Norethisterone enanthate has neither a direct effect on the testis nor on the epididymis: a study in adult male cynomolgus monkeys (Macaca fascicularis).
OBJECTIVE
Norethisterone enanthate (NETE) is evaluated in trials of hormonal male contraception. It has been speculated that progestins may exert their contraceptive effects not only by suppressing gonadotropins but also by direct effects on male organs. NETE was given to monkeys in which endogenous gonadotropin secretion was suppressed by a gonadotropin releasing hormone (GnRH) antagonist, and replaced by human follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG). If NETE has a direct effect on spermatogenesis and/or epididymal function, some changes in testicular histology, sperm motility and/or morphology should occur soon after exposure to NETE.


METHODS
Fifteen adult intact male monkeys were grouped and treated for a 38-day period. Group I received GnRH antagonist, FSH, hCG and NETE while group II received a regime identical to group I without NETE and group III received only NETE and vehicle. Ejaculates, body weight, testicular biopsies and volume, and hormones were evaluated.


RESULTS
There was a similar pattern of serum FSH and testosterone in groups I and II. Testicular volume and the proportion of tubuli exhibiting spermatids was significantly decreased in group III. There were no significant differences between group I and group II in any parameters measured. The forward progression of sperm was not affected by NETE treatment. The consistently low percentages of grade c sperm indicated no sign of hyperactivation. No changes in the gross morphology of the acrosome were detected.


CONCLUSIONS
Short-term NETE treatment has neither a direct effect on the testis nor on the epididymis in this nonhuman primate model and its contraceptive effects appear to be exerted exclusively through gonadotropin suppression.
Junaidi
Aris
A
Institute of Reproductive Medicine of the University, Münster, Germany.
Luetjens
C Marc
CM
Wistuba
Joachim
J
Kamischke
Axel
A
Yeung
Ching-Hei
CH
Simoni
Manuela
M
Nieschlag
Eberhard
E
D000818:Animals; D001835:Body Weight; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003272:Contraceptive Agents, Male; D004822:Epididymis / Q000187:drug effects*; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D008252:Macaca fascicularis; D008297:Male; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013076:Sperm Count; D013087:Spermatids; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects*; D013739:Testosterone / Q000097:blood
D006063:Chorionic Gonadotropin; D003272:Contraceptive Agents, Male; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D005640:Follicle Stimulating Hormone; C024319:norethindrone enanthate; D009640:Norethindrone