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Original Articles |
Prince Henry’s Institute of Medical Research (Y.Z., R.I.M.) and the Institute of Reproduction and Development (N.G.W., D.M.d.K.), Monash Medical Center, and the Department of Anatomy, Monash University (N.G.W.), Clayton, Victoria 3168; and the Department of Surgery, Monash University, Inner and Eastern Health Care Group, Alfred Hospital (P.R.), Prahran 3181, Australia
Address all correspondence and requests for reprints to: Dr. R. I. McLachlan, Prince Henry’s Institute of Medical Research, P.O. Box 5152, Clayton, Victoria 3168, Australia. E-mail: Rob.MacLachlan{at}med.monash.edu.au
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, im, 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.
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