Antioxidant vitamins supplementation reduce endometriosis related pelvic pain in humans: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to clarify the effect of antioxidant vitamins supplementation on endometriosis-related pain. METHODS: A systematic search of PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNK) databases was conducted to identify relevant studies published in English and Chinese up to 16 March 2023. The search terms used were "endometriosis" OR "endometrioma" OR "endometrium" AND "antioxidant" OR "Vitamin C" OR "Vitamin E" OR "Vitamin D" OR "25-OHD" OR "25(OH)D" OR "25-hydroxyvitamin D". Eligible studies were randomized controlled trials (RCTs) that assessed pain scores using the Visual Analogue Scale (VAS). Mean differences or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the effect of antioxidant vitamins supplementation on endometriosis. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS: A total of 13 RCTs involving 589 patients were included in this meta-analysis. We identified 11 studies that evaluated the effect of antioxidant vitamins supplementation on endometriosis-related pain. The results indicated that the supplementation of antioxidant vitamins can effectively alleviate endometriosis-related pain. Subgroup analysis showed that the supplementation of vitamin E (with or without vitamin C) had a positive effect on improving clinical pelvic pain in patients with chronic pelvic pain. Conversely, supplementation of vitamin D was associated with a reduction in pelvic pain in endometriosis patients, but the difference was not statistically significant compared to the placebo. Additionally, we observed changes in oxidative stress markers following vitamin supplementation. Plasma malondialdehyde (MDA) concentration decreased in patients with endometriosis after antioxidant vitamin supplementation, and the plasma MDA level was inversely correlated with the time and dose of vitamin E and C supplementation. Furthermore, the inflammatory markers in peritoneal fluid, including RANTES, interleukin-6, and monocyte chemoattractant protein-1, significantly decreased after antioxidant therapy. These findings suggest that antioxidant vitamins may alleviate pain in endometriosis patients by reducing inflammation. CONCLUSIONS: The included studies support the potential role of antioxidant vitamins in the management of endometriosis. Supplementation with antioxidant vitamins effectively reduced the severity of dysmenorrhea, improved dyspareunia and pelvic pain, and enhanced quality of life in these patients. Therefore, antioxidant vitamin therapy could be considered as an alternative treatment method, either alone or in combination with other approaches, for endometriosis-related pain. TRIAL REGISTRATION: PROSPERO registration number: CRD42023415198.

Pathway and network-based analysis of genome-wide association studies and RT-PCR validation in polycystic ovary syndrome.

The purpose of this study was to identify promising candidate genes and pathways in polycystic ovary syndrome (PCOS). Microarray dataset GSE345269 obtained from the Gene Expression Omnibus database includes 7 granulosa cell samples from PCOS patients, and 3 normal granulosa cell samples. Differentially expressed genes (DEGs) were screened between PCOS and normal samples. Pathway enrichment analysis was conducted for DEGs using ClueGO and CluePedia plugin of Cytoscape. A Reactome functional interaction (FI) network of the DEGs was built using ReactomeFIViz, and then network modules were extracted, followed by pathway enrichment analysis for the modules. Expression of DEGs in granulosa cell samples was measured using quantitative RT-PCR. A total of 674 DEGs were retained, which were significantly enriched with inflammation and immune-related pathways. Eight modules were extracted from the Reactome FI network. Pathway enrichment analysis revealed significant pathways of each module: module 0, Regulation of RhoA activity and Signaling by Rho GTPases pathways shared ARHGAP4 and ARHGAP9; module 2, GlycoProtein VI-mediated activation cascade pathway was enriched with RHOG; module 3, Thromboxane A2 receptor signaling, Chemokine signaling pathway, CXCR4-mediated signaling events pathways were enriched with LYN, the hub gene of module 3. Results of RT-PCR confirmed the finding of the bioinformatic analysis that ARHGAP4, ARHGAP9, RHOG and LYN were significantly upregulated in PCOS. RhoA-related pathways, GlycoProtein VI-mediated activation cascade pathway, ARHGAP4, ARHGAP9, RHOG and LYN may be involved in the pathogenesis of PCOS.

