Comparison of the effects of gonadotropin-releasing hormone and raloxifeneon the size of uterine leiomyoma

Farnaz Zandvakili, Fariba Seyedoshohadaie, Masoumeh Rezaiee, Nasrin Soofizade, Fariba Farhadifar, Ebrahim Ghaderi

DOI: 10.22122/cdj.v2i1.82


BACKGROUND: Uterine leiomyoma is a prevalent benign tumor. Several studies have shown the positive effects of raloxifene in the treatment of leiomyomas. Since raloxifene has fewer side effects than the gonadotropin-releasing hormone (GnRH) agonist, if proven effective, it can be applied easily. This study aimed to compare the medical effects of raloxifene and GnRH on uterine leiomyoma size.

METHODS: This clinical trial included 53 women with uterine leiomyoma. Participants were randomly divided into 2 groups of raloxifene and GnRH. The GnRH group received 1 dose per month (intramuscular injection) and the raloxifene group received 60 mg raloxifene orally/day for 3 months. The size of the leiomyoma, prior and during the intervention, was determined by a sonographist. During the study, repeated measurement was used for comparing the trend of alterations in the tumor size.

RESULTS: Analysis of changes in leiomyoma tumor size (log of tumor size) by repeated measurement showed that decrease in tumor size in the raloxifene group was significantly higher than GnRH group (P = 0.042). The trends of changes in endometrial thickness were different in the 2 groups and the reduction of thickness was more significant in the GnRH group (P = 0.026).

CONCLUSION: This study showed that raloxifene is an appropriate medicine to reduce the size of uterine leiomyoma and is more effective than GnRH.



Uterus, Leiomyoma, Gonadotropin-Releasing Hormone, Raloxifene

Full Text:



Stewart EA. Uterine fibroids. Lancet 2001; 357(9252): 293-8.

Cox S, Werner C, Hoffman B. Williams Obstetrics. 22nd ed. New York, NY: McGraw-Hill Companies, Incorporated; 2005.

Sheiner E, Bashiri A, Levy A, Hershkovitz R, Katz M, Mazor M. Obstetric characteristics and perinatal outcome of pregnancies with uterine leiomyomas. J Reprod Med 2004; 49(3): 182-6.

Sabry M, Al-Hendy A. Innovative oral treatments of uterine leiomyoma. Obstet Gynecol Int 2012; 2012: 943635.

Palomba S, Falbo A, Russo T, Zullo F. GnRH analogs

for the treatment of symptomatic uterine leiomyomas. Gynecological Surgery 2005; 2(1): 7-13.

Requena A, Herrero J, Landeras J, Navarro E, Neyro JL, Salvador C, et al. Use of letrozole in assisted reproduction: a systematic review and meta-analysis. Hum Reprod Update 2008; 14(6): 571-82.

Gurates B, Parmaksiz C, Kilic G, Celik H, Kumru S, Simsek M. Treatment of symptomatic uterine leiomyoma with letrozole. Reprod Biomed Online 2008; 17(4): 569-74.

Fuchs-Young R, Glasebrook AL, Short LL, Draper MW, Rippy MK, Cole HW, et al. Raloxifene is a tissue-selective agonist/antagonist that functions through the estrogen receptor. Ann N Y Acad Sci 1995; 761: 355-60.

Porter KB, Tsibris JC, Porter GW, Fuchs-Young R, Nicosia SV, O'Brien WF, et al. Effects of raloxifene in a guinea pig model for leiomyomas. Am J Obstet Gynecol 1998; 179(5): 1283-7.

Lethaby AE, Vollenhoven BJ. An evidence-based approach to hormonal therapies for premenopausal women with fibroids. Best Pract Res Clin Obstet Gynaecol 2008; 22(2): 307-31.

Sankaran S, Manyonda IT. Medical management of fibroids. Best Pract Res Clin Obstet Gynaecol 2008; 22(4): 655-76.

Pickersgill A. GnRH agonists and add-back therapy: is there a perfect combination? Br J Obstet Gynaecol 1998; 105(5): 475-85.

