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As federal strategic plans prioritize increasing diversity within the biomedical workforce, and STEM training and outreach programs seek to recruit and retain students from historically underrepresented populations, there is a need for interrogation of traditional demographic descriptors and careful consideration of best practices for obtaining demographic data. To accelerate this work, equity-focused researchers and leaders from STEM programs convened to examine approaches for measuring demographic variables. Gender, race/ethnicity, disability, and disadvantaged background were prioritized given their focus by federal funding agencies. Categories of sex minority, sexual (orientation) minority, and gender minority (SSGM) should be included in demographic measures collected by STEM programs, consistent with recommendations from White House Executive Orders and federal reports. Our manuscript offers operationalized phrasing for demographic questions and recommendations for use across student-serving programs. Inclusive demographics permit the identification of individuals who are being excluded, marginalized, or improperly aggregated, increasing capacity to address inequities in biomedical research training. As trainees do not enter training programs with equal access, accommodations, or preparation, inclusive demographic measures can welcome trainees and inform a nuanced set of program outcomes that facilitate research on intersectionality to support the recruitment and retention of underrepresented students in biomedical research.

The COVID-19 pandemic has strained the resources of the world's healthcare systems. Most individuals with neurodevelopmental disabilities (NDDs) experience significant mental health issues and face substantial barriers in accessing appropriate supports which have been exacerbated during the pandemic. It is unknown the extent to which COVID-19 impacted the demand for and effectiveness of inpatient care for those with NDDs. The impact of COVID-19 on the number of admissions of youth with NDDs to pediatric inpatient psychiatry units, as well as their functioning and length of stay during the first two years of the pandemic was analyzed using Bayesian structural time series models. Admission data of youth with NDDs from four pediatric inpatient units in Alberta, Canada (n = 2144) was examined. Inpatient admissions of youth with NDDs significantly increased following the onset of the pandemic. Compared to the period prior to the pandemic, patients with NDDs had significantly worse overall functioning and received fewer days of treatment. These findings highlight the need for increased resources to support the mental health needs of this vulnerable population and are consistent with other studies in the general population examining the utilization of inpatient psychiatric units during the pandemic.

Objectives: Among Aboriginal children, the year between birth and 1 year of age has the highest mortality rate compared with any other age. Prompt administration of cardiopulmonary resuscitation (CPR) leads to better outcomes and a lower likelihood of ongoing sequalae. Current education on infant CPR is not provided to parents except in certain circumstances in a neonatal intensive care unit. Currently, there are no identified CPR education courses specifically available for Aboriginal or Torres Strait Islander people, meaning that current infant CPR education courses are not culturally responsive. Design: Partnering with an Aboriginal community from the Bindjareb region of the Western Australian Noongar nation, the researchers used a co-design approach and an Aboriginal Participatory Action Research (APAR) design to explore how to deliver culturally safe and responsive infant CPR community education. This resulted in the development of the Koolangka Infant Life Saving Education Framework (KILSEF), which can be used to guide future planning and delivery of culturally safe and responsive community level infant CPR education. Results: The study findings identified that members of the Aboriginal community were very interested in receiving infant CPR education, but the barriers identified from mainstream CPR course delivery need to be removed for the community to benefit from culturally responsive ways of learning. Culturally responsive community CPR education should be provided in culturally safe places and the focus of learning should be on the practical applications of CPR and less on the academic pre-reading and written requirements. Explanations should be provided in lay terms and patience is required to communicate ideas in ways that facilitate understanding, and the course may need to be delivered over several days to accommodate community participant availability. Conclusion: Addressing Aboriginal community concerns and barriers allowed for the implementation of culturally responsive infant resuscitation education which was highly valued by community members and led to increased community confidence and participation in CPR education.

