Hormone Therapy

What We Have Learned from The Testosterone Trials.

TL;DR

The Testosterone Trials demonstrated that testosterone treatment of elderly men with low serum testosterone increases sexual function, hemoglobin, and bone mineral density to moderate degrees, and walking, vitality, and mood slightly, but also increases coronary artery noncalcified plaque volume.

Key Findings

Serum free testosterone decreases more substantially with aging than total testosterone due to increases in sex hormone binding globulin.

  • As men age, serum concentration of total testosterone decreases only slightly
  • Concentration of sex hormone binding globulin increases with age
  • The increase in SHBG causes free testosterone to decrease to a greater degree than total testosterone
  • This hormonal pattern in elderly men formed the basis for participant selection in the Testosterone Trials

Testosterone treatment of elderly men with low serum testosterone improved sexual function to a moderate degree.

  • The improvement in sexual function was characterized as 'moderate'
  • Participants were elderly men with low serum testosterone levels
  • Sexual function was one of the primary outcomes assessed in the Testosterone Trials
  • The Testosterone Trials were a coordinated set of trials examining multiple outcomes simultaneously

Testosterone treatment increased hemoglobin and bone mineral density to moderate degrees in elderly men with low testosterone.

  • The increases in both hemoglobin and bone mineral density were characterized as 'moderate'
  • These outcomes were among the multiple endpoints assessed across the coordinated Testosterone Trials
  • Participants were elderly men selected based on low serum testosterone concentrations

Testosterone treatment produced slight improvements in walking, vitality, and mood in elderly men with low testosterone.

  • Improvements in walking, vitality, and mood were characterized as 'slight', in contrast to the 'moderate' improvements seen in sexual function, hemoglobin, and bone mineral density
  • These outcomes were assessed as separate coordinated trials within the overall Testosterone Trials framework

Testosterone treatment increased coronary artery noncalcified plaque volume.

  • The finding of increased coronary artery noncalcified plaque volume was identified as a safety concern
  • Noncalcified plaque is considered potentially more vulnerable or dangerous than calcified plaque
  • The trials were not large enough or long enough to determine if this finding translates to increased clinical heart disease events

The Testosterone Trials were insufficient in size and duration to determine whether testosterone treatment increases risk of clinical heart disease or prostate disease.

  • The authors explicitly state the trials 'were not large enough or long enough' to assess cardiovascular or prostate disease clinical endpoints
  • This limitation applies to both clinical heart disease outcomes and prostate disease outcomes
  • The finding of increased noncalcified plaque volume raises concern but cannot be linked to hard clinical cardiovascular outcomes based on these trials alone

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Citation

Snyder P. (2022). What We Have Learned from The Testosterone Trials.. The Urologic clinics of North America. https://doi.org/10.1016/j.ucl.2022.07.007