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Prostate cancer: prognostic value of serum testosteroneDieser Volltext ist serum testosterone reserviert für Angehöriger medizinischer Fachkreise. Sie haben die Maximalzahl an Artikeln für unregistrierte besucher erreicht. Leider konnten wir sie nicht log-in. Wir möchten sicher sein, dass Sie die Webseite von Univadis wirklich verlassen möchten. Bitte klicken Sie dazu auf den folgenden externen Link:. Why this matters Data serum testosterone the association between serum testosterone levels, PCa aggressiveness, testosteron ankurbeln patient prognosis are conflicting.
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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— We used data from men recruited for the prospective population-based Study of Health in Pomerania, with measured serum testosterone levels at baseline and deaths during an average 7.
A total serum testosterone level of less than 8. 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. 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.
In cause-specific analyses, low serum testosterone levels predicted increased risk of death from cardiovascular disease CVD HR 2. 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. See page for the editorial comment on this article doi: The association of low serum testosterone levels and mortality has been investigated in few population-based studies, which demonstrated conflicting results.
Recent reports from the European Prospective Investigation into Cancer in Norfolk EPIC-Norfolk , 6 the Rancho Bernado, 7 and the osteoporotic fractures in men MrOS Sweden study 8 demonstrated that older men with lower serum testosterone levels had a greater risk of dying, compared with men with higher serum testosterone levels.
In contrast, two other prospective cohort studies reported no association between low serum testosterone levels and premature death. First, we seek to characterize the group of men with low serum testosterone levels. Second, we want to investigate if there is an association of low serum testosterone levels with all-cause or cause-specific mortality in a prospective population-based cohort of men aged 20— Third, we aim to identify a cut-off for the definition of low serum testosterone by exploring the highest predictive value in terms of mortality risk.
The study conformed to the principles of the Declaration of Helsinki as reflected by an a priori approval of the Ethics Committee of the University of Greifswald. This resulted in a final study population of men. Socio-demographic and behavioural characteristics and medical history were assessed by computer-aided personal interviews.
Mean daily alcohol consumption was calculated using beverage-specific pure ethanol volume proportions. Smoking habits were assessed by dividing men into categories of current, former, and never smokers. Men who participated in physical training during summer or winter for at least 1 h a week were classified as being physically active.
Waist circumference WC was measured to the nearest 0. Height was measured to the nearest 1 cm using a digital ultrasound instrument and weight was measured to the nearest 0.
Body mass index was calculated as weight in kilograms divided by the square of height in metres. Diabetes mellitus, chronic bronchitis, myocardial infarction, and stroke were identified from self-reported physician's diagnoses. A blood sample was drawn from the cubital vein in the supine position. The samples were taken between 7 a. Creatinine clearance CrCl was estimated using the Cockroft—Gault formula. Serum low-density lipoprotein cholesterol was measured applying a precipitation procedure using dextran sulphate Immuno, Heidelberg, Germany on an Epos Eppendorf, Hamburg, Germany.
Measurements of testosterone were performed during December and January An aliquot of two alternating levels of a third-party commercial control material Bio-Rad Lyphochek Immunoassay Plus Control, lot and lot ; Bio-Rad, Munich, Germany was included in each series in single determination.
The inter-assay coefficient of variation was Serum testosterone levels below 8. All assays were performed according to the manufacturers' recommendations by skilled technical personal. In addition, the laboratory takes part in official quarterly German external proficiency testing programs.
Information on vital status was acquired at regular intervals from the time of enrolment into the study through 31 August Subjects were included in the analysis until the time of either death or when they were censored due to study end or failure to follow-up.
The number of months between baseline examination and censoring was used as follow-up length. The mean duration of follow-up was 7. Death certificates were requested from the local health authority of the residence of death and were coded by a certified nosologist according to the International Classification of Diseases, 10th revision ICD Additionally, two internists H.
A third internist H. Categorical data are expressed as percentages and continuous data are expressed as medians 25th; 75th percentiles. To assess the association between serum testosterone levels and mortality, we used Cox proportional hazards regression models.
Different stepwise models were implemented adjusted for age, WC, smoking habits, high-risk alcohol use, and physical activity, as well as renal insufficiency and DHEAS levels.
All models were rerun for cause-specific mortality analyses. P -value for trend was calculated with continuous serum testosterone levels. The following sensitivity analyses were conducted. Second, to adjust for possible bias introduced by informative censoring, inverse probability weighting was used. And finally, the sample was stratified by blood sampling time. Models testing for mediation estimated the association of serum testosterone with mortality in multivariable Cox models, controlling for the intermediate variable each in a separate model.
We used both graphical and hypotheses testing methods for examining the proportional hazard assumption. Kaplan—Meier survival curves were used to illustrate the association of serum testosterone level and all-cause mortality, with differences tested by a log-rank test. To compare the predictability of testosterone along with standard mortality risk factors age, smoking habits, alcohol consumption, physical activity, and WC , we estimated area under receiver operating characteristic curves AUCs area from fully adjusted Cox models and tested their difference.
