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Vol. 68, No. 3, 2009
Issue release date: October 2009
Section title: Original Article
Free Access
Gynecol Obstet Invest 2009;68:167–170
(DOI:10.1159/000230713)

Thiazolidinediones as Therapy for Endometriosis: A Case Series

Moravek M.B.a · Ward E.A.a · Lebovic D.I.a, b
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology,aUniversity of Michigan, Ann Arbor, Mich. and bUniversity of Wisconsin, Madison, Wisc., USA
email Corresponding Author

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.

© 2009 S. Karger AG, Basel


  

Key Words

  • Endometriosis
  • Thiazolidinediones
  • Pelvic pain
  • Rosiglitazone
  • Infertility

References

  1. Eskenazi B, Warner ML: Epidemiology of endometriosis. Obstet Gynecol Clin North Am 1997;24:235–258.
  2. D’Hooghe TM, Debrock S, et al: Endometriosis and subfertility: is the relationship resolved? Semin Reprod Med 2003;21:243–254.
  3. Guo SW, Wang Y: The prevalence of endometriosis in women with chronic pelvic pain. Gynecol Obstet Invest 2006;62:121–130.
  4. Petta CA, Ferriani RA, et al: Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis. Hum Reprod 2005;20:1993–1998.
  5. Treatment of pelvic pain associated with endometriosis. Fertil Steril 2006;86(suppl 5):S18–S27.
  6. Mihalyi A, Simsa P, et al: Emerging drugs in endometriosis. Expert Opin Emerg Drugs 2006;11:503–524.
  7. Surrey ES, Hornstein MD: Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long-term follow-up. Obstet Gynecol 2002;99:709–719.
  8. Hughes E, Brown J, et al: Ovulation suppression for endometriosis. Cochrane Database Syst Rev 2007;CD000155.
  9. Pritts EA, Zhao D, et al: PPAR-gamma decreases endometrial stromal cell transcription and translation of RANTES in vitro. J Clin Endocrinol Metab 2002;87:1841–1844.
  10. Ohama Y, Harada T, et al: Peroxisome proliferator-activated receptor-gamma ligand reduced tumor necrosis factor-alpha-induced interleukin-8 production and growth in endometriotic stromal cells. Fertil Steril 2008;89:311–317.
  11. Hornung D, Waite LL, et al: Nuclear peroxisome proliferator-activated receptors alpha and gamma have opposing effects on monocyte chemotaxis in endometriosis. J Clin Endocrinol Metab 2001;86:3108–3114.
  12. Hornung D, Chao VA, et al: Thiazolidinedione inhibition of peritoneal inflammation. Gynecol Obstet Invest 2003;55:20–24.
  13. Giudice LC, Kao LC: Endometriosis. Lancet 2004;364:1789–1799.
  14. Giaginis C, Margeli A, et al: Peroxisome proliferator-activated receptor-gamma ligands as investigational modulators of angiogenesis. Expert Opin Investig Drugs 2007;16:1561–1572.
  15. Lebovic DI, Kir M, et al: Peroxisome proliferator-activated receptor-gamma induces regression of endometrial explants in a rat model of endometriosis. Fertil Steril 2004;82(suppl 3):1008–1013.
  16. Lebovic DI, Mwenda JM, et al: PPAR-gamma receptor ligand induces regression of endometrial explants in baboons: a prospective, randomized, placebo- and drug-controlled study. Fertil Steril 2007;88(suppl 4):1108–1119.

