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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 pharmacokinetics and bioavailability of testosterone were studied in adult male rhesus monkeys (n = 9), injected with 50 mg of testosterone enanthate (TE) once every 14 days for a total of 32 months. Control animals were injected with 0.2 mL olive oil. Serum testosterone levels increased sharply within 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. Subsequent injections of TE caused a similar pharmacokinetic profile until the 55th injection; testosterone levels on day 3 declined from the 56 to 58th injection and remained in a lower range until the last injection. Repeated injections of TE increased the bioavailability of testosterone as shown by the Area Under the Curve. The nocturnal (22.00 h) surge in testosterone levels during the pretreatment phase was abolished by TE injections. TE injections altered the metabolism of testosterone by the liver, as studied in vitro; while liver from control animals converted testosterone to androstenedione as the major metabolite, androsterone was the major metabolite in chronically TE-treated animals. Spermatogenesis and the associated increase in testicular 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 in circulating testosterone levels after each injection. Possibly in response to these elevated levels, there was a change in the metabolism of testosterone by the liver as observed in vitro.