Sex Steroid Hormone Concentrations and Risk of Death in US Men (original) (raw)
Related papers
Clinical Endocrinology, 2014
Epidemiological studies have found that men with low or low normal endogenous testosterone are at an increased risk of mortality than those with higher levels. Cardiovascular disease accounts for the greater proportion of deaths in those with low testosterone. Cancer and respiratory deaths in some of the studies are also significantly more prevalent. Diseasespecific studies have identified that there are higher mortality rates in men with cardiovascular, respiratory and renal diseases, type 2 diabetes and cancer with low testosterone. Obesity, metabolic syndrome, type 2 diabetes, cardiovascular disease and inflammatory disorders are all associated with an increased prevalence of testosterone deficiency. Two major questions that arise from these findings are (1) is testosterone deficiency directly involved in the pathogenesis of these conditions and/or a contributory factor impairing the body's natural defences or is it merely a biomarker of ill health and the severity of underlying disease process? (2) Does testosterone replacement therapy retard disease progression and ultimately enhance the clinical prognosis and survival? This review will discuss the current state of knowledge and discuss whether or not there are any answers to either of these questions. There is convincing evidence that low testosterone is a biomarker for disease severity and mortality. Testosterone deficiency is associated with adverse effects on certain cardiovascular risk factors that when combined could potentially promote atherosclerosis. The issue of whether or not testosterone replacement therapy improves outcomes is controversial. Two retrospective studies in men with diagnosed hypogonadism with or without type 2 diabetes have reported significantly improved survival.
European Heart Journal, 2010
Aims Although the association of low serum testosterone levels with mortality has gained strength in recent research, there are few population-based studies on this issue. This study examined whether low serum testosterone levels are a risk factor for all-cause or cause-specific mortality in a population-based sample of men aged 20-79. Methods and results We used data from 1954 men recruited for the prospective population-based Study of Health in Pomerania, with measured serum testosterone levels at baseline and 195 deaths during an average 7.2-year follow-up. A total serum testosterone level of less than 8.7 nmol/L (250 ng/dL) was classified as low. The relationships of low serum testosterone levels with all-cause and cause-specific mortality were analysed by Cox proportional hazards regression models. Men with low serum testosterone levels had a significantly higher mortality from all causes than men with higher serum testosterone levels (HR 2.24; 95% CI 1.41-3.57). After adjusting for waist circumference, smoking habits, high-risk alcohol use, physical activity, renal insufficiency, and levels of dehydroepiandrosterone sulfate, low serum testosterone levels continued to be associated with increased mortality (HR 2.32; 95% CI 1.38-3.89). In cause-specific analyses, low serum testosterone levels predicted increased risk of death from cardiovascular disease (CVD) (HR 2.56; 95% CI 1.15-6.52) and cancer (HR 3.46; 95% CI 1.68-6.68), but not from respiratory diseases or other causes. Conclusion Low serum testosterone levels were associated with an increased risk of all-cause mortality independent of numerous risk factors. As serum testosterone levels are inversely related to mortality due to CVD and cancer, it may be used as a predictive marker.
Lower testosterone levels are associated with higher risk of death in men
Evolution, Medicine, and Public Health
Background and Objectives Testosterone plays an important role in regulating male development, reproduction and health. Declining levels across the lifespan may reflect, or even contribute to, chronic disease and mortality in men. Methodology Relationships between testosterone levels and male mortality were analyzed using data from multiple samples of the cross-sectional National Health and Nutrition Examination Survey (n = 10 225). Target outcomes included known deaths from heart disease, malignant neoplasms, chronic lower respiratory diseases, cerebrovascular diseases, Alzheimer’s disease, diabetes mellitus, influenza and pneumonia, kidney diseases, and accidents or unintentional injuries. Results Results of discrete-time hazard models revealed that lower levels of testosterone were related to higher mortality for the majority of disease categories in either an age-dependent or age-independent fashion. Analysis of all-cause mortality—which included deaths from any known disease—al...
