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Aromatase Expression in Endometriosis and Its Significance

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Endometriosis

Abstract

Endometriosis is a chronic inflammatory disease frequently observed in the ovary, pelvic peritoneum, and rectovaginal septum. The growth and progression of an endometriotic lesion depends on a sex steroid, estrogen. Aromatase, a key enzyme in estrogen biosynthesis, is highly expressed in the endometriotic tissue, resulting in in situ production of estrogen that, in addition to endocrine estrogen from the ovary, may contribute to the etiology and progression of endometriosis. The aberrant expression of aromatase together with the elevated expression of 17β-hydroxysteroid dehydrogenase type 1 and the absence of 17β-hydroxysteroid dehydrogenase type 2 observed in the endometriotic tissue would contribute to an increase in the tissue concentration of estrogen. Aromatase expression is regulated at multiple levels, from the transcription of CYP19A1 and epigenetic codes to posttranslational modification and degradation of the protein. Among the multiple promoters of CYP19A1, the most proximal promoter PII is the most active in endometriosis and is regulated by cAMP, prostaglandin E2, steroidogenic factor-1, and possibly the end product estrogen. Hypomethylation of CpG islands on CYP19A1 observed in the endometriotic tissue may contribute to the upregulation of aromatase expression.

Similar to spontaneous menopause, inhibition of in situ estrogen biosynthesis may regress endometriosis. The use of aromatase inhibitors (AIs), which selectively inhibit aromatase activity in human tissues, is a possible treatment for inhibiting local estrogen biosynthesis in endometriosis. AIs have been used as monotherapy or in combination therapies with progestins, oral contraceptive pills, and gonadotropin-releasing hormone agonists to reduce endometriosis-related pain in premenopausal women.

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References

  1. Simpson ER. Sources of estrogen and their importance. J Steroid Biochem Mol Biol. 2003;86(3–5):225–30.

    Article  CAS  PubMed  Google Scholar 

  2. Bulun SE, Sebastian S, Takayama K, Suzuki T, Sasano H, Shozu M. The human CYP19 (aromatase P450) gene: update on physiologic roles and genomic organization of promoters. J Steroid Biochem Mol Biol. 2003;86(3–5):219–24.

    Article  CAS  PubMed  Google Scholar 

  3. Bulun SE, Lin Z, Imir G, Amin S, Demura M, Yilmaz B, Martin R, Utsunomiya H, Thung S, Gurates B, Tamura M, Langoi D, Deb S. Regulation of aromatase expression in estrogen-responsive breast and uterine disease: from bench to treatment. Pharmacol Rev. 2005;57(3):359–83.

    Article  CAS  PubMed  Google Scholar 

  4. Izawa M, Inoue M, Osaki M, Ito H, Harada T, Terakawa N, Ikeguchi M. Cytochrome P450 aromatase gene (CYP19) expression in gastric cancer. Gastric Cancer. 2008;11(2):103–10.

    Article  CAS  PubMed  Google Scholar 

  5. Demura M, Demura Y, Ameshima S, Ishizaki T, Sasaki M, Miyamori I, Yamagishi M, Takeda Y, Bulun SE. Changes in aromatase (CYP19) gene promoter usage in non-small cell lung cancer. Lung Cancer. 2011;73(3):289–93.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Sato R, Suzuki T, Katayose Y, Miura K, Shiiba K, Miki Y, Kamogawa Y, Yamamoto K, Takayuki 2nd, Egawa S, Unno M, Sasano H. Aromatase in colon carcinoma. Anticancer Res. 2012;32(8):3069–75.

    Google Scholar 

  7. Mor G, Yue W, Santen RJ, Gutierrez L, Eliza M, Berstein LM, Harada N, Wang J, Lysiak J, Diano S, Naftolin F. Macrophages, estrogen and the microenvironment of breast cancer. J Steroid Biochem Mol Biol. 1998;67(5–6):403–11.

    Article  CAS  PubMed  Google Scholar 

  8. Kamat A, Hinshelwood MM, Murry BA, Mendelson CR. Mechanisms in tissue-specific regulation of estrogen biosynthesis in humans. Trends Endocrinol Metab. 2002;13(3):122–8.

