Efficacy of melatonin and letrozole combination therapy compared to letrozole alone in the treatment of symptomatic endometrioma in infertile women
DOI:
https://doi.org/10.18203/2320-1770.ijrcog20252709Keywords:
Endometrioma, Endometriosis, Letrozole, Melatonin, Infertile womenAbstract
Background: Endometriosis is an estrogen-driven inflammatory condition involving endometrial tissue growth outside the uterus. Letrozole, an aromatase inhibitor, lowers estrogen levels to reduce pain and lesion size. Melatonin offers additional benefits through its antioxidant, anti-inflammatory, and anti-proliferative effects on endometrial tissue. The present study was conducted to compare the effects of a combination of melatonin and letrozole with letrozole alone in infertile women with symptomatic endometrioma.
Methods: This randomized controlled trial was conducted in the Department of Reproductive Endocrinology and Infertility of Bangabandhu Sheikh Mujib Medical University from July, 2023 to June, 2024. Total 40 infertile women with symptomatic endometrioma were included in this study. They were randomly allocated to receive either tab. letrozole 2.5 mg, twice daily plus tab. melatonin 3mg, 3 tablets at night daily or only tab. letrozole 2.5 mg, twice daily for 3 months.
Results: Mean VAS score (6.88±2.39 vs 2.64±1.96) and mean size of endometrioma (3.77±1.22 vs 3.05±1.17 cm) were significantly decreased after 3 months of treatment with melatonin and letrozole combination therapy and mean VAS score (7.11±1.81 vs 3.22±1.89) and mean size of endometrioma (3.81±1.00 cm vs 3.27±0.85) were also significantly decreased after 3 months of treatment with letrozole alone group .But there were no statistically significant difference in terms of reducing pain score and size of endometrioma when compared between two groups.
Conclusions: Melatonin and letrozole combination therapy compared to letrozole alone provide similar efficacy on symptomatic endometrioma in terms of reduction of pain score and size of endometrioma.
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References
Khine YM, Taniguchi F, Harada T. Clinical management of endometriosis-associated infertility. Reprod Med Biol. 2016;15(4):217-25. DOI: https://doi.org/10.1007/s12522-016-0237-9
Hamid AMSA, Madkour WAI, Moawad A, AbdElzaher M, Roberts MP. Does cabergoline help in decreasing endometrioma size compared to LHRH agonist? A prospective randomized study. Arch Gynecol Obstet. 2014;290(4):677-82. DOI: https://doi.org/10.1007/s00404-014-3242-4
Alborzi S, Keramati P, Younesi M, Samsami A, Dadras N. The impact of laparoscopic cystectomy on ovarian reserve in patients with unilateral and bilateral endometriomas. Fertil Steril. 2014;101(2):427-34. DOI: https://doi.org/10.1016/j.fertnstert.2013.10.019
Gurates B, Bulun SE. Endometriosis: the ultimate hormonal disease. Semin Reprod Med. 2003;21(2):125-34. DOI: https://doi.org/10.1055/s-2003-41319
Zeitoun K, Takayama K, Sasano H, Suzuki T, Moghrabi N, Andersson S, et al. Deficient 17β-hydroxysteroid dehydrogenase type 2 expression in endometriosis: failure to metabolize 17β-estradiol. J Clin Endocrinol Metab. 1998;83(12):4474-80. DOI: https://doi.org/10.1210/jc.83.12.4474
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 Relat Cancer. 1999;6(2):293-301. DOI: https://doi.org/10.1677/erc.0.0060293
Reiter RJ, Calvo JR, Karbownik M, Qi W, Tan DX. Melatonin and its relation to the immune system and inflammation. Ann N Y Acad Sci. 2000;917(1):376-86. DOI: https://doi.org/10.1111/j.1749-6632.2000.tb05402.x
