Skip to main content
SpringerLink
Log in

Bleeding Associated with Hormonal Contraceptives: Understanding and Managing a Common Problem

  • Family Planning (A Burke, Section Editor)
  • Published:
Current Obstetrics and Gynecology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Changes in menstrual bleeding are common with hormonal contraceptives, and unfavorable bleeding profiles are leading reasons for method dissatisfaction and discontinuation. Studies suggest that acceptance of menstrual disturbance is highly dependent on appropriate counseling. This review presents an overview of the pathophysiology of uterine bleeding related to hormonal contraceptive use, the expected bleeding profiles of the various hormonal contraceptives, and evidence supporting various management strategies for treatment of unscheduled bleeding.

Recent Findings

Published trials on treatments for bleeding with hormonal contraceptives are heterogeneous in methodology and outcome measures. Overall, data show mixed results and disappointingly small treatment effects for medications studied to manage unscheduled bleeding. Short courses of NSAIDs and oral estrogen may have modest benefits. Tranexamic acid and mifepristone require larger trials and additional study.

Summary

Treatment of bleeding associated with hormonal contraception hinges on understanding the bleeding profiles of the hormonal contraceptives, employing anticipatory counseling, and understanding the spectrum and limitations of treatment options for menstrual disturbance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Moreau C, Cleland K, Trussell J. Contraceptive discontinuation attributed to method dissatisfaction in the United States. Contraception. 2007;76(4):267–72. doi:10.1016/j.contraception.2007.06.008.

    Article  PubMed  Google Scholar 

  2. Lei ZW, Wu SC, Garceau RJ, Jiang S, Yang QZ, Wang WL, et al. Effect of pretreatment counseling on discontinuation rates in Chinese women given depo-medroxyprogesterone acetate for contraception. Contraception. 1996;53(6):357–61.

    Article  CAS  PubMed  Google Scholar 

  3. Backman T, Huhtala S, Luoto R, Tuominen J, Raurama I, Koskenvuo M. Advance information improves user satisfaction with the levonorgestrel intrauterine system. Obstet Gynecol. 2002;99:608–13.

    PubMed  Google Scholar 

  4. •• Maybin JA, Critchley HO. Menstrual physiology: implications for endometrial pathology and beyond. Hum Reprod Update. 2015;21(6):748–61. doi:10.1093/humupd/dmv038. A thorough review of the pathophysiology of human menstruation with discussion of possible therapeutic targets.

  5. Fraser IS, Critchley HO, Broder M, Munro MG. The FIGO recommendations on terminologies and definitions for normal and abnormal uterine bleeding. Semin Reprod Med. 2011;29(5):383–90. doi:10.1055/s-0031-1287662.

    Article  PubMed  Google Scholar 

  6. Guzeloglu Kayisli O, Kayisli UA, Basar M, Semerci N, Schatz F, Lockwood CJ. Progestins upregulate FKBP51 expression in human endometrial stromal cells to induce functional progesterone and glucocorticoid withdrawal: implications for contraceptive- associated abnormal uterine bleeding. PLoS One. 2015;10(10):e0137855. doi:10.1371/journal.pone.0137855.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Milling Smith OP, Critchley HOD. Progestogen only contraception and endometrial breakthrough bleeding. Angiogenesis. 2005;8:117–26.

    Article  Google Scholar 

  8. Kaneshiro B, Alison Edelmanb CH, Pandhare J, Soli FM, Jensen JT. Effect of oral contraceptives and doxycycline on endometrial MMP-2 AND MMP-9 activity. Contraception. 2015; doi:10.1016/j.contraception.2015.09.006.

  9. Semerci N, Basar M, Kayisli OG, Schatz F, Kayisli UA, Lockwood CJ. Whole genome analysis of long-acting progestin only contraceptive treated vascular smooth muscle cells identifies suppression of CCL2 mediated stat1 signaling in inducing abnormal uterine bleeding. Reprod Sci. 2015;22:113A.

    Article  Google Scholar 

  10. Shapiro JP, Basar M, Kayisli UA, Guzeloglu-Kayisli O, Joseph Huang S, Suarez AA, et al. Mass spectrometry identification of potential mediators of progestin-only contraceptive-induced abnormal uterine bleeding in human endometrial stromal cells. Contraception. 2015;91(3):253–60. doi:10.1016/j.contraception.2014.11.005.