    Article  CAS  PubMed  Google Scholar 

  9. Liu M, Ingle JN, Fridley BL, Buzdar AU, Robson ME, Kubo M, Wang L, Batzler A, Jenkins GD, Pietrzak TL, Carlson EE, Goetz MP, Northfelt DW, Perez EA, Williard CV, Schaid DJ, Nakamura Y, Weinshilboum RM. TSPYL5 SNPs: association with plasma estradiol concentrations and aromatase expression. Mol Endocrinol. 2013;27(4):657–70.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Simpson ER, Dowsett M. Aromatase and its inhibitors: significance for breast cancer therapy. Recent Prog Horm Res. 2002;57:317–38.

    Article  CAS  PubMed  Google Scholar 

  11. Ishikawa H, Reierstad S, Demura M, Rademaker AW, Kasai T, Inoue M, Usui H, Shozu M, Bulun SE. High aromatase expression in uterine leiomyoma tissues of African-American women. J Clin Endocrinol Metab. 2009;94(5):1752–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Verma MK, Miki Y, Sasano H. Aromatase in human lung carcinoma. Steroids. 2011;76(8):759–64.

    Article  CAS  PubMed  Google Scholar 

  13. Segawa T, Shozu M, Murakami K, Kasai T, Shinohara K, Nomura K, Ohno S, Inoue M. Aromatase expression in stromal cells of endometrioid endometrial cancer correlates with poor survival. Clin Cancer Res. 2005;11(6):2188–94.

    Article  CAS  PubMed  Google Scholar 

  14. Agarwal VR, Bulun SE, Leitch M, Rohrich R, Simpson ER. Use of alternative promoters to express the aromatase cytochrome P450 (CYP19) gene in breast adipose tissues of cancer-free and breast cancer patients. J Clin Endocrinol Metab. 1996;81(11):3843–9.

    CAS  PubMed  Google Scholar 

  15. Harada N, Matsumoto T, Yoshimura N, Sakamoto H, Honda S. Analysis of transcriptional regulation of human breast aromatase by in vitro and in vivo studies. J Steroid Biochem Mol Biol. 2001;79(1–5):151–6.

    Article  CAS  PubMed  Google Scholar 

  16. Szczepanska M, Wirstlein P, Skrzypczak J, Jagodzinski PP. Polymorphic variants of CYP17 and CYP19A and risk of infertility in endometriosis. Acta Obstet Gynecol Scand. 2013;92:1188–93.

    CAS  PubMed  Google Scholar 

  17. Lamp M, Peters M, Reinmaa E, Haller-Kikkatalo K, Kaart T, Kadastik U, Karro H, Metspalu A, Salumets A. Polymorphisms in ESR1, ESR2 and HSD17B1 genes are associated with fertility status in endometriosis. Gynecol Endocrinol. 2011;27(6):425–33.

    Article  CAS  PubMed  Google Scholar 

  18. Vietri MT, Cioffi M, Sessa M, Simeone S, Bontempo P, Trabucco E, Ardovino M, Colacurci N, Molinari AM, Cobellis L. CYP17 and CYP19 gene polymorphisms in women affected with endometriosis. Fertil Steril. 2009;92(5):1532–5.

    Article  CAS  PubMed  Google Scholar 

  19. Hur SE, Lee S, Lee JY, Moon HS, Kim HL, Chung HW. Polymorphisms and haplotypes of the gene encoding the estrogen-metabolizing CYP19 gene in Korean women: no association with advanced-stage endometriosis. J Hum Genet. 2007;52(9):703–11.

    Article  CAS  PubMed  Google Scholar 

  20. Huber A, Keck CC, Hefler LA, Schneeberger C, Huber JC, Bentz EK, Tempfer CB. Ten estrogen-related polymorphisms and endometriosis: a study of multiple gene-gene interactions. Obstet Gynecol. 2005;106(5):1025–31.