The Journal of Clinical Endocrinology & Metabolism, 2015
Context: Testosterone (T) levels have been associated with mortality, but controversy exists. Objective: Our objective was to investigate associations between serum levels of total T, SHBG, free T, estradiol, LH and FSH, and subsequent mortality with up to 30 years of follow-up. Design: This was a prospective cohort study consisting of men participating in four independent population-based surveys (MONICA I-III and Inter99) from 1982 to 2001 and followed until December 2012 with complete registry follow-up. Setting and Participants: A total of 5350 randomly selected men from the general population aged 30, 40, 50, 60, or 70 years at baseline participated. Main Outcomes and Measures: All-cause mortality, cardiovascular disease (CVD) mortality, and cancer mortality were the main outcomes. Results: A total of 1533 men died during the follow-up period; 428 from CVD and 480 from cancer. Cox proportional hazard models revealed that men in highest LH quartile had an increased allcause mortality compared to lowest quartile (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.14-1.53). Likewise, increased quartiles of LH/T and estradiol increased the risk of all-cause mortality (HR, 1.23; 95% CI, 1.06-1.43; HR, 1.23; 95% CI 1.06-1.43). No association to T levels was found. Higher LH levels were associated with increased cancer mortality (HR, 1.42; 95% CI, 1.10-1.84) independently of smoking status. Lower CVD mortality was seen for men with T in the highest quartile compared to lowest (HR, 0.72; 95% CI, 0.53-0.98). Furthermore, negative trends were seen for SHBG and free T in relation to CVD mortality, however insignificant. Conclusion: The observed positive association of LH and LH/T, but not T, with all-cause mortality suggests that a compensated impaired Leydig cell function may be a risk factor for death by all causes in men. Our findings underpin the clinical importance of including LH measurement in the diagnostic work-up of male patients seeking help for possible androgen insufficiency.
Circulation, 2007
Methods and Results-We examined the prospective relationship between endogenous testosterone concentrations and mortality due to all causes, cardiovascular disease, and cancer in a nested case-control study based on 11 606 men aged 40 to 79 years surveyed in 1993 to 1997 and followed up to 2003. Among those without prevalent cancer or cardiovascular disease, 825 men who subsequently died were compared with a control group of 1489 men still alive, matched for age and date of baseline visit. Endogenous testosterone concentrations at baseline were inversely related to mortality due to all causes (825 deaths), cardiovascular disease (369 deaths), and cancer (304 deaths). Odds ratios (95% confidence intervals) for mortality for increasing quartiles of endogenous testosterone compared with the lowest quartile were 0.75 (0.55 to 1.00), 0.62 (0.45 to 0.84), and 0.59 (0.42 to 0.85), respectively (PϽ0.001 for trend after adjustment for age, date of visit, body mass index, systolic blood pressure, blood cholesterol, cigarette smoking, diabetes mellitus, alcohol intake, physical activity, social class, education, dehydroepiandrosterone sulfate, androstanediol glucuronide, and sex hormone binding globulin). An increase of 6 nmol/L serum testosterone (Ϸ1 SD) was associated with a 0.81 (95% confidence interval 0.71 to 0.92, PϽ0.01) multivariable-adjusted odds ratio for mortality. Inverse relationships were also observed for deaths due to cardiovascular causes and cancer and after the exclusion of deaths that occurred in the first 2 years. Conclusions-In men, endogenous testosterone concentrations are inversely related to mortality due to cardiovascular disease and all causes. Low testosterone may be a predictive marker for those at high risk of cardiovascular disease.
