Monitoring for adverse effects of testosterone replacement therapy
Adverse testosterone effects include common effects (which can be mild and reversible) or more serious effects, for which monitoring is needed. Monitoring for clinical response and serious adverse effects of testosterone replacement therapy includes a summary of monitoring for adverse events.
Common adverse effects from testosterone replacement therapy include truncal seborrhoea and acne (particularly with testosterone ester injections), modest weight gain (under 3 kg) and reduced spermatogenesis. Increased truncal hair, temporal hair loss or balding, and gynaecomastia can also occur. Adverse effects generally reverse when therapy is stopped.
Serious adverse effects from testosterone replacement therapy are uncommon but include polycythaemia, prostate growth, and transient worsening of obstructive sleep apnoea. Risk of cardiovascular events and venous thromboembolism may be increased in men taking testosterone, but evidence to confirm this association is lacking.
Polycythaemia occurs most often with short-acting injectable testosterone (esters and enantate forms). Measure haemoglobin and haematocrit at baseline, then 3 months after starting therapy, then annually. Exclude other causes of secondary polycythaemia (including smoking, obstructive sleep apnoea, and respiratory failure). Polycythaemia is treated by interrupting therapy, dose reduction or increasing the dose interval. Occasionally, venesection is required.
Testosterone therapy reverses the reduced prostate volume and prostate specific antigen (PSA) concentration that occur in male androgen deficiency. This prostate growth can lead to elevated prostate specific antigen (PSA), which, if monitored, may prompt investigation for prostate cancer. There is no association between testosterone replacement and incident prostate cancer, except that men with lifelong untreated androgen deficiency are at reduced risk.
For individuals at substantial risk of pre-existing prostate cancer, measure PSA before starting testosterone therapy. If warranted by symptoms, perform digital rectal examination, or refer for urological assessment. Prostate cancer risk may be increased if any of the following are present:
- prostatic symptoms
- a strong family history1
- previous serum PSA concentration more than 4 nanogram/mL.
For asymptomatic men, PSA testing before or during testosterone replacement constitutes prostate cancer screening. Given there is no consensus about population screening for prostate cancer, this issue should be addressed by the testosterone prescriber according to existing guidelines, which support discussing screening in males aged 50 to 69 years at average risk using a decision aid2.
If prostate screening and monitoring is chosen, at the time of writing, guidelines suggest measuring PSA at baseline, then 3 to 12 months after starting testosterone therapy, then every 2 years.
Risk of cardiovascular events may be increased in frail older men taking testosterone, although the evidence for an effect of testosterone is mixed and the association is unconfirmed. The T-Trials cardiovascular trial3 observed a greater 12-month increase in the primary endpoint, noncalcified coronary plaque volume, in testosterone-treated males, but the clinical relevance of this remains undefined. Assess cardiovascular risk before starting testosterone therapy and manage risk factors as for the general population. Closely monitor older people (particularly those with frailty) and those with cardiovascular disease, kidney failure or severe hypertension. Testosterone therapy can cause fluid overload from sodium and fluid retention, which can exacerbate these conditions.