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

Abstract

Levonorgestrel butanoate, 0.25, 1.0 and 2.5 mg/kg, administered as two injections 60 days apart (groups II, III, IV), failed to suppress spermatogenesis consistently and uniformly in adult bonnet monkeys (group size, n=6) compared to controls (group I). Levonorgestrel butanoate at the same doses combined with two simultaneous injections of 40 mg testosterone buciclate (groups V, VI, VII), consistently suppressed spermatogenesis in the period 60-240 days and in most animals to azoospermia or severe oligozoospermia (<5 x 106/mL) during days 90-210. The degree and duration of suppression were 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 progressive 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 sharp decrease until day 67. The second injection increased testosterone levels 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 decrease until day 150 to below baseline values. Peak levels of serum levonorgestrel 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 when levonorgestrel butanoate is combined with a long-acting androgen and injected at two-monthly intervals, effective and reversible suppression of spermatogenesis is achieved.