High estradiol and low testosterone levels are associated with critical illness in male but not in female COVID-19 patients: a retrospective cohort study.
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ABSTRACT:
SUBMITTER: Schroeder M
PROVIDER: S-EPMC8451658 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The prevailing view of sexual differentiation of mammalian brain is that androgen synthesized in the fetal and neonatal testis and aromatized centrally during a perinatal sensitive period is the sole source of brain estradiol and the primary determinant of sex differences. Subregions of the diencephalon are among the most sexually dimorphic in the brain, and there are well-established sex differences in the amount of testosterone and estradiol measured in the hypothalamus and preoptic area during the perinatal period. We previously reported unexpectedly high estradiol in the hippocampus and cortex of both male and female newborn rat. This prompted a thorough investigation of the developmental profile of steroids in the rat brain using RIA to quantify the level of estradiol, testosterone, and dihydrotestosterone in discrete subregions of the brain from embryonic d 19 to adulthood. Plasma estradiol levels from individual animals were assessed when sufficient sample was available. A significant sex difference in hypothalamic testosterone prior to birth was consistent with previous findings. Postnatally, there was a distinct pattern of changing steroid concentrations in each brain region, and these were unrelated to circulating steroid. Removal of the gonads and adrenals at birth did not significantly reduce steroids in any brain region assayed 3 d later. Aromatase activity was detectable in all brain areas at birth, and the difference in activity level paralleled the observed regional differences in estradiol content. Based on these findings, we propose that steroidogenesis in the brain, independent of peripherally derived precursors, may play a critical role in mammalian brain development of both sexes, beyond the establishment of sex differences.
| S-EPMC3033055 | biostudies-literature
Project description:PurposeTo understand the epidemiology and healthcare use of critically ill patients experiencing homelessness compared to critically ill patients with stable housing.MethodsThis retrospective population-based cohort study included adults admitted to any ICU in Alberta, Canada, for a 3-year period. Administrative and clinical data from the hospital, ICU and emergency department were used to examine healthcare resource use (processes of care, ICU and hospital length of stay, hospital readmission and emergency room visits). Regression was used to quantify differences in healthcare use by housing status.Results2.3% (n = 1086) of patients admitted to the ICU were experiencing homelessness; these patients were younger, more commonly admitted for medical reasons and had fewer comorbidities compared to those with stable housing. Processes of care in the ICU were mostly similar, but healthcare use after ICU was different; patients experiencing homelessness who survived their index hospitalization were more than twice as likely to have a visit to the emergency department (OR = 2.3 times, 95% CI 2.0-2.6, < 0.001) or be readmitted to hospital (OR = 2.1, 95% CI 1.8-2.4, p < 0.001) within 30 days, and stayed 10.1 days longer in hospital (95% CI 8.6-11.6, p < 0.001), compared with those who have stable housing.ConclusionsPatients experiencing homelessness have different characteristics at ICU admission and have similar processes of care in ICU, but their subsequent use of healthcare resources was higher than patients with stable housing. These findings can inform strategies to prepare patients experiencing homelessness for discharge from the ICU to reduce healthcare resource use after critical illness.
| S-EPMC10699027 | biostudies-literature
Project description:BackgroundWe have previously demonstrated that elevated serum estradiol (E(2)) at intensive care unit (ICU) admission is associated with death in the critically ill, regardless of sex. However, little is known about how changes in initial E(2) during the course of care might signal increasing patient acuity or risk of death. We hypothesized that changes from baseline serum E(2) during the course of critical illness are more strongly associated with mortality than a single E(2) level at admission.Study designA prospective cohort of 1,408 critically ill or injured nonpregnant adult patients requiring ICU care for ≥48 hours with admission and subsequent E(2) levels was studied. Demographics, illness severity, and E(2) levels were examined, and the probability of mortality was modeled with multivariate logistic regression. Changes in E(2) were examined by both analysis of variance and logistic regression.ResultsOverall mortality was 14.1% [95% confidence interval (CI) 12.3% to 16%]. Both admission and subsequent E(2) levels were independently associated with mortality [admission E(2) odds ratio 1.1 (CI 1.0 to 1.2); repeat estradiol odds ratio 1.3 (CI 1.2 to1.4)], with subsequent values being stronger. Changes in E(2) were independently associated with mortality [odds ratio 1.1 (CI 1.0 to 1.16)] and improved regression model performance. The regression model produced an area under the receiver operating characteristic curve of 0.80 (CI 0.77 to 0.83).ConclusionsAlthough high admission levels of E(2) are associated with mortality, changes from baseline E(2) in critically ill or injured adults are independently associated with mortality. Future studies of E(2) dynamics may yield new indicators of patient acuity and illuminate underlying mechanisms for targeted therapy.
| S-EPMC3073628 | biostudies-literature
Project description:RationaleFactors associated with one-year mortality after recovery from critical illness are not well understood. Clinicians generally lack information regarding post-hospital discharge outcomes of patients from the intensive care unit, which may be important when counseling patients and families.ObjectiveWe sought to determine which factors among patients who survived for at least 30 days post-ICU admission are associated with one-year mortality.MethodsSingle-center, longitudinal retrospective cohort study of all ICU patients admitted to a tertiary-care academic medical center from 2001-2012 who survived ≥30 days from ICU admission. Cox's proportional hazards model was used to identify the variables that are associated with one-year mortality. The primary outcome was one-year mortality.Results32,420 patients met the inclusion criteria and were included in the study. Among patients who survived to ≥30 days, 28,583 (88.2%) survived for greater than one year, whereas 3,837 (11.8%) did not. Variables associated with decreased one-year survival include: increased age, malignancy, number of hospital admissions within the prior year, duration of mechanical ventilation and vasoactive agent use, sepsis, history of congestive heart failure, end-stage renal disease, cirrhosis, chronic obstructive pulmonary disease, and the need for renal replacement therapy. Numerous effect modifications between these factors were found.ConclusionAmong survivors of critical illness, a significant number survive less than one year. More research is needed to help clinicians accurately identify those patients who, despite surviving their acute illness, are likely to suffer one-year mortality, and thereby to improve the quality of the decisions and care that impact this outcome.
| S-EPMC5947984 | biostudies-literature
Project description:The effects of testosterone on early atherogenesis and the role of aromatase, an enzyme that converts testosterone to estrogens, were assessed in low density lipoprotein receptor-deficient male mice fed a Western diet. Castration of male mice increased the extent of fatty streak lesion formation in the aortic origin compared with testes-intact animals. Administration of anastrazole, a selective aromatase inhibitor, to testes-intact males increased lesion formation to the same extent as that observed with orchidectomized animals. Testosterone supplementation of orchidectomized animals reduced lesion formation when compared with orchidectomized animals receiving the placebo. This attenuating effect of testosterone was not observed when the animals were treated simultaneously with the aromatase inhibitor. The beneficial effects of testosterone on early atherogenesis were not explained by changes in lipid levels. Estradiol administration to orchidectomized males attenuated lesion formation to the same extent as testosterone administration. Aromatase was expressed in the aorta of these animals as assessed by reverse transcription-PCR and immunohistochemistry. These results indicate that testosterone attenuates early atherogenesis most likely by being converted to estrogens by the enzyme aromatase expressed in the vessel wall.
| S-EPMC30697 | biostudies-literature
Project description:Testosterone is known to be essential for sexual maturation as well as for the display of behavioural traits linked to reproduction. At the same time, external factors such as the presence of receptive females may affect testosterone levels, stressing the hormone's substantial role in reproductive success. It is therefore of major interest to investigate the links between androgens, behaviour and the social environment especially in species that rely on a resilient reproduction rate, such as the white rhinoceros (WR). We collected faecal samples of 16 male Southern WR (Ceratotherium simum simum) aged between 1 and 44 years from 11 European zoos. Audio and video recordings were simultaneously taken from five of the study males that were sexually mature and had direct contact with receptive females. Our results showed a positive correlation of faecal testosterone metabolite (fTM) concentrations and progressing age up until adulthood followed by a decline in older males. While previous reproductive success did not show any effect, the access to receptive females resulted in higher fTM levels. Thereby, fTM concentrations remained at the same level regardless of the receptivity phase, while social cohesion with respective females, affiliative behaviour as well as call rates of Pant and Hiss distinctly peaked during the receptive compared to the non-receptive periods. Conclusively, the immediate presence of receptive females poses a female effect that enhances the overall androgen levels in males and, thus, might facilitate their reproductive success. However, androgens do not seem to be the main driver of behavioural changes during courtship or mating. By linking endocrinological and socio-behavioural factors, we were able to provide an applicable basis for non-invasive monitoring of reproductive behaviour in male WR in captivity, thereby contributing to deeper understanding of potential reproduction impairments in a species whose population in captivity remains not fully self-sustaining.
| S-EPMC8084027 | biostudies-literature
Project description:Background and Purpose- Although exogenous hormone therapy (HT) use has been associated with increased risk of ischemic stroke in postmenopausal women, it remains unknown whether sex hormone levels contribute to ischemic stroke risk. We aimed to estimate associations between plasma sex hormone levels and ischemic stroke risk, by HT status, in a nested case-control study of postmenopausal women from the NHS (Nurses' Health Study). Methods- Women with confirmed incident ischemic stroke (n=419) were matched with controls (n=419) by age, HT use, and other factors. Plasma estradiol and testosterone levels were measured using liquid chromatography tandem mass spectrometry; SHBG (sex hormone-binding globulin) was assayed by electrochemiluminescence immunoassay. Associations of total and free estradiol and testosterone, the estradiol/testosterone ratio, and SHBG with ischemic stroke were estimated using conditional logistic regressions stratified by HT status with adjustment for matching and cardiovascular risk factors. Results- Current HT users had different hormone profiles from never/past users. No clear linear trends were observed between estradiol (total or free) levels or the estradiol/testosterone ratio and ischemic stroke risk among either current users (Ptrend>0.1) or never/past users (Ptrend>0.6). For both current and never/past users, the associations between some of the sex hormones and ischemic stroke differed by body mass index categories (Pinteraction≤0.04). For women with a body mass index <25 kg/m2, a higher estradiol/testosterone ratio was associated with significantly elevated ischemic stroke risk among current users (Ptrend=0.01), and higher levels of total and free estradiol were significantly associated with higher ischemic stroke risk among never/past users (Ptrend≤0.04). Testosterone and SHBG were not associated with ischemic stroke in either current or never/past users. Conclusions- Our findings do not support a role of sex hormone levels in mediating ischemic stroke risk among postmenopausal women. Replications in additional larger studies are required.