Many training initiatives are underway to increase implementation of evidence-based practice (EBPs) in mental healthcare. However, little is known about what types of trainings and supports yield the highest reach and engagement. Supported by a tax-funded, countywide initiative to improve access to quality care for youths, the current mixed methods study evaluates mental health (MH) provider reach, or registering for the training initiative, and engagement, or participation in training activities, for several EBP training and implementation supports. MH providers were offered free 1) formal EBP workshops; 2) a biweekly learning community; 3) individual case consultation; and 4) confidential online clinical feedback system. To register, interested providers (N = 698) completed a web-based assessment measuring clinical practice information, organizational implementation climate, and EBP knowledge, attitudes, and practices. Thirteen providers, selected via purposeful sampling stratified by level of participation, completed semi-structured qualitative interviews. While the training initiative achieved high reach (66% of county agencies had a provider register), far fewer providers engaged substantially in training. Quantitative results indicated that providers whose professional discipline was not psychology, had higher baseline EBP knowledge, more extensive use of common evidence-based strategies, and less extensive use of other therapy strategies, engaged in more training. Rapid qualitative analysis of interviews expanded upon these findings and illuminated provider, organizational, system, practical, and training activity-specific barriers and facilitators to engagement. Findings suggest the importance of identifying strategies for improving provider engagement in training activities beyond workshops. Implications for future research and training initiatives are discussed.

BACKGROUND: Cancer health research relies on large-scale cohorts to derive generalizable results for different populations. While traditional epidemiological cohorts often use costly random sampling or self-motivated, preselected groups, a shift toward health system-based cohorts has emerged. However, such cohorts depend on participants remaining within a single system. Recent consumer engagement models using smartphone-based communication, driving projects, and social media have begun to upend these paradigms. METHODS: We initiated the Healthy Oregon Project (HOP) to support basic and clinical cancer research. HOP study employs a novel, cost-effective remote recruitment approach to effectively establish a large-scale cohort for population-based studies. The recruitment leverages the unique email account, the HOP website, and social media platforms to direct smartphone users to the study app, which facilitates saliva sample collection and survey administration. Monthly newsletters further facilitate engagement and outreach to broader communities. RESULTS: By the end of 2022, the HOP has enrolled approximately 35,000 participants aged 18-100 years (median = 44.2 years), comprising more than 1% of the Oregon adult population. Among those who have app access, ∼87% provided consent to genetic screening. The HOP monthly email newsletters have an average open rate of 38%. Efforts continue to be made to improve survey response rates. CONCLUSION: This study underscores the efficacy of remote recruitment approaches in establishing large-scale cohorts for population-based cancer studies. The implementation of the study facilitates the collection of extensive survey and biological data into a repository that can be broadly shared and supports collaborative clinical and translational research.

Abstract Background Huntington’s disease (HD) is a genetic neurological disorder predominantly characterised by the progressive loss of GABAergic medium spiny neurons in the striatum resulting in motor dysfunction. One potential strategy for the treatment of HD is the development of cell replacement therapies to restore neuronal circuitry and function by the replacement of lost neurons. We propose the generation of lineage-specific human lateral ganglionic eminence precursors (hiLGEP) using direct reprogramming technology provides a novel and clinically viable cell source for cell replacement therapy for HD. Methods hiLGEPs were derived by direct reprogramming of adult human dermal fibroblasts (aHDFs) using chemically modified mRNA (cmRNA) and a defined reprogramming medium. hiLGEPs were differentiated in vitro using an optimised striatal differentiation medium. Acquisition of a striatal precursor and neural cell fate was assessed through gene expression and immunocytochemical analysis of key markers. hiLGEP-derived striatal neuron functionality in vitro was demonstrated by calcium imaging using Cal-520. To investigate the ability for hiLGEP to survive, differentiate and functionally integrate in vivo, we transplanted hiLGEPs into the striatum of quinolinic acid (QA)-lesioned rats and performed behavioural assessment using the cylinder test over the course of 14 weeks. Survival and differentiation of hiLGEPs was assessed at 8 and 14-weeks post-transplant by immunohistochemical analysis. Results We demonstrate the capability to generate hiLGEPs from aHDFs using cmRNA encoding the pro-neural genes SOX2 and PAX6, combined with a reprogramming medium containing Gö6983, Y-27,632, N-2 and Activin A. hiLGEPs generated functional DARPP32 + neurons following 14 days of culture in BrainPhys™ media supplemented with dorsomorphin and Activin A. We investigated the ability for hiLGEPs to survive transplantation, differentiate to medium spiny-like striatal neurons and improve motor function in the QA lesion rat model of HD. Fourteen weeks after transplantation, we observed STEM121 + neurons co-expressing MAP2, DARPP32, GAD65/67, or GABA. Rats transplanted with hiLGEPs also demonstrated reduction in motor function impairment as determined by spontaneous exploratory forelimb use when compared to saline transplanted animals. Conclusion This study provides proof-of-concept and demonstrates for the first time that aHDFs can be directly reprogrammed to hiLGEPs which survive transplantation, undergo neuronal differentiation to generate medium spiny-like striatal neurons, and reduce functional impairment in the QA lesion rat model of HD.

