Effects of long-term treatment with testosterone enanthate in rhesus monkeys: I. Pharmacokinetics of testosterone, testicular volume and liver metabolism of testosterone

The effects of long-term administration of testosterone enanthate on the ph armacokinetics and bioavailability of testosterone were studied in adult ma le rhesus monkeys (n = 9), injected with 50 mg of testosterone enanthate (T E) once every 14 days for a total of 32 months. Control animals were inject ed with 0.2 mt olive oil. Serum testosterone levels increased sharply withi n 24 h of the first injection of TE and reached a peak on day 3 followed by a sharp decline, but baseline values were not reached even by day 14. Subs equent injections of TE caused a similar pharmacokinetic profile until the 55th injection; testosterone levels on day 3 declined from the 56 to 58th i njection and remained in a lower range until the last injection. Repeated i njections of TE increased the bioavailability of testosterone as shown by t he Area Under the Curve. The nocturnal (22.00 h) surge in testosterone leve ls during the pretreatment phase was abolished by TE injections. TE injecti ons altered the metabolism of testosterone by the liver, as studied in vitr o; while liver from control animals converted testosterone to androstenedio ne as the major metabolite, androsterone was the major metabolite in chroni cally TE-treated animals. Spermatogenesis and the associated increase in te sticular volume observed in control animals in winter were suppressed in TE -treated animals. The results indicate that repeated TE injections elevate serum testosterone to supra-physiological levels with marked fluctuations i n circulating testosterone levels after each injection. Possibly in respons e to these elevated levels, there was a change in the metabolism of testost erone by the liver as observed in vitro.