title: Pharmacokinetics of testosterone undecanoate injected alone or in combination with norethisterone enanthate in healthy men.
abstract: Long-acting injectable testosterone undecanoate (TU) is a promising androgen for male hormonal contraception. As a prerequisite for a planned multicenter male contraceptive efficacy study, we studied the pharmacokinetics of 2 doses of TU alone or in combination with norethisterone enanthate (NETE) in a prospective 2-center study, randomized for TU dose in each center. Twenty healthy male volunteers in each center were administered intramuscular injections of 750 or 1000 mg TU alone or in combination with 200 mg of NETE IM every 8 weeks for 3 injections. There were no significant differences in maximum concentration and area under the curve (AUC) for serum total and free testosterone (T) between the TU 750 and 1000 mg groups, irrespective of whether TU was administered with 200 mg of NETE. TU 1000 mg IM alone or with NETE at 8-weekly intervals resulted in linear increases in average concentration and AUC of serum total and free T with each injection. Accumulation ratios of serum total and free T levels (calculated as 8 weeks post- to preinjection levels) for each period showed significant increases in the TU+ NETE groups. Serum gonadotropins levels and sperm concentration were more consistently suppressed in the TU 1000 mg + NETE group. We conclude that despite some accumulation of T, TU 1000 mg + NETE 200 mg administered every 8 weeks may be preferable for the future contraceptive efficacy study because of more complete suppression of gonadotropins and spermatogenesis.
authors.affiliation: Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, USA.
authors.forename: Ammar
authors.initials: A
authors.lastname: Qoubaitary
authors.forename: Cristina
authors.initials: C
authors.lastname: Meriggiola
authors.forename: Chiu Ming
authors.initials: CM
authors.lastname: Ng
authors.forename: Leslie
authors.initials: L
authors.lastname: Lumbreras
authors.forename: Silvia
authors.initials: S
authors.lastname: Cerpolini
authors.forename: G
authors.initials: G
authors.lastname: Pelusi
authors.forename: Peter D
authors.initials: PD
authors.lastname: Christensen
authors.forename: Laura
authors.initials: L
authors.lastname: Hull
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Swerdloff
authors.forename: Christina
authors.initials: C
authors.lastname: Wang
mesh_terms: D000328:Adult; D013196:Dihydrotestosterone / Q000097:blood; D004338:Drug Combinations; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone; D006801:Humans; D007273:Injections, Intramuscular; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011446:Prospective Studies; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013076:Sperm Count; D013092:Spermatogenesis-Blocking Agents / Q000493:pharmacokinetics*; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D004338:Drug Combinations; D012738:Sex Hormone-Binding Globulin; D013092:Spermatogenesis-Blocking Agents; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C010792:testosterone undecanoate; C024319:norethindrone enanthate; D009640:Norethindrone