The primary site of metastasis for epithelial ovarian cancer (EOC) is the peritoneum, and it occurs through a multistep process that begins with adhesive contacts between cancer cells and mesothelial cells. Despite evidence that Notch signaling has a role in ovarian cancer, it is unclear how exactly it contributes to ovarian cancer omental metastasis, as well as the cellular dynamics and intrinsic pathways that drive this tropism. Here we show that tumor cells produced the Notch ligand Jagged2 is a clinically and functionally critical mediator of ovarian cancer omental metastasis by activating the Notch signaling in single-layered omental mesothelial cells. In turn, Jagged2 promotes tumor growth and therapeutic resistance by stimulating IL-6 release from mesothelial cells. Additionally, Jagged2 is a potent downstream mediator of the omental metastasis cytokine TGF-β that is released during omental destruction. Importantly, therapeutic inhibition of Jagged2-mediated omental metastasis was significantly improved by directly disrupting the Notch pathway in omental mesothelial cells. These findings highlight the key role of Jagged2 to the functional interplay between the TGF-β and the Notch signaling pathways during the metastatic process of ovarian cancer cells to the omentum and identify the Notch signaling molecule as a precision therapeutic target for ovarian cancer metastasis.

Objective: We investigated the potential relationship between endometriosis and risk of ovarian, endometrial, cervical, and breast cancers using the National Inpatient Sample (NIS) database. Methods: We utilized the International Classification of Diseases (ICD-10) system to identify relevant codes from the NIS database (2016–2019). Univariate and multivariate regression analyses (adjusted for age, race, hospital region, hospital teaching status, income Zip score, smoking, alcohol use, and hormonal replacement therapy) were conducted to evaluate the association between endometriosis and gynecologic cancers and summarized as odds ratios (ORs) with 95% confidence intervals (CIs). Results: In the examined dataset, there were 1164 and 225,323 gynecologic cancer patients with and without endometriosis, respectively. Univariate analysis showed endometriosis was significantly associated with a higher risk of ovarian (OR = 3.42, 95% CI: 3.05–3.84, p < 0.001) and endometrial (OR = 3.35, 95% CI: 2.97–3.79, p < 0.001) cancers. There was no significant association between endometriosis and cervical cancer (OR = 1.05, 95% CI: 0.85–1.28, p = 0.663). Interestingly, endometriosis was significantly associated with a low risk of breast cancer (OR = 0.12, 95% CI: 0.10–0.17, p < 0.001). Multivariate analysis after Bonferroni correction (p < 0.006) showed that endometriosis was significantly associated with a high risk of ovarian (adjusted OR = 3.34, 95% CI: 2.97–3.75, p < 0.001) and endometrial (adjusted OR = 3.61, 95% CI: 3.12–4.08, p < 0.001) cancers. Conversely, there was no significant association between endometriosis and cervical cancer (OR = 0.80, 95% CI: 0.65–0.99, p = 0.036). Conclusions: Patients with endometriosis exhibited unique gynecologic cancer risk profiles, with higher risks for ovarian and endometrial cancers, and no significant risk for cervical cancer. The observed connection between endometriosis and a reduced risk of breast cancer remains a perplexing phenomenon, which cannot be put into context to date.

Cancer remains a significant global health concern, and understanding factors that regulate cancer development is important. The microbiome, with its potential role in cancer development, progression, and treatment, has garnered increasing attention in recent years. The cervicovaginal and gastrointestinal microbiomes in females constitute complex biological ecosystems. Although the gut microbiome has been extensively studied, little is known about the cervicovaginal microbiome. The microbiome plays a crucial role in maintaining local microenvironments and tissue homeostasis, but dysbiosis can disrupt this fine balance and contribute to pathological ramifications leading to cancer. This review explores the current understanding of the microbiome’s correlation with gynecological cancers and highlights the potential of microbiome-based interventions to improve outcomes in these cancers. In addition, this review underscores the gaps and limitations in the literature, such as findings in specific ethnicities compared with understudied ethnicities. In addition, discrepancies in molecular techniques and terminology (microbiome vs. microbiota) used in the literature are addressed. Emerging evidence linking gynecological cancers and dysbiosis underscores microbiota as a potential target for cancer prevention and therapy. Manipulating the microbiome, such as through the use of probiotics, prebiotics, antibiotics, or vaginal and fecal transplantation, has demonstrated benefits in the treatment of chronic and inflammatory conditions. Further translational research in this field is needed to integrate the benefits of beneficial microorganisms in the fight against gynecological cancers.

