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Journal of Neurosurgery Dec 2023The relationship between patient and meningioma characteristics and hormone receptors (HRs) of progesterone, estrogen, and androgen remains poorly defined despite... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The relationship between patient and meningioma characteristics and hormone receptors (HRs) of progesterone, estrogen, and androgen remains poorly defined despite literature suggesting that meningiomas are sensitive to gonadal steroid hormones. Therefore, the authors sought to collect and compare data on this topic by performing a systematic review and meta-analysis of reported studies of HR status in meningiomas.
METHODS
A MEDLINE PubMed literature review conducted for articles published between January 1, 1951, and December 31, 2020, resulted in 634 unduplicated articles concerning meningiomas and HRs. There were 114 articles that met the criteria of detailed detection protocols for progesterone receptor (PR), estrogen receptor (ER), and/or androgen receptor (AR) using immunohistochemistry (IHC) or ligand-binding (LB) assays and simultaneous reporting of HR status with at least one variable among age, sex, histology, location, grade, or recurrence. Between-study heterogeneity and risk of bias were evaluated using graphical and statistical methods. The authors performed a multilevel meta-analysis using random-effects modeling on aggregated data (n = 4447) and individual participant data (n = 1363) with subgroup results summarized as pooled effects. A mixed-effects meta-regression using individual participant data was performed to analyze independently associated variables.
RESULTS
The 114 selected articles included data for 5810 patients with 6092 tumors analyzed to determine the expression of three HRs in human meningiomas: PRs, ARs, and ERs. The proportions of HR+ meningiomas were estimated to be 0.76 (95% CI 0.72-0.80) for PR+ and 0.50 (95% CI 0.33-0.66) for AR+ meningiomas. ER+ meningioma detection varied depending on the measurement method used and was 0.06 (95% CI 0.03-0.10) with IHC and 0.11 (95% CI 0.06-0.20) with LB assays. There were associations between age and PR and ER expression that varied between male and female patients. PR+ and AR+ were more common in female patients (OR 1.84, 95% CI 1.47-2.29 for PR and OR 4.16, 95% CI 1.62-10.68 for AR). Additionally, PR+ meningiomas were enriched in skull base locations (OR 1.89, 95% CI 1.03-3.48) and meningothelial histology (OR 1.86, 95% CI 1.23-2.81). A meta-regression showed that PR+ was independently associated with age (OR 1.11 95% CI 1.09-1.13; p < 0.0001) and WHO grade I tumors (OR 8.09, 95% CI 3.55-18.44; p < 0.0001). ER+ was negatively associated with meningothelial histology (OR 0.94, 95% CI 0.86-0.98; p = 0.044) and positively associated with convexity location (OR 1.12, 95% CI 1.05-1.18; p = 0.0003).
CONCLUSIONS
The association between HRs and meningioma features has been investigated but unexplained for decades. In this study the authors demonstrated that HR status has a strong association with known meningioma features, including WHO grade, age, female sex, histology, and anatomical location. Identifying these independent associations allows for a better understanding of meningioma heterogeneity and provides a foundation for revisiting targeted hormonal therapy in meningioma on the basis of proper patient stratification according to HR status.
Topics: Humans; Male; Female; Meningioma; Meningeal Neoplasms; Immunohistochemistry; Skull Base; Receptors, Estrogen; Gonadal Steroid Hormones
PubMed: 37243565
DOI: 10.3171/2023.3.JNS221838 -
Harvard Review of PsychiatryRepetitive transcranial magnetic stimulation (rTMS) has emerged as a promising alternative for the treatment of major depressive disorder (MDD), although its clinical...
Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising alternative for the treatment of major depressive disorder (MDD), although its clinical effectiveness varies substantially. The effects of sex hormone fluctuations on cortical excitability have been identified as potential factors that can explain this variability. However, data on how sex hormone changes affect clinical response to rTMS is limited. To address this gap, we reviewed the literature examining the effects of sex hormones and hormonal treatments on transcranial magnetic stimulation (TMS) measures of cortical excitability. Results show that variations of endogenous estrogen, testosterone, and progesterone have modulatory effects on TMS-derived measures of cortical excitability. Specifically, higher levels of estrogen and testosterone were associated with greater cortical excitability, while higher progesterone was associated with lower cortical excitability. This highlights the importance of additional investigation into the effects of hormonal changes on rTMS outcomes and circuit-specific physiological variables. These results call for TMS clinicians to consider performing more frequent motor threshold (MT) assessments in patients receiving high doses of estrogen, testosterone, and progesterone in cases such as in vitro fertilization, hormone replacement therapy, and gender-affirming hormonal treatments. It may also be important to consider physiological hormonal fluctuations and their impact on depressive symptoms and the MT when treating female patients with rTMS.
