title: Effects of testosterone plus medroxyprogesterone acetate on semen quality, reproductive hormones, and germ cell populations in normal young men.
abstract: Testosterone (T) treatment suppresses gonadotropin levels and sperm counts in normal men, but the addition of a progestin may improve the efficacy of hormonal contraception. This study aimed to investigate the speed and extent of suppression of testicular germ cell number induced by T plus or minus progestin treatment and correlate these changes with serum gonadotropins and inhibin B levels, testicular androgens, and sperm output. Thirty normal fertile men (31-46 yr) received either testosterone enanthate (TE, 200 mg im weekly) alone or TE plus depot medroxyprogesterone acetate (DMPA, 300 mg im once) for 2, 6, or 12 wk (n = 5 per group) before vasectomy and testis biopsy. Five men (controls) proceeded directly to surgery. The inclusion of DMPA led to a more rapid fall in serum FSH/LH levels (time to 10% baseline: FSH; 12.6 +/- 2.6 vs. 7.9 +/- 1.4 d; LH, 9.9 +/- 3.4 vs. 3.4 +/- 1.7 d, TE vs. TE+DMPA, respectively, mean +/- SD, both P < 0.0001), yet the mean time to reach a sperm count 10% of baseline was not different (23.7 +/- 7.3 vs. 25.3 +/- 13.9 d, NS). The maximum extent of FSH/LH suppression was identical at 12 wk (mean serum FSH 1.2 and 1.6%, and mean LH 0.3 and 0.2% of baseline: TE vs. TE+ DMPA, respectively) as was sperm count suppression (5 of 5 and 4 of 5 men, respectively, with sperm counts < or =0.1 x 10(6)/ml). Serum inhibin decreased to 55% control at 12 wk in the TE+DMPA group (P < 0.05) but was unchanged by TE treatment (86% control, NS). Testicular T levels declined to approximately 2% of control levels, but testicular dihydrotestosterone and 5alpha-androstane-3alpha,17beta-diol (Adiol) levels were not different to control. Germ cell numbers as determined by stereological methods did not differ between TE and TE+DMPA except at 2 wk when type B spermatogonia and early spermatocytes were significantly lower in the TE+DMPA group (P < 0.05). In all groups, a marked inhibition of Apale-->B spermatogonial maturation was seen along with a striking inhibition of spermiation. We conclude that: 1) the addition of DMPA hastens the onset of FSH/LH suppression, correlating with a more rapid impairment of spermatogonial development, but in the longer term, neither germ cell number nor sperm count differed; 2) testicular dihydrotestosterone and Adiol levels are maintained during FSH/LH suppression despite markedly reduced T levels suggesting up-regulation of testicular 5alpha-reductase activity; and 3) spermatogonial inhibition is a consistent feature, but spermiation inhibition is also striking and is an important determinant of sperm output.
authors.affiliation: Prince Henry's Institute of Medical Research, Monash Medical Centre, Clayton, Victoria, Australia 3168. rob.mclachlan@med.monash.edu.au
authors.forename: Robert I
authors.initials: RI
authors.lastname: McLachlan
authors.forename: Liza
authors.initials: L
authors.lastname: O'Donnell
authors.forename: Peter G
authors.initials: PG
authors.lastname: Stanton
authors.forename: Georgia
authors.initials: G
authors.lastname: Balourdos
authors.forename: Mark
authors.initials: M
authors.lastname: Frydenberg
authors.forename: David M
authors.initials: DM
authors.lastname: de Kretser
authors.forename: David M
authors.initials: DM
authors.lastname: Robertson
mesh_terms: D000328:Adult; D003272:Contraceptive Agents, Male / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D005640:Follicle Stimulating Hormone / Q000037:antagonists & inhibitors; D012739:Gonadal Steroid Hormones / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007265:Inhibins / Q000037:antagonists & inhibitors; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors; D008297:Male; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D012016:Reference Values; D012661:Semen / Q000187:drug effects*; D013076:Sperm Count; D013737:Testis / Q000378:metabolism; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D003272:Contraceptive Agents, Male; D012739:Gonadal Steroid Hormones; D013739:Testosterone; D007265:Inhibins; C004648:testosterone enanthate; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D017258:Medroxyprogesterone Acetate