Mitochondrial impairment and oxidative stress in leukocytes after testosterone administration to female-to-male transsexuals

J Sex Med. 2014 Feb;11(2):454-61. doi: 10.1111/jsm.12376. Epub 2013 Nov 20.


Introduction: Testosterone undecanoate (T) treatment is common in female-to-male transsexuals (FtMs) but can induce impairment of mitochondrial function and oxidative stress.

Aim: The effect of T treatment on the mitochondrial function and redox state of leukocytes of FtMs subjects was evaluated.

Methods: This was an observational study conducted in a university hospital. Fifty-seven FtMs were treated with T (1,000 mg) for 12 weeks, after which anthropometric and metabolic parameters and mitochondrial function were evaluated.

Main outcome measures: Anthropometric and metabolic parameters were evaluated. Mitochondrial function was studied by assessing mitochondrial oxygen (O2) consumption, membrane potential, reactive oxygen species (ROS) production, glutathione levels (GSH), and the reduced glutathione/oxidized glutathione (GSH)/(GSSG) ratio in polymorphonuclear cells.

Results: T treatment led to mitochondrial impairment in FtMs as a result of a decrease in mitochondria O2 consumption, the membrane potential, GSH levels, and the (GSH)/(GSSG) ratio and an increase in ROS production. Mitochondrial O2 consumption and membrane potential negatively correlated with T levels, which was further confirmed that the T treatment had induced mitochondrial dysfunction. T also produced a significant increase in total testosterone, free androgenic index, and atherogenic index of plasma, and a decrease in sex hormone-binding globulin and high-density lipoprotein cholesterol.

Conclusions: Treatment of FtMs with T can induce impairment of mitochondrial function and a state of oxidative stress. This effect should be taken into account in order to modulate possible comorbidities in these patients.

Keywords: Gender Dysphoria; Hormone Therapy in Female-to-Male Transsexuals; Leukocytes; Mitochondria; Oxidative Stress; Testosterone; Transsexuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Glutathione / metabolism
  • Humans
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Male
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidation-Reduction
  • Oxidative Stress*
  • Oxygen / metabolism
  • Oxygen Consumption
  • Reactive Oxygen Species / metabolism
  • Sex Hormone-Binding Globulin / metabolism
  • Sex Reassignment Procedures / adverse effects*
  • Testosterone / administration & dosage
  • Testosterone / adverse effects
  • Testosterone / analogs & derivatives*
  • Transsexualism / chemically induced*
  • Young Adult


  • Reactive Oxygen Species
  • Sex Hormone-Binding Globulin
  • Testosterone
  • Glutathione
  • testosterone undecanoate
  • Oxygen