    Article  CAS  PubMed  Google Scholar 

  21. Wang HS, Wu HM, Cheng BH, Yen CF, Chang PY, Chao A, Lee YS, Huang HD, Wang TH. Functional analyses of endometriosis-related polymorphisms in the estrogen synthesis and metabolism-related genes. PLoS One. 2012;7(11):e47374.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Tsuchiya M, Nakao H, Katoh T, Sasaki H, Hiroshima M, Tanaka T, Matsunaga T, Hanaoka T, Tsugane S, Ikenoue T. Association between endometriosis and genetic polymorphisms of the estradiol-synthesizing enzyme genes HSD17B1 and CYP19. Hum Reprod. 2005;20(4):974–8.

    Article  CAS  PubMed  Google Scholar 

  23. Trabert B, Schwartz SM, Peters U, De Roos AJ, Chen C, Scholes D, Holt VL. Genetic variation in the sex hormone metabolic pathway and endometriosis risk: an evaluation of candidate genes. Fertil Steril. 2011;96(6):1401–6.e3.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Arvanitis DA, Koumantakis GE, Goumenou AG, Matalliotakis IM, Koumantakis EE, Spandidos DA. CYP1A1, CYP19, and GSTM1 polymorphisms increase the risk of endometriosis. Fertil Steril. 2003;79 Suppl 1:702–9.

    Article  PubMed  Google Scholar 

  25. Zhao H, Chen ZJ. Genetic association studies in female reproduction: from candidate-gene approaches to genome-wide mapping. Mol Hum Reprod. 2013;19(10):644–54.

    Google Scholar 

  26. Izawa M, Taniguchi F, Uegaki T, Takai E, Iwabe T, Terakawa N, Harada T. Demethylation of a nonpromoter cytosine-phosphate-guanine island in the aromatase gene may cause the aberrant up-regulation in endometriotic tissues. Fertil Steril. 2011;95(1):33–9.

    Article  CAS  PubMed  Google Scholar 

  27. van Kaam KJ, Delvoux B, Romano A, D’Hooghe T, Dunselman GA, Groothuis PG. Deoxyribonucleic acid methyltransferases and methyl-CpG-binding domain proteins in human endometrium and endometriosis. Fertil Steril. 2011;95(4):1421–7.

    Article  PubMed  Google Scholar 

  28. Izawa M, Harada T, Taniguchi F, Ohama Y, Takenaka Y, Terakawa N. An epigenetic disorder may cause aberrant expression of aromatase gene in endometriotic stromal cells. Fertil Steril. 2008;89(5 Suppl):1390–6.

    Article  CAS  PubMed  Google Scholar 

  29. Lee L, Asada H, Kizuka F, Tamura I, Maekawa R, Taketani T, Sato S, Yamagata Y, Tamura H, Sugino N. Changes in histone modification and DNA methylation of the StAR and Cyp19a1 promoter regions in granulosa cells undergoing luteinization during ovulation in rats. Endocrinology. 2013;154(1):458–70.

    Article  CAS  PubMed  Google Scholar 

  30. Kong YW, Ferland-McCollough D, Jackson TJ, Bushell M. MicroRNAs in cancer management. Lancet Oncol. 2012;13(6):e249–58.

    Article  CAS  PubMed  Google Scholar 

  31. Donadeu FX, Schauer SN, Sontakke SD. Involvement of miRNAs in ovarian follicular and luteal development. J Endocrinol. 2012;215(3):323–34.

    Article  CAS  PubMed  Google Scholar 

  32. Kumar P, Luo Y, Tudela C, Alexander JM, Mendelson CR. The c-Myc-regulated microRNA-17~92 (miR-17~92) and miR-106a ~ 363 clusters target hCYP19A1 and hGCM1 to inhibit human trophoblast differentiation. Mol Cell Biol. 2013;33(9):1782–96.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Panda H, Chuang TD, Luo X, Chegini N. Endometrial miR-181a and miR-98 expression is altered during transition from normal into cancerous state and target PGR, PGRMC1, CYP19A1, DDX3X, and TIMP3. J Clin Endocrinol Metab. 2012;97(7):E1316–26.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Shozu M, Sumitani H, Murakami K, Segawa T, Yang HJ, Inoue M. Regulation of aromatase activity in bone-derived cells: possible role of mitogen-activated protein kinase. J Steroid Biochem Mol Biol. 2001;79(1–5):61–5.

