Abstract
BackgroundAdjunct testosterone therapy improves lean body mass, quality of life, and physical activity in patients with advanced cancers; however, the effects of testosterone on cardiac morphology and function are unknown. Accordingly, as an ancillary analysis of a randomized, placebo-controlled trial investigating the efficacy of testosterone supplementation on body composition in men and women with advanced cancers, we explored whether testosterone supplementation could prevent or reverse left ventricular (LV) atrophy and dysfunction.MethodsMen and women recently diagnosed with late stage (≥IIB) or recurrent head and neck or cervical cancer who were scheduled to receive standard of care chemotherapy or concurrent chemoradiation were administered an adjunct 7 week treatment of weekly intramuscular injections of either 100 mg testosterone (T, n = 1 M/5F) or placebo (P, n = 6 M/4F) in a double-blinded randomized fashion. LV morphology (wall thickness), systolic function (ejection fraction, EF), diastolic function (E/A; E’/E), arterial elastance (Ea), end-systolic elastance (Ees), and ventricular-arterial coupling (Ea/Ees) were assessed.ResultsNo significant differences were observed in LV posterior wall thickness in placebo (pre: 1.10 ± 0.1 cm; post: 1.16 ± 0.2 cm; p = 0.11) or testosterone groups (pre: 0.99 ± 0.1 cm; post: 1.14 ± 0.20 cm; p = 0.22). Compared with placebo, testosterone significantly improved LVEF (placebo: − 1.8 ± 4.3%; testosterone: + 6.2 ± 4.3%; p < 0.05), Ea (placebo: 0.0 ± 0.2 mmHg/mL; testosterone: − 0.3 ± 0.2 mmHg/mL; p < 0.05), and Ea/Ees (placebo: 0.0 ± 0.1; testosterone: − 0.2 ± 0.1; p < 0.05).ConclusionsIn patients with advanced cancers, testosterone was associated with favorable changes in left ventricular systolic function, arterial elastance, and ventricular-arterial coupling. Given the small sample size, the promising multisystem benefits of testosterone warrants further evaluation in a definitive randomized trial.Trial registrationThis study was prospectively registered on ClinicalTrials.gov (NCT00878995; date of registration: April 9, 2009).
Highlights
Adjunct testosterone therapy improves lean body mass, quality of life, and physical activity in patients with advanced cancers; the effects of testosterone on cardiac morphology and function are unknown
Patient characteristics Men and women recently diagnosed with late stage (IIB or higher) or recurrent head and neck or cervical cancer who were scheduled to receive standard of care chemotherapy or chemoradiotherapy were recruited to participate
left ventricular (LV) morphology, resting heart rate, and blood pressure No significant differences were observed in LV posterior wall thickness in placebo or testosterone group; Fig. 1
Summary
Adjunct testosterone therapy improves lean body mass, quality of life, and physical activity in patients with advanced cancers; the effects of testosterone on cardiac morphology and function are unknown. As an ancillary analysis of a randomized, placebo-controlled trial investigating the efficacy of testosterone supplementation on body composition in men and women with advanced cancers, we explored whether testosterone supplementation could prevent or reverse left ventricular (LV) atrophy and dysfunction. Cancer cachexia is a complex, multifactorial syndrome characterized by a progressive loss of skeletal muscle mass with or without loss of fat mass that cannot be fully reversed by conventional nutritional support [1]. Cancer cachexia involves the loss of skeletal muscle, and results in pathologic alterations within the heart [4, 5]. The global nature of cachexia portends the requirement for multifactorial treatment strategies with the capacity to augment or reverse whole-organism atrophy
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