October 2019

Irregular bleeding caused by hormonal methods and IUDs can be inconvenient and frustrating. Clinicians must not dismiss the impact of spotting, increased, or prolonged bleeding: they are major reasons for patients to discontinue their method. Here, from the authors of Contraceptive Technology,^[1]is a run-down of strategies for managing unscheduled bleeding associated with the various contraceptive methods, beginning with some general guidance.

First things first: preparation. Preventing contraceptive method discontinuation can frequently be as simple as informing patients in advance that changes will occur in their menstrual cycles. Informed patients can better prepare for irregular bleeding that may be temporary or otherwise tolerable. If a user has recently initiated a new method, review the patient’s bleeding patterns (phone apps) to see if there is any improvement over time.

Evaluation. Persistent abnormal bleeding requires clinical evaluation because not all nuisance bleeding can be attributed to the contraceptive method. When patients present with unscheduled bleeding, rule out pregnancy. Also assess whether gynecological problems may be the culprit, such as cervicitis, cervical cancer, or endometrial polyps. In addition, bleeding may accompany endometritis. Once these problems have been ruled out as causes of abnormal bleeding, reassurance can be helpful.

First-line treatment. For many patients with heavy or prolonged bleeding, non-steroidal anti-inflammatory drugs (NSAIDs) offer a first-line therapy. Trials have not demonstrated the superiority of one NSAID product over another. Because local prostaglandin production is involved with excessive bleeding, any prostaglandin synthetase inhibitor should help; in contrast, aspirin and acetaminophen do not.

Progestin-only Contraceptives

Progestin-only methods can be associated with menstrual changes because progesterone down-regulates estrogen receptors on the endometrial cells.^[2] The endometrial cells cannot detect the patient’s estradiol, so no proliferation (healing) takes place and no endometrium builds up to be sloughed. First-line therapies include NSAIDS and ‘time.’ Other therapies that have been used to manage irregular bleeding induced by progestin-only contraceptives include estrogen (or a combined hormonal contraceptive), tamoxifen, tranexamic acid, mifepristone combined with an estrogen, and doxycycline.^[3]

LNG IUDs^[4]

Individuals initiating use of an LNG IUD should be counseled to expect changes in their menses. For most users, the number of bleeding and spotting days decreases considerably after the first 3 months of use. When this bleeding is problematic, use of naproxen (500 mg twice daily for the first 5 days of each month) can be helpful.^[5]

New onset of unscheduled bleeding (or postcoital or heavy bleeding) in an IUD user may indicate IUD expulsion or pregnancy (intrauterine or ectopic), and so should be promptly evaluated.

Implants^[6]

Because the circulating levels of etonorgestrel (ENG) are so low, the addition of combined hormonal contraceptives to control bothersome heavy or prolonged bleeding or spotting is generally well tolerated. Monophasic combined oral contraceptives can be given cyclically or continuously (using only active pills). The vaginal ring is especially useful in treating such abnormal bleeding, because it provides continuous steady levels of hormonal support. Most patients usually only need 2 to 3 months of treatment to give them some relief, but others may benefit from more lengthy use of the combination therapy—implant for contraception, pill or vaginal ring for bleeding control. However, some may prefer implant removal if short-term interventions do not provide them adequate relief

Injectable Contraception^[7]

If bleeding occurs shortly after beginning DMPA, counsel patients that irregular bleeding decreases over time with use of DMPA. The overall incidence of irregular bleeding is 70% in the first year, with a decrease in irregular bleeding with each reinjection, and rates as low as 10% after the first year.^[8] Unscheduled bleeding and spotting observed in prolonged use of DMPA may be managed initially by a 5 to 7 day course of NSAIDS.^[9],[10] If this does not adequately control symptoms, other options include one or more cycles of combined oral contraceptives or exogenous estrogen.^[11]

Each of these interventions has been shown to decrease bleeding in the short term; however, when these interventions are discontinued, irregular bleeding patterns resume.^10,11 Patients may be educated to repeat these interventions as needed when symptoms recur. A Cochrane review concluded that, while some patients may benefit to a degree from these interventions, there is not enough evidence to recommend routine use of any one regimen to treat menstrual irregularities with DMPA, especially in the long term.^[12]

Other agents that show promising data for management of irregular bleeding include antiprogestins such as mifepristone^[13] and antifibrinolytics such as tranexamic acid,^[14] but additional larger, well-controlled studies are needed.¹² Matrix metalloproteinase inhibitors such as doxycycline, have not been found to be effective in improving irregular bleeding with DMPA.^[15]

Counseling helps continuation rates. Explain to patients that the irregular bleeding might return but, over time, the likelihood of amenorrhea will increase; in the context of DMPA use, amenorrhea is not harmful and does not require treatment.