A posteriori power analyses were calculated using an nQuery Advisor program nQuery Advisor 6. This manuscript was written in accordance with the STROBE statement, giving guidelines for reporting of observational studies. During the 13 person-years of follow-up, men had died, reflecting a death rate of 14 deaths per person-years. Furthermore, men with low serum testosterone levels had significantly lower serum DHEAS levels and higher serum creatinine levels compared with men with higher serum testosterone levels.
There were no significant differences concerning cohabitation, educational level, LDL-cholesterol, high-risk alcohol use, or prevalences of chronic bronchitis, myocardial infarction, or stroke. This association was independent of age HR 2. Estimates did not change substantially after excluding first-year deaths HR 2. In cause-specific mortality analysis, low serum testosterone levels were significantly associated with an increased mortality caused by CVD HR 2. Multivariable models for low serum testosterone levels associated with all-cause and cause-specific mortality.
Hazard ratios for low serum testosterone levels associated with all-cause mortality adjusted for potential mediators. Covariables were added one at a time to model 3. Sensitivity analysis with sample stratified by blood sampling time confirmed the revealed association of low serum testosterone levels with mortality in men with blood drawn before 11 a.
Further sensitivity analysis of the testosterone—mortality association by different cut-offs from recent studies revealed that serum testosterone levels between 8. To estimate the possible bias introduced by informative censoring, we re-analysed the re-weighted study sample.
Analysing predictability, we found that testosterone only slightly improves the risk prediction of mortality AUCs area of 0. Alternatively, assessing dichotomized interaction terms of serum testosterone levels with bivariate covariates, we were not able to identify any significant dichotomous interaction coefficients.
We performed a posteriori power analyses to assess the minimum detectable relative risk for mortality in the comparison between men with low and higher serum testosterone levels. Given the real proportion of men with low testosterone levels, our study size was large enough to detect a minimum relative risk for mortality of 2. Association of low testosterone levels with all-cause mortality by different cut-offs from recent studies.
To the best of our knowledge, this is the first prospective population-based study that confirmed the previously reported association between low serum testosterone levels and mortality. In contrast, low serum testosterone levels were not associated with premature death in two other prospective cohort studies, the Massachusetts Male Aging study MMAS , 9 the Caerphilly study, 10 and InCHIANTI reporting that low concentrations of a combination of hormones, but not testosterone alone, were associated with death.
The mean follow-up time in studies reporting a negative association Therefore, distinct follow-up times cannot explain the differences between the studies.
Because the optimal testosterone concentration is still a subject of debate, arbitrary cut-offs for the definition of low serum testosterone levels could be a reason for the different findings. When we assessed the association of low serum testosterone levels with mortality by different cut-offs from recent studies, levels between 8. However, a long overdue agreement about the optimal serum testosterone concentration needs to be determined.
Also differences in assay methods are not likely to cause different associations: The automated immunoassay used in our study showed a higher concordance 22 , 23 with the latter assay and might not be the reason for differences, as previously suggested. This finding is in line with the general recommendation that, due to a maintained diurnal rhythm in healthy men into the seventh decade of life, 24 serum samples for testosterone determination should be obtained between 7.
Testicular function is suppressed in many acute and chronic illnesses resulting in reduced serum testosterone. Therefore, we carefully adjusted for medical morbidity and other clinical covariables and continued to find an association between low serum testosterone levels and mortality.
This finding is in line with recent results demonstrating an inverse association of serum testosterone levels with all-cause and CVD mortality in male patients with chronic kidney disease 32 or heart failure.
The observed association between low serum testosterone levels and mortality was not specific to a single aetiology. Low serum testosterone levels were strongly associated with deaths due to both CVD and cancer. During the past decades, reports linked differences in serum testosterone levels to various cardiovascular risk factors and also directly to CVD and death. The MMAS reported an association of low serum testosterone levels with mortality from cancer and respiratory disease.
Limitations arise from the lack of measured free testosterone, SHBG, or albumin for calculation of bioavailable testosterone, as well as from single measurement of testosterone. But this and previous studies 6 , 7 , 9 , 10 were based on a single measurement of serum testosterone, which is believed to be accurate for population studies. Also symptoms of qualitative hypogonadism were not assessed in our study, to draw any conclusions above laboratory diagnosis of hypogonadism by low serum total testosterone levels.
The major strength of our study is the use of data from a large population-based sample of men with a broad age range from 20 to 79 years, still revealing an increased risk of mortality independent of age, adiposity, and lifestyle factors. This association cannot be explained by pre-existing disease and was not specific to a single cause of death. However, as the exact mechanism by which testosterone may cause an increased risk of death is currently not known, 35 we propose testosterone being a risk marker, rather than risk factor.
A risk marker is not assumed to play an aetiological or direct causal role, but is mainly useful to improve our ability to predict risk.
Thieme E-Journals - Erfahrungsheilkunde / Abstract
Rapid Rise of Serum Testosterone Following Discontinuation of Long Term Treatment of Prostate Carcinoma with an. LHRH-Agonist. W. Kreis. D.R.. Budman . Testosteron Spiegel im Alter bei gesunden Männern. S. Mitchell et al Longitudinal Effects of Aging on Serum Testosterone Levels in Healthy Men, JCEM Juni The scope of the present investigation was measurement of serum testosterone levels in different age groups. Materials and methods Serum.