Fertility and Sterility
Volume 93, Issue 1 , Pages 192-198 , 1 January 2010

A randomized, controlled clinical trial comparing the effects of aromatase inhibitor (letrozole) and gonadotropin-releasing hormone agonist (triptorelin) on uterine leiomyoma volume and hormonal status

  • Mohammad Ebrahim Parsanezhad, M.D.

      Affiliations

    • Department of Gynecology and Obstetrics, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
    • Corresponding Author InformationReprint requests: Mohammad Ebrahim Parsanezhad, M.D., Division of Infertility and Gynecologic Endoscopy, Department of Obstetrics and Gynecology, Shiraz University of Medical Sciences, P.O. Box 71345-1657, Shiraz, Iran (FAX: 98-711-229-6486).
  • ,
  • Mina Azmoon

      Affiliations

    • Department of Gynecology and Obstetrics, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
  • ,
  • Saeed Alborzi, M.D.

      Affiliations

    • Department of Gynecology and Obstetrics, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
  • ,
  • Abdoreza Rajaeefard

      Affiliations

    • Department of Statistical Sciences, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
  • ,
  • Afsun Zarei, M.D.

      Affiliations

    • Department of Gynecology and Obstetrics, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
  • ,
  • Talieh Kazerooni, M.D.

      Affiliations

    • Department of Gynecology and Obstetrics, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
  • ,
  • Vivian Frank, M.D.

      Affiliations

    • Gynecologic Endoscopy Division, Diako Teaching Center of Göttingen University, Bremen, Germany
  • ,
  • Ernst Hienrich Schmidt, M.D.

      Affiliations

    • Gynecologic Endoscopy Division, Diako Teaching Center of Göttingen University, Bremen, Germany

Received 13 May 2008 ,Revised 16 September 2008 ,Accepted 19 September 2008.

