Project description:IntroductionPregnancy is associated with several hormonal changes which influence the developing fetus. Variations in maternal endogenous hormones and prepregnancy use of hormonal preparations have been linked to asthma and allergy in the offspring, but findings are inconsistent. We plan to undertake a systematic review to synthesise the evidence on the association between endogenous and exogenous maternal sex hormones and the risk of asthma and allergy in the offspring.Methods and analysisWe will search Medline, Embase, Cochrane Library, Institute of Scientific Information Web of Science, Cumulative Index of Nursing and Allied Health, Scopus, Google Scholar, Allied and Complementary Medicine Database, Global Health, Psychological Information (PsycINFO), Centre for Agriculture and Bioscience (CAB) International and WHO Global Health Library from inception until 2016 to identify relevant studies on the topic. Additional studies will be identified by searching databases of proceedings of international conferences, contacting international experts in the field and searching the references cited in identified studies. We will include analytical epidemiological studies. Two researchers will independently screen identified studies, undertake data extraction and assess risk of bias in eligible studies, while a third reviewer will arbitrate any disagreement. We will use the Effective Public Health Practice Project tool to assess the risk of bias in the studies. We will perform a random-effects meta-analysis to synthesise the evidence. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to rate the strength and quality of the overall evidence with respect to each outcome.Ethics and disseminationEthical approval is not required since the study is a systematic review of published literature. Our findings will be reported in a peer-reviewed scientific journal.Prospero registration numberCRD42016048324.
Project description:IntroductionFemale sex steroid hormones have been implicated in sex-related differences in the development and clinical outcomes of asthma. The role of exogenous sex steroids, however, remains unclear. Our recent systematic review highlighted the lack of high-quality population-based studies investigating this subject. We aim to investigate whether the use of hormonal contraception and hormone replacement therapy (HRT), subtypes and route of administration are associated with asthma onset and clinical outcomes in reproductive age and perimenopausal/postmenopausal females.Methods and analysisUsing the Optimum Patient Care Research Database (OPCRD), a national primary care database in the UK, we will construct a retrospective longitudinal cohort of reproductive age (16-45 years) and perimenopausal/postmenopausal (46-70 years) females. We will estimate the risk of new-onset asthma using Cox regression and multilevel modelling for repeated asthma outcomes, such as asthma attacks. We will adjust for confounding factors in all analyses. We will evaluate interactions between the use of exogenous sex hormones and body mass index and smoking by calculating the relative excess risk due to interaction and the attributable proportion due to interaction. With 90% power, we need 23 700 reproductive age females to detect a 20% reduction (risk ratio 0.8) in asthma attacks for use of any hormonal contraception and 6000 perimenopausal/postmenopausal females to detect a 40% (risk ratio 1.40) increased risk of asthma attacks for use of any HRT.Ethics and disseminationWe have obtained approval (ADEPT1317) from the Anonymised Data Ethics and Protocol Transparency Committee which grants project-specific ethics approvals for the use of OPCRD data. Optimum Patient Care has an existing NHS Health Research Authority ethics approval for the use of OPCRD data for research (15/EM/150). We will present our findings at national and international scientific meetings and publish the results in international peer-reviewed journals.Trial registration numberEUPAS22967.
Project description:BackgroundPublished findings suggest sex differences in lung cancer risk and a potential role for sex steroid hormones. Our aim was to perform a meta-analysis to investigate the effects of sex steroid hormone exposure specifically on the risk of lung cancer in women.MethodsThe PubMed, MEDLINE, Web of Science, and EMBASE databases were searched. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for female lung cancer risk associated with sex steroid hormones were calculated overall and by study design, publication year, population, and smoking status. Sensitivity analysis, publication bias, and subgroup analysis were performed.ResultsForty-eight studies published between 1987 and 2019 were included in the study with a total of 31,592 female lung cancer cases and 1,416,320 subjects without lung cancer. Overall, higher levels of sex steroid hormones, both endogenous (OR: 0.92, 95% CI: 0.87-0.98) and exogenous (OR: 0.86, 95% CI: 0.80-0.93), significantly decreased the risk of female lung cancer by 10% (OR: 0.90, 95% CI: 0.86-0.95). The risk of lung cancer decreased more significantly with a higher level of sex steroid hormones in non-smoking women (OR: 0.88, 95% CI: 0.78-0.99) than in smoking women (OR: 0.98, 95% CI: 0.77-1.03), especially in Asia women (OR: 0.84, 95% CI: 0.74-0.96).ConclusionsOur meta-analysis reveals an association between higher levels of sex steroid hormone exposure and the decreased risk of female lung cancer. Surveillance of sex steroid hormones might be used for identifying populations at high risk for lung cancer, especially among non-smoking women.