    Article  CAS  PubMed  Google Scholar 

  35. Charlier TD, Harada N, Balthazart J, Cornil CA. Human and quail aromatase activity is rapidly and reversibly inhibited by phosphorylating conditions. Endocrinology. 2011;152(11):4199–210.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Zhang B, Shozu M, Okada M, Ishikawa H, Kasai T, Murakami K, Nomura K, Harada N, Inoue M. Insulin-like growth factor I enhances the expression of aromatase P450 by inhibiting autophagy. Endocrinology. 2010;151(10):4949–58.

    Article  CAS  PubMed  Google Scholar 

  37. Wang H, Li R, Hu Y. The alternative noncoding exons 1 of aromatase (Cyp19) gene modulate gene expression in a posttranscriptional manner. Endocrinology. 2009;150(7):3301–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Noble LS, Takayama K, Zeitoun KM, Putman JM, Johns DA, Hinshelwood MM, Agarwal VR, Zhao Y, Carr BR, Bulun SE. Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells. J Clin Endocrinol Metab. 1997;82(2):600–6.

    CAS  PubMed  Google Scholar 

  39. Attar E, Tokunaga H, Imir G, Yilmaz MB, Redwine D, Putman M, Gurates B, Attar R, Yaegashi N, Hales DB, Bulun SE. Prostaglandin E2 via steroidogenic factor-1 coordinately regulates transcription of steroidogenic genes necessary for estrogen synthesis in endometriosis. J Clin Endocrinol Metab. 2009;94(2):623–31.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Bukulmez O, Hardy DB, Carr BR, Auchus RJ, Toloubeydokhti T, Word RA, Mendelson CR. Androstenedione up-regulation of endometrial aromatase expression via local conversion to estrogen: potential relevance to the pathogenesis of endometriosis. J Clin Endocrinol Metab. 2008;93(9):3471–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Velasco I, Rueda J, Acien P. Aromatase expression in endometriotic tissues and cell cultures of patients with endometriosis. Mol Hum Reprod. 2006;12(6):377–81.

    Article  CAS  PubMed  Google Scholar 

  42. Zeitoun KM, Bulun SE. Aromatase: a key molecule in the pathophysiology of endometriosis and a therapeutic target. Fertil Steril. 1999;72(6):961–9.

    Article  CAS  PubMed  Google Scholar 

  43. Zeitoun K, Takayama K, Sasano H, Suzuki T, Moghrabi N, Andersson S, Johns A, Meng L, Putman M, Carr B, Bulun SE. Deficient 17beta-hydroxysteroid dehydrogenase type 2 expression in endometriosis: failure to metabolize 17beta-estradiol. J Clin Endocrinol Metab. 1998;83(12):4474–80.

    CAS  PubMed  Google Scholar 

  44. Delvoux B, Groothuis P, D'Hooghe T, Kyama C, Dunselman G, Romano A. Increased production of 17beta-estradiol in endometriosis lesions is the result of impaired metabolism. J Clin Endocrinol Metab. 2009;94(3):876–83.

    Article  CAS  PubMed  Google Scholar 

  45. Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–79.

    Article  CAS  PubMed  Google Scholar 

  46. Kitawaki J, Kado N, Ishihara H, Koshiba H, Kitaoka Y, Honjo H. Endometriosis: the pathophysiology as an estrogen-dependent disease. J Steroid Biochem Mol Biol. 2002;83(1–5):149–55.

    Article  CAS  PubMed  Google Scholar 

  47. Bulun SE, Zeitoun KM, Takayama K, Sasano H. Estrogen biosynthesis in endometriosis: molecular basis and clinical relevance. J Mol Endocrinol. 2000;25(1):35–42.

    Article  CAS  PubMed  Google Scholar 

  48. Smuc T, Pucelj MR, Sinkovec J, Husen B, Thole H, Lanisnik Rizner T. Expression analysis of the genes involved in estradiol and progesterone action in human ovarian endometriosis. Gynecol Endocrinol. 2007;23(2):105–11.

