Clotrimazole is effective for the regression of endometriotic implants in a Wistar rat experimental model of endometriosis

The present work aimed to evaluate molecular, angiogenic and inflammatory changes induced by clotrimazole (CTZ) on endometriosis lesions. For this, thirty female Wistar rats with surgically implanted autologous endometrium were treated with CTZ or vehicle (200 mg/kg) via esophageal gavage for 15 consecutive days. CTZ treatment significantly decreased the growth and the size of the implants, and histological examination indicated regression and atrophy, with no toxicity to the animals. The levels of the angiogenic markers VEGF and VEGFR-2 were significantly decreased in CTZ group. The treatment also promotes a reduction on PGE(2) and TNF-alpha levels. All these effects involve the amelioration of ERK1/2, Akt, AMPK and PERK signaling upon CTZ treatment. In conclusion, CTZ promoted an overall amelioration of endometriosis in a rat model due to the anti-angiogenic properties of the drug. Therefore, our results support the proposal of a clinical trial using CTZ for the treatment of endometriosis.