Thiazolidinediones as Therapy for Endometriosis: A Case Series

Abstract

Background: Current medical therapies for endometriosis result in delayed conception and have not been shown to provide any fertile benefit subsequent to treatment. Thiazolidinediones (TZDs) do not impede conception and have been shown to reduce endometriotic lesions in animal models; however, no studies have been performed in humans. The aim of this study was to provide preliminary data about the effectiveness of a TZD in treating endometriosis-related pain. Methods: Case series of women with endometriosis recruited from the University of Michigan as part of an open-label prospective phase 2a clinical trial. Participants were given rosiglitazone, 4 mg daily, for 6 months. Subjective endometriosis symptoms were assessed using a modified Biberoglu and Behrman symptom severity scale and the McGill pain questionnaire. Results: Two of the 3 patients exhibited improvement in severity of symptoms and pain levels with a concurrent decrease in pain medication, while 1 experienced no change. Rosiglitazone was well tolerated by all patients. Conclusions: Combined with data gathered from studies in rats and nonhuman primates, the results from this study offer positive justification for using TZDs as a well-tolerated treatment for endometriosis that can address pain without impeding ovulation and without the need for add-back therapy.

The inhibitory effect of celecoxib and rosiglitazone on experimental endometriosis

“…In endometriosis treatment, an overall beneficial effect has been reported after administration of rosiglitazone in a reduced number of patients with endometriosis, including ameliorating endometriosis symptoms and pain (45). It is noteworthy that rosiglitazone not only does not impede ovulation (45) but also has been reported to help restore spontaneous ovulation (46), an improvement over current medical therapies for endometriosis (45).…”

“…It is noteworthy that rosiglitazone not only does not impede ovulation (45) but also has been reported to help restore spontaneous ovulation (46), an improvement over current medical therapies for endometriosis (45). In addition, it has been reported that rosiglitazone does not cause any alteration to the mouse fetus when administered during pregnancy (25).…”

Nuclear Receptors of the Peroxisome Proliferator-Activated Receptor (PPAR) Family in Gestational Diabetes: From Animal Models to Clinical Trials1

“…Hence, the therapeutic spectrum of TZDs may be extended to include an additional patient population, women with endometriosis. However, to date only case series have reported benefits of TZDs in the treatment of endometriosis [50].…”

“…PPARG activators such as pioglitazone and TZD-R are widely used in patients with DM 2 [79]. Besides their role in targeting metabolism, pleitropic functions such as antiproliferative and anti-inflammatory effects have been described [50]. In contrast, TZDs can promote weight gain and peripheral edema and increase the risk of myocardial ischemia (especially TZD-R versus placebo) [80,81].…”

Peroxisome proliferating activating receptor gamma–independent attenuation of interleukin 6 and interleukin 8 secretion from primary endometrial stromal cells by thiazolidinediones

“…The size of surgically induced endometriotic lesions was reduced by ciglitazone in rats (2) and by rosiglitazone in baboons (3), whereas pioglitazone prevented their establishment in baboon (4) and inhibited postsurgical adhesion in a chimeric model of human endometrial biopsies in immunocompromised mice (5). Rosiglitazone has also reduced pain reported in a human case series (6). Although TZDs are available for clinical use they have also been plagued by side effects.…”