    Article  CAS  PubMed  Google Scholar 

  49. Dassen H, Punyadeera C, Kamps R, Delvoux B, Van Langendonckt A, Donnez J, Husen B, Thole H, Dunselman G, Groothuis P. Estrogen metabolizing enzymes in endometrium and endometriosis. Hum Reprod. 2007;22(12):3148–58.

    Article  CAS  PubMed  Google Scholar 

  50. Lu B, Jiang YJ, Choy PC. 17-Beta estradiol enhances prostaglandin E2 production in human U937-derived macrophages. Mol Cell Biochem. 2004;262(1–2):101–10.

    Article  CAS  PubMed  Google Scholar 

  51. Tamura M, Deb S, Sebastian S, Okamura K, Bulun SE. Estrogen up-regulates cyclooxygenase-2 via estrogen receptor in human uterine microvascular endothelial cells. Fertil Steril. 2004;81(5):1351–6.

    Article  CAS  PubMed  Google Scholar 

  52. Pellegrini C, Gori I, Achtari C, Hornung D, Chardonnens E, Wunder D, Fiche M, Canny GO. The expression of estrogen receptors as well as GREB1, c-MYC, and cyclin D1, estrogen-regulated genes implicated in proliferation, is increased in peritoneal endometriosis. Fertil Steril. 2012;98(5):1200–8.

    Article  CAS  PubMed  Google Scholar 

  53. Matsuzaki S, Murakami T, Uehara S, Canis M, Sasano H, Okamura K. Expression of estrogen receptor alpha and beta in peritoneal and ovarian endometriosis. Fertil Steril. 2001;75(6):1198–205.

    Article  CAS  PubMed  Google Scholar 

  54. Smuc T, Hevir N, Ribic-Pucelj M, Husen B, Thole H, Rizner TL. Disturbed estrogen and progesterone action in ovarian endometriosis. Mol Cell Endocrinol. 2009;301(1–2):59–64.

    Article  CAS  PubMed  Google Scholar 

  55. Trukhacheva E, Lin Z, Reierstad S, Cheng YH, Milad M, Bulun SE. Estrogen receptor (ER) beta regulates ERalpha expression in stromal cells derived from ovarian endometriosis. J Clin Endocrinol Metab. 2009;94(2):615–22.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Velasco I, Acien P, Campos A, Acien MI, Ruiz-Macia E. Interleukin-6 and other soluble factors in peritoneal fluid and endometriomas and their relation to pain and aromatase expression. J Reprod Immunol. 2010;84(2):199–205.

    Article  CAS  PubMed  Google Scholar 

  57. Veillat V, Sengers V, Metz CN, Roger T, Leboeuf M, Mailloux J, Akoum A. Macrophage migration inhibitory factor is involved in a positive feedback loop increasing aromatase expression in endometriosis. Am J Pathol. 2012;181(3):917–27.

    Article  CAS  PubMed  Google Scholar 

  58. Xue Q, Lin Z, Yin P, Milad MP, Cheng YH, Confino E, Reierstad S, Bulun SE. Transcriptional activation of steroidogenic factor-1 by hypomethylation of the 5' CpG island in endometriosis. J Clin Endocrinol Metab. 2007;92(8):3261–7.

    Article  CAS  PubMed  Google Scholar 

  59. Santen RJ, Harvey HA. Use of aromatase inhibitors in breast carcinoma. Endocr Relat Cancer. 1999;6(1):75–92.

    Article  CAS  PubMed  Google Scholar 

  60. Miller WR, Stuart M, Sahmoud T, Dixon JM. Anastrozole ('Arimidex') blocks oestrogen synthesis both peripherally and within the breast in postmenopausal women with large operable breast cancer. Br J Cancer. 2002;87(9):950–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Petit T, Dufour P, Tannock I. A critical evaluation of the role of aromatase inhibitors as adjuvant therapy for postmenopausal women with breast cancer. Endocr Relat Cancer. 2011;18(3):R79–89.

    Article  CAS  PubMed  Google Scholar 

  62. Gibson L, Lawrence D, Dawson C, Bliss J. Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Cochrane Database Syst Rev. 2009;4:CD003370.

