Accuracy of First and Second Generation Testosterone Assays and Improvement through Sample Extraction

To the Editor: The monitoring of antiandrogen treatment in patients with prostate cancer, investigation of hyperandrogenism in women, and evaluation of infants with ambiguous genitalia require accurate measurement of low testosterone concentrations. However, testosterone immunoassays have been shown to be inaccurate and often to overestimate testosterone concentrations in the low range (1). A working group of the Endocrine Society recently reviewed this concern and presented several recommendations to ensure the accuracy of future testosterone testing for improvement of diagnosis and treatment of disease (2). In the present study we evaluated the current situation with regard to the accuracy of 7 testosterone immunoassays, including 2 second generation assays, by comparison with isotope-dilution liquid chromatography–tandem mass spectrometry (ID-LC-MS/MS). In addition, we investigated the possible improvement of these immunoassays by diethyl ether sample extraction. Serum from 50 men, 50 women, and 16 children (age 4–16 years) was collected, divided into aliquots, and stored (−20 °C) until analysis. All investigations conformed to the ethics standards of the Helsinki Declaration. Total serum testosterone was measured singly …