This systematic review and meta-analysis aimed to examine the effect of the antioxidant alpha-lipoic acid (ALA) on various cardiometabolic risk factors and hormonal parameters in patients with polycystic ovary syndrome (PCOS). We searched PubMed, EMBASE, SCOPUS, Cochrane Library, and Web of Science databases without language restrictions until May 2023 to find randomized controlled trials (RCTs) that assessed the impact of ALA supplementation on anthropometric, glycemic, lipid, oxidative stress, and hormonal parameters in women with PCOS. Outcomes were summarized using the standardized mean difference (SMD) and 95% confidence interval (CI) in a random-effects model. An I2 statistic of >60% established significant between-study heterogeneity. The overall certainty of the evidence for each outcome was determined using the grading of recommendations, assessment, development, and evaluations system. Seven RCTs met the inclusion criteria. The ALA group had significant reductions in fasting blood sugar (fasting blood sugar (FBS), n=7 RCTs, SMD, -0.60; 95% CI, -1.10 to -0.10; I2=63.54%, moderate certainty of evidence) and homeostatic model assessment for insulin resistance (homeostatic model assessment of insulin resistance (HOMA-IR), n=4 RCTs, SMD, -2.03; 95% CI, -3.85 to -0.20; I2=96.32%, low certainty of evidence) compared with the control group. However, significant differences were observed between the groups in body mass index, insulin, estrogen, follicle-stimulating hormone, luteinizing hormone, testosterone, low-density lipoprotein, highdensity lipoprotein, triglyceride, total cholesterol, malondialdehyde, or total antioxidant capacity profiles. ALA supplementation improves FBS and HOMA-IR levels in women with PCOS. ALA consumption is an effective complementary therapy for the management of women with PCOS.

PURPOSE:Menopause is associated with disturbances in the metabolism of lipids. Moreover, during the postmenopausal period, female subjects are more prone to develop dyslipidemia. Omega-3 fatty acids, which exert cardioprotective, anti-inflammatory, and lipid-lowering actions, are commonly recommended in postmenopausal women. However, their effect on serum lipids in this population remains unclear. This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to clarify this research question. METHODS:We systematically searched the Web of Science, Scopus, PubMed/MEDLINE, and EMBASE databases from their inception until January 3, 2022. The DerSimonian and Laird random-effects model was used to combine effect sizes. FINDINGS:Omega-3 fatty acid supplementation resulted in a decrease in triglyceride concentrations (weighted mean difference [WMD], -17.8 mg/dL; 95% CI, -26 to -9.6; P < 0.001), particularly in the RCTs that lasted ≤16 weeks (WMD, -18.6 mg/dL), when the baseline triglyceride concentrations were ≥150 mg/dL (WMD, -22.8 mg/dL), in individuals with a body mass index ≥30 kg/m2 (WMD, -19.3 mg/dL), and when the dose of omega-3 fatty acids was ≥1 g/d (WMD, -21.10 mg/dL). LDL-C (WMD, 4.1 mg/dL; 95% CI, 1.80 to 6.36; P < 0.001) and HDL-C (WMD, 2.1 mg/dL; 95% CI, 0.97 to 3.2; P < 0.001) values increased. Total cholesterol levels (WMD, -0.15 mg/dL; 95% CI, -4 to 3.74; P = 0.94) remained unchanged after administration of omega-3 fatty acids. IMPLICATIONS:In postmenopausal women, supplementation with omega-3 fatty acids resulted in a significant reduction in triglyceride concentrations and a modest elevation in HDL-C and LDL-C levels, whereas this intervention did not affect total cholesterol values.

