Original Report: Patient-Oriented, Translational Research
Association between Testosterone and Mortality Risk among U.S. Males Receiving DialysisYu J.a · Ravel V.A.a · You A.S.a · Streja E.a · Rivara M.B.b · Potukuchi P.K.e · Brunelli S.M.c · Kovesdy C.P.d, e · Kalantar-Zadeh K.a · Rhee C.M.a
aHarold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, bKidney Research Institute and Harborview Medical Center, Division of Nephrology, University of Washington, Seattle, WA, cDaVita Clinical Research, Minneapolis, MN, and dMemphis Veterans Affairs Medical Center, and eDivision of Nephrology, University of Tennessee Health Science Center, Memphis, TN, USA
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Article / Publication Details
Background: Among the general population, low circulating testosterone levels are associated with higher risk of cardiovascular disease and death. While testosterone deficiency is common in dialysis patients, studies of testosterone and mortality in this population are ambiguous and overlapping. We hypothesized that lower testosterone levels are associated with higher mortality in male dialysis patients. Methods: We examined a nationally representative cohort of male dialysis patients from a large US dialysis organization who underwent one or more total testosterone measurements from 1/2007 to 12/2011. The association between total testosterone categorized as quartiles and all-cause mortality was studied using Cox models adjusted for expanded case-mix and laboratory covariates. We also examined total testosterone as a continuous predictor of all-cause mortality using restricted cubic splines. Results: Among 624 male dialysis patients, 51% of patients demonstrated testosterone deficiency (total testosterone <300 ng/dL); median (IQR) total testosterone levels were 297 (190-424) ng/mL. In expanded case-mix + laboratory adjusted Cox analyses, we observed a graded association between lower testosterone levels and higher mortality risk (ref: quartile 3): adjusted hazard ratios (95% CI) 2.32 (1.33-4.06), 1.80 (0.99-3.28), and 0.68 (0.32-1.42) for Quartiles 1, 2, and 4, respectively. In adjusted spline analyses, the lower testosterone-higher mortality risk association declined with higher testosterone levels until the value reached a threshold of 400 ng/dL above which risk plateaued. Conclusion: Lower testosterone levels were independently associated with higher mortality risk in male dialysis patients. Further studies are needed to determine underlying mechanisms, and whether testosterone replacement ameliorates death risk in this population.
© 2017 S. Karger AG, Basel
- Araujo AB, Kupelian V, Page ST, Handelsman DJ, Bremner WJ, McKinlay JB: Sex steroids and all-cause and cause-specific mortality in men. Arch Intern Med. 2007;167:1252-1260.
- Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR: Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2001;86:724-731.
- Laughlin GA, Barrett-Connor E, Bergstrom J: Low serum testosterone and mortality in older men. J Clin Endocrinol Metab 2008;93:68-75.
- Sharma R, Oni OA, Gupta K, Chen G, Sharma M, Dawn B, Sharma R, Parashara D, Savin VJ, Ambrose JA, Barua RS: Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Eur Heart J 2015;36:2706-2715.
- Yeap BB, Alfonso H, Chubb SA, Handelsman DJ, Hankey GJ, Almeida OP, Golledge J, Norman PE, Flicker L: In older men an optimal plasma testosterone is associated with reduced all-cause mortality and higher dihydrotestosterone with reduced ischemic heart disease mortality, while estradiol levels do not predict mortality. J Clin Endocrinol Metab 2014;99:E9-E18.
- Kakiya R, Shoji T, Hayashi T, Tatsumi-Shimomura N, Tsujimoto Y, Tabata T, Shima H, Mori K, Fukumoto S, Tahara H, Koyama H, Emoto M, Ishimura E, Nishizawa Y, Inaba M: Decreased serum adrenal androgen dehydroepiandrosterone sulfate and mortality in hemodialysis patients. Nephrol Dial Transplant 2012;27:3915-3922.
URD System: USRDS 2013 Annual Data Report: Atlas of Chronic Kidney DIsease and End-Stage Renal Disease in the United States. Bethesda, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2013.
- Carrero JJ, Qureshi AR, Nakashima A, Arver S, Parini P, Lindholm B, Barany P, Heimburger O, Stenvinkel P: Prevalence and clinical implications of testosterone deficiency in men with end-stage renal disease. Nephrol Dial Transplant 2011;26:184-190.
- Gungor O, Kircelli F, Carrero JJ, Asci G, Toz H, Tatar E, Hur E, Sever MS, Arinsoy T, Ok E: Endogenous testosterone and mortality in male hemodialysis patients: is it the result of aging? Clin J Am Soc Nephrol 2010;5:2018-2023.
- Carrero JJ: Testosterone deficiency at the crossroads of cardiometabolic complications in CKD. Am J Kidney Dis 2014;64:322-325.
- Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH: The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab 2004;89:3313-3318.
- Schmidt A, Luger A, Horl WH: Sexual hormone abnormalities in male patients with renal failure. Nephrol Dial Transplant 2002;17:368-371.