Topics: Humans; Female; Transcranial Magnetic Stimulation; Depressive Disorder, Major; Progesterone; Evoked Potentials, Motor; Cortical Excitability; Estrogens; Testosterone
PubMed: 37171472
DOI: 10.1097/HRP.0000000000000366 -
Frontiers in Human Neuroscience 2023First, to discuss sex differences in auditory function between women and men, and whether cyclic fluctuations in levels of female sex hormones (i.e., estradiol and... (Review)
Review
AIMS
First, to discuss sex differences in auditory function between women and men, and whether cyclic fluctuations in levels of female sex hormones (i.e., estradiol and progesterone) affect auditory function in pre-menopausal and post-menopausal women. Second, to systematically review the literature concerning the discussed patterns in order to give an overview of the methodologies used in research. Last, to identify the gap in knowledge and to make recommendations for future work.
METHODS FOR THE SYSTEMATIC REVIEW
Population, Exposure, Control, Outcome and Study design (PECOS) criteria were used in developing the review questions. The review protocol follows the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was pre-registered in the Prospective Register of Systematic Reviews (PROSPERO; CRD42020201480). Data Sources: EMBASE, PubMed, MEDLINE (Ovid), PsycINFO, ComDisDome, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL) via Cochrane Library, and scanning reference lists of relevant studies, and internet resources (i.e., Mendeley) were used. Only studies published between 1999 and 2022, in English, or in English translation, were included. The quality of evidence was assessed using the Newcastle-Ottawa Scale (NOS).
RESULTS
Sex differences: Women had more sensitive hearing (measured at the level of peripheral and central auditory system) than men. Cyclic fluctuations: Auditory function in women fluctuated during the menstrual cycle, while no such fluctuations in men over the same time period were reported. Hearing sensitivity improved in women during the late follicular phase, and decrease during the luteal phase, implying an effect of female sex hormones, although the specific effects of estradiol and progesterone fluctuations on the central auditory system remain unclear. Hearing sensitivity in women declined rapidly at the onset of menopause.
CONCLUSION
The review has shown the following. Consistent sex differences exist in auditory function across the auditory pathway with pre-menopausal women often showing better function than age-matched men. Moreover, pre-menopausal women show fluctuations in hearing function across the menstrual cycle with a better function during the peak of estradiol or when the ratio of estradiol to progesterone is high. Third, menopause marks the onset of hearing loss in women, characterized by a rapid decline in hearing sensitivity and a more pronounced loss than in age-matched men. Finally, the systematic review highlights the need for well-designed and -controlled studies to evaluate the influence of estradiol and progesterone on hearing by consistently including control groups (e.g., age-matched man), using objective tests to measure hormonal levels (e.g., in saliva or blood), and by testing participants at different points across the menstrual cycle.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020201480, identifier CRD42020201480.
PubMed: 37151900
DOI: 10.3389/fnhum.2023.1077409 -
Frontiers in Oncology 2023Aberrant expression of fatty acid synthase (FASN) was demonstrated in various tumors including breast cancer. A meta-analysis was conducted to investigate the role of... (Review)
Review
BACKGROUND
Aberrant expression of fatty acid synthase (FASN) was demonstrated in various tumors including breast cancer. A meta-analysis was conducted to investigate the role of FASN in breast cancer development and its potential prognostic significance.
METHODS
The Web of Science, PubMed, Embase, and Cochrane Library databases were searched to identify studies that evaluated the relationship between FASN expression and overall survival (OS), relapse-free survival (RFS), and disease-free survival (DFS) of breast cancer patients. To analyze the clinicopathological and prognostic values of FASN expression in breast cancer, pooled hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were clustered based on random-effects models. To confirm whether the findings were stable and impartial, a sensitivity analysis was performed, and publication bias was estimated. Data were analyzed using Engauge Digitizer version 5.4 and Stata version 15.0.
