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The testosterone:androstenedione ratio in male undermasculinization

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OBJECTIVE

Recent reports suggest that low testosterone:androstenedione (T:A) ratio following hCG stimulation may be a useful method of diagnosing 17β-hydroxysteroid dehydrogenase-3 (17 βHSD3) deficiency. The aim of this study was to establish the range of T:A ratios in cases of undermasculinization with proven aetiologies other than 17 βHSD3.DESIGN

Register-based study of cases of male undermasculinization reported to a central database by clinicians.SUBJECTS

Amongst the 421 cases of under-masculinization, 114 cases had testosterone and androstenedione levels before and after hCG stimulation. Of the 114, there were 18 cases of abnormal testes, 17 cases of complete androgen insensitivity syndrome (CAIS), 68 cases of partial AIS (PAIS). Of the 17 cases of CAIS, 13 had evidence of androgen receptor (AR) dysfunction; in the PAIS cohort, 26 cases had evidence of AR dysfunction.METHODS

Analysis of T:A ratios in the above cohorts and comparison of these ratios to those in a group of previously described cases of 17 βHSD3 deficiency with a mean ratio of 0·4 (SD: 0·2)RESULTS

The median age (range) for the CAIS, PAIS and abnormal testes cohort was 1·25 years (0·06–16·5), 0·7 years (0·02–40·3) and 0·5 years (0·04–6·5), respectively. In CAIS, the median T:A rose from 0·4 (0·1 to 8·0) to 4·5 (0·5–16·7); in PAIS, median T:A rose from 0·7 (0·1 to 15) to 3·9 (0·3–20·5); in cases with abnormal testes, median T:A rose from 0·4 (0·1 to 5·6) to 0·6 (0·1–3·6). The median post-hCG T:A ratio was significantly lower in the abnormal testes cohort (P < 0·01). None of the cases of AIS with AR mutation had a low T:A ratio. Only four out of 84 cases diagnosed as AIS had a T:A ratio less than 0·8 (mean + 2SD in 17βHSD3 deficiency). In one of the four cases, the T:A ratio rose to 3·5 following a prolonged hCG stimulation test.

Deficiency of 17βHSD3 should be considered in 46XY undermasculinization if the post-hCG stimulation T:A ratio is less than 0·8. However, low T:A ratios may be encountered in conditions such as abnormal testes. Before embarking on mutational analysis, we would also recommend careful evaluation for testicular dysgenesis including a prolonged hCG stimulation test in cases with a low T:A ratio.
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Document Type: Research Article

Publication date: December 1, 2000

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