Contraceptive Rings & Patches^[16]

Extended or continuous ring use may be associated with an increase in unscheduled bleeding, as can prolonged (>21 day) use of a single ring. Unscheduled bleeding tends to be more common in the first months and then decreases significantly over the first year of use.^{[17],[18],[19]} Those who experience persistent or prolonged breakthrough bleeding/spotting with extended ring cycling may benefit from a 4-day hormone-free interval.^[20] One recommendation is to follow a flexible “bleeding-signaled” regimen. That is, individuals use the ring continuously until they experience 4 or more days of consecutive bleeding or spotting, at which point they remove the ring for 4 days, and then insert a new ring on the fifth day. A recent study demonstrated that this approached stopped the bleeding episode within 4 days in about 50% of ring users, and within 7 days in over 90%.¹⁹

Although patch users may experience more breakthrough bleeding and spotting in the first 2 cycles, subsequent cycle control^[21] is comparable to that seen with COCs.^[22],[23]

Progestin-only Pills^[24]

The most common complaint of progestin-only pill users is irregular bleeding. Abnormal bleeding in women using progestin-only pills (POPs) can be managed by a number of approaches, including reassurance, prostaglandin inhibitors, estrogen supplementation, or a method switch. Unscheduled bleeding rates are generally higher with POPs than with combined hormonal contraceptives.

Combined Oral Contraceptives^[25]

Initial combined oral contraceptive (COC) use is associated with unscheduled bleeding and the timing of initiation (i.e., Quick Start versus Sunday start) does not change the amount or duration of this bleeding.^[26] Over time, bleeding should become more scheduled when using a COC that has a scheduled withdrawal week. Advise patients that overall the amount of bleeding they experience during a scheduled withdrawal is typically less than during natural menstruation. Likely the most common reason for unscheduled spotting or bleeding is missed or late pills.

Extended-cycling formulations with skipped or delayed withdrawal can have a longer duration of unscheduled bleeding, but for most users that bleeding will improve over time.^[27] If unscheduled bleeding becomes a nuisance with extended cycling, a 3 to 4 day break in COC use^[28] or supplementing with a pill containing norethindrone acetate^[29] may result in more days of amenorrhea.

Before changing COC type because of complaints of unscheduled bleeding, rule out more likely or more serious causes, such as pregnancy, infection (vaginitis and cervicitis), or medications that interfere with COC metabolism (certain anticonvulsants, St. John’s Wort, rifampin). Consider changing the patient’s COC formulation if unscheduled spotting or bleeding persists after the first several months of use. Switch earlier if a patient is planning to discontinue due to the bleeding pattern. No research indicates that any specific COC formulation is best at eliminating unscheduled spotting or bleeding.

Copper IUDs⁴

Copper IUD users should be counseled to expect some changes in their menstrual bleeding patterns; initial difficulties with bleeding and pain improve for many people after their first 2 months of use of a copper IUD.^[30] Use of nonsteroidal anti-inflammatory drugs (NSAIDs), such as naproxen taken twice daily, can reduce excessive menstrual flow as well as dysmenorrhea.^[31] If hemoglobin levels drop, consider oral iron supplementation. Patients with persistent heavy menses and dysmenorrhea may consider replacing their copper IUD with an LNG IUD.  Caution: See also the discussion in the LNG IUD section on New onset of unscheduled bleeding. If there is concern of endometrial hyperplasia with use of a TCu380A, biopsy the endometrium using a pipelle with the TCu380A left in place.