RESULTS
Five studies involving 855 participants were included. Patients with higher FASN expression did not have a shorter survival period compared to those with lower FASN expression (summary HR: OS, 0.73 [95% CI, 0.41-1.32; P=0.300]; DFS/RFS, 1.65 [95% CI, 0.61-4.43; P=0.323]). However, increased FASN expression was correlated with large tumor size (OR, 2.04; 95% CI, 1.04-4.00; P=0.038), higher human epidermal growth factor receptor 2 (HER2) positivity (OR, 1.53; 95% CI, 1.05-2.23; P=0.028). No significant associations were observed between FASN expression and histological grade (OR, 0.92; 95% CI, 0.41-2.04; P=0.832), Tumor Node Metastasis (TNM) stage (OR, 1.11; 95% CI, 0.49-2.53; P=0.795), nodal metastasis (OR, 1.42; 95% CI, 0.84-2.38; P=0.183), Ki-67 labelling index (OR, 0.64; 95% CI, 0.15-2.63; P=0.533), estrogen receptor (ER) status (OR, 0.90; 95% CI, 0.61-1.32; P=0.586), or progesterone receptor (PR) status (OR, 0.67; 95% CI, 0.29-1.56; P=0.354).
CONCLUSION
FASN is associated with HER2 expression and may contribute to tumor growth, but it has no significant impact on the overall prognosis of breast cancer.
PubMed: 37124526
DOI: 10.3389/fonc.2023.1153076 -
Advances in Nutrition (Bethesda, Md.) Jul 2023Breast cancer (BC) poses an important burden of disease, which probably could be reduced by adopting healthy lifestyles like healthy body weight, healthy diet, and... (Meta-Analysis)
Meta-Analysis Review
Breast cancer (BC) poses an important burden of disease, which probably could be reduced by adopting healthy lifestyles like healthy body weight, healthy diet, and physical activity, among others. Many studies have reported that adherence to healthy lifestyles may decrease BC risk. The main objective of this study was to estimate a summary association of studies evaluating a healthy lifestyle index and BC risk. A systematic review and meta-analysis following the Cochrane methodology were carried out. Observational studies, including healthy lifestyle indices and their association with BC, were searched from 4 databases. For the meta-analysis, random-effects model was used to evaluate overall BC risk, BC by molecular subtype and menopausal status. Thirty-one studies were included in the systematic review, and 29 studies in the meta-analysis. When the highest vs. the lowest category to a healthy lifestyle index were compared, the study identified a 20% risk reduction for BC in prospective studies (hazard ratio [HR] 0.80 95% CI: 0.78, 0.83) and an odds ratio (OR) of 0.74 (95% CI: 0.63, 0.86) for retrospective studies. The inverse association remained statistically significant when stratified by menopausal status, except for premenopausal BC in prospective studies. Furthermore, an inverse association was found for molecular subtypes estrogen receptor (ER+)/progesterone receptor (PR+): HR = 0.68 (95%CI: 0.63, 0.73), ER+/PR-: HR = 0.78 (95% CI: 0.67, 0.90) and ER-/PR-: HR = 0.77 (95% CI: 0.64, 0.92). Most studies scored at a low risk of bias and a moderate score for the certainty of the evidence. Adherence to a healthy lifestyle reduces the risk of BC, regardless of its molecular subtypes, which should be considered a priority to generate recommendations for BC prevention at a population level. International prospective register of systematic reviews (PROSPERO) ID: CRD42021267759.
Topics: Humans; Female; Breast Neoplasms; Prospective Studies; Retrospective Studies; Risk; Life Style; Risk Factors
PubMed: 37085092
DOI: 10.1016/j.advnut.2023.04.007 -
Chinese Medical Journal Apr 2023Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer (CRC). We performed a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer (CRC). We performed a network meta-analysis to summarize such evidence and assess the efficacy and safety of these agents.
METHODS
We searched PubMed, Embase, and the Cochrane Library for studies published in English until October 31, 2021 that fit our inclusion criteria. We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of candidate agents (low-dose aspirin [Asp], high-dose Asp, cyclooxygenase-2 inhibitors [coxibs], calcium, vitamin D, folic acid, ursodeoxycholic acid [UDCA], estrogen, and progesterone, alone or in combination) for preventing colorectal adenoma and CRC. Cochrane risk-of-bias assessment tool was employed to evaluate the quality of each included study.
