The testosterone trials: Results and conclusions

Description

The testosterone trials comprise 7 randomized controlled trials (RCT). It is the largest series of RCT, including 788 men with low testosterone, who were treated with either testosterone or placebo for 1 year. The testosterone dose was adjusted to attempt to keep testosterone levels in mid-normal range for young men.

The 7 trials each investigated the following outcomes:

  • Sexual function
  • Physical function
  • Vitality
  • Cognitive function
  • Anemia
  • Bone
  • Cardiovascular

The studies included men aged 65 years or older with testosterone levels below (275 ng/dL = 9.5 nmol/L).

The main results from all TTrials are as follows:1

  • Testosterone treatment of 1 year for older men with low testosterone improved all aspects of sexual function.
  • Testosterone treatment of 1 year for older men with low testosterone improved walking distance by a small amount.
  • Testosterone treatment of 1 year for older men with low testosterone did not improve vitality but slightly improved mood and depressive symptoms.
  • Testosterone treatment of 1 year for older men with low testosterone improved hemoglobin and corrected mild to moderate anemia.
  • Testosterone treatment of 1 year for older men with low testosterone markedly increased the volumetric bone mineral density and estimated bone strength.
  • Testosterone treatment of 1 year for older men with low testosterone increased the coronary artery plaque volume.
  • Testosterone treatment of 1 year for older men with low testosterone was not associated with more cardiovascular or prostate adverse events; however, the number of men and the duration of treatment were not sufficient to draw definitive conclusions about the risks of this treatment.

If testosterone does affect cardiovascular risk, it might do so by altering any one of several cardiovascular risk factors, such as lipids, glucose metabolism, coagulation, and inflammation. Therefore, in all men participating in the TTrials, several biomarkers of cardiovascular risk were measured at baseline and after 3 and 12 months of treatment.2 Compared with placebo, testosterone treatment significantly decreased total cholesterol (-6.1 mg/dL), fasting insulin (adjusted mean difference, 21.7 mIU/mL) and HOMA-IR (homeostatic model assessment of insulin resistance). Testosterone did not change the total cholesterol/HDL cholesterol ratio, triglycerides, D-dimer, C-reactive protein, interleukin 6, troponin, glucose, or HbA1c.2

The increase in coronary artery plaque volume3 deserves a comment. An analysis of the individual plaque components revealed that the increase was confined to the fibrous component of the plaque, which provides for plaque stability.4 Fatty and necrotic portions, characterized by low attenuation and indicative of a vulnerable plaque4, as well as calcified plaque volume were not affected by testosterone treatment. Thus, testosterone therapy may have resulted in stabilization of coronary plaques. This finding is consistent with retrospective reports of decreased major adverse cardiovascular events and reduced mortality after testosterone therapy.5


 

Speakers

Prof. Dr. med. Marija Pfeifer

Glenn Cunningham, MD
Distinguished Professor Emeritus, Department of Medicine, Baylor College of Medicine

References

  • Snyder PJ, Bhasin S, Cunningham GR, et al. Lessons From the Testosterone Trials. Endocr Rev. 2018 Jun 1;39(3):369-386. Return to content
  • Mohler ER 3rd, Ellenberg SS, Lewis CE, et al. The Effect of Testosterone on Cardiovascular Biomarkers in the Testosterone Trials. J Clin Endocrinol Metab. 2018 Feb 1;103(2):681-688. Return to content
  • Budoff MJ, Ellenberg SS, Lewis CE, et al. Testosterone treatment and coronary artery plaque volume in older men with low testosterone. JAMA. 2017; 317(7):708-716. Return to content
  • Ahmadi A, Stone GW, Leipsic J, et al. Prognostic determinants of coronary atherosclerosis in stable ischemic heart disease: anatomy, physiology, or morphology? Circ Res. 2016;119(2):317-329. Return to content
  • Sharma R, Oni OA, Gupta K, et al. Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Eur Heart J. 2015;36(40):2706-2715. Return to content