Background and Objectives: Cardiovascular disease (CVD) is a major contributor to the high mortality rate among individuals with ovarian cancer. Nevertheless, there is limited understanding regarding the specific patient attributes that might impact the risk of CVD in this group. Materials and Methods: A retrospective cohort study was performed using the SEER database to analyze primary ovarian cancer cases from 2000 to 2019. Multivariable logistic regression analysis was employed to identify patient characteristics linked to cardiovascular mortality. Results: The cohort included 41,930 cases of patients who were alive, 54,829 cases of cancer-related deaths, 3003 cases of cardiovascular-related deaths, and 10,238 cases with other causes of death. Poorly differentiated cancer cells and distant metastasis were associated with a higher risk of cardiovascular mortality. Logistic regression analysis identified age, year of diagnosis, race, laterality, and staging as significant risk factors for cardiovascular cause of death. The risk of cardiovascular cause of death was lower in patients aged 31–60 and higher in those aged over 60 years old, and the risk also increased with a later year of diagnosis. Patients who were not white were at a higher risk of cardiovascular cause of death. Additionally, bilateral ovarian cancer and distant staging disease were linked to elevated risks of cardiovascular cause of death. Conclusion: Cardiovascular mortality is a significant concern in ovarian cancer patients, and several patient characteristics are associated with an increased risk. Our study suggests that targeted interventions to improve cardiovascular health in high-risk patients, such as those with comorbidities or an advanced stage at diagnosis, may improve survival in this population.

Background and Objectives: Abdominal hysterectomy is a major surgery that is often associated with pronounced postsurgical pain. The objective of this research is to conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) and nonrandomized comparative trials (NCTs) that have surveyed the analgesic benefits and morbidity of intraoperative superior hypogastric plexus (SHP) block (intervention) compared with no SHP block (control) during abdominal hysterectomy. Materials and Methods: The Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, Web of Science, PubMed, Scopus, and Embase were searched from inception until 8 May 2022. The Cochrane Collaboration tool and Newcastle-Ottawa Scale were used to evaluate the risk of bias of RCTs and NCTs, respectively. In a random effects mode, the data were pooled as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). Results: Five studies (four RCTs and one NCT) comprising 210 patients (SHP block = 107 and control = 103) were analyzed. The overall postsurgical pain score (n = 5 studies, MD = -1.08, 95% CI [-1.41, -0.75], p < 0.001), postsurgical opioid consumption (n = 4 studies, MD = -18.90 morphine milligram equivalent, 95% CI, [-22.19, -15.61], p < 0.001), and mean time to mobilization (n = 2 studies, MD = -1.33 h, 95% CI [-1.98, -0.68], p < 0.001) were significantly decreased in the SHP block group contrasted with the control arm. Nevertheless, there was no significant variance between both arms regarding operation time, intraoperative blood loss, postsurgical NSAID consumption, and hospital stay. There were no major side effects or sympathetic block-related aftermaths in both groups. Conclusions: During abdominal hysterectomy and receiving perioperative multimodal analgesia, the administration of intraoperative SHP block is largely safe and exhibits better analgesic effects compared to cases without administration of SHP block.

Cardiovascular disease (CVD) is the greatest cause of premature death and disability globally. Numerous therapeutic strategies have been developed to improve and prevent the adverse cardiovascular events, including nutritional approaches. This systematic review and meta-analysis summarized the evidence on orange juice consumption on CVD risk factors. Four databases were searched up to September 2020. Ten randomized controlled trials were included in the final analysis. Pooled results demonstrated a significant effect of orange juice on glucose (WMD: -2.92 mg/dl, 95% CI: -5.327, -0.530, p = 0.017), insulin (WMD: -1.229 mu U/ml, 95% CI: -2.083, -0.374, p = 0.005), HOMA-IR (WMD: -0.464, 95% CI: -0.747, -0.181, p = 0.001), total cholesterol (WMD: -9.84 mg/dl, 95% CI: -15.43, -4.24, p = 0.001), LDL-C (WMD: -9.14 mg/dl, 95% CI: -15.79, -2.49, p = 0.007), and CRP (WMD: -0.467 mg/l, 95% CI: -0.815, -0.120, p = 0.008) compared to control group. However, the effect of orange juice on body composition factors and other CVD risk factors was not significant compared to control group. These lowering effects of glucose, HOMA-IR, total cholesterol, and LDL-C were robust in subgroups with orange juice consumption >= 500 ml/day. This meta-analysis suggests that orange juice may be beneficial in improving several CVD risk factors.