    Article  CAS  PubMed  Google Scholar 

  11. Xulane Precribing Information. Morgantown, WV: Mylan Pharmaceuticals, Inc.; 2016.

  12. NuvaRing Prescribing Information. Whitehouse Station, NJ: Merck & Co., Inc.; 2016.

  13. Van Vliet HA, Grimes DA, Helmerhorst FM, Schulz KF. Biphasic versus triphasic oral contraceptives for contraception. Cochrane Database Syst Rev. 2006;3:CD003283. doi:10.1002/14651858.CD003283.pub2.

    Google Scholar 

  14. Van Vliet HA, Grimes DA, Helmerhorst FM, Schulz KF. Biphasic versus monophasic oral contraceptives for contraception. Cochrane Database Syst Rev. 2006;3:CD002032. doi:10.1002/14651858.CD002032.pub2.

    Google Scholar 

  15. Van Vliet HA, Grimes DA, Lopez LM, Schulz KF, Helmerhorst FM. Triphasic versus monophasic oral contraceptives for contraception. Cochrane Database Syst Rev. 2011;11:CD003553. doi:10.1002/14651858.CD003553.pub3.

    Google Scholar 

  16. Van Vliet HA, Raps M, Lopez LM, Helmerhorst FM. Quadriphasic versus monophasic oral contraceptives for contraception. Cochrane Database Syst Rev. 2011;11:CD009038. doi:10.1002/14651858.CD009038.pub2.

    Google Scholar 

  17. Briggs P, Serrani M, Vogtländer K, Parke S. Continuation rates, bleeding profile acceptability, and satisfaction of women using an oral contraceptive pill containing estradiol valerate and dienogest versus a progestogen-only pill after switching from an ethinylestradiol-containing pill in a real-life setting: results of the CONTENT study. International Journal of Women's Health. 2016;8:477–87.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Apter D, Zimmerman Y, Beekman L, Mawet M, Maillard C, Foidart JM, et al. Bleeding pattern and cycle control with estetrol-containing combined oral contraceptives: results from a phase II, randomised, dose-finding study (FIESTA). Contraception. 2016;94(4):366–73. doi:10.1016/j.contraception.2016.04.015.

    Article  CAS  PubMed  Google Scholar 

  19. Audet M-C, Moreau M, Koltun WD, Waldbaum AS, Shangold G, Fisher AC, et al. Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: a randomized controlled trial. JAMA.285(18):2347–54.

  20. Fan GS, Ren M, Di W, Su P, Chang Q, Wu S, et al. Efficacy and safety of the contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive in Chinese women: a 1-year randomised trial. The European journal of contraception & reproductive health care: the official journal of the European Society of Contraception. 2016;21(4):303–9. doi:10.1080/13625187.2016.1186269.

    Article  CAS  Google Scholar 

  21. Jain S, Vaid NB, Narang Y, Suneja A, Guleria K. A randomised controlled trial comparing the efficacy and side-effects of intravaginal ring (Nuvaring®) with combined oral hormonal preparation in dysfunctional uterine bleeding. J Clin Diagn Res. 2016;10(3):QC21–4. doi:10.7860/JCDR/2016/16545.7516.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Merz M, Kroll R, Lynen R, Bangerter K. Bleeding pattern and cycle control of a low-dose transdermal contraceptive patch compared with a combined oral contraceptive: a randomized study. Contraception. 2015;91(2):113–20. doi:10.1016/j.contraception.2014.10.004.

    Article  CAS  PubMed  Google Scholar 

  23. Gruber D, Skrivanek A, Serrani M, Lanius V, Merz M. A comparison of bleeding patterns and cycle control using two transdermal contraceptive systems: a multicenter, open-label, randomized study. Contraception. 2015;91(2):105–12. doi:10.1016/j.contraception.2014.10.003.

    Article  CAS  PubMed  Google Scholar 

  24. Kaunitz AM, Portman D, Westhoff CL, Archer DF, Mishell DR Jr, Rubin A, et al. Low-dose levonorgestrel and ethinyl estradiol patch and pill: a randomized controlled trial. Obstet Gynecol. 2014;123(2 Pt 1):295–303. doi:10.1097/AOG.0000000000000095.

