Mitochondrial Impairment and Oxidative Stress in Leukocytes after Testosterone Administration to Female-To-Male Transsexuals

Abstract

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.

Testosterone induces apoptosis in vascular smooth muscle cells via extrinsic apoptotic pathway with mitochondria-generated reactive oxygen species involvement

“…In line with our data, testosterone-induced ROS generation has been reported in rodent VSMCs (11) and renal cells (22), as well as in human prostate cancer cells (60) and leukocytes (23,63). Similarly to VSMCs, in the macula densa-like cell line MMDD1, testosterone induces O 2 Ϫ generation via activation of NAD(P)H oxidase and androgen receptor-dependent pathways.…”

“…This effect is associated with an increase in tubulo- glomerular feedback, which results in lower tubular perfusion and altered control of renal microcirculation, potentially contributing to the higher prevalence of hypertension and renal injury in males (22). In human leukocytes, testosterone undecanoate, used in female-to-male transsexuals, decreases mitochondria O 2 consumption and membrane potential and induces oxidative stress (63). Elevation of circulating androgens (dehydroepiandrosterone) in healthy ovulatory reproductive-age women, as occurs in women with polycystic ovary syndrome, also increases leukocyte ROS generation, p47 phox gene expression, and plasma thiobarbituric acid reactive substances (23).…”

Testosterone depletion increases the susceptibility of brain tissue to oxidative damage in a restraint stress mouse model

“…; Victor et al . ). Unlike estrogen, however, testosterone has not yet been well characterized in terms of how it affects the brain, especially under psychological stress.…”

Oxidative Stress Induction in Monosex Nile Tilapia (Oreochromis niloticus, Linnaeus, 1758): A Field Study on the Side Effects of Methyltestosterone

“…In addition, testosterone induced changes in the oxidative status of rat testis by reducing TAC [32]. Enhanced reactive oxygen species production, and depleted antioxidant enzyme levels and activities are linked to testosterone administration in several published articles [33][34][35]. It seemed that increased reactive oxygen species generation, as manifested by increased TPX and MDA levels in this study, consumed antioxidant reserves of sex reversed Nile tilapia.…”