We postulated that the addition of a combined types I and II, 5alpha-reductase inhibitor (
dutasteride) or long-acting
GnRH antagonist (
acyline) to combination
testosterone plus
levonorgestrel treatment may be advantageous in the suppression of spermatogenesis for
male contraception. This study aimed to examine effects of novel combination
contraceptive regimens on serum
gonadotropins and
androgens and sperm concentration.This study was divided into three phases: screening (2 wk), treatment (8 wk), and recovery (4 wk). Twenty-two men (n = 5-6/group) received 8 wk of treatment with
testosterone enanthate (TE, 100 mg im weekly) combined with one of the following: 1)
levonorgestrel (LNG) 125 mug orally daily; 2) LNG 125 microg plus
dutasteride 0.5 mg orally daily; 3)
acyline 300 microg/kg sc every 2 wk (as a comparator for any additional
progestin effects); or 4) LNG 125 microg orally daily plus
acyline 300 microg/kg sc every 2 wk. Serum
gonadotropin levels were similarly suppressed by all treatments, falling to a nadir between 1.2 and 3.4% and 0.5 and 0.8% baseline for FSH and LH, respectively (P < 0.05). Serum
dihydrotestosterone levels were significantly (P < 0.05) decreased in the
dutasteride group throughout the treatment period to a nadir of 31% baseline (wk 7). No significant differences in sperm concentrations among treatment groups were seen. Severe
oligospermia (0.1-3 million/ml) or
azoospermia was seen in none of five and four of five in TE + LNG; two of six and four of six in TE + LNG +
dutasteride; two of six and four of six in TE +
acyline; and one of five and three of five in TE + LNG +
acyline groups, respectively. There was one nonresponder in each of the TE + LNG and TE + LNG +
acyline groups.We conclude that the addition of a combined types I and II, 5alpha-
reductase inhibitor or long-acting
GnRH antagonist to a
testosterone plus LNG regimen provides no additional suppression of
gonadotropins or sperm concentration over an 8-wk treatment period. However, further evaluation of the effects of these regimens on the testis (including testicular
steroid levels and germ cell maturation) and the treatment of larger numbers of men (and for longer periods) may provide data to support their place in
contraceptive development.