    PubMed  Google Scholar 

  63. Turkistani A, Marsh S. Pharmacogenomics of third-generation aromatase inhibitors. Expert Opin Pharmacother. 2012;13(9):1299–307.

    Article  CAS  PubMed  Google Scholar 

  64. Pavone ME, Bulun SE. Aromatase inhibitors for the treatment of endometriosis. Fertil Steril. 2012;98(6):1370–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Lintermans A, Neven P, Paridaens R. Drug safety evaluation of exemestane. Expert Opin Drug Saf. 2011;10(3):473–87.

    Article  CAS  PubMed  Google Scholar 

  66. Buzdar AU. Pharmacology and pharmacokinetics of the newer generation aromatase inhibitors. Clin Cancer Res. 2003;9(1 Pt 2):468S–72472.

    CAS  PubMed  Google Scholar 

  67. Gluck S. Exemestane as first-line therapy in postmenopausal women with recurrent or metastatic breast cancer. Am J Clin Oncol. 2010;33(3):314–9.

    PubMed  Google Scholar 

  68. Lonning PE. Oestrogen suppression–lessons from clinical studies. Best Pract Res Clin Endocrinol Metab. 2004;18(1):33–45.

    Article  CAS  PubMed  Google Scholar 

  69. Puhalla S, Brufsky A, Davidson N. Adjuvant endocrine therapy for premenopausal women with breast cancer. Breast. 2009;18 Suppl 3:S122–30.

    Article  PubMed Central  PubMed  Google Scholar 

  70. Badawy A, Elnashar A, Totongy M. Clomiphene citrate or aromatase inhibitors for superovulation in women with unexplained infertility undergoing intrauterine insemination: a prospective randomized trial. Fertil Steril. 2009;92(4):1355–9.

    Article  PubMed  Google Scholar 

  71. Bundred NJ. Aromatase inhibitors and bone health. Curr Opin Obstet Gynecol. 2009;21(1):60–7.

    Article  PubMed  Google Scholar 

  72. Amir E, Seruga B, Niraula S, Carlsson L, Ocana A. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst. 2011;103(17):1299–309.

    Article  CAS  PubMed  Google Scholar 

  73. Takayama K, Zeitoun K, Gunby RT, Sasano H, Carr BR, Bulun SE. Treatment of severe postmenopausal endometriosis with an aromatase inhibitor. Fertil Steril. 1998;69(4):709–13.

    Article  CAS  PubMed  Google Scholar 

  74. Hefler LA, Grimm C, van Trotsenburg M, Nagele F. Role of the vaginally administered aromatase inhibitor anastrozole in women with rectovaginal endometriosis: a pilot study. Fertil Steril. 2005;84(4):1033–6.

    Article  CAS  PubMed  Google Scholar 

  75. Alborzi S, Hamedi B, Omidvar A, Dehbashi S, Alborzi M. A comparison of the effect of short-term aromatase inhibitor (letrozole) and GnRH agonist (triptorelin) versus case control on pregnancy rate and symptom and sign recurrence after laparoscopic treatment of endometriosis. Arch Gynecol Obstet. 2011;284(1):105–10.

    Article  CAS  PubMed  Google Scholar 

  76. Verma A, Konje JC. Successful treatment of refractory endometriosis-related chronic pelvic pain with aromatase inhibitors in premenopausal patients. Eur J Obstet Gynecol Reprod Biol. 2009;143(2):112–5.

    Article  CAS  PubMed  Google Scholar 

  77. Ailawadi RK, Jobanputra S, Kataria M, Gurates B, Bulun SE. Treatment of endometriosis and chronic pelvic pain with letrozole and norethindrone acetate: a pilot study. Fertil Steril. 2004;81(2):290–6. doi:10.1016/j.fertnstert.2003.09.029.

    Article  CAS  PubMed  Google Scholar 

  78. Shippen ER, West Jr WJ. Successful treatment of severe endometriosis in two premenopausal women with an aromatase inhibitor. Fertil Steril. 2004;81(5):1395–8.

