Does testosterone treatment exacerbate the risk of cardiovascular events in men with type 2 diabetes and a high risk of cardiovascular events?
In men with type 2 diabetes mellitus (T2DM) and lowered testosterone levels at high risk of cardiovascular events, testosterone replacement therapy does not increase two biomarkers of subclinical cardiac injury, according to the first randomized controlled trial (RCT) of testosterone treatment in men with diabetes to assess the effect of treatment on these two cardiac biomarkers.
Cardiovascular disease is a leading cause of death in older men, especially in those with coexisting T2DM. Testosterone prescriptions for middle-aged to older men have risen dramatically in recent years, and studies of testosterone replacement therapy and the cardiovascular effects in men have shown mixed results. “Therefore, a better understanding of the effects of testosterone treatment on cardiovascular health in men is important” in T2DM, stated the researchers, led by Emily J. Gianatti of the Endocrine Unit, Austin Health, University of Melbourne in Melbourne, Australia.
Recent studies show that the biomarkers N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) can help predict the risk of cardiovascular events in patients with T2DM.
The researchers conducted a randomized, double-blind, parallel, placebo-controlled trial of 88 men, aged 35–70 years, with T2DM and a low total testosterone level who were at high risk of cardiovascular events as defined by 10-year United Kingdom Prospective Diabetes Study (UKPDS) coronary heart disease (CHD) risk. They were randomly assigned to 40 weeks of intramuscular testosterone treatment (45 patients) or matching placebo (43 patients).
The results show that testosterone treatment reduced NT-proBNP over the 40 weeks across the testosterone and placebo groups, but did not change hs-cTnT. Six men, three in each group, experienced an adverse cardiac event, displaying already higher baseline NT-proBNP and hs-cTnT levels, an indication of preexisting cardiac disease.
At baseline, 10-year UKPDS CHD risk was associated positively with NT-proBNP and hs-cTnT and inversely with testosterone, but there was no significant association between testosterone and cardiac biomarkers.
The researchers concluded that “we did not find evidence that testosterone treatment leads to an increase of NT-proBNP or hs-cTnT, biomarkers of subclinical cardiac injury and increased cardiovascular risk. In fact, a significant reduction in NT-proBNP was seen with treatment with no change in hs-cTnT. Although numbers were small, men who experienced cardiovascular events during testosterone treatment had increased baseline levels of NT-proBNP and hs-cTnT compared to men who were free of such events.”
The researchers suggest several reasons why natriuretic peptides may have an effect on testosterone. “Overall, the current data raise the possibility that testosterone promotes salt and water retention by inhibiting the release of natriuretic peptides, although not all data concurs, and further study is required,” they stated. “An alternative explanation, also consistent with the current data and with RCTs of testosterone treatment reporting improvements in outcomes in men with heart failure, is the possibility that testosterone could improve myocardial function, secondarily decreasing NT-proBNP.”
They suggested that future studies should evaluate whether men with elevated cardiovascular biomarkers are at risk of testosterone-associated adverse cardiovascular events, such as the exacerbation of subclinical cardiac failure.
Reference: Gianatti EJ, et al. Effect of testosterone treatment on cardiac biomarkers in a randomized controlled trial of men with type 2 diabetes. Clin Endocrinol (Oxf). 2016 Jan;84(1):55-62.