Objective Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two increasing important problems among children. This study aims to explore the link between maternal polycystic ovary syndrome (PCOS) and the risk of ASD and ADHD in the offspring. Method The MOOSE guidelines were followed in the conduct of this meta-analysis. A literature search was done in PubMed/MEDLINE, Scopus, and Web of Science from inception until January 2021. The DerSimonian and Laird random-effects model was used to estimate the combined risk ratios (RR) and 95% confidence intervals (CI). Sensitivity analysis was also used to investigate the effect of each study on the combined results. Results Seven studies, with 1,358,696 participants, comprising 7,334 ADHD cases and 3,920 ASD cases, were included in this study. Children born to mothers with maternal PCOS had higher risks of developing ASD (RR = 1.46, 95% CI: 1.26-1.69, I-2 = 64%) and ADHD (RR = 1.43, 95% CI: 1.35-1.41, I-2 = 0%) when compared with children born to mothers without maternal PCOS. Conclusion This study showed that there might be a link between maternal PCOS and the risk of developing ASD and ADHD in the offspring. This important issue must be considered in PCOS women during and after pregnancy.

Background and aim: The effect of tamoxifen administration on serum lipids in females remains unclear. The studies which have explored this topic have produced conflicting results, probably due to discrepancies in the length of the intervention, differences in baseline variables or other factors. To answer this research question, we decided to conduct this systematic review and meta-analysis to assess the effects of tamoxifen on the lipid profile in women. Methods: A comprehensive search was conducted in Web of Science, Scopus, PubMed/Medline and Embase, from the inception of these databases up to June 2021. We used a random effects meta-analysis to generate the combined results. Results: The overall findings were generated from 18 eligible trials. As compared to placebo, tamoxifen led to a notable reduction of the total cholesterol (TC) (WMD: 23.03 mg/dL, 95% CI: 25.94 to 20.12, P<0.001), and the low-density lipoprotein-cholesterol (LDL-C) (WMD: 18.68 mg/dL, 95% CI: 24.31 to 13.04, P<0.001). However, tamoxifen did not alter triglycerides (TG) concentrations (WMD: +1.06 mg/dL, 95% CI: 11.08 to 13.20, P = 0.864) significantly. A pronounced reduction of the high-density lipoprotein-cholesterol (HDL-C) was noted in the RCTs with a duration of <= 52 weeks (WMD: 2.06 mg/dL) and when tamoxifen was administered in participants with a BMI >= 25 kg/m(2) (WMD: 1.42 mg/dL). Notable reductions in TC (WMD: 23.57 mg/dL) and LDL-C (WMD: 19.21 mg/dL) was detected when the dose of tamoxifen was >= 20 mg/day. Moreover, a significant reduction of TC (WMD: 20.23 mg/dL) and LDL-C (WMD: 24.13 mg/dL) was observed in the RCTs with a duration of <= 52 weeks. Conclusion: Tamoxifen can alter the lipid profile in females, particularly by decreasing TC, LDL-C and HDL-C. Tamoxifen can further reduce TC and LDL-C if the dose of administration is >= 20 mg/day, the treatment duration is <= 52 weeks and if it prescribed in subjects with dyslipidemia.

Purpose: We aimed to investigate the impact of anas-trozole administration on the traditional components of the lipid profile (ie, total cholesterol [TC], LDL-C, HDL-C, and triglycerides [TGs]) by means of a systematic review and meta-analysis of randomized controlled trials.Methods: We searched the PubMed/Medline, Sco-pus, Embase, and Web of Science databases for relevant randomized controlled trials published in the English language until January 18, 2022. The weighted mean difference (WMD) and 95% CIs were calculated using a random-effects model (DerSimonian and Laird methods).Findings: Anastrozole administration significantly lowered TC concentrations when the treatment duration was <= 3 months (WMD = -2.73 mg/dL; 95% CI, -5.09 to -0.38 mg/dL; P = 0.02) and when the baseline TC concentration was >= 200 mg/dL (WMD = -3.64 mg/dL; 95% CI, -6.30 to -0.98 mg/dL; P = 0.007). HDL-C levels decreased after anastrozole administration when the treatment duration was > 3 months (WMD = -1.67 mg/dL; 95% CI, -3.24 to -0.10 mg/dL; P = 0.03). Anastrozole administration had no impact on TG or LDL-C values.Implications: Anastrozole administration in humans can decrease TC and HDL-C levels but has no effect on LDL-C or TG concentrations. (Clin Ther. 2022;44:1214-1224.) (c) 2022 Elsevier Inc.

