title: Stereological evaluation of human spermatogenesis after suppression by testosterone treatment: heterogeneous pattern of spermatogenic impairment.
abstract: Testosterone (T) treatment suppresses gonadotropin levels in normal men and is a promising reversible contraceptive that induces azoospermia in approximately 70% of subjects and oligospermia in the remainder; however, the basis of this variable response is unclear. This study aimed to investigate this reported variable response by examining the spermatogenic process and quantitating germ cell number in men after T-induced gonadotropin withdrawal. Ten normal fertile men (31-46 yr), already planning to undergo vasectomy, either received T enanthate (200 mg, i.m., weekly) for 19-24 weeks (n = 5; TE group) or proceeded directly to surgery (n = 5; controls), at which time a unilateral testicular biopsy was taken, and germ cell numbers were estimated using the optical disector stereological method. In response to TE treatment, serum T levels rose 2-fold, and FSH/LH levels became undetectable. Sperm counts fell to azoospermia in 4 men and to 21 million/mL in the fifth man. The mean number of type A spermatogonia per 100 Sertoli cells was unchanged, but type B spermatogonia fell markedly to 10% of the control values, and later germ cell types decreased to 11-18% of the control values. The pattern of germ cell suppression varied widely and showed no relationship with sperm count or the time to azoospermia. Despite the presence of elongated spermatids (1.4-20% of the control), four men remained azoospermic. Two TE subjects with similar early germ cell complements and elongated spermatid numbers had sperm counts of zero and 21 million/mL; the latter man demonstrated marked variability in germ cell numbers between adjacent tubules. We conclude that 1) the principal spermatogenic lesion in TE-treated men is the marked (90%) inhibition of type A-->B spermatogonial maturation. Other sites are also affected, particularly the release and/or survival of elongated spermatids during transit; and 2) a steady state in germ cell number may not be established even after 4-5 months of TE treatment. The findings suggest that TE treatment does not adequately or consistently withdraw hormonal support for spermatogenesis, leading to variable between- and within-individual patterns of germ cell suppression.
authors.affiliation: Prince Henry's Institute of Medical Research, Monash Medical Center, Clayton, Victoria, Australia.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhengwei
authors.forename: N G
authors.initials: NG
authors.lastname: Wreford
authors.forename: P
authors.initials: P
authors.lastname: Royce
authors.forename: D M
authors.initials: DM
authors.lastname: de Kretser
authors.forename: R I
authors.initials: RI
authors.lastname: McLachlan
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003272:Contraceptive Agents, Male / Q000627:therapeutic use*; D003864:Depression, Chemical; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007265:Inhibins / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D013076:Sperm Count / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013739:Testosterone / Q000097:blood / Q000627:therapeutic use*
chemical_list: D003272:Contraceptive Agents, Male; D013739:Testosterone; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone