title: Potential role of aromatase inhibitors in the treatment of endometriosis.
abstract: Endometriosis is an estrogen-dependent chronic inflammatory disease affecting 5%-10% of reproductive-age women, with a prevalence of 5%-50% in infertile women and >33% of women with chronic pelvic pain. Third-generation aromatase inhibitors (AIs) are approved adjuvants for the treatment of estrogen receptor-positive breast cancer. Molecular studies have revealed the presence of aromatase P450, the key enzyme in the biosynthesis of ovarian estradiol, inside the endometriotic tissue, indicating local synthesis of estradiol. Thereby, AIs represent an appealing medical option for the management of different aspects of this enigmatic disease, especially pelvic pain and infertility. Accordingly, this review aims to evaluate the potential role of AIs in the treatment of endometriosis-associated symptoms, mainly pain and infertility. Notably, several studies have demonstrated that the combination of AIs with conventional therapy as oral contraceptive pills, progestins, or gonadotropin-releasing hormone analogs can be used to control endometriosis-associated pain and pain recurrence in premenopausal women, particularly those with pain due to rectovaginal endometriosis refractory to other medical or surgical treatment. Some case reports have shown promising results in the treatment of postmenopausal endometriosis as first-line treatment, when surgery is contraindicated, or as second-line treatment in the case of postoperative recurrence. Third-generation AIs, especially letrozole, have challenged clomiphene citrate as an ovulation-induction agent in patients with polycystic ovary syndrome and in cases of unexplained infertility. However, few studies are available regarding the use of AIs to treat endometriosis-associated infertility. Therefore, larger multicenter randomized trials using AIs for the treatment of endometriosis-associated infertility are needed to clarify its effect. The safety of AIs for ovulation induction or superovulation has generated a lively discussion. Data from recent retrospective and prospective studies have supported its safety.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: Hatem
authors.initials: H
authors.lastname: Abu Hashim
keywords: anastrozole; aromatase inhibitors; endometriosis; infertility; letrozole; pelvic pain
references.citation: Am J Obstet Gynecol. 2005 Feb;192(2):381-6
references.pmid: 15695975
references.citation: Am J Surg. 1955 Aug;90(2):331-7
references.pmid: 13238688
references.citation: Hum Reprod Update. 2012 May-Jun;18(3):301-12
references.pmid: 22431566
references.citation: J Natl Cancer Inst. 2006 Sep 20;98(18):1285-91
references.pmid: 16985247
references.citation: Fertil Steril. 2012 Sep;98(3):511-9
references.pmid: 22819144
references.citation: Hum Reprod Update. 2000 Sep-Oct;6(5):413-8
references.pmid: 11045871
references.citation: Hum Reprod. 2004 Jan;19(1):160-7
references.pmid: 14688176
references.citation: BJOG. 2008 Jun;115(7):818-22
references.pmid: 18485158
references.citation: Reprod Biol Endocrinol. 2011 Jun 21;9:87
references.pmid: 21693036
references.citation: Gynecol Obstet Invest. 2006;62(3):121-30
references.pmid: 16675908
references.citation: Aust N Z J Obstet Gynaecol. 2007 Jun;47(3):222-5
references.pmid: 17550490
references.citation: Lancet. 2005 Aug 6-12;366(9484):455-62
references.pmid: 16084253
references.citation: Obstet Gynecol. 2007 Jun;109(6):1421-3
references.pmid: 17540816
references.citation: Fertil Steril. 2006 Sep;86(3):566-71
references.pmid: 16952506
references.citation: Acta Obstet Gynecol Scand. 2004 Apr;83(4):395-400
references.pmid: 15005789
references.citation: Reprod Biol Endocrinol. 2011 Jun 21;9:90
references.pmid: 21693039
references.citation: Am J Obstet Gynecol. 2007 Apr;196(4):391.e1-7; discussion 391.e7-8
references.pmid: 17403431
references.citation: Fertil Steril. 2009 Sep;92(3):1170.e1-1170.e4
references.pmid: 19591983
references.citation: Arch Gynecol Obstet. 2012 Jun;285(6):1737-45
references.pmid: 22392485
references.citation: Fertil Steril. 2005 Aug;84(2):300-4
references.pmid: 16084868
references.citation: Reprod Biol Endocrinol. 2011 Jun 21;9:84
references.pmid: 21693030
references.citation: Fertil Steril. 1998 Apr;69(4):709-13
references.pmid: 9548162
references.citation: Fertil Steril. 2008 Aug;90(2):247-57
references.pmid: 18672121
references.citation: Eur J Obstet Gynecol Reprod Biol. 2005 Feb 1;118(2):265-6