RESULTS
Thirty-two randomized controlled trials (278,694 participants) comparing 13 different interventions were included. Coxibs significantly reduced the risk of colorectal adenoma (risk ratio [RR]: 0.59, 95% confidence interval [CI]: 0.44-0.79, six trials involving 5486 participants), advanced adenoma (RR: 0.63, 95% CI: 0.43-0.92, four trials involving 4723 participants), and metachronous adenoma (RR: 0.58, 95% CI: 0.43-0.79, five trials involving 5258 participants) compared with placebo. Coxibs also significantly increased the risk of severe adverse events (RR: 1.29, 95% CI: 1.13-1.47, six trials involving 7109 participants). Other interventions, including Asp, folic acid, UDCA, vitamin D, and calcium, did not reduce the risk of colorectal adenoma in the general and high-risk populations compared with placebo.
CONCLUSIONS
Considering the balance between benefits and harms, regular use of coxibs for prevention of colorectal adenoma was not supported by the current evidence. Benefit of low-dose Asp for chemoprevention of colorectal adenoma still requires further evidence.
REGISTRATION
PROSPERO, No. CRD42022296376.
Topics: Humans; Cyclooxygenase 2 Inhibitors; Calcium; Network Meta-Analysis; Vitamins; Colorectal Neoplasms; Chemoprevention; Aspirin; Adenoma; Vitamin D
PubMed: 37027286
DOI: 10.1097/CM9.0000000000002514 -
Frontiers in Medicine 2023Preterm birth is the leading cause of childhood mortality and morbidity. We aimed to provide a comprehensive systematic review on randomized controlled trials (RCTs) on... (Review)
Review
BACKGROUND
Preterm birth is the leading cause of childhood mortality and morbidity. We aimed to provide a comprehensive systematic review on randomized controlled trials (RCTs) on progesterone, cerclage, pessary, and acetylsalicylic acid (ASA) to prevent preterm birth in asymptomatic women with singleton pregnancies defined as risk of preterm birth and multifetal pregnancies.
METHODS
Six databases (including PubMed, Embase, Medline, the Cochrane Library) were searched up to February 2022. RCTs published in English or Scandinavian languages were included through a consensus process. Abstracts and duplicates were excluded. The trials were critically appraised by pairs of reviewers. The Cochrane risk-of-bias tool was used for risk of bias assessment. Predefined outcomes including preterm birth, perinatal/neonatal/maternal mortality and morbidity, were pooled in meta-analyses using RevMan 5.4, stratified for high and low risk of bias trials. The certainty of evidence was assessed using the GRADE approach. The systematic review followed the PRISMA guideline.
RESULTS
The search identified 2,309 articles, of which 87 were included in the assessment: 71 original RCTs and 16 secondary publications with 23,886 women and 32,893 offspring. Conclusions were based solely on trials with low risk of bias ( = 50).Singleton pregnancies: Progesterone compared with placebo, reduced the risk of preterm birth <37 gestational weeks: 26.8% vs. 30.2% (Risk Ratio [RR] 0.82 [95% Confidence Interval [CI] 0.71 to 0.95]) (high certainty of evidence, 14 trials) thereby reducing neonatal mortality and respiratory distress syndrome. Cerclage probably reduced the risk of preterm birth <37 gestational weeks: 29.0% vs. 37.6% (RR 0.78 [95% CI 0.69 to 0.88]) (moderate certainty of evidence, four open trials). In addition, perinatal mortality may be reduced by cerclage. Pessary did not demonstrate any overall effect. ASA did not affect any outcome, but evidence was based on one underpowered study.Multifetal pregnancies: The effect of progesterone, cerclage, or pessary was minimal, if any. No study supported improved long-term outcome of the children.
CONCLUSION
Progesterone and probably also cerclage have a protective effect against preterm birth in asymptomatic women with a singleton pregnancy at risk of preterm birth. Further trials of ASA are needed. Prevention of preterm birth requires screening programs to identify women at risk of preterm birth.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021234946].
PubMed: 36936217
DOI: 10.3389/fmed.2023.1111315 -
Archives of Gynecology and Obstetrics Jan 2024The immune system is influenced by many factors, including female sex hormones. The extent of this influence, however, is not completely understood so far. This... (Review)
Review
PURPOSE
The immune system is influenced by many factors, including female sex hormones. The extent of this influence, however, is not completely understood so far. This systematic literature review aims at giving an overview of the existing concepts on how endogenous progesterone influences the female immune system along the menstrual cycle.
