Tamoxifen for treatment of abnormal uterine bleeding in etonorgstrel implant users: a randomized clinical trial
DOI:
https://doi.org/10.18203/2320-1770.ijrcog20194876Keywords:
Abnormal uterine bleeding, Contraception, Family planning, Implants, Oral contraceptives, TamoxifenAbstract
Background: The current study aims to compare the use of tamoxifen and oral contraceptive pills in women using implanon and complain with irregular uterine bleeding.
Methods: Women attended family planning clinic using implanon presented by bleeding were invited to participate in the study. They were randomized into two groups: Group A: 100 women received Tamoxifen 10 mg twice daily for 10 days taken at the onset of an episode of bleeding or spotting episode. Group B: 100 women received Combined oral contraceptive pills (microcept) once daily for 21 days take at the onset of an episode of bleeding or spotting episode.
Results: No difference regarding the baseline criteria of both groups. No difference between both groups regarding the duration of irregular bleeding in the implanon users (p=0.090). Additionally, the number of bleeding days and spotting in the last month was similar in both groups (p=0.554). The percentage of women who stopped bleeding during the period of treatment is 84% in the tamoxifen group and 92% in the COCs group, but the COCs needs longer treatment time, where the mean of days required to stop bleeding is 5.03±1.8 days in the tamoxifen group and 6.5±2.5 in the COCs group. Headache and nausea were the most prominent adverse effects found in the COCs group (p=0.000).
Conclusions: Oral administration of tamoxifen 10 mg twice daily for 10 days is effective on stopping bleeding attacks in implanon users.
References
Abdel-Aleem H, d'Arcangues C, Gaffield KMV, Gülmezogl AM. Treatment of vaginal bleeding irregularities induced by progestin only contraceptives. Cochrane Database Syst Rev. 2013;10:1002-465.
Petra M, CaseyMargaret E, LongMary L, MarnachJessica EB. Bleeding related to etonogestrel subdermal implant in a US population. Contracept. 2011;83:426-30.
Curtis KM, Tepper NK, Jatlaoui TC, Berry-Bibee E, Horton LG, Zapata LB, et al. U.S. selected practice recommendations for contraceptive use; 2016;65:1-66.
Speroff L, Darney PD. A clinical guide for contraception. Lippincott Williams and Wilkins; 2010.
ESHRE Capri Workshop Group. Ovarian and endometrial function during hormonal contraception. Human Reprod. 2001;16(7):1527-35.
Kaneshiro B, Edelman A, Dash C, Pandhare J, Soli FM, Jensen JT. Effect of oral contraceptives and doxycycline on endometrial MMP-2 and MMP-9 activity. Contracept. 2016;93:65-9
Winner B, Peipert JF, Zhao Q, Buckel C, Madden T, Allsworth JE, et al. Effectiveness of long-acting reversible contraception. N Engl J Med. 2012;21: 366.
Branum AM, Jones J. Trends in long-acting reversible contraception use among U.S. women aged 15-44. NCHS Data Brief. 2015;188:1-8.
Balogun OR, Olaomo N, Adeniran AS, Fawole AA. Implanon subdermal implant: an emerging method of contraception in Ilorin.2014:3:1–5.
[10] Spring LM, Gupta A, Reynolds KL, Gadd MA, Ellisen LW, Isakoff SJ, et al. Neoadjuvant endocrine therapy for estrogen receptor-positive breast cancer. A systematic review and meta-analysis. JAMA Oncol. 2016;2:1477-86.
Hu R, Hilakivi-Clarke L, Clarke R. Molecular mechanisms of tamoxifen-associated endometrial cancer. Oncology Letters. 2015;9(4):1495-501.
Simmons KB, Edelman AB, Fu R, Jensen JT. Tamoxifen for the treatment of breakthrough bleeding with the etonogestrel implant: a randomized controlled trial. Contracept. 2017;2:198-204.
Bacon JL. Abnormal uterine bleeding: current classification and clinical management. Obstet Gynecol Clin North America. 2017;44:179-93.
American College of Obstetricians and Gynecologists. ACOG committee opinion no. 557: Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women. Obstet Gynecol. 2013;121:891.
Hou MY, McNicholas C, Creinin MD. Combined oral contraceptive treatment for bleeding complaints with the etonogestrel contraceptive implant: a randomized controlled trial. Eu J Contracept Repro Health Care. 2016;15:1-6.
Sordal T, Inki P, Draeby J, O'Flynn M, Schmelter T. Management of initial bleeding or spotting after levonorgestrel-releasing intrauterines system placement: a randomized controlled trial. Obstet Gynecol. 2013;121:934-41.
Diaz S, Croxatto HB, Pavez M, Belhadj H, Stern J, Sivin I. Clinical assessment of treatments for prolonged bleeding in users of Norplantn implants. Contracept. 1990;42:97-109.
Tantiwattanakul P, Taneepanichskul S. Effect of mefenamic acid on controlling irregular uterine bleeding in DMPA users. Contracept. 2004:70:277-9.
Subakir SB, Setiadi E, Affandi B, Pringgoutomo S, Freisleben HJ. Benefits of vitamin E supplementation to Norplant users in vitro and in vivo studies. Toxicol. 2000;148:173-8
Grow DR, Reece MT. The role of selective estrogen receptor modulators in the treatment of endometrial bleeding in women using long-acting progestin contraception. Hum Reprod. 2000;15:1-6.
Williams RF, Kloosterboer JH, Verbost PM, Hodgen GD. Once monthly antiprogestin controls menstrual bleeding during progestin- only contraception in primates. J Soc Gynecol Investig. 1997;4:134A.
Lindner DJ, Borden EC. Effects of tamoxifen and interferon-beta or the combination on tumor-induced angiogenesis. Int J Cancer. 1997;71:456-1.
Gagliardi A, Collins DC. Inhibition of angiogenesis by antiestrogens. Cancer Res. 1993;53:533-5.
Patriarca MT, Simoes RD, Smaniotto S. Morphological action of tamoxifen in the endometrium of persistent estrous rats. Acta Obstet Gynecol Scand. 1996;75:707-10.
Cohen I, Beyth Y, Altaras MM. Estrogen and progesterone receptor expression in postmenopausal tamoxifen-exposed endometrial pathologies. Gynecol Oncol. 1997;67:8-15.
Hickey M, Fraser IS. Surface vascularization and endometrial appearance in women with menorrhagia or using levonorgestrel contraceptive implants. Implications for the mechanisms of break- through bleeding. Hum Reprod. 2002;17:2428-34.
Critchley H, Brenner RM, Henderson TA, Williams K, Nayak NR, Slayden OD. Estrogen receptor beta, but not estrogen receptor alpha, is present in the vascular endothelium of the human and nonhuman primate endometrium. J Clin Endocrinal Metab. 2001;86:1370-8.
Alvarez-Sanchez F, Brache V, Thevenin F, Cochon L, Faundes A. Hormonal treatment for bleeding irregularities in Norplant implant users. Am J Obstet Gynecol. 1996;174:919-22.
Witjaksono J, Lau TM, Affandi B, Rogers PA. Oestrogentreatment for increased bleeding in Norplant users: preliminary results. Human Reprod. 1996;11:109-14.