Project description:IntroductionThe role of female sex hormones and their influence on asthma's development and natural history remain uncertain. Our study aims to enhance understanding of exogenous sex hormones' role in asthma development and manifestation, considering phenotypic heterogeneity and focusing on metabolic syndrome-linked asthma that has shown increased severity in females.Methods and analysisA cohort study using primary care data from the Clinical Practice Research Datalink (CPRD) databases linked with additional data sources (Hospital Episode Statistics, ethnicity and deprivation) will include individuals aged 16-70 years, spanning 1 January 2005 to 31 December 2019. We will use appropriate statistical learning methods depending on the outcome: extended Cox regression for late-onset asthma; Poisson or negative binomial regression for asthma exacerbations; binary logistic regression for asthma control; and ordered logistic regression for asthma severity. Asthma exacerbation will be defined based on the American Thoracic Society/European Respiratory Society Task Force definition as the presence of either one of an asthma-related accident and emergency department visit, an asthma-related (unscheduled) hospital admission or an acute course of oral corticosteroids (OCS) with evidence of asthma-related medical event and/or review within 2 weeks of OCS prescription. Poor asthma control in any given month will be defined by the occurrence of an exacerbation episode or use of short-acting beta agonist. Asthma severity will be defined based on the British Thoracic Society asthma severity steps. Asthma phenotypes will be identified using k-means clustering. Analyses will be undertaken using both GOLD and Aurum to ensure coverage across UK nations.Ethics and disseminationCPRD has received ethics approval from the Health Research Authority (East Midlands-Derby, REC reference number 21/EM/065) to support research using anonymised data. Approval to conduct this study was obtained through CPRD's Research Data Governance process. The results will be disseminated through academic publications and conference presentations, contributing to the understanding and practice of asthma management, particularly in the context of the impacts of exogenous sex steroid hormones.
Project description:BackgroundEvidence on the role of exogenous female sex steroid hormones in asthma development in women remains conflicting. We sought to quantify the potential causal role of hormonal contraceptives and menopausal hormone therapy (MHT) in the development of asthma in women.MethodsWe conducted a matched case-control study based on the West Sweden Asthma Study, nested in a representative cohort of 15,003 women aged 16-75 years, with 8-year follow-up (2008-2016). Data were analyzed using Frequentist and Bayesian conditional logistic regression models.ResultsWe included 114 cases and 717 controls. In Frequentist analysis, the odds ratio (OR) for new-onset asthma with ever use of hormonal contraceptives was 2.13 (95% confidence interval [CI] 1.03-4.38). Subgroup analyses showed that the OR increased consistently with older baseline age. The OR for new-onset asthma with ever MHT use among menopausal women was 1.17 (95% CI 0.49-2.82). In Bayesian analysis, the ORs for ever use of hormonal contraceptives and MHT were, respectively, 1.11 (95% posterior interval [PI] 0.79-1.55) and 1.18 (95% PI 0.92-1.52). The respective probability of each OR being larger than 1 was 72.3% and 90.6%.ConclusionsAlthough use of hormonal contraceptives was associated with an increased risk of asthma, this may be explained by selection of women by baseline asthma status, given the upward trend in the effect estimate with older age. This indicates that use of hormonal contraceptives may in fact decrease asthma risk in women. Use of MHT may increase asthma risk in menopausal women.
Project description:Preclinical data suggest that endogenous sex steroid hormones may be implicated in colorectal cancer (CRC) development, however, findings from epidemiological studies are conflicting. The aim of this systematic review and meta-analysis was to investigate the associations between endogenous concentrations of sex hormones and CRC risk. PubMed and Scopus were searched until June 2020 for prospective studies evaluating the association between pre-diagnostic plasma/serum concentrations of estradiol, testosterone and sex-hormone binding globulin (SHBG) and CRC risk. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated using the inverse-variance weighted random-effects model based on the DerSimonian-Laird estimator. Eight studies were included in the meta-analysis after evaluating 3,859 non-duplicate records. Four of the eight studies had a nested case-control design, one study was a case-cohort and the rest three studies were cohort studies, and they included on average 295 cases (range:48-732) and 2,105 controls. No associations were found for endogenous sex steroid hormones in men or post-menopausal women with CRC risk, with evidence for substantial heterogeneity observed among women. Findings from this meta-analysis do not support presence of associations between pre-diagnostic concentrations of testosterone, estradiol and SHBG with incident CRC risk in men and post-menopausal women.
