Two unsuccessful clinical trials on endometriosis and a few lessons learned.

In 1999, a phase II clinical trial on the use of fulvestrant to treat endometriosis was launched; yet after 7 years there is still no report on its outcome. In 2005, another trial on the use of raloxifene to treat endometriosis was terminated early due to unfavorable outcome. The two apparently unsuccessful clinical trials on endometriosis have taught us a few important lessons. First, we need to understand endometriosis through more basic research. We have also been reminded that human endometriosis trials differ from animal studies; anatomy and physiology are often divergent, and outcome measures are certainly different. Ectopic endometrium can differ significantly from eutopic tissue, and this issue needs to be more thoroughly explored. We believe human cell lines will prove to be an inexpensive and valuable tool for future preliminary evaluation of medical therapies as well as discerning pathophysiologic processes of the disease. Based on our current understanding of endometriosis, some concrete benchmarks can be established for testing or screening potential compounds in vitro. Finally, estrogen receptor modulators are often tissue-, cell-, and context-specific in their actions; they should not be simplistically grouped together nor should extrapolations from one compound to another be undertaken in a cavalier manner. Copyright 2007 S. Karger AG, Basel.