Integrated analyses for genetic markers of polycystic ovary syndrome with 9 case-control studies of gene expression profiles.

Due to genetic heterogeneity and variable diagnostic criteria, genetic studies of polycystic ovary syndrome are particularly challenging. Furthermore, lack of sufficiently large cohorts limits the identification of susceptibility genes contributing to polycystic ovary syndrome. Here, we carried out a systematic search of studies deposited in the Gene Expression Omnibus database through August 31, 2016. The present analyses included studies with: 1) patients with polycystic ovary syndrome and normal controls, 2) gene expression profiling of messenger RNA, and 3) sufficient data for our analysis. Ultimately, a total of 9 studies with 13 datasets met the inclusion criteria and were performed for the subsequent integrated analyses. Through comprehensive analyses, there were 13 genetic factors overlapped in all datasets and identified as significant specific genes for polycystic ovary syndrome. After quality control assessment, there were six datasets remained. Further gene ontology enrichment and pathway analyses suggested that differentially expressed genes mainly enriched in oocyte pathways. These findings provide potential molecular markers for diagnosis and prognosis of polycystic ovary syndrome, and need in-depth studies on the exact function and mechanism in polycystic ovary syndrome.

Leptin Levels in Women With Polycystic Ovary Syndrome: A Systematic Review and a Meta-Analysis.

OBJECTIVE: Conflicting results regarding leptin levels in women with polycystic ovary syndrome (PCOS) have been reported. We summarize all available evidence from human participant studies to evaluate leptin levels in PCOS. DATA SOURCES: PubMed, ClinicalTrials.gov , and Web of Science databases were searched with English-language restriction for only human beings from the inception to December 31, 2015. Search terms included PCOS (polycystic ovary syndrome or PCOS) and leptin. METHODS OF STUDY SELECTION: A total of 238 studies were reviewed, and a total of 19 studies, involving 991 women with PCOS and 898 controls, were eligible for our meta-analysis. Studies were eligible if provided leptin means and standard deviation in women with PCOS and healthy women controls. RESULTS: Parameters, such as body mass index, insulin resistance (IR), and total testosterone, which may influence leptin levels were extracted. Data were collected and analyzed by RevMan 5.3 and Stata/SE14.0. The pooling analysis of all relevant studies revealed that leptin levels were significantly higher in patients with PCOS than in controls, with standardized mean difference of 1.62 (95% confidence interval: 1.01-2.23). However, the heterogeneity across studies was considerable and not eliminated in subgroup analyses. Meta-regression analysis further suggested that the heterogeneity might be relevant to variability in IR and study location. CONCLUSION: Elevated leptin levels are detected in women with PCOS compared with non-PCOS controls. Higher leptin levels may be correlated with IR, metabolic disorder, infertility, and even cardiovascular disease risk in PCOS, which may contribute to the etiology and development of PCOS.

Expression of anti-Müllerian hormone in two rat models of polycystic ovary syndrome.

AIM: Anti-Müllerian hormone (AMH) levels are two to three times higher in patients with polycystic ovary syndrome (PCOS), but the mechanism of increased AMH levels in PCOS remains unclear. The purpose of our experiment was to investigate a change in AMH levels in two kinds of commonly used rat models and to determine an ideal model for future research of AMH in the pathogenesis of PCOS. METHODS: Thirty female Sprague Dawley rats were treated using two modeling methods: implantation of a levonorgestrel silastic implant or injection with sodium prasterone sulfate plus human chorionic gonadotropin (hCG). Rats in the control group were implanted with a blank silastic stick. Serum steroid concentrations, ovarian morphology and ovarian expression of AMH and AMH-receptor II (RII) proteins were determined and their correlations were studied. RESULTS: The results from the levonorgestrel and hCG group were closer to those displayed by human PCOS patients than the sodium prasterone sulfate and hCG group. Ovarian local expression of AMH and AMH-RII was increased in these both models compared with the control group; however, an elevation of serum AMH concentration was not observed (12.53 ± 0.99 ng/ml and 13.22 ± 1.09 ng/ml vs 16.30 ± 0.98 ng/ml). CONCLUSION: The levonorgestrel and hCG model is more suitable for the study of PCOS in puberty.