Schwertner A, Dos Santos CCC, Costa GD, Deitos A, de Souza A, de Souza ICC, et al. Efficacy of melatonin in the treatment of endometriosis: a phase II, randomized, double-blind, placebo-controlled trial. Pain. 2013;154(6):874-81. DOI: https://doi.org/10.1016/j.pain.2013.02.025
Söderman L, Böttiger Y, Edlund M, Järnbert-Pettersson H, Marions L. Adjuvant use of melatonin for pain management in endometriosis-associated pelvic pain-A randomized double-blinded, placebo-controlled trial. PLoS One. 2023;18(6):e0286182. DOI: https://doi.org/10.1371/journal.pone.0286182
Esposito E, Paterniti I, Mazzon E, Bramanti P, Cuzzocrea S. Melatonin reduces hyperalgesia associated with inflammation. J Pineal Res. 2010;49(4):321-31. DOI: https://doi.org/10.1111/j.1600-079X.2010.00796.x
Stefani LC, Muller S, Torres IL, Razzolini B, Rozisky JR, Fregni F, et al. A phase II, randomized, double-blind, placebo-controlled, dose-response trial of the melatonin effect on the pain threshold of healthy subjects. PLoS One. 2013;8(10):e74107. DOI: https://doi.org/10.1371/journal.pone.0074107
Yildirim G, Attar R, Fıçıcıoğlu C, Karateke A, Özkan F, Kılıç E, et al. The combination of letrozole and melatonin causes regression in size not histopathological scores on endometriosis in an experimental rat model. J Turk Ger Gynecol Assoc. 2009;10(4):199-204.
Yildirim G, Attar R, Ozkan F, Kumbak B, Ficicioglu C, Yesildaglar N. The effects of letrozole and melatonin on surgically induced endometriosis in a rat model: a preliminary study. Fertil Steril. 2010;93(6):1787-92. DOI: https://doi.org/10.1016/j.fertnstert.2009.09.021
Yilmaz B, Kilic S, Aksakal O, Ertas IE, Tanrisever GG, Aksoy Y, et al. Melatonin causes regression of endometriotic implants in rats by modulating angiogenesis, tissue levels of antioxidants and matrix metalloproteinases. Arch Gynecol Obstet. 2015;292:209-16. DOI: https://doi.org/10.1007/s00404-014-3599-4
Guney M, Oral B, Karahan N, Mungan T. Regression of endometrial explants in a rat model of endometriosis treated with melatonin. Fertil Steril. 2008;89(4):934-42. DOI: https://doi.org/10.1016/j.fertnstert.2007.04.023
Cetinkaya N, Attar R, Yildirim G, Ficicioglu C, Ozkan F, Yilmaz B, et al. The effects of different doses of melatonin treatment on endometrial implants in an oophorectomized rat endometriosis model. Arch Gynecol Obstet. 2015;291(3):591-8. DOI: https://doi.org/10.1007/s00404-014-3466-3
Madny EH. Efficacy of letrozole in treatment of endometriosis-related pain. Middle East Fertil Soc J. 2014;19(1):64-8. DOI: https://doi.org/10.1016/j.mefs.2013.04.007
Amir M, Ishrat S, Nasrin I, Halder S, Rahman F, Hossain MRZ. Letrozole versus dienogest in endometrioma recurrent after surgery: a randomized controlled trial. Int J Reprod Contracept Obstet Gynecol. 2022;11(10):2715-22. DOI: https://doi.org/10.18203/2320-1770.ijrcog20222371
Razzi S, Fava A, Sartini A, De Simone S, Cobellis L, Petraglia F. Treatment of severe recurrent endometriosis with an aromatase inhibitor in a young ovariectomised woman. BJOG. 2004;111(2):182-4. DOI: https://doi.org/10.1046/j.1471-0528.2003.00038.x
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. DOI: https://doi.org/10.1016/j.fertnstert.2005.04.059
Koninckx PR, Craessaerts M, Timmerman D, Cornillie F, Kennedy S. Anti-TNF-α treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial. Hum Reprod. 2008;23(9):2017-23. DOI: https://doi.org/10.1093/humrep/den177