BMI), lipid accumulation product index (LAP), visceral adiposity index (VAI) and a body shape index (ABSI) in women with prior GDM and the non-GDM groups after further adjustment for age and BMI. RESULTS: Median follow-up years for the GDM and non-GDM groups were 12.12 and 11.62 years, respectively. Women with GDM at initiation had worse adiposity indices than their healthy counterparts. While overall odds of obesity in women with prior GDM were significantly higher those of the non-GDM groups (OR: 1.35; 95% CI, 1.03-1.7; P = 0.03), both these groups overtime revealed a positive trend in obesity (P trend < 0.001), an incremental trend which was less pronounced in GDM women (OR: 0.87; 95% CI, 0.80, 0.95; P interaction = 0.001). Women with prior GDM had higher odds of central obesity, compared to non-GDM groups (OR: 1.44; 95% CI, 1.06-1.96; P = 0.02) and showed a significant an incremental trend overtime for both groups (P trend < 0.001 for both) without statistically significant interaction in terms of their GDM status (P interaction = 0.134). Mean VAI in women with prior GDM was significantly higher than the non-GDM group (19.7, 95%CI: 6.24, 33.15, P = 0.004), although both groups overtime experienced a negative trend (- 10.9, 95%CI: -13.1, - 2.1, P < 0.001); the GDM group showed a higher decrease in VAI (mean changes: -6.62; 95% CI, - 11,-2.1; P interaction = 0.001). However overtime there was a positive trend in LAP and ABSI among both women with and without prior-GDM, though the mean changes were less obvious in women with prior GDM. CONCLUSION: Women with prior GDM gained better control of their adiposity than non-GDM women. Nevertheless the increasing numbers of individuals with GDM and uncontrolled adiposity indices, require prompt attention be paid to the issue.