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J Clin Endocrinol Metab. 2013 Mar;98(3):1198-206. doi: 10.1210/jc.2012-3527. Epub 2013 Jan 24.
[h=1]Androgen synthesis in the gonadotropin-suppressed human testes can be markedly suppressed by ketoconazole.[/h]Roth MY, Nya-Ngatchou JJ, Lin K, Page ST, Anawalt BD, Matsumoto AM, Marck BT, Bremner WJ, Amory JK.
[h=3]Source[/h]Departments of Internal Medicine, University of Washington, 1959 NE Pacific Street, Box 357138, Seattle, Washington 98195, USA. [email protected]
[h=3]Abstract[/h][h=4]CONTEXT:[/h]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.
[h=4]OBJECTIVE:[/h]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.
[h=4]DESIGN/SETTING/PATIENTS:[/h]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.
[h=4]RESULTS:[/h]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.
[h=4]CONCLUSION:[/h]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.
<dl class="rprtid"><dt>PMID:</dt><dd>23348398</dd><dd> [PubMed - indexed for MEDLINE] </dd><dd>
</dd><dt>PMCID:</dt><dd>PMC3590466</dd><dd> [Available on 2014/3/1]
</dd></dl>
[h=1]Androgen synthesis in the gonadotropin-suppressed human testes can be markedly suppressed by ketoconazole.[/h]Roth MY, Nya-Ngatchou JJ, Lin K, Page ST, Anawalt BD, Matsumoto AM, Marck BT, Bremner WJ, Amory JK.
[h=3]Source[/h]Departments of Internal Medicine, University of Washington, 1959 NE Pacific Street, Box 357138, Seattle, Washington 98195, USA. [email protected]
[h=3]Abstract[/h][h=4]CONTEXT:[/h]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.
[h=4]OBJECTIVE:[/h]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.
[h=4]DESIGN/SETTING/PATIENTS:[/h]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.
[h=4]RESULTS:[/h]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.
[h=4]CONCLUSION:[/h]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.
<dl class="rprtid"><dt>PMID:</dt><dd>23348398</dd><dd> [PubMed - indexed for MEDLINE] </dd><dd>
</dd><dt>PMCID:</dt><dd>PMC3590466</dd><dd> [Available on 2014/3/1]
</dd></dl>