Higher Endogenous Testosterone Levels Associated with Increased Risk of Coronary Heart Disease in Elderly Men: A Prospective Study.

Sueoka, KT; Ewing, SK; Ensrud, KE; Laughlin, GA; Ar, Hoffman; Varosy, PD; Stefanick, ML; Barrett-Connor, E; Stone, KL; Bauer, DC

doi:10.1210/endo-meetings.2010.part2.or.or17-1

Cited by 4 publications

(4 citation statements)

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“…Finally, previous studies did not take MetS status into account, while our analysis was limited to men without MetS who, by definition, have less comorbidities and are healthier compared to men overall. Conversely, our results are consistent with other studies on the risk of death from coronary heart disease [ 16 , 17 ] and CV events [ 3 , 4 ]. This is also in keeping with a meta-analysis of 27 clinical trials (n=2,994 men) showing increased CV risk in men treated with exogenous testosterone compared to placebo [ 18 ].…”

Section: Discussionsupporting

confidence: 93%

Testosterone Level and Cause-Specific Mortality in Older Men without Metabolic Syndrome

Laouali

Brailly-Tabard²,

Helmer

et al. 2020

Epidemiol Health

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OBJECTIVES: Previous studies have reported controversial findings regarding the association of testosterone with mortality in older men. This heterogeneity might be partially explained by comorbidities and the presence of metabolic syndrome, as well as differential associations according to causes of death. METHODS: We used data from a random subsample of the Three-City study, in which hormone levels were measured in 338 men ≥65 years without metabolic syndrome who were followed-up for 12 years. Vital status was determined for all participants from different sources. We used inverse-probability-weighted Cox regression to estimate the hazard ratios (HRs) of cause-specific mortality and 95% confidence intervals (CIs). RESULTS: Over the follow-up period, 130 men died (30 from cardiovascular disease, 45 from cancer, 55 from other causes). The association of testosterone with mortality showed significant heterogeneity across causes of death (p=0.027 and p=0.022 for total and bioavailable testosterone, respectively). Higher testosterone levels were associated with increased cardiovascular mortality (HR for 1-standard deviation increase, 1.86; 95% CI, 1.28 to 2.71 and 1.50; 95% CI, 1.04 to 2.17 for total and bioavailable testosterone, respectively). By contrast, there were no significant associations of testosterone with mortality from cancer and other causes. CONCLUSIONS: Our data suggest that the association of testosterone with mortality in men without metabolic syndrome might be differential according to the cause of death. These findings may partially explain the heterogeneity across studies on the relationship between testosterone levels and mortality.

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Section: Discussionsupporting

confidence: 93%

Testosterone Level and Cause-Specific Mortality in Older Men without Metabolic Syndrome

Laouali

Brailly-Tabard²,

Helmer

et al. 2020

Epidemiol Health

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“…Although many reports indicate that low testosterone levels are associated with high risk of cardiovascular disease and that testosterone replacement improves cardiovascular and metabolic functions, [7][8][9] other studies indicate that older men with higher testosterone levels are more likely to have cardiovascular disease. 10,11 Testosterone effects on the vasculature are contradictory and include modulation of vascular tone, 12 proliferation of vascular smooth muscle cells (VSMCs), 13 and regulation of apoptosis in endothelial cells.…”

mentioning

confidence: 99%

Testosterone Induces Vascular Smooth Muscle Cell Migration by NADPH Oxidase and c-Src–Dependent Pathways

et al. 2012

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Abstract-Testosterone has been implicated in vascular remodeling associated with hypertension. Molecular mechanisms underlying this are elusive, but oxidative stress may be important. We hypothesized that testosterone stimulates generation of reactive oxygen species (ROS) and migration of vascular smooth muscle cells (VSMCs), with enhanced effects in cells from spontaneously hypertensive rats (SHRs). The mechanisms (genomic and nongenomic) whereby testosterone induces ROS generation and the role of c-Src, a regulator of redox-sensitive migration, were determined. VSMCs from male Wistar-Kyoto rats and SHRs were stimulated with testosterone (10 Ϫ7 mol/L, 0 -120 minutes).

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“…The size of plotted points refers are proportional to the inverse of the corresponding SEs (indicative of relative weightings), with lines demonstrating the fitted model and 95% CIs. Plotted estimates are numbered as from the following articles (cohort studies): 1=Srinath et al 48 (ARIC); 2=Chan et al 37 (BHS); 3=Hsu et al 9 (CHAMP); 4=Shores et al 50 (CHS); 5=Lee et al 43 (EMAS); 6=Chan et al 41 (HIMS); 7=Ohlsson et al 44 (MrOS Sweden); 8=Kische et al 46 (SHIP); 9=Sueoka et al 53 (MrOS USA); 10=Pencina et al 57 (FHS); 11=Li et al 56 (MAILES). *=includes articles from two additional studies (FHS, MAILES) that were not identified from systematic searches but by colleagues.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2021

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ObjectivesThe 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.SettingCommunity-dwelling men.Participants20 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 measuresPlanned 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.ResultsScreening 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).ConclusionsAnalyses 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 numberPROSPERO: CRD42019139668.

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Higher Endogenous Testosterone Levels Associated with Increased Risk of Coronary Heart Disease in Elderly Men: A Prospective Study.

Cited by 4 publications

References 0 publications

Testosterone Level and Cause-Specific Mortality in Older Men without Metabolic Syndrome

Testosterone Level and Cause-Specific Mortality in Older Men without Metabolic Syndrome

Testosterone Induces Vascular Smooth Muscle Cell Migration by NADPH Oxidase and c-Src–Dependent Pathways

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

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