Trends in ectopic pregnancy, hydatidiform mole and miscarriage in the largest obstetrics and gynaecology hospital in China from 2003 to 2013.

BACKGROUND: Ectopic pregnancies, miscarriages and hydatidiform moles are the major types of pathological pregnancies in the early gestations of pregnancy and constitute an important public health problem. The trends and incidences of these pathological pregnancies may vary by ethnicity and geographical regions. This has not been fully investigated in the Chinese population. In this study we retrospectively report the trends of pathological pregnancies in Chinese population. METHODS: Data on 22,511 women with ectopic pregnancy, hydatidiform mole and miscarriage were collected from the largest obstetrics and gynaecology hospital in China from 2003 to 2013. Data included age at diagnosis and the annual number of women with diagnosed ectopic pregnancy, hydatidiform mole and miscarriage. RESULTS: The total number of ectopic pregnancy, hydatidiform mole and miscarriage was increased 3.5folds in 2013 compared to 2003. Ectopic pregnancy is the leading pathological pregnancy and miscarriage is increasing at a greater rate among the pathological pregnancies. The median age of women with hydatidiform mole at diagnosis significantly increased from 25.5 years to 29 years (p = 0.002), however the median age for other pathological pregnancies was not different between 2003 and 2013. The number of women with hydatidiform mole at diagnosis who were over 40 years old has increased. The mean maternal age is increased from 28.1 years old in 2003 to 29.4 years old in 2013 in this hospital. CONCLUSION: We speculate that the increased maternal age may contribute to the increase in these pathological pregnancies between 2003 and 2013 in China.

Visceral adiposity index as a predictor of clinical severity and therapeutic outcome of PCOS.

Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disease which often accompany with abnormal fat distribution. Visceral adiposity has association with abnormal lipid metabolic, pro-inflammatory activity, insulin resistance (IR) and hyperandrogenism. Increased visceral adiposity raises the risk of metabolic syndrome, type 2 diabetes and cardiovascular (CV) events, and aggravates ovulatory dysfunction and hyperandrogenism in PCOS women. Visceral adiposity index (VAI), a simple surrogate maker of visceral adipose dysfunction and visceral adiposity, is a predictor of IR, and link hyperinsulinemia, hyperandrogenism and anovulation. This review aims to discuss the visceral adiposity situation in PCOS women, and suggests that VAI may be a useful predictor of clinical severity and therapeutic outcome of PCOS.

Trends in gynaecological cancers in the largest obstetrics and gynaecology hospital in China from 2003 to 2013.

The incidence and the trend of gynaecological cancers have been suggested to vary by ethnicity and geographical regions. Whether the incidence and type of gynaecological cancers in China is different have not been fully investigated. In this study, we reported the trend of gynaecological cancers in China. Data on 13,518 women with gynaecological cancers were collected from the largest obstetrics and gynaecology hospital in China from 2003 to 2013. Data included age at diagnosis and the annual number of women with diagnosed endometrial, ovarian, cervical cancer and other gynaecological cancers. The number of women with diagnosed gynaecological cancers increased by almost sixfold in 2013 compared to that in 2003. It was largely due to the increase of women with newly diagnosed cervical cancer. The percentage of women with endometrial and ovarian cancer within total gynaecological cancers was decreased, whilst the percentage of cervical cancer significantly increased between 2003 and 2013. The mean age of women with endometrial or ovarian cancer at diagnosis was 53 or 48 years, respectively, which was no difference over 11 years. However, the mean age of women with cervical cancer at diagnosis was significantly delayed from 42 years in 2003 to 46 years since 2011. This was also confirmed by the age-specific distribution of gynaecological cancers over 11 years. Our study found that the age onset of endometrial and ovarian cancer has not changed over 11 years. But the age onset of cervical cancer is delayed since 2011 in China.