PPAR-gamma receptor ligand induces regression of endometrial explants in baboons: a prospective, randomized, placebo- and drug-controlled study.
OBJECTIVE
To determine the effects of a thiazolidinedione (TZD) agonist of peroxisome proliferator-activated receptor (PPAR)-gamma, rosiglitazone, in a baboon model of established endometriosis.


METHODS
Prospective, randomized, placebo-controlled study.


METHODS
Experimental surgery laboratory at the Institute of Primate Research in Nairobi, Kenya.


METHODS
Endometriosis was induced using intrapelvic injection of eutopic menstrual endometrium in 12 female baboons with a normal pelvis that had undergone at least one menstrual cycle since the time of captivity.


METHODS
Induction of endometriosis by laparoscopy was performed in 12 baboons with a normal pelvis. Endometrial tissue was extracted from each baboon by curettage, and a standard amount of endometrium was then seeded onto several peritoneal sites. About 34-68 days after the induction of laparoscopy, a pretreatment laparoscopy (baseline disease assessment) was performed in the baboons to record the extent of endometriotic lesions. The 12 baboons were randomized into three groups and treated from the day after the staging laparoscopy for a total duration of 30 days. They received phosphate-buffered saline tablets (n = 4, placebo control; placebo tablets once a day by mouth for 30 days), GnRH-antagonists (n = 4, active control; ganirelix acetate 125 microg/day for 30 days), or rosiglitazone (n = 4, test drug, 2 mg by mouth each day for 30 days). A third and final laparoscopy on day 30 after the start of treatment was performed to record the extent of endometriosis. The type of lesion (typical, red, white, or suspicious) was recorded. Biopsies were obtained to confirm the histological presence of endometriosis.


METHODS
A videolaparoscopy was performed 30 days after treatment to document the number and surface area of endometriotic lesions as well as to calculate the revised American Society for Reproductive Medicine score and stage.


RESULTS
The surface area of endometriotic lesions was statistically significantly lower in rosiglitazone-treated baboons when compared with the placebo group. Baboons treated with rosiglitazone or ganirelix had a greater negative relative change in surface area of peritoneal endometriotic lesions than controls. The overall weighted appearance of the lesion types suggests that rosiglitazone may deter the development of newer endometriotic lesions.


CONCLUSIONS
A PPAR-gamma ligand, rosiglitazone, effectively diminishes the burden of endometriosis disease in a baboon endometriosis model. This animal model holds promise that a TZD drug may be helpful in women with endometriosis.
Lebovic
Dan I
DI
Reproductive Endocrinology Division, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan 48109, USA. lebovic@umich.edu
Mwenda
Jason M
JM
Chai
Daniel C
DC
Mueller
Michael D
MD
Santi
Allessandro
A
Fisseha
Senait
S
D'Hooghe
Thomas
T
D000818:Animals; D002828:Choristoma / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004715:Endometriosis / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D004717:Endometrium; D005260:Female; D008024:Ligands; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism / Q000502:physiology; D010215:Papio; D010529:Peritoneal Cavity; D011446:Prospective Studies; D011897:Random Allocation; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone