Evaluation of the effect of aromatase inhibitor in reducing the size of endometrioma


  • Selina Afroz Ansary Junior Consultant, OSD (DGH, Mhakhali) Attachment, Department of Reproductive Endocrinology and Infertility, BSMMU, Dhaka, Bangladesh
  • Shakeela Ishrat Department of Reproductive Endocrinology and Infertility, BSMMU, Dhaka, Bangladesh
  • Jesmine Banu Department of Reproductive Endocrinology and Infertility, BSMMU, Dhaka, Bangladesh
  • Parveen Fatima Department of Reproductive Endocrinology and Infertility, BSMMU, Dhaka, Bangladesh
  • Faria Nasreen National Institute of Nuclear Medicine and Allied Sciences (NINMAS), Dhaka, Bangladesh
  • Israt Jahan Junior Consultant, OSD (DGH, Mhakhali) Attachment, Department of Reproductive Endocrinology and Infertility, BSMMU, Dhaka, Bangladesh
  • Shajia Afrin Junior Consultant, OSD (DGH, Mhakhali) Attachment, Department of Reproductive Endocrinology and Infertility, BSMMU, Dhaka, Bangladesh
  • Khaleda Nasreen Junior Consultant, OSD (DGH, Mhakhali) Attachment, Department of Reproductive Endocrinology and Infertility, BSMMU, Dhaka, Bangladesh
  • Mohammad Mohsin Department of Critical Care Medicine, OSD (DGHS, Mohakhali), Attachment-Dhaka Medical College, Bangladesh




Aromatase inhibitor, Endometrioma


Background: Endometriosis is a chronic and progressive estrogen-dependent disorder that can result in substantial morbidity, including pelvic pain, multiple operations, and infertility. Endometriosis can be ovarian, peritoneal or deep infiltrative. Blocking estrogen production by inhibiting aromatization, aromatase inhibitor (letrozole) has been shown to reduce the size of endometrioma and endometriosis associated pain. Aim of the study was to evaluate the effect of aromatase inhibitor in reducing the size of endometrioma.

Methods: A prospective non comparative observational study was conducted in the Department of Reproductive Endocrinology and Infertility of BSMMU on 30 women with ovarian endometrioma during the period of April 2019 to March 2020. Women were treated with aromatase inhibitor (letrozole) 2.5 mg, norethisterone 5 mg, calcium 1200 mg, and vitamin D 800 IU daily for 6 months. Transvaginal ultrasound was performed at baseline, 3 months and 6 months after treatment to assess the mean diameter and volume of endometriomas. Statistical analyses were carried out by using the Statistical Package for Social Sciences version 23.0.

Results: More than 50% reduction in volume occurred in 90% of endometrioma. In one (3.3%) case endometrioma disappeared completely after 6 months. There was statistically significant reduction of size of endometrioma (estimated by mean diameter and volume) and pain. Volume decrease was linearly related to baseline endometrioma volume and inversely related to baseline body mass index (BMI). The side effects were mild and well tolerated by the patients.

Conclusions: Treatment of ovarian endometrioma with aromatase inhibitor combined with progestin add-back for 6 months cause substantial reduction in size of endometrioma and associated pain.


Vercellini P, Viganò P, Somigliana E, Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2014;10(5):261-75.

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

Adamson GD, Pasta DJ. 2010. Endometriosis fertility index: the new, validated endometriosis staging system. Fertil Steril. 2010;94(5):1609-15.

Giudice LC, Kao L. Endometriosis. Lancet. 2004;364(1):1789-99.

Busacca M, Vignali M. Ovarian endometriosis: from pathogenesis to surgical treatment. Curr Opin Obstet Gynecol. 2003;15(4):321-6.

Sanchez AM, Viganò P, Somigliana E, Panina-Bordignon P, Vercellini P, Candiani M. The distinguishing cellular and molecular features of the endometriotic ovarian cyst: from pathophysiology to the potential endometrioma-mediated damage to the ovary. Hum Reprod Update. 2014;20(2):217-30.

Bulun SE, Zeitoun K, Takayama K, Noble L, Michael D, Simpson E, et al. Estrogen production in endometriosis and use of aromatase inhibitors to treat endometriosis. Endocr Rel Cancer. 1999;6(2):293-301.

Noble LS, Takayama K, Zeitoun KM, Putman JM, Johns DA, Hinshelwood MM, et al. 1997. Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells. J Clin Endocrinol Metab. 1997;82(2):600-6.

Sun HS, Hsiao KY, Hsu CC, Wu MH, Tsai SJ, 2003. Transactivation of steroidogenic acute regulatory protein in human endometriotic stromal cells is mediated by the prostaglandin EP2 receptor. Endocrinology. 2003;144(9):3934-42.

Attar E, Bulun SE, 2006b. Aromatase inhibitors: the next generation of therapeutics for endometriosis? Fertil Steril. 2006;85(5):1307-18.

Zeitoun K, Takayama K, Sasano H, Suzuki T, Moghrabi N, Andersson S, et al. 1998. Deficient 17β-hydroxysteroid dehydrogenase type 2 expression in endometriosis: failure to metabolize 17β-estradiol. J Clin Endocrinol Metab. 1998;83(12):4474-80.

Agarwal SK, Foster WG. Reduction in endometrioma size with three months of aromatase inhibition and progestin add-back. Bio Med Res Int. 2015;2015.

