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: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.
Project description:BACKGROUND:Although pre-puberty asthma is more prevalent in males, after puberty through middle-age, asthma is more prevalent in females. The surge of sex hormones with puberty might explain this gender switch. METHODS:To examine the effects of sex hormones on lung function and symptoms with puberty, Tanner stage was assessed in 187 children 6-18 years of age (59% severe) enrolled in the NIH/NHLBI Severe Asthma Research Program (SARP). The effects of circulating sex hormones (n?=?68; testosterone, dehydroepiandrosterone sulfate (DHEA-S), estrogen, and progesterone) on lung function and 4 week symptom control (ACQ6) in cross-section were tested by linear regression. RESULTS:From pre-/early to late puberty, lung function did not change significantly but ACQ6 scores improved in males with severe asthma. By contrast females had lower post-BD FEV1% and FVC% and worse ACQ6 scores with late puberty assessed by breast development. In males log DHEA-S levels, which increased by Tanner stage, associated positively with pre- and post-BD FEV1%, pre-BD FVC %, and negatively (improved) with ACQ6. Patients treated with high-dose inhaled corticosteroids had similar levels of circulating DHEA-S. In females, estradiol levels increased by Tanner stage, and associated negatively with pre-BD FEV1% and FVC %. CONCLUSIONS:These results support beneficial effects of androgens on lung function and symptom control and weak deleterious effects of estradiol on lung function in children with asthma. Longitudinal data are necessary to confirm these cross-sectional findings and to further elucidate hormonal mechanisms informing sex differences in asthma features with puberty. TRIAL REGISTRATION:ClinicalTrials.gov registration number: NCT01748175 .
Project description:Trichotillomania is several times more common in women and has peak onset around puberty. The role of sex hormones, however, has received little research. 11 adolescent girls with trichotillomania, post-menarche and not taking birth control, were examined on a variety of clinical measures. Participants provided saliva samples for analysis of estradiol, progesterone, and testosterone levels. Lower progesterone was associated with more severe symptoms and lower levels of all hormones were associated with worse overall functioning. Adolescents with trichotillomania exhibit a range of hormone levels but that lower levels of certain hormones may have important clinical associations.