Lack of analytical interference of dydrogesterone in progesterone immunoassays

Objectives: Progesterone, a sex steroid, is measured in serum by immunoassay in a variety of clinical contexts. One potential limitation of steroid hormone immunoassays is interference caused by compounds with structural similarity to the target steroid of the assay. Dydrogesterone (DYD), an orally active stereoisomer of progesterone, is used for various indications in women's health. Herein, we report a systematic in vitro investigation of potential interference of DYD and its active metabolite 20 alpha-dihydrodydrogesterone (DHD) in seven widely used, commercially available progesterone assays. Methods: Routine human plasma samples were anonymized and pooled to create three graded concentration levels of progesterone (P4 high, P4 medium, P4 low). Each pooled P4 plasma sample (6-7 mL) was spiked at high, medium, and "none" concentration with DYD/DHD and was divided into 0.5 mL aliquots. The blinded aliquots were analyzed by seven different laboratories with their routine progesterone assay (six different immunoassays and one liquid chromatography-tandem mass spectrometry assay, respectively) within the Dutch working group on endocrine laboratory diagnostics of the Dutch Foundation for Quality Assessments in Medical Laboratories. Results: The sample recovery rate (P4 result obtained for sample spiked with DYD/DHD, divided by the result obtained for the corresponding sample with no DYD/DHD x 100) was within a +/- 10% window for the medium and high P4 concentrations, but more variable for the low P4 samples. The latter is, however, attributable to high interand intra-method variability at low P4 concentrations. Conclusions: This study does not indicate any relevant interference of DYD/DHD within routinely used progesterone assays.