Advantages and Challenges of Mass Spectrometry Assays for Steroid Hormones

Although steroid hormones have been measured, primarily in urine, by gas chromatography-mass spectrometry (GC-MS) assays for many years, in the past decade both clinical and research laboratories have dramatically increased usage of liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for measuring circulating levels of steroid hormones. Because of their high validity and throughput, mass spectrometry (MS) assays have replaced conventional radioimmunoassays (RIAs) and direct immunoassays for steroid hormones in larger reference laboratories, and they are touted to become the "gold standard" for steroid hormone quantitation. These advances in MS assays present several major challenges, which include the affordability of smaller laboratories to purchase MS instruments and pay for related operating costs; improving assay sensitivity, especially for measuring low estradiol levels in postmenopausal women and women treated with aromatase inhibitors; developing assays for quantitating profiles of steroid hormone metabolites in serum and tissues; standardizing steroid MS assays; and obtaining reliable reference intervals. The present review discusses the advantages of MS assays over conventional RIAs and direct immunoassays in steroid hormone measurements, and points out some of the important challenges facing the rapid increase in usage of MS assays.