Suppression of spermatogenesis to azoospermia by combined administration of GnRH antagonist and 19-nortestosterone cannot be maintained by this non-aromatizable androgen alone.
BACKGROUND
For male hormonal contraception, combined administration of gonadotrophin-releasing hormone (GnRH) antagonists and androgens effectively suppresses spermatogenesis to azoospermia. In non-human primates this suppression can be maintained more easily by androgens alone.


METHODS
A clinical trial with six healthy volunteers was performed to test this approach in man. Loading doses of 10 mg/day of the GnRH antagonist cetrorelix were given subcutaneously for 5 days, followed by maintenance doses of 2 mg/day up to week 12. At 2 weeks after the first GnRH antagonist injection, androgen substitution was initiated with a loading dose of 400 mg 19-nortestosterone hexyloxyphenylpropionate (19NT-HPP) intramuscularly, followed by injections of 200 mg 19NT-HPP every 3 weeks up to week 26.


RESULTS
Serum concentrations of LH, FSH and testosterone were effectively suppressed by cetrorelix administration. Within 12 weeks, azoospermia was achieved in all six volunteers. After cessation of cetrorelix injections in week 12, gonadotrophins and testosterone increased significantly despite continued 19NT-HPP injections. In parallel, spermatogenesis was restimulated in five of six volunteers.


CONCLUSIONS
Combined administration of cetrorelix and 19NT-HPP leads to azoospermia within 3 months. However, complete azoospermia cannot be maintained by continued injections of the non-aromatizable 19NT-HPP alone.
Behre
H M
HM
Institute of Reproductive Medicine of the University (WHO Collaborating Centre for Research in Human Reproduction), D-48129 Münster, Germany.
Kliesch
S
S
Lemcke
B
B
von Eckardstein
S
S
Nieschlag
E
E
D000293:Adolescent; D000328:Adult; D045930:Anabolic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D003272:Contraceptive Agents, Male / Q000008:administration & dosage* / Q000494:pharmacology; D004542:Ejaculation; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007265:Inhibins / Q000097:blood; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D009277:Nandrolone / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000494:pharmacology; D009845:Oligospermia / Q000139:chemically induced*; D011388:Prolactin / Q000097:blood; D011467:Prostate / Q000033:anatomy & histology / Q000187:drug effects; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D012725:Sexual Behavior / Q000187:drug effects; D013076:Sperm Count; D013081:Sperm Motility; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects; D013739:Testosterone / Q000097:blood
D045930:Anabolic Agents; D003272:Contraceptive Agents, Male; D006454:Hemoglobins; D012738:Sex Hormone-Binding Globulin; C422364:inhibin B; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; D007265:Inhibins; C034345:19-nortestosterone 4-hexoxyphenylpropionate; D009277:Nandrolone; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C062876:cetrorelix