Effects of testosterone on exercise capacity in postmenopausal women with stage B heart failure

Asymptomatic individuals with stage B heart failure (HF) often have reduced exercise capacity. As exogenous testosterone may have favorable skeletal muscle and vasculature effects, this study investigated whether transdermal testosterone improves exercise capacity in women with stage B HF. In this single-center, double-blind, randomized, placebo-controlled crossover trial involving women aged ≥55 years with stage B HF (defined as cardiac remodeling and/or diastolic dysfunction) and reduced exercise capacity (<100% age-predicted peak oxygen uptake V˙O2peak]), participants were randomly allocated to transdermal testosterone 5 mg/day or identical placebo for 4 months with cross-over after a 4-week washout. The primary outcome was change in V˙O2peak. Secondary outcomes included changes to cardiac structure and function assessed by echocardiography and cardiac magnetic resonance imaging, and subjective quality of life. Thirty-eight participants (median age 72 years, range 60–80 years; median body mass index 33.2 kg/m2 [P25–P75 28.7–35.9 kg/m2]) completed the study. Testosterone treatment increased circulating serum testosterone concentrations and was well tolerated, with no adverse treatment-related events. Testosterone treatment had no significant effect on V˙O2peak (β = –0.05, 95% confidence interval = –0.74, 0.65, p = 0.897), cardiac structure or indices of cardiac function, or quality of life. Transdermal testosterone treatment did not improve exercise capacity in postmenopausal women with stage B HF. People with pre-heart failure, also known as stage B heart failure (HF), often have reduced exercise capability. As some studies have shown testosterone might increase muscle strength and blood flow, this study was undertaken to determine whether treating women with stage B HF might improve their exercise capacity. Women with stage B HF aged at least 55 years were randomly allocated to treatment with a transdermal testosterone cream or identical placebo for 4 months. After a 4-week break the participants were swapped over to the treatment they did not receive first. The dose of the testosterone was that known to restore blood testosterone levels to those seen in premenopausal women. The included participants had an exercise test and echocardiogram at the beginning and end of each 4-month treatment period, and a subset also had cardiac magnetic resonance imaging. Thirty-eight participants, median age 72 years, range 60–80 years and median body mass index 33.2 kg/m2, completed the study. No significant effect was seen for testosterone treatment on peak oxygen consumption during exercise, heart muscle structure cardiac structure, other measure of heart function, or quality of life. Testosterone treatment increased circulating serum testosterone concentrations and was well tolerated, with no adverse treatment-related events. However, in women with stage B HF, transdermal testosterone did not improve exercise capacity or impact cardiac function.