References 

  1. Cheng MH, Wang PH. Uterine myoma: a condition amenable to medical therapy?. Expert Opin Emerg Drugs. 2008;13:119–133
  2. Haney AF. Clinical decision making regarding leiomyomata: what we need in the next millennium. Environ Health Perspect. 2000;108(Suppl 5):835–839
  3. Brandon DD, Erickson TE, Keenan EJ, Strawn EY, Novy MJ, Burry KA, et al. Estrogen receptor gene expression in human uterine leiomyomata. J Clin Endocrinol Metab. 1995;80:1876–1881
  4. Bulun SE, Simpson ER, Word RA. Expression of the CYP19 gene and its product aromatase cytochrome P450 in human uterine leiomyoma tissues and cells in culture. J Clin Endocrinol Metab. 1994;78:736–743
  5. Sumitani H, Shozu M, Segawa T, Murakami K, Yang HJ, Shimada K, et al. In situ estrogen synthesized by aromatase P450 in uterine leiomyoma cells promotes cell growth probably via an autocrine/intracrine mechanism. Endocrinology. 2000;141:3852–3861
  6. Gabb RG, Stone GM. Uptake and metabolism of tritiated oestradiol and oestrone by human endometrial and myometrial tissue in vitro. J Endocrinol. 1974;62:109–123
  7. Pollow K, Sinnecker G, Boquoi E, Pollow B. In vitro conversion of estradiol-17beta into estrone in normal human myometrium and leiomyoma. J Clin Chem Clin Biochem. 1978;16:493–502
  8. Eiletz J, Genz T, Pollow K, Schmidt-Gollwitzer M. Sex steroid levels in serum, myometrium, and fibromyomata in correlation with cytoplasmic receptors and 17 beta-HSD activity in different age-groups and phases of the menstrual cycle. Arch Gynecol. 1980;229:13–28
  9. Newton CJ, James VH. 17 beta-hydroxysteroid dehydrogenase activity in leiomyoma and myometrium and its relationship to concentrations of oestrone, oestradiol and progesterone throughout the menstrual cycle. J Steroid Biochem. 1985;22:487–493
  10. Bulun SE, Imir G, Utsunomiya H, Thung S, Gurates B, Tamura M, et al. Aromatase in endometriosis and uterine leiomyomata. J Steroid Biochem Mol Biol. 2005;95:57–62
  11. Wallach EE, Vlahos NF. Uterine myomas: an overview of development, clinical features, and management. Obstet Gynecol. 2004;104:393–406
  12. Lepine LA, Hillis SD, Marchbanks PA, Koonin LM, Morrow B, Kieke BA, et al. Hysterectomy surveillance—United States, 1980–1993. MMWR CDC Surveill Summ. 1997;46:1–15
  13. Stewart EA. Uterine fibroids. Lancet. 2001;357:293–298
  14. Donnez J, Jadoul P. What are the implications of myomas on fertility? A need for a debate?. Hum Reprod. 2002;17:101–107
  15. Myers ER, Goodwin S, Landow W, Mauro M, Peterson E, Pron G, et al. Prospective data collection of a new procedure by a specialty society: the FIBROID registry. Obstet Gynecol. 2005;106:44–51
  16. Smart OC, Hindley JT, Regan L, Gedroyc WG. Gonadotropin releasing hormone and magnetic-resonance guided ultrasound surgery for uterine leiomyoma. Obstet Gynecol. 2006;108:49–54
  17. Dickner SK, Cooper JM, Diaz D. A nonincisional, Doppler-guided transvaginal approach to uterine artery identification and control of uterine perfusion. J Am Assoc Gynecol Laparosc. 2004;11:55–58
  18. Vilos GA, Vilos EC, Romano W, Abu-Rafea B. Temporary uterine artery occlusion for treatment of menorrhagia and uterine fibroids using an incisionless Doppler-guided transvaginal clamp: case report. Hum Reprod. 2006;21:269–271
  19. De Leo V, la Marca A, Morgante G. Short-term treatment of uterine fibromyomas with danazol. Gynecol Obstet Invest. 1999;47:258–262
  20. De Leo V, Morgante G, La Marca A, Musacchio MC, Sorace M, Cavicchioli C, et al. A benefit-risk assessment of medical treatment for uterine leiomyomas. Drug Saf. 2002;25:759–779
  21. Palomba S, Sammartino A, Di Carlo C, Affinito P, Zullo F, Nappi C. Effects of raloxifene treatment on uterine leiomyomas in postmenopausal women. Fertil Steril. 2001;76:38–43
  22. 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;87:1502–1508
  23. Friedman AJ, Rein MS, Harrison-Atlas D, Garfield JM, Doubilet PM. A randomized, placebo controlled, double-blind study evaluating leuprolide acetate depot treatment before myomectomy. Fertil Steril. 1989;52:728–733
  24. Fedele L, Vercellini P, Bianchi S, Brioschi D, Dorta M. Treatment with GnRH agonists before myomectomy and the risk of short term myoma recurrence. Br J Obstet Gynaecol. 1990;97:393–396