Abstract RNA sequencing and microarray analysis revealed transcriptional markers expressed in whole blood can differentiate active pulmonary TB (ATB) from other respiratory diseases (ORDs), and latent TB infection (LTBI) from healthy controls (HC). Here we describe a streamlined reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) assay that could be applied at near point-of-care for diagnosing and distinguishing ATB from ORDs and LTBI from HC. A literature review was undertaken to identify the most plausible host-gene markers (HGM) of TB infection. Primers, and dual labelled hydrolysis probes were designed and analytically evaluated for accuracy in an in-vitro model of infection using a lung fibroblast cell-line. Best performing genes were multiplexed into panels of 2–4 targets and taken forward for clinical evaluation. Mycobacteria Growth Indicator Tube and QuantiFERON-TB Gold Plus were used as reference tests for ATB and LTBI respectively. A total of 16 HGM were selected and incorporated into five multiplex RT-qPCR panels. PCR assay efficiency of all evaluated targets was ≥ 90% with a median analytical sensitivity of 292 copies/µl [IQR: 215.0-358.3 copies/µl], and a median limit of quantification of 61.7 copies/µl [IQR: 29.4-176.3 copies/µl]. Clinically, ATB was characterised by higher gene expression than ORDs, while LTBI was associated with lower gene expression than HC, Kruskal-Wallis p

Abstract Background Polycystic ovary syndrome (PCOS), the most common endocrine disorder for women of reproductive age, is associated with increased risk for insulin resistance and type 2 diabetes. Current PCOS treatments insufficiently address the spectrum and severity of the disorder, and there is little evidence-based guidance available for lifestyle management of PCOS, especially through nutritional approaches. Some evidence shows that a very low-carbohydrate diet can improve glucose control compared to low-fat or moderate-carbohydrate diets, leading to improved glucose control and insulin levels that may help to treat symptoms of PCOS. This research investigates whether a very low-carbohydrate diet is more effective in improving glucose control and decreasing symptoms of PCOS in comparison to a DASH diet. Methods The SUPER study aims to address the gap in knowledge about nutritional advice for people with PCOS through a randomized, comparative effectiveness trial comparing two approaches to glucose control: the dietary approaches to stopping hypertension (DASH) diet, and a very low-carbohydrate (VLC) diet. We will randomize 184 women with PCOS with body mass indexes (BMIs) between 25 and 50 kg/m2 to a VLC or DASH diet. All participants will follow a 24-session, 12-month, online diet, and lifestyle intervention that teaches their assigned diet. Participants will receive nutritional education, support from diet coaches, and education about behavioral strategies to improve dietary adherence. The primary outcome measure is HbA1c, and secondary outcomes include glucose variance, lipid and hormone levels (including total and free testosterone), PCOS symptoms, inflammation (measured by high-sensitivity C-reactive protein), body composition and weight, psychological well-being, and intervention feasibility and acceptability. Discussion The SUPER study is a randomized comparative effectiveness trial that compares two promising approaches to glucose control in people with PCOS. The study also aims to assess the effects of each diet on PCOS symptoms. The research addresses an important gap in knowledge regarding nutritional advice for people with PCOS. Trial registration ClinicalTrials.gov NCT05452642. Registered 6 July 2022.

