Dataset Information

Androgen synthesis in the gonadotropin-suppressed human testes can be markedly suppressed by ketoconazole.

ABSTRACT:

Context

The concentration of intratesticular testosterone (IT-T) required for human spermatogenesis is unknown because spermatogenesis can persist despite the markedly reduced IT-T concentrations observed with LH suppression. Methods to lower IT-T further are needed to determine the relationship between IT-T and spermatogenesis.

Objective

The objective of the study was to determine the effect of inhibiting the synthesis and metabolism of testosterone (T) on IT-T in gonadotropin-suppressed human testes.

Design/setting/patients

Forty normal men participated in a blinded, placebo-controlled, randomized trial at an academic center. INTERVENTION/OUTCOME MEASURES: All men were first administered the GnRH antagonist acyline to suppress LH. Forty-eight hours after acyline administration, subjects were randomly assigned to placebo, ketoconazole (to inhibit T synthesis) at 400 or 800 mg, dutasteride (to inhibit T metabolism) 2.5 mg, or anastrazole (to inhibit T metabolism) 1 mg, daily for 7 days (n = 8/group). Intratesticular steroid concentrations were measured 48 hours after acyline administration alone and again after 7 days of combination treatment.

Results

After 7 days of combination treatment, the median IT-T (25th, 75th percentile) in the placebo group was 14 (8.0, 21.2) ng/mL. IT-T was reduced to 3.7 (2.5, 7.1) ng/mL in the ketoconazole 400 mg group and 1.7 (0.8, 4.0) ng/mL in the ketoconazole 800 mg group (P < .001 vs placebo for both comparisons). IT-T concentrations in the dutasteride and anastrazole groups were similar to placebo.

Conclusion

Combining inhibition of steroidogenesis with gonadotropin suppression lowers IT-T more than gonadotropin suppression alone. This combination might be useful to determine the minimum IT-T concentration necessary for human spermatogenesis, information essential for developing male hormonal contraceptives.

SUBMITTER: Roth MY

PROVIDER: S-EPMC3590466 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Publications

Androgen synthesis in the gonadotropin-suppressed human testes can be markedly suppressed by ketoconazole.

Roth M Y MY Nya-Ngatchou J J S JJ Lin K K Page S T ST Anawalt B D BD Matsumoto A M AM Marck B T BT Bremner W J WJ Amory J K JK

The Journal of clinical endocrinology and metabolism 20130124 3

<h4>Context</h4>The concentration of intratesticular testosterone (IT-T) required for human spermatogenesis is unknown because spermatogenesis can persist despite the markedly reduced IT-T concentrations observed with LH suppression. Methods to lower IT-T further are needed to determine the relationship between IT-T and spermatogenesis.<h4>Objective</h4>The objective of the study was to determine the effect of inhibiting the synthesis and metabolism of testosterone (T) on IT-T in gonadotropin-su ...[more]

PMID: 23348398

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Dataset Information

Androgen synthesis in the gonadotropin-suppressed human testes can be markedly suppressed by ketoconazole.

Context

Objective

Design/setting/patients

Results

Conclusion

Publications

Androgen synthesis in the gonadotropin-suppressed human testes can be markedly suppressed by ketoconazole.

Similar Datasets

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