  25. Shaw RW. Mechanism of LHRH analogue action in uterine fibroids. Horm Res. 1989;32(Suppl 1):150–153
  26. Golan A, Bukovsky I, Pansky M, Schneider D, Weinraub Z, Caspi E. Pre-operative gonadotrophin-releasing hormone agonist treatment in surgery for uterine leiomyomata. Hum Reprod. 1993;8:450–452
  27. Zullo F, Pellicano M, De Stefano R, Zupi E, Mastrantonio P. A prospective randomized study to evaluate leuprolide acetate treatment before laparoscopic myomectomy: efficacy and ultrasonographic predictors. Am J Obstet Gynecol. 1998;178:108–112
  28. Campo S, Garcea N. Laparoscopic myomectomy in premenopausal women with and without preoperative treatment using gonadotrophin-releasing hormone analogues. Hum Reprod. 1999;14:44–48
  29. Stovall TG, Muneyyirci-Delale O, Summitt RL, Scialli AR. GnRH agonist and iron versus placebo and iron in the anemic patient before surgery for leiomyomas: a randomized controlled trial. Leuprolide Acetate Study Group. Obstet Gynecol. 1995;86:65–71
  30. Hornstein MD, Surrey ES, Weisberg GW, Casino LA. Leuprolide acetate depot and hormonal add-back in endometriosis: a 12-month study. Lupron Add-Back Study Group. Obstet Gynecol. 1998;91:16–24
  31. Shozu M, Murakami K, Segawa T, Kasai T, Inoue M. Successful treatment of a symptomatic uterine leiomyoma in a perimenopausal woman with a nonsteroidal aromatase inhibitor. Fertil Steril. 2003;79:628–631
  32. Bozzini N, Rodrigues CJ, Petti DA, Bevilacqua RG, Goncalves SP, Pinotti JA. Effects of treatment with treatment with gonadotropin releasing hormone agonist on the uterine leiomyomata structure. Acta Obstet Gynecol Scand. 2003;82:330–334
  33. Adamson GD. Treatment of uterine fibroids: current findings with gonadotropin releasing hormone agonist. Am J Obstet Gynecol. 1992;166:746–751
  34. Perry CM, Brogden RN, Goserelin . A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in benign gynaecological disorders. Drugs. 1996;51:319–346
  35. Sumitani H, Shozu M, Segawa T, Murakami K, Yang H-J, Shimada K, et al. In situ estrogen synthesized by aromatase P450 in uterine leiomyoma cells promotes cell growth probably via an autocrine/intracrine mechanism. Endocrinology. 2000;141:3852–3861
  36. Pasqualini JR, Cornier E, Grenier J, Vella C, Schatz B, Netter A. Effect of decapeptyl, an agonistic analog of gonadotropin-releasing hormone on estrogens, estrogen sulfates, and progesterone receptors in leiomyoma and myometrium. Fertil Steril. 1990;53:1012–1017
  37. Shozu M, Murakami K, Inoue M. Aromatase and leiomyoma of the uterus. Semin Reprod Med. 2004;22:51–60
  38. Shozu M, Murakami K, Segawa T, Kasai T, Inoue M. Successful treatment of a symptomatic uterine leiomyoma in a perimenopausal woman with a nonsteroidal aromatase inhibitor. Fertile Steril. 2003;79:628–631
  39. Iveson TJ, Smith IE, Ahern J, Smithers DA, Trunet PF, Dowsett M. Phase I study of the oral nonsteroidal aromatase inhibitor CGS 20267 in postmenopausal patients with advanced breast cancer. Cancer Res. 1993;53:266–270
  40. Harding SG, Pesce A, McMillan L. Symptomatic ascites complicating GnRH analogue use for myoma shrinkage. Br J Obstet Gynaecol. 1993;100:1054–1056
  41. Friedman AJ. Acute urinary retention after gonadotropin-releasing hormone agonist treatment for leiomyomata uteri. Fertil Steril. 1993;59:677–678
  42. Hansen LM, Batzer FR, Corson SL, Bello S. Obesity and GnRH action. Report of a case with contribution by peripherally derived estrogens. J Reprod Med. 1997;42:247–250
  43. Shozu M, Sumitani H, Segawa T, Yang HJ, Murakami K, Kasai T, et al. Over-expression of aromatase P-450 in leiomyoma tissues is driven through the promoter I.4 of aromatase P-450. J Clin Endocrinol Metab. 2002;87:2540–2548
  44. Mitwally MF, Casper RF. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril. 2001;75:305–309

 M.E.P. has nothing to disclose. M.A. has nothing to disclose. S.A. has nothing to disclose. A.R. has nothing to disclose. A.Z. has nothing to disclose. T.K. has nothing to disclose. V.F. has nothing to disclose. E.H.S. has nothing to disclose.

PII: S0015-0282(08)04057-0

doi: 10.1016/j.fertnstert.2008.09.064

Fertility and Sterility
Volume 93, Issue 1 , Pages 192-198 , 1 January 2010