title: Novel male hormonal contraceptive combinations: the hormonal and spermatogenic effects of testosterone and levonorgestrel combined with a 5alpha-reductase inhibitor or gonadotropin-releasing hormone antagonist.
abstract: 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.
authors.affiliation: Prince Henry's Institute of Medical Research and Department of Obstetrics and Gynaecology, Monash University, Monash Medical Centre, P.O. Box 5152, Clayton, Victoria 3168, Australia. kati.matthiesson@phimr.monash.edu.au
authors.forename: Kati L
authors.initials: KL
authors.lastname: Matthiesson
authors.forename: John K
authors.initials: JK
authors.lastname: Amory
authors.forename: Richard
authors.initials: R
authors.lastname: Berger
authors.forename: Antony
authors.initials: A
authors.lastname: Ugoni
authors.forename: Robert I
authors.initials: RI
authors.lastname: McLachlan
authors.forename: William J
authors.initials: WJ
authors.lastname: Bremner
mesh_terms: D000328:Adult; D042944:Cholestenone 5 alpha-Reductase / Q000037:antagonists & inhibitors*; D003272:Contraceptive Agents, Male / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013076:Sperm Count; D013091:Spermatogenesis / Q000187:drug effects*; D013739:Testosterone / Q000008:administration & dosage* / Q000097:blood
chemical_list: D003272:Contraceptive Agents, Male; D012738:Sex Hormone-Binding Globulin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D016912:Levonorgestrel; D007986:Luteinizing Hormone; D042944:Cholestenone 5 alpha-Reductase