    Article  PubMed  Google Scholar 

  79. Ferrero S, Camerini G, Seracchioli R, Ragni N, Venturini PL, Remorgida V. Letrozole combined with norethisterone acetate compared with norethisterone acetate alone in the treatment of pain symptoms caused by endometriosis. Hum Reprod. 2009;24(12):3033–41.

    Article  CAS  PubMed  Google Scholar 

  80. Amsterdam LL, Gentry W, Jobanputra S, Wolf M, Rubin SD, Bulun SE. Anastrozole and oral contraceptives: a novel treatment for endometriosis. Fertil Steril. 2005;84(2):300–4.

    Article  CAS  PubMed  Google Scholar 

  81. Lall Seal S, Kamilya G, Mukherji J, De A, Ghosh D, Majhi AK. Aromatase inhibitors in recurrent ovarian endometriomas: report of five cases with literature review. Fertil Steril. 2011;95(1):291.e15–8.

    Google Scholar 

  82. Soysal S, Soysal ME, Ozer S, Gul N, Gezgin T. The effects of post-surgical administration of goserelin plus anastrozole compared to goserelin alone in patients with severe endometriosis: a prospective randomized trial. Hum Reprod. 2004;19(1):160–7.

    Article  PubMed  Google Scholar 

  83. Ferrero S, Venturini PL, Gillott DJ, Remorgida V. Letrozole and norethisterone acetate versus letrozole and triptorelin in the treatment of endometriosis related pain symptoms: a randomized controlled trial. Reprod Biol Endocrinol. 2011;9:88.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. 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(2):305–9.

    Article  CAS  PubMed  Google Scholar 

  85. Pavone ME, Bulun SE. Clinical review: the use of aromatase inhibitors for ovulation induction and superovulation. J Clin Endocrinol Metab. 2013;98(5):1838–44.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  86. He D, Jiang F. Meta-analysis of letrozole versus clomiphene citrate in polycystic ovary syndrome. Reprod Biomed Online. 2011;23(1):91–6.

    Article  CAS  PubMed  Google Scholar 

  87. Samani FG, Farzadi L, Nezami N, Tarzamni MK, Soleimani F. Endometrial and follicular development following letrozole intervention in unexplained infertile patients failed to get pregnant with clomiphene citrate. Arch Gynecol Obstet. 2009;280(2):201–5.

    Article  CAS  PubMed  Google Scholar 

  88. Fouda UM, Sayed AM. Extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing intrauterine insemination: a randomized controlled trial. Reprod Biol Endocrinol. 2011;9:84.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  89. Abu Hashim H, El Rakhawy M, Abd Elaal I. Randomized comparison of superovulation with letrozole vs. clomiphene citrate in an IUI program for women with recently surgically treated minimal to mild endometriosis. Acta Obstet Gynecol Scand. 2012;91(3):338–45.

    Article  CAS  PubMed  Google Scholar 

  90. Tulandi T, Martin J, Al-Fadhli R, Kabli N, Forman R, Hitkari J, Librach C, Greenblatt E, Casper RF. Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril. 2006;85(6):1761–5.

    Article  CAS  PubMed  Google Scholar 

  91. Sasson IE, Taylor HS. Aromatase inhibitor for treatment of a recurrent abdominal wall endometrioma in a postmenopausal woman. Fertil Steril. 2009;92(3):1170.e1–4.

    Article  Google Scholar 

  92. Oxholm D, Knudsen UB, Kryger-Baggesen N, Ravn P. Postmenopausal endometriosis. Acta Obstet Gynecol Scand. 2007;86(10):1158–64.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan

    Hiroshi Ishikawa M.D., Ph.D. & Makio Shozu M.D., Ph.D.

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  1. Hiroshi Ishikawa M.D., Ph.D.
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Correspondence to Makio Shozu M.D., Ph.D. .

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  1. Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, Yonago, Tottori, Japan

    Tasuku Harada

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Ishikawa, H., Shozu, M. (2014). Aromatase Expression in Endometriosis and Its Significance. In: Harada, T. (eds) Endometriosis. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54421-0_11

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  • DOI: https://doi.org/10.1007/978-4-431-54421-0_11

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  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-54420-3

  • Online ISBN: 978-4-431-54421-0

  • eBook Packages: MedicineMedicine (R0)

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