Objective: To collate evidence from randomized controlled trials (RCTs) and nonrandomized controlled trials (NCTs) on the efficacy and safety of vasopressin versus passive control (placebo/no treatment) during myomectomy.Methods: Six information sources were screened until 25-June-2022. The Cochrane Collaboration tool and Newcastle-Ottawa Scale were used to evaluate the risk of bias. Data were summarized as mean difference or risk ratio with 95% confidence interval in a random-effects model.Results: Eleven studies, comprising 1067 patients (vasopressin=567 and control=500) were analyzed. For RCTs (n = 8), the overall quality included 'high risk' (n = 4), 'low risk' (n = 2), and 'some concerns' (n = 2). For NCTs (n = 3), the overall quality included 'good' (n = 2) and 'fair' (n = 1). The mean intraoperative blood loss, mean difference in hemoglobin level, mean difference in hematocrit level, rate of perioperative blood trans-fusion, and mean operative time were significantly reduced in favor of the vasopressin group compared with the control group. However, there was no significant difference between both groups regarding the mean hospital stay. Pertaining to safety endpoints, after omission of an outlier study, the rate of drug-related car-diovascular adverse events did not significantly differ between both groups. There was no quantitative evi-dence of publication bias for the endpoint of intraoperative blood loss.Conclusion: Among patients undergoing myomectomy, prophylactic administration of vasopressin was largely safe and correlated with significant reductions in intraoperative blood loss and associated morbidities compared with a passive control intervention. Nonetheless, the conclusions should be cautiously interpreted owing to the low-evidence quality and the used doses varied greatly between studies.(c) 2022 Elsevier Masson SAS. All rights reserved.

Background Inconsistencies exist with regard to the influence of omega-3 supplementation on 25-hydroxyvitamin D (25(OH)D) levels, which could be attributed to many factors, such as the duration and dose of omega-3 supplementation, and individuals' baseline 25(OH)D levels. Therefore, to address the inconsistencies, we conducted a systematic review and dose-response meta-analysis to accurately determine the effect of omega-3 supplementation on 25(OH)D levels in humans. Methods We performed a comprehensive literature search in Web of Science, PubMed/Medline, Scopus, and Embase databases from inception up to January 2020. We included only randomized controlled trials (RCTs). We used weighted mean difference (WMD) with 95% confidence interval (CI) to assess the influence of omega-3 supplementation on serum 25(OH)D levels using the random-effects model. Results Our pooled results of 10 RCTs demonstrated an overall significant increase in 25(OH)D levels following omega-3 intake (WMD = 3.77 ng/ml, 95% CI: 1.29, 6.25). In addition, 25(OH)D levels were significantly increased when the intervention duration lasted >8 weeks and when the baseline serum 25(OH)D level was <20 ng/ml. Moreover, omega-3 intake <= 1000 mg/day resulted in higher 25(OH)D levels compared to omega-3 intake >1000 mg/day. Conclusion In conclusion, omega-3 supplementation increased 25(OH)D concentrations, particularly with dosages <= 1000 mg/day and intervention durations >8 weeks.

We aimed to perform a systematic review and meta-analysis of all randomized placebo-controlled trials (RCTs) that examined the analgesic benefits of preemptive pregabalin among patients undergoing minimally invasive hysterectomy. Five major databases were systematically screened from inception until August 29, 2021 Relevant studies were evaluated for risk of bias. Endpoints were analyzed using the random-effects model and pooled as the mean difference or risk ratio with a 95% confidence interval. Four studies with seven treatment arms met the inclusion criteria. The total sample size was 304 patients: 193 and 111 patients were allocated to the pregabalin and placebo groups, respectively. Overall, the included studies revealed a low risk of bias. The summary results revealed that the mean postoperative pain scores at rest were significantly lower in the pregabalin group than in the control group at 0, 2, 4, 6, 12, and 24 hours. Moreover, the mean postoperative pain scores on movement/coughing were significantly lower in the pregabalin group than in the control group at 12 and 24 hours. The rate of patients who were opioid-free postoperatively was significantly higher in the pregabalin group than in the control group. There was no significant difference between the groups in terms of the mean postoperative time to first rescue analgesic and the rates of adverse events. Compared with placebo, preemptive pregabalin was largely safe, and was correlated with superior analgesic effects in terms of lower postoperative pain scores and higher opioid-sparing effects. Additional RCTs are needed to confirm these findings.