    Article  CAS  PubMed  Google Scholar 

  25. • Szarewski A, von Stenglin A, Rybowski S. Women’s attitudes towards monthly bleeding: results of a global population-based survey. The European journal of contraception & reproductive health care: the official journal of the European Society of Contraception. 2012;17(4):270–83. doi:10.3109/13625187.2012.684811. A global study to determine the preferred bleeding pattern among women using contraception.

    Article  Google Scholar 

  26. Edelman A, Micks E, Gallo MF, Jensen JT, Grimes DA. Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives for contraception. Cochrane Database Syst Rev. 2014;7:CD004695. doi:10.1002/14651858.CD004695.pub3.

    Google Scholar 

  27. Weisberg E, Merki-Feld GS, McGeechan K, Fraser IS. Randomized comparison of bleeding patterns in women using a combined contraceptive vaginal ring or a low-dose combined oral contraceptive on a menstrually signaled regimen. Contraception. 2015;91(2):121–6. doi:10.1016/j.contraception.2014.10.006.

    Article  CAS  PubMed  Google Scholar 

  28. Diedrich JT, Zhao Q, Madden T, Secura GM, Peipert JF. Three-year continuation of reversible contraception. Am J Obstet Gynecol. 2015;213(5):662.e1–8.

    Article  Google Scholar 

  29. Zigler RE, McNicholas C. Unscheduled vaginal bleeding with progestin-only contraceptive use. Am J Obstet Gynecol. 2016; doi:10.1016/j.ajog.2016.12.008.

  30. Hubacher D, Lopez L, Steiner MJ, Dorflinger L. Menstrual pattern changes from levonorgestrel subdermal implants and DMPA: systematic review and evidence-based comparisons. Contraception. 2009;80:113–8.

    Article  CAS  PubMed  Google Scholar 

  31. Mirena Prescribing Information. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2016.

  32. Wu JP, Pickle S. Extended use of the intrauterine device: a literature review and recommendations for clinical practice. Contraception. 2014;89(6):495–503. doi:10.1016/j.contraception.2014.02.011.

    Article  PubMed  Google Scholar 

  33. McNicholas C, Maddipati R, Zhao Q, Swor E, Peipert JF. Use of the etonogestrel implant and levonorgestrel intrauterine device beyond the US Food and Drug Administration approved duration. Obstet Gynecol. 2015;125:599–604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Diedrich JT, Desai S, Zhao Q, Secura G, Madden T, Peipert JF. Association of short-term bleeding and cramping patterns with long-acting reversible contraceptive method satisfaction. Am J Obstet Gynecol. 2015;212(1):50e1–8.

    Article  Google Scholar 

  35. Pakarinen PI, Luukkainen T, Laine H. The effect of local intrauterine levonorgestrel administration on endometrial thickness and uterine blood circulation. Hum Reprod. 1995;10:2390–4.

    Article  CAS  PubMed  Google Scholar 

  36. Bachman G, Korner P. Bleeding patterns associated with non-oral hormonal contraceptives: a review of the literature. Contraception. 2009;79:247–58.

    Article  Google Scholar 

  37. Grunloh DS, Casner T, Secura GM, Peipert JF, Madden T. Characteristics associated with discontinuation of long-acting reversible contraception within the first 6 months of use. Obstet Gynecol. 2013;122:1214–21.

    Article  CAS  PubMed  Google Scholar 

  38. Eisenberg DL, Schreiber CA, Turok DK, Teal SB, Westhoff CL, Creinin MD. Three-year efficacy and safety of a new 52-mg levonorgestrel-releasing intrauterine system. Contraception. 2015;92:10–6.

    Article  CAS  PubMed  Google Scholar 

  39. Liletta Prescribing Information. Irvine, CA: Allergan USA Inc.; 2016.

  40. Kyleena Precribing Information. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2016.

  41. Skyla Prescribing Information. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2016.

  42. Gemzell-Danielsson K, Schellschmidt I, Apter D. A randomized, phase II study describing the efficacy, bleeding profile, and safety of two low-dose levonorgestrel-releasing intrauterine contraceptive systems and Mirena. Fertil Steril. 2012;97(3):616–22.e1-e3.