[1] Hatcher RA, Nelson AL, Trussell J, Cwiak C, Cason P, Policar MS, Edelman A, Aiken ARA, Marrazzo J, Kowal D, eds. Contraceptive technology. 21st ed. New York, NY: Ayer Company Publishers, Inc., 2018.

[2] Nelson AL, Shulman L. Menstrual cycle: normal patterns, menstrual disorders, and menstrually-related problems. In: Hatcher, et al. [N 1].

[3] 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:CD003449.

[4] Dean G, Schwarz EB. Intrauterine devices. In: Hatcher RA

[5] 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;206:129.e1–8.

[6] Nelson AL, Crabtree-Sokol D, Grentzer J. Contraceptive implants. In: Hatcher, et al. [N 1].

[7] Wu W, Bartz D. Injectable contraceptives. In: Hatcher, et al. [N 1].

[8] Gardner JM, Mishell DR, Jr. Analysis of bleeding patterns and resumption of fertility following discontinuation of a long acting injectable contraceptive. Fertil Steril 1970;21:286–91.

[9] Nathirojanakun P, Taneepanichskul S, Sappakitkumjorn N. Efficacy of a selective COX-2 inhibitor for controlling irregular uterine bleeding in DMPA users. Contraception 2006;73:584–7.

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

[11] Said S, Sadek W, Rocca 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.

[12] 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:CD003449.

[13] 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;68:1115–9.

[14] Senthong AJ, Taneepanichskul S. The effect of tranexamic acid for treatment irregular uterine bleeding secondary to DMPA use. J Med Assoc Thai 2009;92:461–5.

[15] 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.

[16] Nanda K, Burke AE. Contraceptive patcher and vaginal contraceptive ring. In: Hatcher, et al. [N 1].

[17] Miller L, Verhoeven CH, Hout J. Extended regimens of the contraceptive vaginal ring: a randomized trial. Obs Gynecol 2005;106:473–82.

[18] Guazzelli CA, Barreiros FA, Barbosa R, de Araujo FF, Moron AF. Extended regimens of the vaginal contraceptive ring: cycle control. Contraception 2009;80:430–5.

[19] 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;91:121–6.

[20] Sulak PJ, Smith V, Coffee A, Witt I, Kuehl AL, Kuehl TJ. Frequency and management of breakthrough bleeding with continuous use of the transvaginal contraceptive ring: a randomized controlled trial. Obs Gynecol 2008;112:563–71.

[21] Sucato GS, Land SR, Murray PJ, Cecchini R, Gold MA. Adolescents’ experiences using the contraceptive patch versus pills. J Pediatr Adolesc Gynecol 2011;24:197–203.

[22] Audet MC, Moreau M, Koltun WD, et al. Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: a randomized controlled trial. JAMA 2001;285:2347–54.

[23] Miller L, Hughes JP. Continuous combination oral contraceptive pills to eliminate withdrawal bleeding: a randomized trial. Obs Gynecol 2003;101:653–61.

[24] Raymond AG, Grossman D. Progestin-only pills. In: Hatcher, at al. [N 1].

[25] Cwiak C, Edelman AB. Combined oral contraceptive pills. In: Hatcher, et al. [N 1].

[26] Westhoff C, Morroni C, Kerns J, Murphy PA. Bleeding patterns after immediate vs. conventional oral contraceptive initiation: a randomized, controlled trial. Fertil Steril 2003;79:322–9.

[27] 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:Cd004695.

[28] Sulak PJ, Kuehl TJ, Coffee A, Willis S. Prospective analysis of occurrence and management of breakthrough bleeding during an extended oral contraceptive regimen. Am J Obstet Gynecol 2006;195:935–41.

[29] Edelman AB, Koontz SL, Nichols MD, Jensen JT. Continuous oral contraceptives: are bleeding patterns dependent on the hormones given? Obstet Gynecol 2006;107:657–65.

[30] Hubacher D, Chen PL, Park S. Side effects from the copper IUD: do they decrease over time? Contraception 2009;79:356–62.

[31] Ylikorkala O. Prostaglandin synthesis inhibitors in menorrhagia, intrauterine contraceptive device-induced side effects and endometriosis. Pharmacol Toxicol 1994;75 Suppl 2:86–8.