Objective: To conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) that inspected the efficacy and safety of prophylactic TXA compared with control (placebo/no treatment) among women undergoing vaginal delivery on reducing postpartum blood loss and related morbidities. Methods: Six databases were screened from inception until 06-December-2021. The pooled data were summarized as mean difference or risk ratio, respectively, with 95% confidence interval in a fixed- or random-effects model. Results: Sixteen studies comprising 17 RCT treatment arms were included. There were 7122 patients; 3611 and 3511 patients were allocated to prophylactic TXA and control groups, respectively. Overall, the included RCTs had a low risk of bias. Prophylactic TXA correlated with a significant decrease in mean postpartum blood loss and mean change in hemoglobin/hematocrit. Moreover, prophylactic TXA was linked to decreased incidence rates of postpartum hemorrhage, need for blood transfusion, and need for additional uterotonic agents. Nevertheless, prophylactic TXA culminated in significantly higher incidence rates of nausea, vomiting, and diarrhea, all of which were well-tolerated. There was no increased risk of thromboembolic events. Leave-one-out sensitivity analysis confirmed the robustness of efficacy endpoints. There was no publication bias for the endpoint of mean postpartum blood loss. Conclusion: Among patients undergoing vaginal delivery, prophylactic TXA during active management of third stage of labor (AMTSL) appeared largely safe and correlated with a significant decrease in postpartum blood loss and related morbidities compared with control intervention. Prophylactic TXA should be integrated as a "formal" component of AMTSL among women undergoing vaginal delivery. (c) 2022 Elsevier Masson SAS. All rights reserved.

We systematically investigated the efficacy and safety of EMLA (5% lidocaine-prilocaine cream) versus placebo for pain relief among infertile patients undergoing hysterosalpingography (HSG). We screened four databases from inception until 25 November 2020. We included only randomised placebo-controlled trials (RCTs) and assessed their risk of bias. The main efficacy outcomes included safety and pain scores during the different stages of HSG. The pooled outcomes were summarised as mean difference (MD) with 95% confidence interval (CI). Three RCTs were included, comprising 258 patients (131 and 127 patients received EMLA and placebo, respectively). All RCTs revealed an overall low risk of bias. EMLA significantly reduced pain perception during cervical instrumentation of tenaculum and cannula (MD = -1.53, 95% CI [-2.59, -0.47], p = 0.005) and at 24 h after completion of HSG (MD = -1.30, 95% CI [-2.57, -0.03], p = 0.04). Despite EMLA decreased pain perception during the other procedural stages of HSG, the differences were not statistically significant compared with placebo. EMLA was safe and free of local and systemic adverse reactions. This meta-analysis advocates that topical application of 5% EMLA cream is safe and correlates with decreased pain perception during HSG, particularly during the cervical instrumentation step and at 24 h after HSG completion.

Background and aim: The impact of 17 beta-estradiol plus norethisterone acetate administration on serum lipids in women is controversial as previously published studies have produced conflicting results. Thus, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to investigate the effects of 17 beta-estradiol plus norethisterone acetate therapy on total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in females. Methods: We searched the PubMed/MEDLINE, Scopus, Embase, and Web of Science databases for relevant trials published in English until 15 July 2021. The weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated using a random-effects model (the DerSimonian and Laird methods). Results: A total of 32 RCTs were included in the final analysis. Treatment with 17 beta-estradiol plus norethisterone acetate significantly decreased LDL-C (WMD: -13.49 mg/dL, 95% CI: -16.46 to -10.52; P < 0.001), HDL-C (WMD: -3.57 mg/dL, 95% CI: 5.56 to -1.58; P < 0.001), TC (WMD: -19.33 mg/dL, 95% CI: -24.14 to -14.52; P < 0.001), and TG (WMD: -10.86 mg/dL, 95% CI: -16.06 to -5.13; P < 0.001) levels in females. The non-linear dose-response meta-analysis revealed a negative correlation between HDL-C levels and increased treatment periods (P. 0.001). Conclusion: Evidence to date suggests that the administration of 17 beta-estradiol plus norethisterone acetate in females reduces LDL-C, HDL-C, TC, and TG concentrations. Future investigations should clarify whether the reduction in HDL-C following the administration of 17 beta-estradiol plus norethisterone acetate is clinically significant and poses any risks to the subjects who receive this treatment.

