A non-human primate study (baboon; Papio hamadryas) to determine if a long-acting progestogen, levonorgestrel butanoate, combined with a long-acting androgen, testosterone buciclate, can suppress spermatogenesis: I. Dose-finding study.

This study in adult male baboons was conducted to establish the dose of a long-acting progestogen, levonorgestrel butanoate, and that of a long-acting androgen, testosterone buciclate, which, when combined, would achieve optimal and prolonged suppression of spermatogenesis. Two intramuscular injections of levonorgestrel butanoate at 3-month intervals and in the dose range 1-8 mg/kg reduced sperm production and plasma concentrations of testosterone, LH and FSH for periods of up to 6 months. The suppression of sperm production was greatest and most prolonged in the 4 mg/kg group. Two intramuscular injections of testosterone buciclate at 3-month intervals, and at doses of 4 and 8 mg/kg, induced variable changes in circulating levels of testosterone, elevated by the higher dose, and caused sperm suppression, in some animals to azoospermia. It was concluded that 8 mg/kg testosterone buciclate would provide adequate androgen replacement when combined with 4 mg/kg levonorgestrel butanoate as a putative male contraceptive regimen.

A non-human primate study (baboon; Papio hamadryas) to determine if a long-acting progestogen, levonorgestrel butanoate, combined with a long-acting androgen, testosterone buciclate, can suppress spermatogenesis: II. Efficacy study.

Two combined injections of levonorgestrel butanoate (4 mg/kg) and testosterone buciclate (8 mg/kg) at 3-month intervals to adult male baboons initiated a decrease in sperm concentration from baseline values of 490x10(6)/ml to minimum values of 17x10(6/ml. This suppression was sustained until week 32, during which time between one and three azoospermic samples were collected from each of four out of five treated baboons in the period 10-24 weeks. Circulating plasma levels of LH and testosterone decreased to approximately 20-75% of baseline values. Plasma levels of cortisol declined to significantly reduced levels at weeks 22 and 36-44. All values returned to the baseline range by week 48. The combined administration of progestogen and androgen induced a more marked and sustained suppression to severe oligozoospermia or azoospermia than did the equivalent dose of progestogen alone (Goncharov et al., 1995). Although the dose of testosterone buciclate used did not maintain peripheral levels of testosterone in the normal range, it did not restimulate spermatogenesis. It was concluded that a combination drug regimen based on the novel long-acting levonorgestrel and testosterone esters could provide a contraceptive option for men.