Dataset Information

Systematic review and meta-analyses on associations of endogenous testosterone concentration with health outcomes in community-dwelling men

ABSTRACT:

Objectives

The overall study aim is to clarify the relation of endogenous sex hormones with major health outcomes in men. This paper reports a systematic review focusing on published estimates for testosterone associations.

Setting

Community-dwelling men.

Participants

20 180 adult men participated in the final set of studies identified and selected from a systematic review. Eligible studies included prospective cohort studies with plasma or serum testosterone concentrations measured for adult men using mass spectrometry with at least 5 years of follow-up data and one of the specified outcome measures recorded. Only published or grey literature items written in English were considered.

Primary and secondary outcome measures

Planned prospective outcome measures: cardiovascular disease (CVD) events, CVD deaths, all-cause mortality, cancer deaths, cancer diagnoses, cognitive decline, dementia. Meta-analyses were of the most frequently reported outcomes in selected studies: CVD deaths and all-cause mortality. Succinct characterisations of testosterone associations with other outcomes are also presented.

Results

Screening of 1994 deduplicated items identified 9 suitable studies, with an additional 2 identified by colleagues (11 in total). Summary estimates of mean testosterone concentration and age at recruitment for 20 180 adult men were 15.4±0.7 nmol/L and 64.9±3.3 year. Despite considerable variation in mean testosterone, a metaregression estimated no significant dependence on mean age at recruitment among studies (slope=−0.03, 95% CI −0.11 to 0.06). Meta-analyses demonstrated negligible heterogeneity and no significant effect of a 5 nmol/L increase in testosterone on the risk of all-cause mortality (HR=0.96, 95% CI 0.89 to 1.03) or death from CVD (HR=0.95, 95% CI 0.83 to 1.08).

Conclusions

Analyses of published estimates did not demonstrate associations of endogenous testosterone with CVD deaths or with all-cause mortality. Suggested further research includes the planned individual participant data meta-analyses for selected studies, enabling the investigation of non-linear summary effects.

PROSPERO registration number

PROSPERO: CRD42019139668.

SUBMITTER: Marriott R

PROVIDER: S-EPMC8565564 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:IntroductionThis study aims to clarify the role(s) of endogenous sex hormones to influence health outcomes in men, specifically to define the associations of plasma testosterone with incidence of cardiovascular events, cancer, dementia and mortality risk, and to identify factors predicting testosterone concentrations. Data will be accrued from at least three Australian, two European and four North American population-based cohorts involving approximately 20?000 men.Methods and analysisEligible studies include prospective cohort studies with baseline testosterone concentrations measured using mass spectrometry and 5?years of follow-up data on incident cardiovascular events, mortality, cancer diagnoses or deaths, new-onset dementia or decline in cognitive function recorded. Data for men, who were not taking androgens or drugs suppressing testosterone production, metabolism or action; and had no prior orchidectomy, are eligible. Systematic literature searches were conducted from 14 June 2019 to 31 December 2019, with no date range set for searches. Aggregate level data will be sought where individual participant data (IPD) are not available. One-stage IPD random-effects meta-analyses will be performed, using linear mixed models, generalised linear mixed models and either stratified or frailty-augmented Cox regression models. Heterogeneity in estimates from different studies will be quantified and bias investigated using funnel plots. Effect size estimates will be presented in forest plots and non-negligible heterogeneity and bias investigated using subgroup or meta-regression analyses.Ethics and disseminationEthics approvals obtained for each of the participating cohorts state that participants have consented to have their data collected and used for research purposes. The Androgens In Men Study has been assessed as exempt from ethics review by the Human Ethics office at the University of Western Australia (file reference number RA/4/20/5014). Each of the component studies had obtained ethics approvals; please refer to respective component studies for details. Research findings will be disseminated to the scientific and broader community via the publication of four research articles, with each involving a separate set of IPD meta-analyses (articles will investigate different, distinct outcomes), at scientific conferences and meetings of relevant professional societies. Collaborating cohort studies will disseminate findings to study participants and local communities.Prospero registration numberCRD42019139668.