Abstract In the United Kingdom, the management of bovine tuberculosis (bTB) challenges the coexistence of people and wildlife. Control of this cattle disease is hindered by transmission of its causative agent, Mycobacterium bovis, between cattle and badgers Meles meles. Badger culling has formed an element of bTB control policy for decades, but current government policy envisions expanding badger vaccination. Farming leaders are sceptical, citing concerns that badger vaccination would be impractical and potentially ineffective. We report on a 4‐year badger vaccination initiative in an 11 km2 area which, atypically, was initiated by local farmers, delivered by scientists and conservationists, and co‐funded by all three. Participating landholders cited controversies around culling and a desire to support neighbours as their primary reasons for adopting vaccination. The number of badgers vaccinated per km2 (5.6 km−2 in 2019) exceeded the number culled on nearby land (2.9 km−2 in 2019), and the estimated proportion vaccinated (74%, 95% confidence interval [CI] 40%–137%) exceeded the 30% threshold predicted by models to be necessary to control M. bovis. Farmers were content with how vaccination was delivered, and felt that it built trust with wildlife professionals. The percentage of badgers testing positive for M. bovis declined from 16.0% (95% CI 4.5%–36.1%) at the start of vaccination to 0% (95% CI 0%–9.7%) in the final year. With neither replication nor unvaccinated controls, this small‐scale case study does not demonstrate a causal link between badger vaccination and bTB epidemiology, but it does suggest that larger‐scale evaluation of badger vaccination would be warranted. Farmers reported that their enthusiasm for badger vaccination had increased after participating for 4 years. They considered vaccination to have been effective, and good value for money, and wished to continue with it. Synthesis and applications: Although small‐scale, this case study suggests that badger vaccination can be a technically effective and socially acceptable component of bTB control. A wider rollout of badger vaccination is more likely if it is led by the farming community, rather than by conservationists or government, and is combined with scientific monitoring. Read the free Plain Language Summary for this article on the Journal blog.

Background: People with learning disabilities have the right to choose where they live. However, evidence suggests people's choices are limited due to a shortage of housing. Methods: 200 Lives was a mixed methods research project, which evaluated supported living and residential care for people with learning disabilities in England; 107 people with learning disabilities took part, 77 from supported living and 30 from residential care. Findings: Two-thirds of people in supported living compared to half of those in residential care chose the place they were currently living in; however, less than half of all participants looked at another property before moving to their current house. People in supported living were significantly more likely to have chosen who they lived with. Reasons for moving mainly consisted of reactive moves following an issue with the previous living situation. Many people had not considered moving in the future. Conclusion: Findings suggest that people's choices about where to live were constrained regarding the properties on offer and who to live with. This suggests that people's housing rights were not being upheld. Support and housing providers should ensure that housing can adapt to people's changing needs and wishes over the course of their lives.

Cancer research training programs build our future biomedical workforce. Training is often centered for students residing close to research institutions, making access more challenging for rural students. A cancer research training program was developed for high school students residing in five geographical regions across Oregon. Training was tiered in duration and intensity across the three years, including a one-week Introduction program and subsequent 10-week summer research training programs (Immersion and Intensive). A total of 60 students participated in in-person and/or virtual training, with Immersion students receiving mentored shadowing experiences in clinical care, public health, and outreach in their home communities. Laboratory rotations at a research-intensive institution enabled students to sample research environments before selecting an area of interest for Intensive training the following summer. Aligning with Self-Determination Theory, the Knight Scholars Program aims to build competence, relatedness, and autonomy of its trainees in biomedical sciences. The program exposed students to a wide range of interprofessional careers and collaborative teams, enabling scholars to envision themselves in various paths. Results show strong gains in interest and research self-efficacy for both Introduction and Immersion scholars, with findings highlighting the importance of representation within mentoring and training efforts.

