Male hormonal contraception: a double-blind, placebo-controlled study.
BACKGROUND
This study was performed to assess spermatogenesis suppression and safety of a new combination of an etonogestrel (ENG) implant combined with testosterone undecanoate (TU) injections for male contraception. This is the first large placebo-controlled study for male hormonal contraception.


METHODS
In this double-blind, multicenter study, we randomly assigned 354 healthy men to receive either a low- or high-release ENG implant sc combined with im TU injections (750 mg every 10 or 12 wk or 1000 mg every 12 wk) or placebo implant and injections. Treatment duration was 42 or 44 wk and posttreatment follow-up at least 24 wk.


RESULTS
Overall, spermatogenesis was suppressed to 1 million/ml or less at wk 16 in 89% of men, with approximately 94% in two high-release ENG groups. Suppression was maintained up to the end of the treatment period in 91% of men. For all men who completed the treatment period, 3% never achieved 1 million/ml or less. Median recovery time to a sperm concentration above 20 million/ml was 15 wk (mean 17 wk, 95% confidence interval 16-18 wk). Treatment was well tolerated. As compared with the placebo group, more men in the active treatment groups reported adverse events such as weight gain, mood changes, acne, sweating, or libido change. For both spermatogenesis suppression and safety, differences were small between the active treatment groups.


CONCLUSIONS
The combination of an ENG implant with TU injections is a well-tolerated male hormonal method, providing effective and reversible suppression of spermatogenesis. Although the results are good, there is still room for improvement, possibly by adjusting the dose regimen or changing the mode of application.
Mommers
Ellen
E
Global Clinical Development Department, Organon, part of Schering-Plough, Oss, The Netherlands. ellen.mommers@organon.com
Kersemaekers
Wendy M
WM
Elliesen
Jörg
J
Kepers
Marc
M
Apter
Dan
D
Behre
Hermann M
HM
Beynon
Jennifer
J
Bouloux
Pierre M
PM
Costantino
Antonietta
A
Gerbershagen
Hans-Peter
HP
Grønlund
Lars
L
Heger-Mahn
Doris
D
Huhtaniemi
Ilpo
I
Koldewijn
Evert L
EL
Lange
Corinna
C
Lindenberg
Svend
S
Meriggiola
M Cristina
MC
Meuleman
Eric
E
Mulders
Peter F A
PF
Nieschlag
Eberhard
E
Perheentupa
Antti
A
Solomon
Andrew
A
Väisälä
Leena
L
Wu
Frederick C
FC
Zitzmann
Michael
M
D000328:Adult; D008076:Cholesterol, HDL / Q000097:blood; D003272:Contraceptive Agents, Male / Q000008:administration & dosage*; D017135:Desogestrel / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004343:Drug Implants; D004359:Drug Therapy, Combination; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007267:Injections; D008297:Male; D013091:Spermatogenesis / Q000187:drug effects; D013739:Testosterone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
D008076:Cholesterol, HDL; D003272:Contraceptive Agents, Male; D004343:Drug Implants; C044815:etonogestrel; D013739:Testosterone; D017135:Desogestrel; D005640:Follicle Stimulating Hormone; C010792:testosterone undecanoate