METHODS
The inclusion criteria were healthy female subjects in their reproductive age with a regular menstrual cycle. The exclusion criteria were exogenous progesterone, animal models, nonhealthy study populations and pregnancy. This led to 18 papers covered in this review. The search was performed using the databases EMBASE, Ovid MEDLINE and Epub, and the last search was conducted on September 18, 2020. Our findings were analyzed in four categories: cellular immune defense, humoral immune defense, objective and subjective clinical parameters.
RESULTS
We demonstrated that progesterone acts in an immunosuppressive way, favoring a Th-2-like cytokine profile. Further, we showed that progesterone inhibits mast cell degranulation and relaxes smooth muscle cells. Furthermore, we found supporting evidence for a so-called window of vulnerability after ovulation, where immune functions are lowered and mediated through progesterone.
CONCLUSION
The clinical relevance of these findings is not completely understood yet. As the sample sizes of included studies were rather small and the content of them was broad, further investigations are needed to define to which extent the described changes actually clinically meaningful, whether they are capable of influencing the female health and how these findings can be used to increase well-being.
Topics: Female; Humans; Immune System; Menstrual Cycle; Ovulation; Progesterone; Reproduction
PubMed: 36933040
DOI: 10.1007/s00404-023-06996-9 -
Heliyon Mar 2023Sex steroids are powerful modulators of the immune system and they may affect the immune response and inflammatory consequences of COVID-19. This systematic review aims...
Sex steroids are powerful modulators of the immune system and they may affect the immune response and inflammatory consequences of COVID-19. This systematic review aims to explore the impact of sex steroids on COVID-19 mortality and complications. We looked up the keywords of the study in Scopus, PubMed, and Web of Science. All related original articles published in English, as of October 16, 2021, were reviewed to be included in our research. Concerns regarding the effect of sex hormones on COVID-19, eight full texts have been identified for the conclusion. In these studies, the relationship between estradiol and COVID-19 mortality has been mentioned. The most significant findings were the higher COVID-19 mortality rate in men, compared to women; also, in menopausal women compared to younger women and who received estradiol. In two studies, oral contraceptive pills had a protective effect on the morbidity of SARS-CoV-2 infection. In a randomized controlled trial, subcutaneous injection of progesterone in hospitalized men significantly reduced their symptoms and need for oxygen therapy. Hormone replacement therapy was positively associated with reducing COVID-19 symptoms. Although the results were insufficient for a conclusion, this study represents estrogen as an appropriate pharmacological method for preventing and diminishing the inflammation related to COVID-19 disease. However, future prospective studies and clinical trials are needed to clarify and approve this protective effect.
PubMed: 36873532
DOI: 10.1016/j.heliyon.2023.e14218 -
Talanta Jun 2023The hormones human chorionic gonadotropin, progesterone, estrogen and four of its metabolites (estradiol, estrone, estriol, estetrol), as well as relaxin play an... (Review)
Review
The hormones human chorionic gonadotropin, progesterone, estrogen and four of its metabolites (estradiol, estrone, estriol, estetrol), as well as relaxin play an essential role in the development of the fetus during the first trimester. Imbalances in these hormones during the first trimester have been directly linked to miscarriages. However, frequent monitoring of the hormones is limited by the current conventional centralized analytical tools that do not allow a rapid response time. Electrochemical sensing is considered an ideal tool to detect hormones owing to its advantages such as quick response, user-friendliness, low economic costs, and possibility of use in point-of-care settings. Electrochemical detection of pregnancy hormones is an emerging field that has been demonstrated primarily at research level. Thus, it is timely with a comprehensive overview of the characteristics of the reported detection techniques. This is the first extensive review focusing on the advances related to electrochemical detection of hormones linked to the first trimester of pregnancy. Additionally, this review offers insights into the main challenges that must be addressed imminently to ensure progress from research to clinical applications.
Topics: Pregnancy; Female; Humans; Pregnancy Trimester, First; Hormones; Estradiol; Estrone; Progesterone; Estrogens; Estriol; Chorionic Gonadotropin
PubMed: 36870154
DOI: 10.1016/j.talanta.2023.124396