measured in a more accessible compartment, are a compatible surrogate for the hormonal environment of the knee joint.This new information also does not yet establish whether our observed associations represent the response to a receptor-mediated process (as in the case of lower estradiol concentrations) or a cytokine-based response (as in the lower urinary 2-hydroxyestrone concentrations), or potentially, both mechanisms. There is little evidence that 2-hydroxyestrogens have binding affinity to the estrogen receptor (4,5), but they appear to have additional important properties, including participation in oxidation/reduction actions (6), and may modulate arachidonic acid metabolism and the cyclooxygenase 1 (COX-1) and COX-2 enzymes.