FIGURE 7.

Mechanism of fatigue related to androgen deprivation therapy. Androgen deprivation therapy, which inhibits androgen receptor signaling, results in steroid hormone metabolism dysregulation and leads to sleep impairment by affecting circadian rhythm regulation, nocturia, and hot flashes. At the same time, androgen deprivation also results in dysregulated carnitine homeostasis and glutathione metabolism, leading to mitochondrial dysfunction and oxidative stress, respectively. Mitochondrial dysfunction further increase oxidative stress and contributes to inflammation-induced sickness behavior that includes fatigue.