    External Resources

  17. Demirturk F, Aytan H, et al: Effect of peroxisome proliferator-activated receptor-gamma agonist rosiglitazone on the induction of endometriosis in an experimental rat model. J Soc Gynecol Investig 2006;13:58–62.
  18. Biberoglu KO, Behrman SJ: Dosage aspects of danazol therapy in endometriosis: short-term and long-term effectiveness. Am J Obstet Gynecol 1981;139:645–654.
  19. Melzack R: The short-form McGill Pain Questionnaire. Pain 1987;30:191–197.
  20. Nissen SE, Wolsk K: Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007;356:2457–2471.
  21. Yaris F, Yaris E, et al: Normal pregnancy outcome following inadvertent exposure to rosiglitazone, gliclazide, and atorvastatin in a diabetic and hypertensive woman. Reprod Toxicol 2004;18:619–621.
  22. Kalyoncu NI, Yaris F, et al: A case of rosiglitazone exposure in the second trimester of pregnancy. Reprod Toxicol 2005;19:563–564.
  23. Derosa G, Cicero AF, et al: Effects of 1 year of treatment with pioglitazone or rosiglitazone added to glimepiride on lipoprotein (a) and homocysteine concentrations in patients with type 2 diabetes mellitus and metabolic syndrome: a multicenter, randomized, double-blind, controlled clinical trial. Clin Ther 2006;28:679–688.
  24. Betteridge DJ: Effects of pioglitazone on lipid and lipoprotein metabolism. Diabetes Obes Metab 2007;9:640–647.
  25. Koninckx PR: Anti-TNF-α treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial. Hum Reprod 2008;9:2017–2023.

    External Resources

  26. Vercellini P, Somigliana E, et al: Endometriosis: current and future medical therapies. Best Pract Res Clin Obstet Gynaecol 2008;22:275–306.

  

Author Contacts

Dan Lebovic
University of Wisconsin, Department of Ob/Gyn
Division of Reproductive Endocrinology and Infertility, H4/628 Clinical Science Center
600 Highland Avenue, Madison, WI 53792-3236 (USA)
Tel. +1 734 262 3990, Fax +1 608 262 9862, E-Mail lebovic@wisc.edu

  

Article Information

Received: November 20, 2008
Accepted after revision: February 3, 2009
Published online: July 30, 2009
Number of Print Pages : 4
Number of Figures : 1, Number of Tables : 1, Number of References : 26

  

Publication Details

Gynecologic and Obstetric Investigation

Vol. 68, No. 3, Year 2009 (Cover Date: October 2009)

Journal Editor: D'Hooghe T. (Leuven)
ISSN: 0378-7346 (Print), eISSN: 1423-002X (Online)

For additional information: http://www.karger.com/GOI


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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.

© 2009 S. Karger AG, Basel


  

Author Contacts

Dan Lebovic
University of Wisconsin, Department of Ob/Gyn
Division of Reproductive Endocrinology and Infertility, H4/628 Clinical Science Center
600 Highland Avenue, Madison, WI 53792-3236 (USA)
Tel. +1 734 262 3990, Fax +1 608 262 9862, E-Mail lebovic@wisc.edu

  

Article Information

Received: November 20, 2008
Accepted after revision: February 3, 2009
Published online: July 30, 2009
Number of Print Pages : 4
Number of Figures : 1, Number of Tables : 1, Number of References : 26

  

Publication Details

Gynecologic and Obstetric Investigation

Vol. 68, No. 3, Year 2009 (Cover Date: October 2009)

Journal Editor: D'Hooghe T. (Leuven)
ISSN: 0378-7346 (Print), eISSN: 1423-002X (Online)

For additional information: http://www.karger.com/GOI


Article / Publication Details

First-Page Preview
Abstract of Original Article

Received: 11/10/2008
Accepted: 3/2/2009
Published online: 7/30/2009
Issue release date: October 2009

Number of Print Pages: 4
Number of Figures: 1
Number of Tables: 1

ISSN: 0378-7346 (Print)
eISSN: 1423-002X (Online)

