Peculiar observations in measuring testosterone in women treated with oral contraceptives supplemented with dehydroepiandrosterone (DHEA)

• Published in: Clinica chimica acta 2014-03, Vol.430, p.92-95
• Main Authors: Heijboer, Annemieke C., Zimmerman, Yvette, de Boer, Theo, Coelingh Bennink, Herjan, Blankenstein, Marinus A.
• Format: Article
• Language: English
• Subjects: Assay; Biological Availability; Chromatography, Liquid; Contraception; Contraceptives, Oral, Combined - administration & dosage; Contraceptives, Oral, Combined - pharmacology; Dehydroepiandrosterone - administration & dosage; Dehydroepiandrosterone - pharmacology; DHEA; Female; Humans; Mass spectrometry; Radioimmunoassay; Reproducibility of Results; Sensitivity and Specificity; Sex Hormone-Binding Globulin - analysis; Sex Hormone-Binding Globulin - metabolism; SHBG; Tandem Mass Spectrometry; Testosterone; Testosterone - blood; Uncertainty
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2013.12.042

Total testosterone is considered to be decreased during the use of combined oral contraceptives. There is, however, considerable concern about the quality of testosterone assays, especially at low levels. We aimed to confirm testosterone levels measured by direct radioimmunoassay in a recent clinical trial with a state-of-the-art LC–MSMS method. Surplus specimens with known testosterone levels collected during the study (Clinical Trial Registration number ISRCTN06414473) were reanalyzed with an LC–MSMS method. This method was compared to another LC–MSMS method that had shown to concur excellently to a reference method. Follow-up experiments were designed to explain the results. In contrast to our expectation, LC–MSMS measurements did not corroborate the data obtained by radioimmunoassay. Subsequent experiments showed that this could be attributed to a strong dependency of the radioimmunoassay on SHBG. Testosterone results (n=198) obtained by direct radioimmunoassay showed a negative correlation to SHBG levels (r=−0.676; p