The Effects of Testosterone Deficiency and Its Replacement on Inflammatory Markers in Rats: A Pilot Study

Testosterone deficiency is linked to low-grade inflammation in humans, but this condition is not replicated in an animal study. The current study aims at determining the effects of testosterone deficiency and its replacement on the circulating inflammatory cytokine level in orchidectomized male rats.

Three-month-old Sprague-Dawley male rats (n = 18) were randomized equally into 3 groups. Bilateral orchidectomy was performed on 2 groups. The sham group was subjected to similar surgical stress, but their testes were retained. One of the orchidectomized groups received intramuscular injection of 7 mg/kg testosterone enanthate suspended in peanut oil weekly and the other 2 groups received equivolume of peanut oil injection. After 8 weeks, the rats were sacrificed and their blood was collected for the analysis of the levels of inflammatory cytokines and testosterone.

Testosterone level was significantly lower in the untreated orchidectomized group compared to the sham group. Testosterone replacement significantly increased the level of testosterone in the orchidectomized rats compared to the sham and untreated orchidectomized rats. Interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNFα) showed an increasing trend in orchidectomized rats, albeit not statistically significant. Interleukin-6 (IL-6) level increased significantly in the orchidectomized group compared to the sham group. Testosterone replacement at the supraphysiological dose did not alter the level of inflammatory cytokines significantly in orchidectomized rats.

Testosterone deficiency can elicit a state of low-grade inflammation, shown by an increase in interleukin-6 level, but exogenous supraphysiological testosterone replacement does not suppress the inflammation.