Project description:BACKGROUND AND OBJECTIVES:Mild hyponatremia is a common finding in older adults; however, the association of lower serum sodium with cognition in older adults is currently unknown. We determined whether lower normal serum sodium is associated with cognitive impairment and risk of cognitive decline in community-dwelling older men. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Five thousand four hundred thirty-five community-dwelling men aged ?65 years who participated in Osteoporotic Fractures in Men, a cohort study with a median follow-up for cognitive function of 4.6 years, were included in this analysis. Multivariable logistic regression was used to examine the association between baseline fasting serum sodium levels and the odds of prevalent cognitive impairment (cross-sectional analysis; modified Mini-Mental Status [3MS] score <1.5 SD [<84] below or Trail Making Test Part B time >1.5 SD above the mean [>223 seconds]) and cognitive decline (prospective analysis [n=3611]; decrease in follow-up 3MS score or increase in Trails B time >1.5 SD of the mean score/time change [>9 or >67 seconds]). RESULTS:Participants were aged 74±6 years with a fasting mean serum sodium level of 141±3 mmol/L. Fifteen percent (n=274), 12% (n=225), and 13% (n=242) had prevalent cognitive impairment in tertiles 1, 2, and 3, respectively. After adjustment, lower serum sodium was associated with prevalent cognitive impairment (tertile 1 [126-140 mmol/L] versus tertile 2 [141-142 mmol/L], odds ratio [OR], 1.30; 95% confidence interval [95% CI], 1.06 to 1.61). Fourteen percent (n=159), 10% (n=125), and 13% (n=159) had cognitive decline in tertiles 1, 2, and 3, respectively. Lower serum sodium was also associated with cognitive decline (tertile 1 versus tertile 2, OR, 1.37; 95% CI, 1.06 to 1.77). Tertile 3 (143-153 mmol/L) was additionally associated with cognitive decline. Results were similar in sensitivity analyses according to clinical cut-offs and by quartiles. CONCLUSIONS:In community-dwelling older men, serum sodium between 126-140, and 126-140 or 143-153 mmol/L, are independently associated with prevalent cognitive impairment and cognitive decline, respectively.

Project description:BackgroundThe present study aimed to investigate longitudinal associations between bone mineral densities (BMDs) and appendicular skeletal muscle (ASM) mass in different regions of the body using three different indicators, in Chinese community-dwelling middle-aged and elderly men.MethodsA total of 1,343 men aged ≥ 40 years from a Chinese community were assessed at baseline (2014-2016), one-year follow-up (2016-2017; n = 648), two-year follow-up (2017-2018; n = 407), and three-year follow up (2018-2019; n = 208). At all the four time-points, measurements included ASM mass and BMDs for all regions of the body using dual-energy X-ray absorptiometry. A questionnaire was completed by patients and biochemical markers were assessed. We applied three different indicators to define ASM mass or lean mass respectively, including the appendicular skeletal muscle index (ASM adjusted by height, ASMI, according to the Asian Working Group for Sarcopenia), skeletal muscle index (ASM adjusted by weight, SMI, according to the International Working Group on Sarcopenia), and the appendicular skeletal muscle/body mass index (ratio of ASM and Body mass index (BMI), ASM/BMI, according to the Foundation for the National Institutes of Health). After adjusting for potential confounders, the generalized additive mixed model (GAMM) was used to analyze the trend in ASM mass over time, and to test the association between ASM mass and regional and whole-body BMDs.ResultsThe incidence of low lean mass was 8.2% defined by ASMI, 16.3% defined by SMI, and 8.3% defined by ASM/BMI. There was a linear relationship between BMDs and ASM mass, and ASMI, ASM/BMI, and SMI gradually decreased with time. After adjusting for covariances, GAMM analysis determined longitudinal associations between BMDs and ASM mass by three indicators respectively: the skull BMD was negatively associated with ASM mass. For each unit increase in skull BMD, ASMI decreased by 0.28 kg/m2 (95% confidence interval (CI) [-0.39 to -0.16]), ASM/BMI decreased by 0.02 m2 (95% CI [-0.03 to -0.00]), and SMI decreased by 0.01% (95% CI[-0.01 to -0.00]). The remaining parameters (including whole-body mean BMD, thoracic spinal BMD, lumbar spinal BMD, hip BMD, femoral neck BMD, pelvic BMD, left arm BMD, right arm BMD, left leg BMD, right leg BMD) were positively correlated with ASM mass. The ASMI increased by 3.07 kg/m2for each unit increase in the femoral neck BMD (95% CI [2.31-3.84]). The ASM/BMI increased by 0.22 m2for each unit increase in the left arm BMD (95% CI [0.12-0.33]), and the SMI increased by 0.05% per unit increase in the left arm BMD (95% CI [0.02-0.08]).ConclusionsCompared to ASMI and ASM/BMI, SMI was more sensitive to screen for the low lean mass. Skull BMD was negatively associated with ASM mass, while BMDs throughout the rest of the body were positively correlated with ASM mass among the middle-aged and elderly Chinese men.