Low Serum Testosterone Increases Mortality Risk among Male Dialysis Patients

Abstract

Men treated with hemodialysis (HD) have a very poor prognosis and an elevated risk of premature cardiovascular disease (CVD). In the general population, associations between low testosterone concentrations and cardiovascular risk have been suggested. We performed a prospective observational study involving a well characterized cohort of 126 men treated with HD to examine the relationship between testosterone concentration and subsequent mortality during a mean follow-up period of 41 mo. Independent of age, serum creatinine, and sexual hormone binding globulin (SHBG), testosterone levels inversely and strongly associated with the inflammatory markers IL-6 and CRP. Patients with a clinical history of CVD had significantly lower testosterone levels. During follow up, 65 deaths occurred, 58% of which were a result of CVD. Men with testosterone values in the lowest tertile had increased all-cause and CVD mortality (crude hazard ratios [HRs] 2.03 [95% CI 1.24 to 3.31] and 3.19 [1.49 to 6.83], respectively), which persisted after adjustment for age, SHBG, previous CVD, diabetes, ACEi/ARB treatment, albumin, and inflammatory markers, but was lost after adjustment for creatinine. In summary, among men treated with HD, testosterone concentrations inversely correlate with all-cause and CVDrelated mortality, as well as with markers of inflammation. Hypogonadism may be an additional treatable risk factor for patients with chronic kidney disease.

Endogenous Testosterone and Mortality in Male Hemodialysis Patients

“…In this sense, we observed a positive association between testosterone levels and dialysis vintage in our study, although this variable was stepwise excluded in multivariate analysis. In the study of Carrero et al (16), univariate associations of testosterone levels with dialysis vintage were not reported, but patients within the lower testosterone tertile tended to have increased dialysis vintage, albeit nonsignificant, which suggests an opposed association than that observed in our material. This finding may indeed indirectly support the idea that individuals with increased testosterone levels could have survived longer, although we should bear in mind that these individuals were likely to be younger as well.…”

“…At first, both cohorts present large differences in age, baseline comorbid conditions, and mortality rates. Surprisingly, despite that our patients were younger, the proportion of testosteronedeficient patients was larger than in Swedish patients, 52% of whom were found to have hypogonadism (16). We do not have a clear explanation for this, but we could speculate that our larger sample size may give a more representative estimation.…”

“…Recently, Carrero et al (16) identified low testosterone levels (lower tertile of distribution in that study) as an independent risk factor for all-cause and CVD mortality in a cohort of 126 prevalent HD Swedish men. In that study, the association with mortality was independent of age, SHBG, inflammation and several comorbidities but dependent of serum creatinine, suggesting a relation with muscle depletion.…”

“…A second remark should be made regarding the quality of our follow-up data. Whereas the Swedish study (16) had no loss to follow-up and did not censor for transplantation, 20% of our patients moved to other clinics and 3.5% received a transplant. In addition, the inaccuracy of our death records prevents us from separating causes of death.…”

“…In a small study that included male HD patients without diabetes, low testosterone levels were associated with endothelial dysfunction and atherosclerosis (15). Interestingly, Carrero et al (16) recently demonstrated in a Swedish HD cohort that low serum testosterone levels were significant predictors of mortality, irrespective of age and inflammation, but this was abolished after correction for serum creatinine, used there as a surrogate of muscle mass (16). In light of the exceedingly elevated (cardiovascular) mortality of HD patients (17), this possibility is an attractive and therapeutically modifiable idea.…”