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Abstract Background Understanding the aetiological organisms causing maternal infections is crucial to inform antibiotic treatment guidelines, but such data are scarce from Sub-Saharan Africa (SSA). We performed this systematic review and meta-analysis to address this gap. Methods Microbiologically confirmed maternal infection data were collected from PubMed, Embase, and African Journals online databases. The search strategy combined terms related to bacterial infection, pregnancy, postnatal period, observational studies, SSA. Exclusion criteria included colonization, asymptomatic infection, and screening studies. Pooled proportions for bacterial isolates and antimicrobial resistance (AMR) were calculated. Quality and completeness of reporting were assessed using the Newcastle–Ottawa and STROBE checklists. Findings We included 14 papers comprising data from 2,575 women from four sources (blood, urine, surgical wound and endocervical). Mixed-growth was commonly reported at 17% (95% CI: 12%-23%), E. coli from 11%(CI:10%-12%), S. aureus from 5%(CI: 5%-6%), Klebsiella spp. at 5%(CI: 4%- 5%) and Streptococcus spp. at 2%(CI: 1%-2%). We observed intra-sample and inter-sample heterogeneity between 88–92% in all meta-analyses. AMR rates were between 19% -77%, the highest with first-line beta-lactam antibiotics. Convenience sampling, and limited reporting of laboratory techniques were areas of concern. Interpretation We provide a comprehensive summary of microbial aetiology of maternal infections in SSA and demonstrate the paucity of data available for this region. We flag the need to review the current local and international empirical treatment guidelines for maternal bacterial infections in SSA because there is high prevalence of AMR among common causative bacteria. Funding This research was supported by the NIHR-Professorship/NIHR300808 and the Wellcome-Strategic-award /206545/Z/17/Z. Trial registration Prospero ID CRD42021238515.

Gay men report poorer body image than straight men, but no research has examined other dimensions of sexual identity (e.g., sexual attraction). Most research also focused on clinical outcomes of body dissatisfaction rather than subclinical influences on quality of life. We examined the association between sexual attraction (i.e., attraction to men or women), body dissatisfaction and quality of life in cisgender men. We hypothesised that: 1) men attracted to men would report higher body dissatisfaction, 2) men attracted to men would report lower quality of life (i.e., psychological, physiological, social, and environmental), 3) body dissatisfaction would be negatively associated with quality of life, and finally 4) body dissatisfaction mediates the association between sexual attraction and quality of life. A cross-sectional study (86 men attracted to men and 87 men attracted to women) supported these hypotheses but showed that sexual attraction was only associated with psychological quality of life. While sexual attraction was only associated with psychological quality of life, there were indirect associations with all quality of life domains acting through body dissatisfaction. Our findings emphasise that men attracted to men are at greater risk of poor body image and that body dissatisfaction is a pervasive health problem, negatively influencing subclinical health and well-being in cisgender men. We also highlight how body dissatisfaction may be one psychological process negatively influencing the psychological quality of life in men attracted to men. More resources should be directed toward preventing body dissatisfaction, particularly in sexual minoritised men.

