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* To whom correspondence should be addressed. E-mail: jamory{at}u.washington.edu.
ABSTRACT
Background: The administration of testosterone plus a
progestogen functions as a male contraceptive by
inhibiting the release of the pituitary gonadotropins.
After 3-4 months of treatment, most men are azoospermic or
severely oligospermic (
1 million sperm/ml). However,
10-20% of men have persistent sperm production despite
profound gonadotropin suppression. Since insulin-like
factor-3 (INSL3) has been shown to prevent germ cell
apoptosis in mice, we hypothesized that INSL3 might be
higher in men with persistent spermatogenesis during
treatment with male hormonal contraceptives.
Study Design: In a retrospective analysis, we measured
serum INSL3 in 107 men from three recent male hormonal
contraceptive studies and determined the relationship
between suppression of spermatogenesis and serum INSL3.
Results: At the end-of-treatment sixty-three men (59%)
were azoospermic and forty-four men (41%) had detectable
sperm in their ejaculate. Baseline INSL3 did not predict
azoospermia; however, end-of-treatment serum INSL3 was
significantly higher in non-azoospermic men compared to
those with azoospermia [median (interquartile range): 95
(73-127) pg/ml vs. 80 (67-101) pg/ml; p=0.03)].
Furthermore, serum INSL3 was positively correlated with
sperm concentration (r = 0.25; p = 0.009) at the
end-of-treatment and was significantly associated with
non-azoospermia by multivariate logistic regression (p =
0.03).
Conclusion: After six months of treatment with a hormonal
male contraceptive regimen, higher serum INSL3
concentrations are associated with persistent sperm
production. INSL3 may play a role in preventing complete
suppression of spermatogenesis in some men on hormonal
contraceptive regimens. This finding suggests that INSL3
could be a potential target for male contraceptive
development.
Key words: Contraception •
Spermatogenesis •
INSL3 •
azoospermia •
oligospermia
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