LOW T/HIGH T TESTOSTERONE AND THE HEART (Invited Lecture)
James D. Marsh, M.D., University of Arkansas for Medical Sciences, Little Rock, AR, USA
Testosterone (T) replacement therapy (TRT) is sometimes prescribed for men with no evident heart disease to enhance sexual function and sense of well-being, and has been proposed as a therapy to improve cardiac contractility. We undertook a series of studies in male rat hearts and myocytes isolated from male rat hearts that had undergone T deprivation by castration and then following T supplementation. Supraphysiological concentration of T produces cardiac hypertrophy, regulates androgen receptor expression, and increases abundance of transcripts for calcium channel proteins and the Na/Ca exchanger. Myosin heavy chain composition is altered and single cell systolic and diastolic function is augmented by T replacement (all p<0.05). In observational clinical studies of CHF patients, low T is associated with increased all-cause mortality. However, low T and mortality may be simply covariates. A large observational study of men with low T who received T replacement therapy showed increased 1 year and 3 year major adverse cardiac events (MACE). At 3 years MACE was 11.3% in men with low T vs. 5.9% for those with normal T at baseline (p<0.0001). A meta-analysis of trials of T replacement and CV outcomes has highly heterogeneous findings. TRT has proven overall benefit only for those with T levels clearly below normal prior to therapy. There is little clinical evidence at this time for improved cardiac function produced by TRT in a broad population of men. Men prescribed TRT must be informed of possible increased CV risk.