Project description:Sex steroid hormones and inflammatory biomarkers are both associated with the development and progression of chronic diseases, but their interrelationship is relatively uncharacterized. We examined the association of sex hormones and sex hormone-binding globulin (SHBG) with biomarkers of inflammation, C-reactive protein (CRP) and white blood cell (WBC) count. The study included data from 809 adult men in the National Health and Nutrition Examination Survey 1999-2004. Geometric means and 95% confidence intervals were estimated separately for CRP and WBC concentrations by sex steroid hormones and SHBG using weighted linear regression models. Higher concentrations of total (slope per one quintile in concentration, -0.18; p-trend, 0.001) and calculated free (slope, -0.13; p-trend, 0.03) testosterone were statistically significantly associated with lower concentrations of CRP, but not with WBC count. Men in the bottom quintile of total testosterone (?3.3 ng/mL), who might be considered to have clinically low testosterone, were more likely to have elevated CRP (?3 mg/L) compared with men in the top four quintiles (OR, 1.61; 95% CI, 1.00-2.61). Total and calculated free estradiol (E2) were positively associated with both CRP (Total E2: slope, 0.14; p-trend, <0.001; Free E2: slope, 0.15; p-trend, <0.001) and WBC (Total E2: slope, 0.02; p-trend, 0.08; Free E2: slope, 0.02; p-trend, 0.02) concentrations. SHBG concentrations were inversely associated with WBC count (slope, -0.03; p-trend, 0.04), but not with CRP. These cross-sectional findings are consistent with the hypothesis that higher androgen and lower oestrogen concentrations may have an anti-inflammatory effect in men.
Project description:Rationale: Women have a higher burden of asthma than men. Although sex hormones may explain sex differences in asthma, their role is unclear.Objectives: To examine sex hormone levels and asthma in adults.Methods: Cross-sectional study of serum levels of free testosterone and estradiol and current asthma in 7,615 adults (3,953 men and 3,662 women) aged 18-79 years who participated in the 2013-2014 and 2015-2016 U.S. National Health and Nutrition Examination Survey. Logistic regression was used for the multivariable analysis of sex hormones and current asthma, which was conducted separately in women and men.Measurements and Main Results: Free testosterone levels in the fourth quartile were associated with lower odds of current asthma in women (odds ratio [OR] for the fourth quartile [Q4] vs. Q1, 0.56; 95% confidence interval [CI], 0.39-0.80). Given an interaction between obesity and sex hormones on current asthma, we stratified the analysis by obesity. In this analysis, elevated free testosterone (OR for Q4 vs. Q1, 0.59; 95% CI, 0.37-0.91) and estradiol (OR for Q4 vs. Q1, 0.43; 95% CI, 0.23-0.78) levels were associated with reduced odds of current asthma in obese women, and an elevated serum estradiol was associated with lower odds of current asthma in nonobese men (OR for Q4 vs. Q1, 0.44; 95% CI, 0.21-0.90).Conclusions: Our findings suggest that sex hormones play a role in known sex differences in asthma in adults. Moreover, our results suggest that obesity modifies the effects of sex hormones on asthma in adults.
Project description:Males and females show differential patterns in connectivity in resting-state networks (RSNs) during normal aging, from early adulthood to late middle age. Age-related differences in network integration (effectiveness of specialized communication at the global network level) and segregation (functional specialization at the local level of specific brain regions) may also differ by sex. These differences may be due at least in part to endogenous hormonal fluctuation, such as that which occurs in females during midlife with the transition to menopause when levels of estrogens and progesterone drop markedly. A limited number of studies that have investigated sex differences in the action of steroid hormones in brain networks. Here we investigated how sex steroid hormones relate to age-network relationships in both males and females, with a focus on network segregation. Females displayed a significant quadratic relationship between age and network segregation for the cerebellar-basal ganglia and salience networks. In both cases, segregation was still increasing through adulthood, highest in midlife, and with a downturn thereafter. However, there were no significant relationships between sex steroid hormone levels and network segregation levels in females, and they did not exhibit significant associations between progesterone or 17β-estradiol and network segregation. Patterns of connectivity between the cerebellum and basal ganglia have been associated with cognitive performance and self-reported balance confidence in older adults. Together, these findings suggest that network segregation patterns with age in females vary by network, and that sex steroid hormones are not associated with this measure of connectivity in this cross-sectional analysis. Though this is a null effect, it remains critical for understanding the extent to which hormones relate to brain network architecture.