Endometriosis: Immunomodulation

The overall goal of this proposal is to assess modulation of immune mechanisms in
endometriosis. Endometriosis is a common ailment affecting approximately five million
reproductive-aged American women. We will test the efficacy of a novel immunomodulatory
drug (peroxisome proliferator activated receptor gamma, PPAR-gamma, agonist), pioglitazone,
to reduce peritoneal fluid cytokine concentrations in women with endometriosis compared with
the non-treated controls (randomized controlled trial). Based on prior studies done by the
investigator highlighting the major role of cytokines and the immune system in the genesis
or propagation of endometriosis, these experiments could lead to improved translational
treatment strategies and a better understanding of endometriosis. Acting through
PPAR-gamma, TZDs inhibit proinflammatory cytokines as well as NF-kB, an important nuclear
transcription factor for the production of many cytokines. Accordingly, since human
endometrial epithelial and stromal cells contain PPAR-gamma, we felt i would be useful to
evaluate the influence of a PPAR-gamma ligand, pioglitazone, on the concentration of
specific peritoneal fluid cytokines.

Comparison: After the pre-trial screening, eligible subjects with presumed endometriosis
and age 18-45 will be consented and randomly assigned to receive either pioglitazone (30 mg,
daily)or no drug for 2 weeks. Peritoneal fluid will be collected at the time of surgery and
the volume measured. All patients enrolled in the study will have their surgery during the
follicular phase of the cycle in order to minimize differences in volume and cytokine
concentration due to the cyclical changes. The primary measure will be the peritoneal fluid
concentration comparisons of the two groups assessing six different cytokines.