Testosterone dose-response relationships with cardiovascular risk markers in androgen-deficient women: a randomized, placebo-controlled trial

J Clin Endocrinol Metab. 2014 Jul;99(7):E1287-93. doi: 10.1210/jc.2013-4160. Epub 2014 Apr 8.

Abstract

Objective: To determine dose-dependent effects of T administration on cardiovascular risk markers in women with low T levels.

Methods: Seventy-one hysterectomized women with or without oophorectomy with total T < 31 ng/dL and/or free T < 3.5 pg/mL received a standardized transdermal estradiol regimen during the 12-week run-in period and were then randomized to receive weekly im injections of placebo or 3-, 6.25-, 12.5-, or 25-mg T enanthate for 24 weeks. Total and free T levels were measured by liquid chromatography-tandem mass spectrometry and equilibrium dialysis, respectively. Insulin resistance and inflammatory markers were measured at baseline and 24 weeks. In a subset of women, magnetic resonance imaging of the abdomen was performed to quantify abdominal fat volume.

Results: Fifty-nine women who completed the 24-week intervention were included in the final analysis. The five groups were similar at baseline. Mean on-treatment nadir total T concentrations were 14, 79, 105, 130, and 232 ng/dL in the placebo group and the 3-, 6.25-, 12.5-, and 25-mg groups, respectively. No significant changes in fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, high sensitivity C-reactive protein, adiponectin, blood pressure, and heart rate were observed at any T dose when compared to placebo. Similarly, no dose- or concentration-dependent changes were observed in abdominal fat on magnetic resonance imaging.

Conclusion: Short-term T administration over a wide range of doses for 24 weeks in women with low T levels was not associated with worsening of cardiovascular risk markers.

Trial registration: ClinicalTrials.gov NCT00494208.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Androgens / deficiency*
  • Biomarkers / blood
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / chemically induced*
  • Dose-Response Relationship, Drug
  • Female
  • Heart Rate / drug effects
  • Hormone Replacement Therapy / adverse effects
  • Humans
  • Inflammation / blood
  • Insulin Resistance
  • Middle Aged
  • Placebos
  • Risk Factors
  • Testosterone / administration & dosage*
  • Testosterone / adverse effects
  • Young Adult

Substances

  • Androgens
  • Biomarkers
  • Placebos
  • Testosterone

Associated data

  • ClinicalTrials.gov/NCT00494208