Adashi EY. Long-term gonadotrophin-releasing hormone agonist therapy: the evolving issue of steroidal 'add-back' paradigms. Hum Reprod 1994; 9(7): 1380-97.

Mosca L. Rationale and overview of the Raloxifene Use for the Heart (RUTH) trial. Ann N Y Acad Sci 2001; 949: 181-5.

Barrett-Connor E, Grady D, Sashegyi A, Anderson PW, Cox DA, Hoszowski K, et al. Raloxifene and cardiovascular events in osteoporotic postmenopausal women: four-year results from the MORE (Multiple Outcomes of Raloxifene Evaluation) randomized trial. JAMA 2002; 287(7): 847-57.

Goldstein SR, Scheele WH, Rajagopalan SK, Wilkie JL, Walsh BW, Parsons AK. A 12-month comparative study of raloxifene, estrogen, and placebo on the postmenopausal endometrium. Obstet Gynecol 2000; 95(1): 95-103.

Clemett D, Spencer CM. Raloxifene: a review of its use in postmenopausal osteoporosis. Drugs 2000; 60(2): 379-411.

Palomba S, Orio F, Morelli M, Russo T, Pellicano M, Zupi E, et al. Raloxifene administration in premenopausal women with uterine leiomyomas: a pilot study. J Clin Endocrinol Metab 2002; 87(8):3603-8.

Palomba S, Orio F, Jr., Morelli M, Russo T, Pellicano M, Nappi C, et al. Raloxifene administration in women treated with gonadotropin-releasing hormone agonist for uterine leiomyomas: effects on bone metabolism. J Clin Endocrinol Metab 2002; 87(10): 4476-81.

Deng L, Wu T, Chen XY, Xie L, Yang J. Selective estrogen receptor modulators (SERMs) for uterine leiomyomas. Cochrane Database Syst Rev 2012; 10: CD005287.

Olive DL, Lindheim SR, Pritts EA. Non-surgical management of leiomyoma: impact on fertility. Curr Opin Obstet Gynecol 2004; 16(3): 239-43.

Shozu M, Sumitani H, Segawa T, Yang HJ, Murakami K, Inoue M. Inhibition of in situ expression of aromatase P450 in leiomyoma of the uterus by leuprorelin acetate. J Clin Endocrinol Metab 2001; 86(11): 5405-11.

Palomba S, Russo T, Orio F, Sammartino A, Sbano FM, Nappi C, et al. Lipid, glucose and homocysteine metabolism in women treated with a GnRH agonist with or without raloxifene. Hum Reprod 2004; 19(2): 415-21.

Boss SM, Huster WJ, Neild JA, Glant MD, Eisenhut CC, Draper MW. Effects of raloxifene hydrochloride on the endometrium of postmenopausal women. Am J Obstet Gynecol 1997; 177(6): 1458-64.

Premkumar A, Venzon DJ, Avila N, Johnson DV, Remaley AT, Forman MR, et al. Gynecologic and hormonal effects of raloxifene in premenopausal women. Fertil Steril 2007; 88(6): 1637-44.

Palomba S, Orio F, Russo T, Falbo A, Cascella T, Doldo P, et al. Long-term effectiveness and safety of GnRH agonist plus raloxifene administration in women with uterine leiomyomas. Hum Reprod 2004; 19(6): 1308-14.

Palomba S, Sammartino A, Di CC, Affinito P, Zullo F, Nappi C. Effects of raloxifene treatment on uterine leiomyomas in postmenopausal women. Fertil Steril 2001; 76(1): 38-43.

Jirecek S, Lee A, Pavo I, Crans G, Eppel W, Wenzl R. Raloxifene prevents the growth of uterine leiomyomas in premenopausal women. Fertil Steril 2004; 81(1): 132-6.

Hansdottir H. Raloxifene for older women: a review of the literature. Clin Interv Aging 2008; 3(1): 45-50.

Sumino H, Ichikawa S, Kasama S, Takahashi T, Kumakura H, Takayama Y, et al. Effects of raloxifene and hormone replacement therapy on forearm skin elasticity in postmenopausal women. Maturitas 2009; 62(1): 53-7.


  • There are currently no refbacks.

Creative Commons Attribution-NonCommercial 4.0

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.