Endogenous Testosterone and Mortality in Male Hemodialysis Patients

Abstract

Background and objectives: Low serum testosterone levels in hemodialysis (HD) patients have recently been associated with cardiovascular risk factors and increased mortality. To confirm this observation, we investigated the predictive role of serum total testosterone levels on mortality in a large group of male HD patients from Turkey.Design, settings, participants, & measurements: A total of 420 prevalent male HD patients were sampled in March 2005 and followed up for all-cause mortality. Serum total testosterone levels were measured by ELISA at baseline and studied in relation to mortality and cardiovascular risk profile.Results: Mean testosterone level was 8.69 ؎ 4.10 (0.17 to 27.40) nmol/L. A large proportion of patients (66%) had testosterone deficiency (<10 nmol/L). In univariate analysis, serum testosterone levels were positively correlated with creatinine and inversely correlated with age, body mass index, and lipid parameters. During an average follow-up of 32 months, 104 (24.8%) patients died. The overall survival rate was significantly lower in patients within the low testosterone tertile (<6.8 nmol/L) compared with those within the high tertile (>10.1 nmol/L; 64 versus 81%; P ‫؍‬ 0.004). A 1-nmol/L increase in serum testosterone level was associated with a 7% decrease in overall mortality (hazard ratio 0.93; 95% confidence interval 0.89 to 0.98; P ‫؍‬ 0.01); however, this association was dependent on age and other risk factors in adjusted Cox regression analyses.Conclusions: Testosterone deficiency is common in male HD patients. Although testosterone levels, per se, predicted mortality in this population, this association was largely dependent on age.

Endogenous Testosterone, Endothelial Dysfunction, and Cardiovascular Events in Men with Nondialysis Chronic Kidney Disease

“…Similar results were also found for free testosterone forms. To our knowledge, this is the first study looking at testosterone concentration versus cardiovascular outcomes in nondialysis CKD, and it complements previous reports linking testosterone with mortality in dialysis patients (7,8,17). However, contrary to our hypothesis, adjustment for FMD values did not significantly affect this relationship, implying that the association between testosterone and cardiovascular outcomes is not fully explained by mechanisms related to impaired vasodilation.…”

“…Low testosterone levels in apparently healthy male populations have been identified as a predisposing risk factor to increased mortality and cardiovascular comorbidity (6). It has recently been reported that low endogenous testosterone values were also associated with increased risk of death in male hemodialysis patients (7,8). Interestingly, testosterone deficiency in men undergoing hemodialysis has also been related to arterial thickening, atherosclerotic plaque occurrence, and reduced flowmediated dilation (FMD) (9).…”

Prolactin Levels, Endothelial Dysfunction, and the Risk of Cardiovascular Events and Mortality in Patients with CKD

“…Although we relate our findings to studies demonstrating a causative role for prolactin, we acknowledge that our observational design cannot determine whether prolactin is a risk factor per se or an intermediate of a larger pathophysiological pathway. For instance, prolactin retention leads to inhibition of gonadotropic hormone production, and testosterone deficiency in male CKD patients has indeed been linked to increased IMT, atherosclerotic plaque occurrence, reduced FMD, systemic inflammation, cardiovascular risk, and mortality (19)(20)(21)(22)(23)(24). Conversely, increased prolactinemia could also be a consequence of decreased dopaminergic activity (8), which would in turn imply an increment in norepinephrine release and that may have adverse effects on endothelial function and on other organs, perhaps favoring myocardial hypertrophy, hypertension, and other cardiovascular comorbidities.…”

“…At present, little is known about the implications of hyperprolactinemia in CKD. This may be relevant because testosterone deficiency, partly a consequence of prolactin-induced inhibition of gonadotropins, has been associated with cardiovascular risk factors and mortality in CKD (19)(20)(21)(22)(23)(24). We hypothesized that prolactin retention in CKD may be a contributing factor to vascular derangements and worse (cardiovascular) outcomes, and we tested this in two independent materials with prospective follow-up, including a cohort of nondialysis CKD patients with assessments of flow-mediated dilation (FMD) and carotid intima-media thickness (IMT), as well as a cohort of prevalent hemodialysis patients with assessments of pulse wave velocity (PWV).…”

Hormones and Arterial Stiffness in Patients with Chronic Kidney Disease

“…The total and free testosterone levels are typically reduced, although the binding capacity and concentration of sex hormonebinding globulin are normal 30,31) . Disturbances in the levels of sex hormones are associated with decreased fertility and libido in addition to increased morbidity and mortality [32][33][34] .…”