references.pmid: 15653219
references.citation: Fertil Steril. 2008 Oct;90(4):1199.e9-11
references.pmid: 17953943
references.citation: Fertil Steril. 2008 Nov;90(5):2004.e7-9
references.pmid: 18555228
references.citation: J Clin Endocrinol Metab. 2006 Mar;91(3):760-71
references.pmid: 16384846
references.citation: Hum Reprod. 2009 Dec;24(12):3033-41
references.pmid: 19726448
references.citation: Fertil Steril. 2004 May;81(5):1395-8
references.pmid: 15136110
references.citation: Obstet Gynecol. 1993 Nov;82(5):780-6
references.pmid: 8414326
references.citation: Fertil Steril. 1997 May;67(5):817-21
references.pmid: 9130884
references.citation: BJOG. 2004 Feb;111(2):182-4
references.pmid: 14723761
references.citation: Fertil Steril. 2005 Oct;84(4):1033-6
references.pmid: 16213868
references.citation: Acta Obstet Gynecol Scand. 2009;88(2):187-91
references.pmid: 19089782
references.citation: N Engl J Med. 2010 Jun 24;362(25):2389-98
references.pmid: 20573927
references.citation: Fertil Steril. 2006 Jun;85(6):1761-5
references.pmid: 16650422
references.citation: Fertil Steril. 2001 Feb;75(2):305-9
references.pmid: 11172831
references.citation: Clin Cancer Res. 1998 Sep;4(9):2089-93
references.pmid: 9748124
references.citation: Drugs. 2009 May 29;69(8):943-52
references.pmid: 19496625
references.citation: Gynecol Endocrinol. 2009 Nov;25(11):762-4
references.pmid: 19903055
references.citation: Fertil Steril. 1990 Dec;54(6):1083-8
references.pmid: 2245833
references.citation: Eur J Obstet Gynecol Reprod Biol. 2009 May;144(1):48-53
references.pmid: 19261371
references.citation: Fertil Steril. 2004 Feb;81(2):290-6
references.pmid: 14967362
references.citation: Reprod Biol Endocrinol. 2011 Jun 21;9:88
references.pmid: 21693037
references.citation: Reprod Biol Endocrinol. 2011 Jun 21;9:89
references.pmid: 21693038
references.citation: Obstet Gynecol. 2010 Jul;116(1):223-236
references.pmid: 20567196
references.citation: Arch Gynecol Obstet. 2011 Jul;284(1):105-10
references.pmid: 20661580
references.citation: Am J Obstet Gynecol. 1971 Apr 15;109(8):1137-44
references.pmid: 5554845
references.citation: J Obstet Gynaecol Can. 2007 Aug;29(8):668-71
references.pmid: 17714621
references.citation: Acta Obstet Gynecol Scand. 2007 Oct;86(10):1158-64
references.pmid: 17851817
references.citation: Fertil Steril. 2009 Sep;92(3):858-859
references.pmid: 17588568
references.citation: Cochrane Database Syst Rev. 2007 Jul 18;(3):CD000155
references.pmid: 17636607
references.citation: Fertil Steril. 2006 Feb;85(2):277-84
references.pmid: 16595197
references.citation: Maturitas. 2003 Nov 20;46(3):239-41
references.pmid: 14585528
references.citation: Fertil Steril. 2012 Dec;98(6):1370-9
references.pmid: 22999792
references.citation: Fertil Steril. 2007 Sep;88(3):724-6
references.pmid: 17331508
references.citation: Fertil Steril. 2008 Nov;90(5 Suppl):S260-9
references.pmid: 19007642
references.citation: Fertil Steril. 1997 Jul;68(1):8-12
references.pmid: 9207576
references.citation: Fertil Steril. 2006 May;85(5):1307-18
references.pmid: 16647373
references.citation: N Engl J Med. 2009 Jan 15;360(3):268-79
references.pmid: 19144942
references.citation: Hum Reprod. 2014 Mar;29(3):400-12
references.pmid: 24435778
references.citation: Reprod Biomed Online. 2005 Oct;11(4):455-7
references.pmid: 16274608
references.citation: Eur J Obstet Gynecol Reprod Biol. 1980 Dec;11(3):195-200
references.pmid: 7194811
references.citation: Clin Breast Cancer. 2004 Sep;5 Suppl 1:S6-S12
references.pmid: 15347433
references.citation: Clin Obstet Gynecol. 2010 Jun;53(2):389-96
references.pmid: 20436315
references.citation: J Clin Endocrinol Metab. 2013 May;98(5):1838-44
references.pmid: 23585659
references.citation: Semin Reprod Med. 2010 Jan;28(1):44-50
references.pmid: 20108182
references.citation: Cochrane Database Syst Rev. 2010 Jan 20;(1):CD001398
references.pmid: 20091519
references.citation: Acta Obstet Gynecol Scand. 2012 Mar;91(3):338-45
references.pmid: 22181973
references.citation: Am J Obstet Gynecol. 1997 Mar;176(3):572-9
references.pmid: 9077609
references.citation: J Minim Invasive Gynecol. 2011 Jul-Aug;18(4):419-27
references.pmid: 21620779
references.citation: Curr Opin Obstet Gynecol. 2010 Aug;22(4):289-94
references.pmid: 20592587
references.citation: J Clin Oncol. 2003 Nov 1;21(21):4042-57
references.pmid: 12963702
references.citation: J Clin Endocrinol Metab. 1981 Aug;53(2):412-7
references.pmid: 7251819