Testosterone replacement therapy: association with mortality in high‐risk patient subgroups

Mann, Amar; Strange, Richard C; König, Carola S; Hackett, Geoffrey; Haider, Ahmad; Haider, Karim Sultan; Desnerck, Peter; Ramachandran, Sudarshan

Abstract

Objectives
We describe studies determining the association between testosterone therapy (TTh) and mortality.

Materials & methods
We used a registry database of 737 men with adult-onset testosterone deficiency defined as presenting with low serum total testosterone (TT) levels ≤12.1 nmol/L and associated symptoms over a near 10-year follow-up. We compared associations between testosterone undecanoate (TU), cardio-metabolic risk factors and mortality using non-parametric statistics followed by separate Cox regression models to determine if any association between TU and morality was independent of age and cardio-metabolic risk factors. Finally, the association between TU and mortality was studied in men stratified by cardio-metabolic risk.

Results
During a median follow-up interquartile range (IQR) of 114 (84–132) months, 94 of the 737 men died. TU (ref: non-treatment) was associated with mortality; hazard ratio = 0.23, 95% confidence intervals = 0.14–0.40. Cox's regression models showed the above association to be independent of baseline age, waist circumference, hemoglobin A1c, lipids, blood pressure, smoking, and type 2 diabetes. These variables remained associated with mortality. We finally stratified the men by the high-risk baseline variables and established that the association between mortality and TU was only evident in men at higher risk. A possible explanation could lie with the “law of initial value,” where greater improvements are evident following treatment in patients with worse baseline values.

Conclusions
This study with long follow-up confirms that TTh is associated with lower mortality in men with adult-onset TD. This association was evident only in men with greater cardio-metabolic risk factors who demonstrated greater benefit.

Citation

Mann, A., Strange, R. C., König, C. S., Hackett, G., Haider, A., Haider, K. S., …Ramachandran, S. (in press). Testosterone replacement therapy: association with mortality in high‐risk patient subgroups. Andrology, https://doi.org/10.1111/andr.13582

• Journal Article Type: Article
• Acceptance Date: Dec 14, 2023
• Online Publication Date: Dec 26, 2023
• Deposit Date: Jan 8, 2024
• Journal: Andrology
• Electronic ISSN: 2047-2927
• Publisher: OMICS International
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1111/andr.13582
• Keywords: adult‐onset testosterone deficiency, heterogeneity, all‐cause mortality, testosterone therapy