Investigation of hormonal male contraception in African men: suppression of spermatogenesis by oral desogestrel with depot testosterone.

BACKGROUND: Suppression of spermatogenesis to azoospermia is required for effective hormonal male contraception, but the degree of suppression varies between ethnic groups. We here report the first study of hormonal suppression of spermatogenesis in two African centres using a regimen of oral progestogen with depot testosterone. METHODS A total of 31 healthy men (21 black) were recruited in Cape Town and 21 men in Sagamu, Nigeria. Subjects were randomized to take either 150 or 300 micro g desogestrel daily p.o. with testosterone pellets. In Cape Town, desogestrel was administered for 24 weeks with 400 mg testosterone re-administered 12 weekly. In Sagamu, desogestrel was administered for 52 weeks with 200 mg testosterone (later increased to 400 mg) re-administered 12-weekly. RESULTS: In Cape Town, 22 men completed at least 20 weeks treatment. Azoospermia was achieved in 8/10 and 8/12 men in the 150 micro g and 300 micro g desogestrel groups. Four men in Sagamu withdrew. Azoospermia was achieved in all 17 men in the two groups. There were no significant changes in lipoprotein or haemoglobin concentrations in any group. CONCLUSION: These data demonstrate that the combination of oral desogestrel with depot testosterone is an effective regimen for suppression of spermatogenesis in African as in Caucasian and Chinese men, with azoospermia achieved in a total of 83/98 (85%) men.

Inhibition of progesterone secretion with trilostane for mid-trimester termination of pregnancy: randomized controlled trials.

BACKGROUND: Progesterone is central to the maintenance of pregnancy, and is thus the ideal target for fertility regulation. Two mechanisms by which progesterone can be targeted are: receptor blockade and reduction of progesterone production through enzyme inhibition. Mifepristone, a receptor blocker, is usually given as 'pretreatment' prior to prostaglandin administration in mid-trimester termination of pregnancy (TOP). Unfortunately, there are difficulties accessing mifepristone in developing countries, and TOP is therefore performed using prostaglandins alone, which results in unacceptably long induction-to-abortion intervals. Trilostane is a 3beta-hydroxysteroid dehydrogenase inhibitor which reduces progesterone production. In these mid-trimester studies it is evaluated as a method of pretreatment prior to misoprostol administration. METHODS: Three consecutive randomized controlled trials comparing different trilostane regimens for pretreatment were performed. In study 1, trilostane was compared with placebo; in study 2, two doses of trilostane were compared (1080 mg and 720 mg); in study 3, the effect of adding danazol to trilostane as combination therapy was evaluated. The primary outcome in all the studies was the induction-to-abortion interval. Serum progesterone, estradiol and cortisol were measured serially during treatment. RESULTS: In study 1, 48 women were randomized. The median induction-to-abortion interval was 9 h in the trilostane group and 18.5 h in the placebo group (P < 0.0001). Progesterone and estradiol production was significantly reduced in the women receiving trilostane, with maintenance of diurnal cortisol variation. Twenty-eight women were randomized in study 2, which demonstrated that there was no significant difference in the induction-to-abortion interval using 1080 mg and 720 mg trilostane when compared with the higher doses used in study 1. Study 3, in which 40 women were included, failed to show any additional benefit using combination therapy with danazol and trilostane. CONCLUSIONS: Trilostane is an effective pretreatment agent in mid-trimester TOP.