    Article  CAS  PubMed  Google Scholar 

  43. Trussell J. Contraceptive failure in the United States. Contraception. 2011;83(5):397–404.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Raymond EG. Contraceptive implants. In: Hatcher RA, Trussell J, Nelson A, Cates W, Stewart F, Kowal D, editors. Contraceptive technology. New York: Ardent Media; 2007. p. 147.

    Google Scholar 

  45. Mansour D, Bahamondes L, Critchley H, Darney P, Fraser IS. The management of unacceptable bleeding patterns in etonogestrel-releasing contraceptive implant users. Contraception. 2011;83(3):202–10.

    Article  CAS  PubMed  Google Scholar 

  46. Darney P, Patel A, Rosen K, Shapiro LS, Kaunitz AM. Safety and efficacy of a single-rod etonogestrel implant (Implanon): results from 11 international clinical trials. Fertil Steril. 2009;91(5):1646–53.

    Article  PubMed  Google Scholar 

  47. Mansour D, Korver T, Marintcheva-Petrova M, Fraser IS. The effects of Implanon on menstrual bleeding patterns. The European journal of contraception & reproductive health care: the official journal of the European Society of Contraception. 2008;13(Suppl 1):13–28.

    Article  CAS  Google Scholar 

  48. Tantiwattanakul P, Taneepanichskul S. Effect of mefenamic acid on controlling irregular uterine bleeding in DMPA users. Contraception. 2004;70:277–9.

    Article  CAS  PubMed  Google Scholar 

  49. Abdel-Aleem H, d'Arcangues C, Vogelsong KM, Gaffield ML, Gulmezoglu AM. Treatment of vaginal bleeding irregularities induced by progestin only contraceptives. Cochrane Database Syst Rev. 2013;7

  50. Phaliwong P, Taneepanichskul S. The effect of mefenamic acid on controlling irregular uterine bleeding second to Implanon use. J Med Assoc Thail. 2004;87(Suppl 3):S64–8.

    Google Scholar 

  51. 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(5):934–41.

    Article  CAS  PubMed  Google Scholar 

  52. Madden T, Proehl S, Allsworth JE, Secura GM, Peipert JF. Naproxen or estradiol for bleeding and spotting with the levonorgestrel intrauterine system: a randomized controlled trial. Am J Obstet Gynecol. 2012;206(2):129.e1–8.

    Article  CAS  Google Scholar 

  53. Shaaban MM, Elwan SI, el-Kabsh MY, Farghaly SA, Thabet N. Effect of levonorgestrel contraceptive implants, Norplant, on blood coagulation. Contraception. 1984;30:421–30.

    Article  CAS  PubMed  Google Scholar 

  54. Viegas OA, Singh K, Koh S, Singh P, Ratnam SS. The effects of Norplant on clinical chemistry in Singaporean acceptors after 1 year of use: I. Hemostatic changes Contraception. 1988;38:313–23.

    Article  CAS  PubMed  Google Scholar 

  55. Said S, Sadek W, Rocca M, Koetsawang S, Kirwat O, Piya-Anant M, et al. Clinical evaluation of the therapeutic effectiveness of ethinyl oestradiol and oestrone sulphate on prolonged bleeding in women using depot medroxyprogesterone acetate for contraception. World Health Organization, Special Programme of Research, Development and Research Training in Human Reproduction, Task Force on Long-acting Systemic Agents for Fertility Regulation. Hum Reprod. 1996;11(Suppl 2):1–13.

    Article  CAS  PubMed  Google Scholar 

  56. Hou MY, McNicholas C, Creinin MD. Combined oral contraceptive treatment for bleeding complaints with the etonogestrel contraceptive implant: a randomized controlled trial. The European journal of contraception & reproductive health care: the official journal of the European Society of Contraception. 2016;15:1–6.

    Google Scholar 

  57. Lukes AS, Kouides PA, Moore KA. Tranexamic acid: a novel oral formulation for the treatment of heavy menstrual bleeding. Women's Health. 2011;7(2):151–8.

    Article  CAS  PubMed  Google Scholar 

  58. Senthong A, Taneepanichskul S. The effect of tranexamic acid for treatment of irregular uterine bleeding secondary to DMPA use. J Med Assoc Thail. 2009;92:461–5.

