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* To whom correspondence should be addressed. E-mail: page{at}u.washington.edu.
Introduction: Male hormonal contraceptive regimens function by suppressing gonadotropin secretion, resulting in a dramatic decrease in testicular androgen biosynthesis and spermatogenesis. Animal studies suggest that persistent intratesticular (iT-) androgen production has a stimulatory effect on spermatogenesis in the setting of gonadotropin suppression. Objectives: We hypothesized that men with incompletely suppressed spermatogenesis (>1 million sperm/ml) during male hormonal contraceptive treatment would have higher iT-androgen concentrations than men who achieved severe oligospermia (<=1 million sperm/ml). Methods: Twenty healthy men, ages 18-55 years enrolled in a 6-month male contraceptive study of transdermal testosterone (T) gel (100mg/day) + depomedroxyprogesterone acetate (300mg IM/12 wks) with or without the GnRH antagonist, acyline (300µg/kg SC/2 wks x 12 wks) were studied. During the 24th week of treatment, subjects underwent fine needle aspirations of the testes and iT-T and dihydrotestosterone (iT-DHT) were measured in testicular fluid by liquid chromatography-tandem mass spectrometry. Results: All men dramatically suppressed spermatogenesis; 15/20 men were severely oligospermic and 5/20 suppressed to 1.5-3.2 million sperm/ml. In all subjects, mean iT-T and iT-DHT concentrations were 35±8 and 5.1±0.8 nmol/L. IT-androgen concentrations did not significantly differ in men who did and did not achieve severe oligospermia (p=0.41 for iT-T; p=0.18 for iT-DHT). Furthermore, there was no significant correlation between iT-T or iT-DHT and sperm concentration after 24 weeks of treatment. Conclusions: In this study of prolonged gonadotropin suppression induced by male hormonal contraceptive treatment, differences in iT-androgens did not explain differences in spermatogenesis. Additional studies to identify factors involved in persistent spermatogenesis despite gonadotropin suppression are warranted.
Key words: Androgen •
Contraception •
Spermatogenesis •
Testis
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