For additional information: http://www.karger.com/GOI


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Eskenazi B, Warner ML: Epidemiology of endometriosis. Obstet Gynecol Clin North Am 1997;24:235–258.
  2. D’Hooghe TM, Debrock S, et al: Endometriosis and subfertility: is the relationship resolved? Semin Reprod Med 2003;21:243–254.
  3. Guo SW, Wang Y: The prevalence of endometriosis in women with chronic pelvic pain. Gynecol Obstet Invest 2006;62:121–130.
  4. Petta CA, Ferriani RA, et al: Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis. Hum Reprod 2005;20:1993–1998.
  5. Treatment of pelvic pain associated with endometriosis. Fertil Steril 2006;86(suppl 5):S18–S27.
  6. Mihalyi A, Simsa P, et al: Emerging drugs in endometriosis. Expert Opin Emerg Drugs 2006;11:503–524.
  7. Surrey ES, Hornstein MD: Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long-term follow-up. Obstet Gynecol 2002;99:709–719.
  8. Hughes E, Brown J, et al: Ovulation suppression for endometriosis. Cochrane Database Syst Rev 2007;CD000155.
  9. Pritts EA, Zhao D, et al: PPAR-gamma decreases endometrial stromal cell transcription and translation of RANTES in vitro. J Clin Endocrinol Metab 2002;87:1841–1844.
  10. Ohama Y, Harada T, et al: Peroxisome proliferator-activated receptor-gamma ligand reduced tumor necrosis factor-alpha-induced interleukin-8 production and growth in endometriotic stromal cells. Fertil Steril 2008;89:311–317.
  11. Hornung D, Waite LL, et al: Nuclear peroxisome proliferator-activated receptors alpha and gamma have opposing effects on monocyte chemotaxis in endometriosis. J Clin Endocrinol Metab 2001;86:3108–3114.
  12. Hornung D, Chao VA, et al: Thiazolidinedione inhibition of peritoneal inflammation. Gynecol Obstet Invest 2003;55:20–24.
  13. Giudice LC, Kao LC: Endometriosis. Lancet 2004;364:1789–1799.
  14. Giaginis C, Margeli A, et al: Peroxisome proliferator-activated receptor-gamma ligands as investigational modulators of angiogenesis. Expert Opin Investig Drugs 2007;16:1561–1572.
  15. Lebovic DI, Kir M, et al: Peroxisome proliferator-activated receptor-gamma induces regression of endometrial explants in a rat model of endometriosis. Fertil Steril 2004;82(suppl 3):1008–1013.
  16. Lebovic DI, Mwenda JM, et al: PPAR-gamma receptor ligand induces regression of endometrial explants in baboons: a prospective, randomized, placebo- and drug-controlled study. Fertil Steril 2007;88(suppl 4):1108–1119.

    External Resources

  17. Demirturk F, Aytan H, et al: Effect of peroxisome proliferator-activated receptor-gamma agonist rosiglitazone on the induction of endometriosis in an experimental rat model. J Soc Gynecol Investig 2006;13:58–62.
  18. Biberoglu KO, Behrman SJ: Dosage aspects of danazol therapy in endometriosis: short-term and long-term effectiveness. Am J Obstet Gynecol 1981;139:645–654.
  19. Melzack R: The short-form McGill Pain Questionnaire. Pain 1987;30:191–197.
  20. Nissen SE, Wolsk K: Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007;356:2457–2471.
  21. Yaris F, Yaris E, et al: Normal pregnancy outcome following inadvertent exposure to rosiglitazone, gliclazide, and atorvastatin in a diabetic and hypertensive woman. Reprod Toxicol 2004;18:619–621.
  22. Kalyoncu NI, Yaris F, et al: A case of rosiglitazone exposure in the second trimester of pregnancy. Reprod Toxicol 2005;19:563–564.
  23. Derosa G, Cicero AF, et al: Effects of 1 year of treatment with pioglitazone or rosiglitazone added to glimepiride on lipoprotein (a) and homocysteine concentrations in patients with type 2 diabetes mellitus and metabolic syndrome: a multicenter, randomized, double-blind, controlled clinical trial. Clin Ther 2006;28:679–688.
  24. Betteridge DJ: Effects of pioglitazone on lipid and lipoprotein metabolism. Diabetes Obes Metab 2007;9:640–647.
  25. Koninckx PR: Anti-TNF-α treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial. Hum Reprod 2008;9:2017–2023.

    External Resources

  26. Vercellini P, Somigliana E, et al: Endometriosis: current and future medical therapies. Best Pract Res Clin Obstet Gynaecol 2008;22:275–306.