    Google Scholar 

  59. • Friedlander E, Kaneshiro B. Therapeutic options for unscheduled bleeding associated with long-acting reversible contraception. Obstet Gynecol Clin N Am. 2015;42(4):593–603. doi:10.1016/j.ogc.2015.07.004. A review of treatment options for unscheduled bleeding associated with long-acting reversible contraceptives.

    Article  Google Scholar 

  60. Weisberg E, Hickey M, Palmer D, O'Connor V, Salamonsen LA, Findlay JK, et al. A pilot study to assess the effect of three short-term treatments on frequent and/or prolonged bleeding compared to placebo in women using Implanon. Hum Reprod. 2006;21(1):295–302.

    Article  CAS  PubMed  Google Scholar 

  61. Weisberg E, Hickey M, Palmer D, O'Connor V, Salamonsen LA, Findlay JK, et al. A randomized controlled trial of treatment options for troublesome uterine bleeding in Implanon users. Hum Reprod. 2009;24(8):1852–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Casey PM, Long ME, Drozdowicz LB, Marnach ML, Weaver AL. Management of etonogestrel subdermal implant-related bleeding. J Reprod Med. 2014;59(5–6):306–12.

    PubMed  Google Scholar 

  63. Abdel-Aleem H, Shaaban OM, Abdel-Aleem MA, Fetih GN. Doxycycline in the treatment of bleeding with DMPA: a double-blinded randomized controlled trial. Contraception. 2012;86:224–30.

    Article  CAS  PubMed  Google Scholar 

  64. Jain JK, Nicosia AF, Nucatola DL, Lu JJ, Kuo J, Felix JC. Mifepristone for the prevention of breakthrough bleeding in new starters of depo-medroxyprogesterone acetate. Steroids. 2003;68(10–13):1115–9. doi:10.1016/s0039-128x(03)00132-6.

    Article  CAS  PubMed  Google Scholar 

  65. Lal S, Kriplani A, Kulshrestha V, Sharma M, Agarwal N. Efficacy of mifepristone in reducing intermenstrual vaginal bleeding in users of the levonorgestrel intrauterine system. Int J Gynecol Obstet. 2010;109(2):128–30.

    Article  Google Scholar 

  66. Grow DR, Reece MT, Hsiu JG, Adams L, Newcomb PM, Williams RF, et al. Chronic antiprogestin therapy produces a stable atrophic endometrium with decreased fibroplast growth factor: a 1-year primate study in contraception and amenorrhea. Fertil Steril. 1998;69(5):936–43.

    Article  CAS  PubMed  Google Scholar 

  67. Abdel-Aleem H, Shaaban OM, Amin AF, Abdel-Aleem AM. Tamoxifen treatment of bleeding irregularities associated with Norplant use. Contraception. 2005;72:432–7.

    Article  CAS  PubMed  Google Scholar 

  68. Warner P, Guttinger A, Glasier AF, Lee RJ, Nickerson S, Brenner RM, et al. Randomized placebo-controlled trial of CDB-2914 in new users of a levonorgestrel-releasing intrauterine system shows only short-lived amelioration of unscheduled bleeding. Hum Reprod. 2010;25(2):345–53.

    Article  CAS  PubMed  Google Scholar 

  69. Canto De Cetina TE, Canto P, Ordonez Luna M. Effect of counseling to improve compliance in Mexican women receiving depot-medroxyprogesterone acetate. Contraception. 2001;63:143–6.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Family Planning, Department of Gynecology and Obstetrics, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, A Building, Room 121, Baltimore, MD, 21224, USA

    Stacey Leigh Rubin & Jennifer A. Robinson

Authors
  1. Stacey Leigh Rubin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jennifer A. Robinson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stacey Leigh Rubin.

Ethics declarations

Conflict of Interest

Stacey Leigh Rubin and Jennifer A. Robinson declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Family Planning

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rubin, S.L., Robinson, J.A. Bleeding Associated with Hormonal Contraceptives: Understanding and Managing a Common Problem. Curr Obstet Gynecol Rep 6, 198–206 (2017). https://doi.org/10.1007/s13669-017-0219-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13669-017-0219-x

Keywords

Search

Navigation