Ferrero S, Remorgida V, Venturini PL, Maggiore ULR. Norethisterone acetate versus norethisterone acetate combined with letrozole for the treatment of ovarian endometriotic cysts: a patient preference study. Eur J Obstet Gynecol Reprod Biol. 2014;174:117-22.

Seal SL, 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):291-315.

Vignali M, Belloni GM, Pietropaolo G, Barbasetti Di Prun A, Barbera V, et al. Effect of dienogest therapy on the size of the endometrioma. Gynecol Endocrinol. 2020;36(8):723-7.

Taniguchi F, Enatsu A, Ota I, Toda T, Arata K, Harada T. Effects of low dose oral contraceptive pill containing drospirenone/ethinylestradiol in patients with endometrioma. Eur J Obstet Gynecol Reprod Biol. 2015;191:116-20.

Xholli A, Filip G, Previtera F, Cagnacci A. 2019s. Modification of endometrioma size during hormone therapy containing dienogest. Gynecol Endocrinol. 2019;36(6):545-9.

Osteen KG, Igarashi TM, Bruner-Tran KL. 2003. Progesterone action in the human endometrium: induction of a unique tissue environment which limits matrix metalloproteinase (MMP) expression. Front Biosci. 2003;8(1):78-86.

Mousa NA, Bedaiwy MA, Casper RF. Aromatase inhibitors in the treatment of severe endometriosis. Obstet Gynecol. 2007;109(6):1421-3.

Taniguchi F, Enatsu A, Ikebuchi A, Yamane E, Moriyama M, Murakami J, et al. Efficacy of norethisterone in patients with ovarian endometrioma. Yonago Acta Medica. 2017;60(3):182-5.

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.

Remorgida V, Abbamonte HL, Ragni N, Fulcheri E, Ferrero S. Letrozole and norethisterone acetate in rectovaginal endometriosis. Fertil Steril. 2007;88(3):724-6.

Chwalisz K, Surrey E, Stanczyk FZ. The hormonal profile of norethindrone acetate: rationale for add-back therapy with gonadotropin-releasing hormone agonists in women with endometriosis. Reprod Sci. 2012;19(6):563-71.

Practice Committee of the American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis: a committee opinion. Fertil Steril. 2014;101(4):927-35.

Franke HR, van de Weijer PH, Pennings TM, van der Mooren MJ. Gonadotropin-releasing hormone agonist plus “add-back” hormone replacement therapy for treatment of endometriosis: a prospective, randomized, placebo-controlled, double-blind trial. Fertil Steril. 2000;74(3):534-9.

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

Razzi S, Fava A, Sartini A, De Simone S, Cobellis L. Petraglia F. 2004. Treatment of severe recurrent endometriosis with an aromatase inhibitor in a young ovariectomised woman. BJOG. 2004;111(2):182-4.

Fatemi HM, Al-Turki HA, Papanikolaou EG, Kosmas L, De Sutter P, Devroey P. Successful treatment of an aggressive recurrent post-menopausal endometriosis with an aromatase inhibitor. Reprod Biomed Online. 2005;11(4):455-7.

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.

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

Remorgida V, Abbamonte HL, Ragni N, Fulcheri E, Ferrero S. Letrozole and desogestrel-only contraceptive pill for the treatment of stage IV endometriosis. ANZ J Obstet Gynaecol. 2007;47(3):222-5.

Madny EH. 2014. Efficacy of letrozole in treatment of endometriosis-related pain. Middle East Fertil Soc J. 2014;19:64-8.

Verma A, Konje JC. 2009. 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.

Muneyyirci-Delale O, Anopa J, Charles C, Mathur D, Parris R, Cutler JB, Salame G, Abulafia O. Medical management of recurrent endometrioma with long-term norethindrone acetate. Int J Wom Health. 2012;4:149.

Del Forno S, Mabrouk M, Arena A, Mattioli G, Giaquinto I, Paradisi R, Seracchioli R. 2019. Dienogest or Norethindrone acetate for the treatment of ovarian endometriomas: Can we avoidsurgery? Eur J Obstet Gynecol Reprod Biol. 2019;238:120-4.

Abushahin F, Goldman KN, Barbieri E, Milad M, Rademaker A, Bulun SE. 2011. Aromatase inhibition for refractory endometriosis-related chronic pelvic pain. Fertil Steril. 2011;96(4):939-42.

Badawy AM, Elnashar AM, Mosbah AA. 2012. Aromatase inhibitors or gonadotropin-releasing hormone agonists for the management of uterine adenomyosis: a randomized controlled trial. Nordic feder Soc Obstet Gynecol. 2012;91:489-95.

Polyzos NP, Fatemi HM, Zavos A, Grimbizis G, Kyrou D, Velasco JG, et al. Aromatase inhibitors in post-menopausal endometriosis. Reprod Biol Endocrinol. 2011;9(1):90.

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

Buzdar AU. 2004. The ATAC (Arimidex®, Tamoxifen, alone or in combination) trial: an update. Clin Breast Cancer. 2004;5:6-12.

Jakesz R, Jonat W, Gnant M, Mittlboeck M, Greil R, Tausch C, et al. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet. 2005;366(9484):455-62.

Hillner BE, Ingle JN, Chlebowski RT, Gralow J, Yee GC, Janjan NA, et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol. 2003;21(21):4042-57.

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






Original Research Articles