New Horizons in Testosterone and the Ageing Male

Tomás Ahern; Frederick C. W. Wu


Age Ageing. 2015;44(2):188-195. 

In This Article

Potential Risks

Contraindications to testosterone therapy include erythrocytosis (haematocrit >52%), prostate cancer, breast cancer, untreated obstructive sleep apnoea, uncontrolled heart failure, severe lower urinary tract symptoms (International Prostate Symptom Score >19) and desire for fertility.[20,21]

Testosterone therapy, through suppression of hepcidin, increases haemoglobin levels by ~1 g/dl and haematocrit by ~3% leading to a >3-fold risk of erythrocytosis.[44]

Testosterone therapy increases prostate-specific antigen levels and (possibly as a result) tends to increase the risk of prostate biopsy.[45] Despite this, current data suggest no increased risk of prostate cancer.[44] Continuing caution is required with respect to the possibility of development of prostate cancer as androgens may have a long latency in promoting the growth of pre-existing prostate cancer, and sufficiently powered RCTs are unlikely to be performed.[46]

As described above, the Testosterone in Older Men with Mobility Limitations trial suggested a possible link between cardiovascular-related events with testosterone therapy (at double the recommended dose).[41] Observational studies and a meta-analysis performed after this trial found also associations between testosterone therapy and a 30–54% increased risk of cardiovascular-related events.[47] The US Food and Drug Administration (FDA) found that all these studies had significant limitations and that currently there is insufficient evidence for an association between testosterone therapy and adverse cardiovascular outcomes. The FDA has, however, sought to make clear that a low testosterone level due to ageing is not an indication for testosterone therapy and that further cardiovascular safety monitoring of testosterone therapy in older men is required.

A recent meta-analysis used the incidence of a new major adverse cardiovascular event (MACE), defined by the composite of cardiovascular death, non-fatal acute myocardial infarction and stroke, and acute coronary syndromes and/or heart failure, as its principal outcome.[48] The authors concluded that testosterone therapy did not increase the risk of MACE (OR 1.01 [0.57–1.77]) overall and decreased MACE incidence in men with T2DM and/or metabolic syndrome (OR 0.19 [0.04–0.85]).