Effects of adjunct testosterone on cardiac morphology and function in advanced cancers: an ancillary analysis of a randomized controlled trial

Abstract

Background Adjunct 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. Methods Men 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. Results No 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). Conclusions In 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 registration This study was prospectively registered on ClinicalTrials.gov (NCT00878995; date of registration: April 9, 2009). Electronic supplementary material The online version of this article (10.1186/s12885-019-6006-5) contains supplementary material, which is available to authorized users.

Cancer and Associated Therapies Impact the Skeletal Muscle Proteome

“…Several proteomic shifts that occurred during CAT were alterations to pathways with known involvement in cardiomyopathy, and despite cardiac muscle being a distinct cell type from skeletal muscle, likely pointed towards similar myopathic processes in skeletal muscle of these patients (Rausch et al, 2021). Nevertheless, it should be noted that an additional ancillary analysis of this study demonstrated that testosterone treatment was associated with improvement in some measures of cardiac function including left ventricular ejection fraction (Scott et al, 2019).…”

Testosterone, cardiomyopathies, and heart failure

“…In an ancillary study of a randomized controlled trial involving men and women with advanced head-and-neck or cervix cancers, 22 the patients were randomly allocated to receive weekly injections of either 100 mg of testosterone enanthate (6 patients, 1 male) or placebo (10 patients) in addition to receiving standard cancer treatment. After 7 weeks of treatment, testosterone improved left ventricular ejection fraction (LVEF: +6.2% ± 4.3%, vs placebo: −1.8% ± 4.3%; P < 0.05) as well as ventricular–vascular coupling.…”