Testosterone Treatment and Mortality in Men with Low Testosterone Levels
The Journal of Clinical Endocrinology & Metabolism, 2012
Context: Low testosterone levels in men have been associated with increased mortality. However, the influence of testosterone treatment on mortality in men with low testosterone levels is not known. Objective: The objective of the study was to examine the association between testosterone treatment and mortality in men with low testosterone levels. Design: This was an observational study of mortality in testosterone-treated compared with untreated men, assessed with time-varying, adjusted Cox proportional hazards regression models. Effect modification by age, diabetes, and coronary heart disease was tested a priori. Setting: The study was conducted with a clinical database that included seven Northwest Veterans Affairs medical centers. Patients: Patients included a cohort of 1031 male veterans, aged older than 40 yr, with low total testosterone [Յ250 ng/dl (8.7 nmol/liter)] and no history of prostate cancer, assessed between January 2001 and December 2002 and followed up through the end of 2005. Main Outcome Measure: Total mortality in testosterone-treated compared with untreated men was measured. Results: Testosterone treatment was initiated in 398 men (39%) during routine clinical care. The mortality in testosterone-treated men was 10.3% compared with 20.7% in untreated men (PϽ0.0001) with a mortality rate of 3.4 deaths per 100 person-years for testosterone-treated men and 5.7 deaths per 100 person-years in men not treated with testosterone. After multivariable adjustment including age, body mass index, testosterone level, medical morbidity, diabetes, and coronary heart disease, testosterone treatment was associated with decreased risk of death (hazard ratio 0.61; 95% confidence interval 0.42-0.88; P ϭ 0.008). No significant effect modification was found by age, diabetes, or coronary heart disease. Conclusions: In an observational cohort of men with low testosterone levels, testosterone treatment was associated with decreased mortality compared with no testosterone treatment. These results should be interpreted cautiously because residual confounding may still be a source of bias. Large, randomized clinical trials are needed to better characterize the health effects of testosterone treatment in older men with low testosterone levels.
Endogenous Testosterone and Mortality in Men: A Systematic Review and Meta-Analysis
The Journal of Clinical Endocrinology & Metabolism, 2011
Context: Low testosterone levels have been associated with outcomes that reduce survival in men. Objective: Our objective was to perform a systematic review and meta-analysis of published studies to evaluate the association between endogenous testosterone and mortality. Data Sources: Data sources included MEDLINE (1966 to December 2010), EMBASE (1988 to December 2010), and reference lists. Study Selection: Eligible studies were published English-language observational studies of men that reported the association between endogenous testosterone and all-cause or cardiovascular disease (CVD) mortality. A two-stage process was used for study selection. 1) Working independently and in duplicate, reviewers screened a subset (10%) of abstracts. Results indicated 96% agreement, and thereafter, abstract screening was conducted in singlicate. 2) All full-text publications were reviewed independently and in duplicate for eligibility. Data Extraction: Reviewers working independently and in duplicate determined methodological quality of studies and extracted descriptive, quality, and outcome data. Data Synthesis: Of 820 studies identified, 21 were included in the systematic review, and 12 were eligible for meta-analysis [n ϭ 11 studies of all-cause mortality (16,184 subjects); n ϭ 7 studies of CVD mortality (11,831 subjects)]. Subject mean age and testosterone level were 61 yr and 487 ng/dl, respectively, and mean follow-up time was 9.7 yr. Between-study heterogeneity was observed among studies of all-cause (P Ͻ .001) and CVD mortality (P ϭ 0.06), limiting the ability to provide valid summary estimates. Heterogeneity in all-cause mortality (higher relative risks) was observed in studies that included older subjects (P ϭ 0.020), reported lower testosterone levels (P ϭ 0.018), followed subjects for a shorter time period (P ϭ 0.010), and sampled blood throughout the day (P ϭ 0.030). Conclusion: Low endogenous testosterone levels are associated with increased risk of all-cause and CVD death in community-based studies of men, but considerable between-study heterogeneity, which was related to study and subject characteristics, suggests that effects are driven by differences between cohorts (e.g. in underlying health status).
Testosterone therapy and mortality risk
International journal of impotence research, 2015
Recent data suggest an increased risk of cardiovascular events and mortality in men on testosterone therapy (TT). To date, there are no long-term, prospective studies to determine safety. In such cases, retrospective observational studies can be helpful. We examined our patient database to determine whether TT altered the risk of all-cause mortality in men. We queried our hormone database for all men with a serum testosterone level and then examined charts to determine testosterone status. In all, 509 men had charts available for review. We linked our patient records to the National Death Index to determine mortality. Of the 509 men who met inclusion criteria, 284 were on TT and 225 did not use testosterone. Age (mean 54 years) and follow-up time (mean 10 years) were similar for both groups. In all, 19 men died-10 (4.4%) men not on TT and 9 (3.2%) men on TT. After adjusting for age and year of evaluation, there was no significant difference in the risk of death based on TT (hazard r...