title: Combined administration of a gonadotropin-releasing hormone antagonist and testosterone in men induces reversible azoospermia without loss of libido.
abstract: GnRH antagonists suppress pituitary and gonadal function by competing with endogenous GnRH for binding to receptors on pituitary gonadotrophs. We studied the effects of GnRH antagonist administration to men in a protocol simulating a likely male contraceptive regimen combined with a low dose of testosterone. The GnRH antagonist Nal-Glu was given daily (10 mg, sc) for 20 weeks to eight normal men, and a low dose of testosterone enanthate (25 mg, sc) was given every week. Sperm counts started declining during week 4, and complete azoospermia was reached within 6-12 weeks in six of the eight subjects. Subjects 7 and 8, whose sperm counts and serum gonadotropin levels were not suppressed after 10 weeks, were given 20 mg Nal-Glu starting at week 10. One became azoospermic at week 16, while the other's total sperm counts continued declining and reached a nadir of 1.4 million by week 20. Sperm motility and viability in this subject were completely suppressed after week 14. Sperm counts returned to baseline levels 12-14 weeks after the end of Nal-Glu administration. The mean serum LH level of the first six subjects decreased from 3 +/- 03. U/L at baseline to less than 0.1 U/L until week 20, and then levels returned to baseline. FSH levels similarly decreased from a combined mean of 3.6 +/- 0.9 U/L at baseline to below 0.3 U/L after 4 weeks of Nal-Glu administration. Serum mean testosterone levels between weekly injections of testosterone enanthate ranged from 27.4 +/- 5.9 to 4.8 +/- 1.4 nmol/L, but remained in the hypogonadal range (less than 10 nmol/L) for 4 of the 7 days. None of the subjects, however, complained of decreased libido or potency, as assessed by a questionnaire. No systemic or significant local side-effects were observed, other than a minimal reaction at the injection site. These data suggest that complete sustained azoospermia can be achieved in man, without loss of libido, by chronic administration of a GnRH antagonist plus testosterone.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
authors.forename: S N
authors.initials: SN
authors.lastname: Pavlou
authors.forename: K
authors.initials: K
authors.lastname: Brewer
authors.forename: M G
authors.initials: MG
authors.lastname: Farley
authors.forename: J
authors.initials: J
authors.lastname: Lindner
authors.forename: M C
authors.initials: MC
authors.lastname: Bastias
authors.forename: B J
authors.initials: BJ
authors.lastname: Rogers
authors.forename: L L
authors.initials: LL
authors.lastname: Swift
authors.forename: J E
authors.initials: JE
authors.lastname: Rivier
authors.forename: W W
authors.initials: WW
authors.lastname: Vale
authors.forename: P M
authors.initials: PM
authors.lastname: Conn
mesh_terms: D000328:Adult; D002470:Cell Survival / Q000187:drug effects; D003272:Contraceptive Agents, Male / Q000009:adverse effects; D004338:Drug Combinations; D012739:Gonadal Steroid Hormones / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D006801:Humans; D007989:Libido / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009845:Oligospermia / Q000139:chemically induced*; D013076:Sperm Count / Q000187:drug effects; D013081:Sperm Motility / Q000187:drug effects; D013739:Testosterone / Q000009:adverse effects
chemical_list: D003272:Contraceptive Agents, Male; D004338:Drug Combinations; D012739:Gonadal Steroid Hormones; D008055:Lipids; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone