Testosterone Deficiency and Exercise Intolerance in Heart Failure: Treatment Implications
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Chronic heart failure (CHF) is characterized by a metabolic shift favoring catabolism with impairment in skeletal muscle bulk and function. There is evidence that low plasma levels of testosterone play a role in this shift, and that hypotestosteronemia could be involved in the impairment of skeletal muscle function and exercise tolerance, which characterize CHF syndrome. Testosterone supplementation at replacement doses has been hypothesized as a potential therapy to counteract anabolic deficiency in CHF also acting on pathophysiological mechanisms, which sustain the progression of CHF. Recent studies have indeed indicated that testosterone supplementation increases functional capacity and muscle performance in patients with CHF. This review summarizes current knowledge on the role of testosterone deficiency in exercise intolerance in CHF and the potential implications of testosterone therapy. The links between testosterone and exercise tolerance in CHF, as well as the potential mechanisms of testosterone benefits in CHF syndrome, are also emphasized. Finally, unsolved issues regarding testosterone therapy in CHF and directions for future research are discussed.
KeywordsHeart failure Exercise tolerance Testosterone
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- 9.•• Jankowska EA, Biel B, Majda J, et al.: Anabolic deficiency in men with chronic heart failure prevalence and detrimental impact on survival. Circulation 2006, 114:1829–1837. This study demonstrated a high prevalence of reduced serum concentrations of anabolic hormones, including testosterone, which were independent markers of a poor prognosis in CHF. CrossRefPubMedGoogle Scholar
- 10.•• Jankowska EA, Gerasimos Filippatos G, Ponikowska B, et al.: Reduction in circulating testosterone relates to exercise capacity in men with chronic heart failure. J Card Fail 2009, 15:442–450. This study indicated that circulating levels of testosterone are directly and independently related to peak oxygen consumption in men with CHF, and that a reduction in circulating testosterone levels was the only predictor of the magnitude of deterioration in peak VO 2 over time. CrossRefPubMedGoogle Scholar
- 15.Sinha-Hikim I, Artaza J, Woodhouse L, et al.: Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy. Am J Physiol 2002, 283:154–164.Google Scholar
- 19.• Kadi F: Cellular and molecular mechanisms responsible for the action of testosterone on human skeletal muscle. A basis for illegal performance enhancement. Br J Pharmacol 2008, 154:522–528. This review emphasized the mechanisms of testosterone action at the skeletal muscle level. CrossRefPubMedGoogle Scholar
- 22.•• Malkin CJ, Pugh PJ, West JN, et al.: Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. Eur Heart J 2006, 27:57–64. This study was the first to demonstrate that testosterone administration is capable of improving functional capacity as assessed by the distance walked at an incremental shuttle walk test. CrossRefPubMedGoogle Scholar
- 23.•• Caminiti G, Volterrani M, Iellamo F, et al.: Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study. J Am Coll Cardiol 2009, 54:919–927. This study first reported the effect of testosterone administration on objective measures of functional capacity, such as VO 2 and VE/VCO 2 slope, and power strength and output of large, weight-bearing muscles in patients with CHF. CrossRefPubMedGoogle Scholar
- 25.Swedberg K, Cleland J, Dargie H, et al.: Guidelines on the diagnosis and treatment of chronic heart failure: executive summary (update 2005). The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J 2005, 26:1115–1140.CrossRefPubMedGoogle Scholar