Abstract Background Pancreatic fibrosis is an early diagnostic feature of the common inherited disorder cystic fibrosis (CF). Many people with CF (pwCF) are pancreatic insufficient from birth and the replacement of acinar tissue with cystic lesions and fibrosis is a progressive phenotype that may later lead to diabetes. Little is known about the initiating events in the fibrotic process though it may be a sequela of inflammation in the pancreatic ducts resulting from loss of CFTR impairing normal fluid secretion. Here we use a sheep model of CF (CFTR −/− ) to examine the evolution of pancreatic disease through gestation. Methods Fetal pancreas was collected at six time points from 50-days of gestation through to term, which is equivalent to ~ 13 weeks to term in human. RNA was extracted from tissue for bulk RNA-seq and single cells were prepared from 80-day, 120-day and term samples for scRNA-seq. Data were validated by immunochemistry. Results Transcriptomic evidence from bulk RNA-seq showed alterations in the CFTR −/− pancreas by 65-days of gestation, which are accompanied by marked pathological changes by 80-days of gestation. These include a fibrotic response, confirmed by immunostaining for COL1A1, αSMA and SPARC, together with acinar loss. Moreover, using scRNA-seq we identify a unique cell population that is significantly overrepresented in the CFTR −/− animals at 80- and 120-days gestation, as are stellate cells at term. Conclusion The transcriptomic changes and cellular imbalance that we observe likely have pivotal roles in the evolution of CF pancreatic disease and may provide therapeutic opportunities to delay or prevent pancreatic destruction in CF.

Abstract Background Approximately one-third of US young adults (18–25 years) have obesity, and there are calls to help young adults lose weight to prevent weight-related chronic conditions. This pilot trial tested the feasibility and acceptability of a very low-carbohydrate (VLC) eating pattern, with supportive positive affect and mindful eating skills, for weight management among young females with obesity. Methods In a single-arm trial, women (N = 17), aged 19–23, with obesity participated in a 4-month diet and lifestyle intervention. Participants were taught how to follow a VLC eating pattern with the help of a coach and 16 weekly web-based sessions. We assessed feasibility and acceptability through session participation, outcome collection, intervention satisfaction, and adverse events. Results Seventeen participants enrolled and 14 (82%) reported body weight at 4 months. Fifteen participants (94% of those beginning the intervention) viewed at least one session, and 8/15 (53%) of these participants were active in the intervention, viewing at least half of the sessions. Among the nine participants who provided 4-month self-report information, intervention satisfaction was high (mean 5.89/7, 95% CI 4.59 to 7.19). Among participants with a 4-month body weight, 7/14 (50%) lost ≥ 5% of their body weight, and of those who were also active in the intervention, 6/7 (86%) lost ≥ 5% of their body weight. There were no serious adverse events. Conclusions The results of this pilot study suggest that a VLC eating pattern may be a feasible and acceptable approach for weight loss in some young women with obesity. Trial registration This trial was registered with ClinicalTrials.gov on August 18, 2021. The trial number is NCT05010083.

Abstract Objective Neurofilament heavy‐chain gene (NEFH) variants are associated with multiple neurodegenerative diseases, however, their relationship with ALS has not been robustly explored. Still, NEFH is commonly included in genetic screening panels worldwide. We therefore aimed to determine if NEFH variants modify ALS risk. Methods Genetic data of 11,130 people with ALS and 7,416 controls from the literature and Project MinE were analysed. We performed meta‐analyses of published case–control studies reporting NEFH variants, and variant analysis of NEFH in Project MinE whole‐genome sequencing data. Results Fixed‐effects meta‐analysis found that rare (MAF

Abstract The World Health Organization End TB strategy aims for a 90% reduction of tuberculosis (TB) incidence by 2035. Systematic testing and treatment of latent TB infection (LTBI) among contacts of active TB patients is recommended as one of the ways to curtail TB incidence. However, there is a shortage of tools to accurately diagnose LTBI. We assessed the appropriateness of whole blood host transcriptomic markers (TM) to diagnose LTBI among household contacts of bacteriologically confirmed index cases compared to HIV negative healthy controls (HC). QuantiFERON-TB Gold Plus Interferon gamma release assay (IGRA) and reverse-transcriptase quantitative PCR were used to determine LTBI and quantify TM expression respectively. Association between TM expression and LTBI was evaluated by logistic regression modelling. A total of 100 participants, 49 TB exposed (TBEx) household contacts and 51 HC, were enrolled. Twenty-five (51%) TBEx individuals tested positive by IGRA, and were denoted as LTBI individuals, and 37 (72.5%) HC were IGRA-negative. Expression of 11 evaluated TM was significantly suppressed among LTBI compared to HC. Out of the 11 TM, ZNF296 and KLF2 expression were strongly associated with LTBI and successfully differentiated LTBI from HC. Paradoxically, 21 (49%) TBEx participants who tested IGRA negative exhibited the same pattern of suppressed TM expression as IGRA positive (LTBI-confirmed individuals). Results suggest that suppression of gene expression underlies LTBI and may be a more sensitive diagnostic biomarker than standard-of-care IGRA.

