Hormone Therapy

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

TL;DR

Testosterone replacement therapy with testosterone undecanoate was associated with lower mortality in men with adult-onset testosterone deficiency, with this association evident only in men with greater cardio-metabolic risk factors who demonstrated greater benefit.

Key Findings

Testosterone undecanoate (TU) treatment was associated with significantly lower mortality compared to non-treatment in men with adult-onset testosterone deficiency.

  • Hazard ratio for TU (ref: non-treatment) was 0.23, 95% confidence intervals = 0.14–0.40
  • Registry database of 737 men with adult-onset testosterone deficiency defined as serum total testosterone ≤12.1 nmol/L with associated symptoms
  • 94 of the 737 men died during the follow-up period
  • Median follow-up interquartile range (IQR) of 114 (84–132) months (near 10-year follow-up)

The association between TU treatment and reduced mortality was independent of multiple baseline cardio-metabolic risk factors.

  • Cox regression models showed the association between TU and mortality was independent of baseline age, waist circumference, hemoglobin A1c, lipids, blood pressure, smoking, and type 2 diabetes
  • The cardio-metabolic risk factor variables themselves remained independently associated with mortality in these models
  • Non-parametric statistics were used prior to Cox regression models

The association between TU treatment and lower mortality was only evident in men stratified into higher cardio-metabolic risk subgroups.

  • Men were stratified by high-risk baseline variables to examine the association between TU and mortality
  • No significant association between TU and mortality was observed in men with lower cardio-metabolic risk
  • The authors attributed this pattern to the 'law of initial value,' where greater improvements are evident following treatment in patients with worse baseline values

The study population consisted of men with adult-onset testosterone deficiency followed for a near 10-year period in a registry database.

  • 737 men were included in the registry database
  • Testosterone deficiency was defined as presenting with low serum total testosterone (TT) levels ≤12.1 nmol/L and associated symptoms
  • Median follow-up IQR of 114 (84–132) months
  • Comparisons were made between TU-treated and non-treated men using both non-parametric statistics and Cox regression models

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Citation

Mann A, Strange R, König C, Hackett G, Haider A, Haider K, et al.. (2024). Testosterone replacement therapy: association with mortality in high-risk patient subgroups.. Andrology. https://doi.org/10.1111/andr.13582