Probably one of most important reasons for observed discrepancies in testosterone measurements lies in "matrix" issue, in cross-reactivity. Immunolite assay and Abbot Architect both cross-react with DHEA and give consistently higher values for serum testosterone in range of castration male values [39,42]. Therefore results of studies, which use direct chemilumi-nescent testosterone assays in clinical setting cannot be compared to studies, which use chromatography followed by mass spectrometry techniques, because they do not measure the same things.
Inaccuracy of present day direct testosterone assays is already recognized in the field of female and male testosterone replacement, in pediatrics  and should be recognized also in the field of prostate cancer. Until indirect testosterone assays applying mass spectroscopy become widely available, publications should set realistic values of castrate levels and precisely state measurement methods used. They may be universally available in the USA, but in Europe, even western university hospitals are not quick in replacing direct immuno-as-says with gas chromatography methods - for example in Ghent they changed only recently, also for reasons like "one can not publish any more anything about testosterone without this method". And even mass spectrometry methods show significant errors and inconsistencies.
On the downside, it becomes clear using direct present day techniques to control castration methods (either chemical or surgical) is not appropriate and invariably leads to disputable results. Above findings also in part explain long term debate about subcapsular or classical simple orchiectomy and part of an occasional finding of non-castrate testosterone level after orchiectomy . Also our own impulse for studying the field come from initial observations that patients after surgical castration have higher testosterone values compared to guideline's requests.
On the upside, direct chemiluminescent assays do measure something. They can unmask occasional testosterone outlier (skipped dose of drug, granuloma formation or an individual in need for more frequent dose of a drug - reduced dose interval, as explained for example in dr. Garnick's editorial comment ). They can identify hypogonadal men with prostate cancer before starting androgen deprivation therapy, who have very bad prognosis or may in the future benefit from modified treatments, like incorporating early use of new antiandro-gens (for example MDV3100 ). They are necessary if one embarks on "on demand" re-dosing of LHRH agonists .
It is obvious chemiluminescent direct testosterone measurements do not show only testosterone values and as such can not serve as a tool to decide which LHRH agonist reduces testosterone more compared to other drugs. But results of such assays, as for example Abbot Architect testosterone assay, are consistent  and according to published and our results, there are great differences in measured levels of androgens in patients on LHRH agonist therapy (740%, from 0.5 to 3.7 nmol/L, 14 - 107 ng/dL). Perhaps, at present a pure speculation, chemiluminescent assays, which give consistent results, only with some cross-reactivity and therefore systematic overestimation of testosterone values in the low range, like Architect and Immunolite, can give estimation of overall serum androgen levels. Importance of extratesticular androgens is becoming more and more evident [62,63]. This may explain findings from Morote et al, who used same technically problematic direct chemiluminiscent assay and found correlation between assay results and time to biochemical progression  or from Perachino et al, who found even correlation between assay results and survival . Also Hashimoto et al , although failing to provide details about their testosterone assay and reporting questionably low testosterone values, report usefulness of testosterone measurement for prediction of antiandrogen treatment results - when testosterone levels were low, no additional clinical benefit of antiandrogen treatment was observed, when testosterone was higher, antiandrogens were useful. If future can confirm those propositions, direct testosterone tests, despite their imprecision for their original purpose, may well serve us in selecting patients for antiandrogen addition to castration or for secondary hormonal treatment, especially in perspective of new androgen manipulating drugs, like abiraterone acetate (Zytiga) and MDV3100 .
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