BACKGROUND: Various factors modulate circulating testosterone in men, affecting interpretation of testosterone measurements. PURPOSE: To clarify factors associated with variations in sex hormone concentrations. DATA SOURCES: Systematic literature searches (to July 2019). STUDY SELECTION: Prospective cohort studies of community-dwelling men with total testosterone measured using mass spectrometry. DATA EXTRACTION: Individual participant data (IPD) (9 studies; n = 21 074) and aggregate data (2 studies; n = 4075). Sociodemographic, lifestyle, and health factors and concentrations of total testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone, and estradiol were extracted. DATA SYNTHESIS: Two-stage random-effects IPD meta-analyses found a nonlinear association of testosterone with age, with negligible change among men aged 17 to 70 years (change per SD increase about the midpoint, -0.27 nmol/L [-7.8 ng/dL] [CI, -0.71 to 0.18 nmol/L {-20.5 to 5.2 ng/dL}]) and decreasing testosterone levels with age for men older than 70 years (-1.55 nmol/L [-44.7 ng/dL] [CI, -2.05 to -1.06 nmol/L {-59.1 to -30.6 ng/dL}]). Testosterone was inversely associated with body mass index (BMI) (change per SD increase, -2.42 nmol/L [-69.7 ng/dL] [CI, -2.70 to -2.13 nmol/L {-77.8 to -61.4 ng/dL}]). Testosterone concentrations were lower for men who were married (mean difference, -0.57 nmol/L [-16.4 ng/dL] [CI, -0.89 to -0.26 nmol/L {-25.6 to -7.5 ng/dL}]); undertook at most 75 minutes of vigorous physical activity per week (-0.51 nmol/L [-14.7 ng/dL] [CI, -0.90 to -0.13 nmol/L {-25.9 to -3.7 ng/dL}]); were former smokers (-0.34 nmol/L [-9.8 ng/dL] [CI, -0.55 to -0.12 nmol/L {-15.9 to -3.5 ng/dL}]); or had hypertension (-0.53 nmol/L [-15.3 ng/dL] [CI, -0.82 to -0.24 nmol/L {-23.6 to -6.9 ng/dL}]), cardiovascular disease (-0.35 nmol/L [-10.1 ng/dL] [CI, -0.55 to -0.15 nmol/L {-15.9 to -4.3 ng/dL}]), cancer (-1.39 nmol/L [-40.1 ng/dL] [CI, -1.79 to -0.99 nmol/L {-51.6 to -28.5 ng/dL}]), or diabetes (-1.43 nmol/L [-41.2 ng/dL] [CI, -1.65 to -1.22 nmol/L {-47.6 to -35.2 ng/dL}]). Sex hormone-binding globulin was directly associated with age and inversely associated with BMI. Luteinizing hormone was directly associated with age in men older than 70 years. LIMITATION: Cross-sectional analysis, heterogeneity between studies and in timing of blood sampling, and imputation for missing data. CONCLUSION: Multiple factors are associated with variation in male testosterone, SHBG, and LH concentrations. Reduced testosterone and increased LH concentrations may indicate impaired testicular function after age 70 years. Interpretation of individual testosterone measurements should account particularly for age older than 70 years, obesity, diabetes, and cancer. PRIMARY FUNDING SOURCE: Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).