Effect of cabergoline and metformin combination therapy in the treatment of infertile women with symptomatic endometrioma: comparison with cabergoline alone

Endometrioma is a prevalent manifestation of endometriosis and a common cause of infertility in women of reproductive age. This study aimed to evaluate the effectiveness of cabergoline alone versus in combination with metformin in infertile women with symptomatic endometrioma.

This randomized controlled trial was conducted in the Department of Reproductive Endocrinology and Infertility, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, from July 2022 to June 2023. This study included 50 women with clinically and sonologically diagnosed cases of endometrioma and dysmenorrhea attending the Reproductive Endocrinology and Infertility outpatient Department. Participants were assigned to two treatment groups: Group A (Cabergoline with metformin) and Group B (Cabergoline alone).

Baseline demographic and clinical characteristics were comparable between the groups. At 3 months, both groups showed significant reductions in pain scores (Group A: 5.38±2.52; Group B: 4.86±1.52) and endometrioma size (Group A: 1.11±0.75 cm; Group B: 0.72±1.10 cm), with slightly higher reductions in Group A. However, the differences were not statistically significant (p>0.05). Endometrioma size reduction was more pronounced in Group A (mean difference: 1.11 cm vs. 0.72 cm; effect size 1.26 vs. 0.75). Side effects were mild and comparable in both groups, with no statistically significant differences.

This study showed that both treatment regimens significantly improved pain and reduced endometrioma size, with no significant difference in outcomes between the groups. The combination of cabergoline and metformin may offer a slight advantage in reducing endometrioma size and improving fertility outcomes. Metrics

Khine YM, Taniguchi F, Harada T. Clinical management of endometriosis-associated infertility. Reprod Med Biol. 2016;15(4):21725. DOI: https://doi.org/10.1007/s12522-016-0237-9 Hamid AMSA, Omar SZ, Al-Hendy A, Samsuddin AR. 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 Delgado-Rosas F, Gómez R, Gaytán M, Morales C, Gutiérrez-Cañas I, Bellido C, et al. The effects of ergot and non-ergot-derived dopamine agonists in an experimental mouse model of endometriosis. Reproduction. 2011;142(5):745-55. DOI: https://doi.org/10.1530/REP-11-0223 Lebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril. 2001;75(1):1-10. DOI: https://doi.org/10.1016/S0015-0282(00)01630-7 May K, Becker CM. Endometriosis and angiogenesis. Minerva Ginecol. 2008;60(3):245-54. Enna SJ, Bylund DB. XPharm: The Comprehensive Pharmacology Reference. Amsterdam: Elsevier; 2008. Basu S, Nagy JA, Pal S, Vasile E, Eckelhoefer IA, Bliss VS, et al. The neurotransmitter dopamine inhibits angiogenesis induced by vascular permeability factor/vascular endothelial growth factor. Nat Med. 2001;7(5):569-74. DOI: https://doi.org/10.1038/87895 DiVasta AD, Srouji SS, Jensen J, Elia G, Lee H, Laufer MR. Nonhormonal therapy for endometriosis: a randomized, placebo-controlled, pilot study of cabergoline versus norethindrone acetate. F&S Rep. 2021;2(4):454-61. DOI: https://doi.org/10.1016/j.xfre.2021.07.003 Lord J, Wilkin T. Metformin in polycystic ovary syndrome. Curr Opin Obstet Gynecol. 2004;16(6):481-6. DOI: https://doi.org/10.1097/00001703-200412000-00008 Bruun JM, Pedersen SB, Richelsen B. Interleukin-8 production in human adipose tissue. Inhibitory effects of anti-diabetic compounds, the thiazolidinedione ciglitazone and the biguanide metformin. Horm Metab Res. 2000;32(11-12):537-41. DOI: https://doi.org/10.1055/s-2007-978682 Foda AA, Aal IA. Metformin as a new therapy for endometriosis, its effects on both clinical picture and cytokines profile. Middle East Fertil Soc J. 2012;17(4):262-7. DOI: https://doi.org/10.1016/j.mefs.2012.09.001 Cheng J, Huang Y, Liu Y, Wang S, Lin X, Jin Y, et al. Metformin alleviates endometriosis and potentiates endometrial receptivity via decreasing VEGF and MMP9 and increasing leukemia inhibitor factor and HOXA10. Front Pharmacol. 2022;13:750208. DOI: https://doi.org/10.3389/fphar.2022.750208 Kyama CM, Debrock S, Mwenda JM, D'Hooghe TM. Endometrial and peritoneal expression of aromatase, cytokines, and adhesion factors in women with endometriosis. Fertil Steril. 2008;89(2):301-10. DOI: https://doi.org/10.1016/j.fertnstert.2007.02.057 Hsieh Li S-M, Ho Y-H, Cheng Y-C, Sung P-H, Chang C-F, Chung S-Y, et al. Metformin causes cancer cell death through downregulation of p53-dependent differentiated embryo chondrocyte 1. J Biomed Sci. 2018;25(1):81. DOI: https://doi.org/10.1186/s12929-018-0478-5 Kyal A, Mandal S, Biswas R, Roy A. Does Cabergoline Help in Decreasing Chronic Pelvic Pain Due to Endometriosis Compared to Medroxyprogesterone Acetate: A Prospective Randomized Study. J South Asian Fed Obstet Gynaecol. 2019;10:167-9. DOI: https://doi.org/10.5005/jp-journals-10006-1582 Shume MM, Yehualashet FA, Mohammed AA, Abate BA. The Effects of Cabergoline Compared to Dienogest in Women with Symptomatic Endometrioma. Fertil Reprod. 2021;3(2):49-54. DOI: https://doi.org/10.1142/S2661318221500067 Takemura Y, Osuga Y, Yoshino O, Hasegawa A, Hirata T, Hirota Y, et al. Metformin suppresses interleukin (IL)-1beta-induced IL-8 production, aromatase activation, and proliferation of endometriotic stromal cells. J Clin Endocrinol Metab. 2007;92(8):3213-8. DOI: https://doi.org/10.1210/jc.2006-2486 Zhou Y, Zhao Y, Wang M, Zhao Y, Liu D, Li F, et al. Metformin suppresses prostaglandin E2-induced cytochrome P450 aromatase gene expression and activity via stimulation of AMP-activated protein kinase in human endometriotic stromal cells. Reprod Sci. 2015;22(9):1162-70. DOI: https://doi.org/10.1177/1933719115590664 Zhang H, Liu R, Zhang G, Wang L, Li L, Han L, et al. Metformin regulates stromal-epithelial cells communication via Wnt2/β-catenin signaling in endometriosis. Mol Cell Endocrinol. 2015;413:61-5. DOI: https://doi.org/10.1016/j.mce.2015.06.011