| S-EPMC7159036 | biostudies-literature
Project description:Environmental exposure to metals is ubiquitous, but its relation to androgen hormone levels is not well understood, especially in children and adolescents. This study aimed to explore the relationship between blood metal concentrations (lead, cadmium, total mercury, selenium, and manganese) and serum total testosterone (TT) levels in 6-19-year-old children and adolescents in the National Health and Nutrition Examination Survey (NHANES) 2011-2012. Weighted multivariable linear regression models using NHANES sampling weights were employed to evaluate the association between log-transformed serum TT and each metal categories in male and female children (age 6-11years) and adolescents (age 12-19 years). We established that blood cadmium and manganese levels were associated with significantly higher serum TT levels in the female adolescents. Additionally, the blood selenium levels in male adolescents were related to significantly higher serum TT. No significant associations between blood lead or total mercury levels and TT were observed in children or adolescents of either sex. These findings suggest that environmental exposure to certain metals could affect serum TT levels in adolescents, which might have important implications for the health of adolescents. Further research is required to confirm and extend our present findings.
| S-EPMC6837506 | biostudies-literature
Project description:Odours of vertebrates often contain information about the major histocompatibility complex (MHC), and are used in kin recognition, mate choice or female investment in pregnancy. It is, however, still unclear whether MHC-linked signals can also affect male reproductive strategies. We used horses (Equus caballus) to study this question under experimental conditions. Twelve stallions were individually exposed either to an unfamiliar MHC-similar mare and then to an unfamiliar MHC-dissimilar mare, or vice versa. Each exposure lasted over a period of four weeks. Peripheral blood testosterone levels were determined weekly. Three ejaculates each were collected in the week after exposure to both mares (i.e. in the ninth week) to determine mean sperm number and sperm velocity. We found high testosterone levels when stallions were kept close to MHC-dissimilar mares and significantly lower ones when kept close to MHC-similar mares. Mean sperm number per ejaculate (but not sperm velocity) was positively correlated to mean testosterone levels and also affected by the order of presentation of mares: sperm numbers were higher if MHC-dissimilar mares were presented last than if MHC-similar mares were presented last. We conclude that MHC-linked signals influence testosterone secretion and semen characteristics, two indicators of male reproductive strategies.
| S-EPMC4424655 | biostudies-literature
Project description:ObjectivesTo describe critically ill children with respiratory infections, classify them by infection syndrome type and determine the prevalence of Mycoplasma pneumoniae detection.Study designA retrospective, single-centre cohort study. All children aged 2 months-18 years with presumed respiratory infection who were admitted to a tertiary hospital paediatric intensive care unit (PICU) between September 2015 and October 2016 were eligible. Subjects were grouped by clinical syndrome (viral respiratory infection, asthma exacerbation, undifferentiated/uncomplicated pneumonia, pneumonia complicated by effusion/empyema and 'other'). All subjects had nasopharyngeal swabs tested for respiratory viruses, M. pneumoniae and Chlamydia pneumoniae.ResultsThere were 221 subjects; the median age was 3.1 years; 44% were female; and 78% had medical comorbidities. The majority (75%) was treated with antibiotics, most often ceftriaxone (90% of treated children). Those with any pneumonia were significantly less likely to have a respiratory virus identified in their nasopharynges and had significantly higher C reactive protein (CRP) values than those in the viral infection and asthma groups. There were 10 subjects in whom M. pneumoniae was detected (4.5%, 95% CI 2.2% to 8.2%). Mycoplasma-positive children were older (difference 3.5 years, 95% CI 0.66 to 6.4 years) and had fewer viral coinfections (30% compared with 69%, p=0.02). The prevalence of Mycoplasma infection in children aged >5 years with any pneumonia was 13.2% (95%CI 4.4% to 28%).ConclusionsThe majority of participants had respiratory viruses detected and were treated with broad-spectrum antibiotics. Differences in CRP and viral prevalence were observed between children with different infection syndrome types. M. pneumoniae infection was not rare in school-aged children with pneumonia admitted to the PICU. Attention to antibiotic treatment and rapid diagnostic testing for Mycoplasma in older, critically ill children should be considered to optimise management and avert morbidity and mortality from respiratory infection.
| S-EPMC7213883 | biostudies-literature