Lynch syndrome (LS) is the most common cause of inherited endometrial cancer (EC). The prevalence and molecular characteristic of LS in Middle Eastern women with EC have been underexplored. To evaluate the frequency of LS in a cohort of EC patients from Saudi Arabia, a total of 436 EC cases were screened utilizing immunohistochemistry (IHC), MLH1 promoter methylation analysis and next-generation sequencing technology. A total of 53 of 436 (12.2%) ECs were classified as DNA mismatch repair-deficient (dMMR). MLH1 promoter hypermethylation was detected in 30 ECs (6.9%). Three ECs (0.7%) were found to be LS harboring germline pathogenic variants (PVs)/likely pathogenic variants (LPVs): two in the MSH2 gene and one in the MSH6 gene. Three ECs (0.7%) were Lynch-like syndrome (LLS) carrying double somatic MSH2 PVs/LPVs. Seven cases were found to have variants of uncertain significance in cancer-related genes other than MMR genes. Our results indicate that LS prevalence is low among Saudi EC patients and LLS is as common as LS in this ethnicity. Our findings could help in better understanding of the prevalence and mutational spectrum of this syndrome in Saudi Arabia, which may help in defining best strategies for LS identification, prevention and genetic counseling for EC patients.

To perform a systematic review and meta-analysis of all randomized controlled trials (RCTs) that evaluated the efficacy and safety of prophylactic tranexamic acid (TXA) versus a control (placebo or no treatment) during hysterectomy for benign conditions. Six databases were screened from inception to January 23, 2022. Eligible studies were assessed for risk of bias. Outcomes were summarized as weighted mean differences and risk ratios with 95% confidence intervals in a random-effects model. Five studies, comprising six arms and 911 patients were included in the study. Two and three studies had an overall unclear and low risk of bias, respectively. Estimated intraoperative blood loss, requirement for postoperative blood transfusion, and requirement for intraoperative topical hemostatic agents were significantly reduced in a prophylactic TXA group when compared with a control group. Moreover, postoperative hemoglobin level was significantly higher in the prophylactic TXA group than in the control group. Conversely, the frequency of self-limiting nausea and vomiting was significantly higher in the prophylactic TXA group than in the control group. There were no significant differences between the groups in terms of surgery duration, hospital stay, and diarrhea rate. All the RCTs reported no incidence of major adverse events in either group, such as mortality, thromboembolic events, visual disturbances, or seizures. There was no publication bias for any outcome, and leave-one-out sensitivity analyses demonstrated stability of the findings. Among patients who underwent hysterectomy for benign conditions, prophylactic TXA appeared largely safe and correlated with substantial reductions in estimated intraoperative blood loss and related morbidities.

We systematically investigated the efficacy and safety of EMLA (5% lidocaine-prilocaine cream) versus placebo for pain relief among infertile patients undergoing hysterosalpingography (HSG). We screened four databases from inception until 25 November 2020. We included only randomised placebo-controlled trials (RCTs) and assessed their risk of bias. The main efficacy outcomes included safety and pain scores during the different stages of HSG. The pooled outcomes were summarised as mean difference (MD) with 95% confidence interval (CI). Three RCTs were included, comprising 258 patients (131 and 127 patients received EMLA and placebo, respectively). All RCTs revealed an overall low risk of bias. EMLA significantly reduced pain perception during cervical instrumentation of tenaculum and cannula (MD = -1.53, 95% CI [-2.59, -0.47], p = 0.005) and at 24 h after completion of HSG (MD = -1.30, 95% CI [-2.57, -0.03], p = 0.04). Despite EMLA decreased pain perception during the other procedural stages of HSG, the differences were not statistically significant compared with placebo. EMLA was safe and free of local and systemic adverse reactions. This meta-analysis advocates that topical application of 5% EMLA cream is safe and correlates with decreased pain perception during HSG, particularly during the cervical instrumentation step and at 24 h after HSG completion.