- Bello AK, Stenvinkel P, Lin M, Hemmelgarn B, Thadhani R, Klarenbach S, Chan C, Zimmerman D, Cembrowski G, Strippoli G, Carrero JJ, Tonelli M: Serum testosterone levels and clinical outcomes in male hemodialysis patients. Am J Kidney Dis 2014;63:268-275.
- Carrero JJ, Qureshi AR, Parini P, Arver S, Lindholm B, Barany P, Heimburger O, Stenvinkel P: Low serum testosterone increases mortality risk among male dialysis patients. J Am Soc Nephrol 2009;20:613-620.
- Grossmann M, Hoermann R, Ng Tang Fui M, Zajac JD, Ierino FL, Roberts MA: Sex steroids levels in chronic kidney disease and kidney transplant recipients: associations with disease severity and prediction of mortality. Clin Endocrinol (Oxf) 2015;82:767-775.
- Kyriazis J, Tzanakis I, Stylianou K, Katsipi I, Moisiadis D, Papadaki A, Mavroeidi V, Kagia S, Karkavitsas N, Daphnis E: Low serum testosterone, arterial stiffness and mortality in male haemodialysis patients. Nephrol Dial Transplant 2011;26:2971-2977.
- Kuttykrishnan S, Kalantar-Zadeh K, Arah OA, Cheung AK, Brunelli S, Heagerty PJ, Katz R, Molnar MZ, Nissenson A, Ravel V, Streja E, Himmelfarb J, Mehrotra R: Predictors of treatment with dialysis modalities in observational studies for comparative effectiveness research. Nephrol Dial Transplant 2015;30:1208-1217.
- Rhee CM, Kim S, Gillen DL, Oztan T, Wang J, Mehrotra R, Kuttykrishnan S, Nguyen DV, Brunelli SM, Kovesdy CP, Brent GA, Kalantar-Zadeh K: Association of thyroid functional disease with mortality in a national cohort of incident hemodialysis patients. J Clin Endocrinol Metab 2015;100:1386-1395.
- Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM: Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010;95:2536-2559.
- Haffner SM, Mykkanen L, Valdez RA, Katz MS: Relationship of sex hormones to lipids and lipoproteins in nondiabetic men. J Clin Endocrinol Metab 1993;77:1610-1605.
- Ohlsson C, Barrett-Connor E, Bhasin S, Orwoll E, Labrie F, Karlsson MK, Ljunggren O, Vandenput L, Mellstrom D, Tivesten A: High serum testosterone is associated with reduced risk of cardiovascular events in elderly men. The MrOS (Osteoporotic Fractures in Men) study in Sweden. J Am Coll Cardiol 2011;58:1674-1681.
- Kaplan SA, Johnson-Levonas AO, Lin J, Shah AK, Meehan AG: Elevated high sensitivity C-reactive protein levels in aging men with low testosterone. Aging Male 2010;13:108-112.
- Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen TP, Valkonen VP, Salonen R, Salonen JT: Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes care. 2004;27:1036-1041.
- Yilmaz MI, Sonmez A, Qureshi AR, Saglam M, Stenvinkel P, Yaman H, Eyileten T, Caglar K, Oguz Y, Taslipinar A, Vural A, Gok M, Unal HU, Yenicesu M, Carrero JJ: Endogenous testosterone, endothelial dysfunction, and cardiovascular events in men with nondialysis chronic kidney disease. Clin J Am Soc Nephrol 2011;6:1617-1625.
- Carrero JJ, Barany P, Yilmaz MI, Qureshi AR, Sonmez A, Heimburger O, Ozgurtas T, Yenicesu M, Lindholm B, Stenvinkel P: Testosterone deficiency is a cause of anaemia and reduced responsiveness to erythropoiesis-stimulating agents in men with chronic kidney disease. Nephrol Dial Transplant. 2012;27:709-715.
- Rhee CM, Lertdumrongluk P, Streja E, Park J, Moradi H, Lau WL, Norris KC, Nissenson AR, Amin AN, Kovesdy CP, Kalantar-Zadeh K: Impact of age, race and ethnicity on dialysis patient survival and kidney transplantation disparities. Am J Nephrol 2014;39:183-194.
- Johansen KL, Mulligan K, Schambelan M. Anabolic effects of nandrolone decanoate in patients receiving dialysis: a randomized controlled trial. JAMA 1999;281:1275-1281.
- Ghorbanihaghjo A, Argani H, Rohbaninoubar M, Rashtchizadeh N: Effect of Nandrolone Decanoate on serum lipoprotein (a) and its isoforms in hemodialysis patients. Lipids Health Dis 2004;3:16.
- Adamu B, Ma'aji SM, Erwin PJ, Tleyjeh IM: Meta-Analysis of Randomized controlled trials on androgens versus erythropoietin for anaemia of chronic kidney disease: implications for developing Countries. Int J Nephrol 2012;2012:580437.
- Haring R, Nauck M, Volzke H, Endlich K, Lendeckel U, Friedrich N, Dorr M, Rettig R, Kroemer HK, Wallaschofski H Low serum testosterone is associated with increased mortality in men with stage 3 or greater nephropathy. Am J Nephrol 2011;33:209-217.
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