Evaluation of plasma and tissue estrogen suppression with third-generation aromatase inhibitors: Of relevance to clinical understanding?

Development of aromatase inhibition and aromatase inhibitors as a therapeutic strategy was initiated through two different pathways. The one pathway went through systematic exploration of aromatase substrate analogues for enzyme inhibitions, subsequently leading to the development of steroidal agents for clinical use. The second involved clinical observation with an unsuccessful anti-epileptic compound named aminoglutethimide, attempting to achieve a “medical adrenalectomy”. Endocrine studies on patients treated with aminoglutethimide lead to direct assessment of in vivo aromatase inhibition in patients on treatment, thus identifying a novel therapeutic strategy. As such, both research programs represent different examples of pioneering translational work leading towards a successful therapeutic strategy. Subsequent studies with respect to total aromatase inhibition have led to successful development of more potent strategies. Most importantly, these studies have revealed a correlation between aromatase inhibition and clinical outcome. Ongoing studies exploring tissue estrogen levels as well as gene expression profiles on therapy may further improve this important therapeutic area.