Evaluation of the ability of levonorgestrel butanoate alone, or in combination with testosterone buciclate, to suppress spermatogenesis in the bonnetmonkey (Macaca radiata)

Levonorgestrel butanoate, 0.25, 1.0 and 2.5 mg/kg, administered as two inje ctions 60 days apart (groups II, III, IV), failed to suppress spermatogenes is consistently and uniformly in adult bonnet monkeys (group size, n = 6) c ompared to controls (group I). Levonorgestrel butanoate at the same doses c ombined with two simultaneous injections of 40 mg testosterone buciclate (g roups V, VI, VII), consistently suppressed spermatogenesis in the period 60 -240 days and in most animals to azoospermia or severe oligozoospermia (< 5 x 10(6)/mL) during days 90-210. The degree and duration of suppression wer e greatest in group VI. Sperm motility declined in all treated animals and spermatozoa in the semen of animals from groups V and VI lost all progressi ve motility in the period 60-150 and 60-210 days, respectively. The changes in testosterone levels were similar in groups V and VI, increasing within 24 h after the combined injection to reach a peak by day 28 followed by a s harp decrease until day 67. The second injection increased testosterone lev els by a lesser degree to peak levels on day 81. In group VII, testosterone levels decreased until day 59 after the first injection but increased to a maximum on day 81 after the second injection followed by a gradual decreas e until day 150 to below baseline values. Peak levels of serum levonorgestr el were observed 1-7 days after injection of levonorgestrel butanoate alone . Clearance of the drug was slow, being detectable in the circulation until day 330 of the 360 day study period in the high dose group. Dose-response increases to peak levels of levonorgestrel were attained on day 7 in groups V, VI and VII, after the first injection. After the second injection, peak levels were seen on day 61 in groups V and VI and on day 81 in group VII. Levonorgestrel was no longer detectable in blood in groups V and VI by days 210 and 300, respectively, but small circulating amounts remained in group VII at the conclusion of the study on day 360. This study indicates that w hen levonorgestrel butanoate is combined with a long-acting androgen and in jected at two-monthly intervals, effective and reversible suppression of sp ermatogenesis is achieved.