Ocs, Breakthrough Bleeding, and Patients' Need to Know

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Patricia A. Lohr, MD, OCs, breakthrough bleeding, and Mitchell D. Creinin, MD Department of Obstetrics, Gynecology and Reproductive Sciences, and patients’ need to know University of Pittsburgh, Pittsburgh, Pa Dr. Lohr reports no financial Managing expectations is as important as relationships relevant to this article. adjusting formulations Dr. Creinin receives grant and research support from, and is a member of the speakers’ bureau of, Berlex, Organon, and Wyeth. He serves as consultant to Berlex and is a member of the speakers’ bureau for Organon. Recommendations for practice to abandon OCs.1,2 What they often don’t know, though, is that breakthrough z Lack of adherence is a common cause of bleeding generally is greatest in the first More on the web breakthrough bleeding. Focus counseling 3 to 4 months after starting OCs,3 and it What’s the range of OCs on ensuring that patients understand and steadily declines and stabilizes by the end available for your patients? can follow pill-taking instructions before of the fourth cycle.4 Timely counsel could The Web version of this article switching pills or contraceptive method enable many of these women to cope has a handy summary. z If breakthrough bleeding extends beyond with the bleeding and stick with an ef- Visit www.obgmanagement.com 4 cycles and a woman wishes to continue fective contraceptive method. Additional using an oral contraceptive, consider incentives are noncontraceptive benefits switching to a pill with a higher ethinyl es- of OCs: improved menstrual regular- tradiol:progestin ratio, either by increasing ity and decreased menstrual blood loss, In this Article the estradiol dose or by decreasing the dysmenorrhea, and risk of ovarian and relative progestin dose endometrial cancer. y Four causes z Breakthrough bleeding may be due to Women who discontinue OCs on of bleeding progestin type; switching from an estrane their own switch to less effective meth- Page 50 1,2 to a gonane may reduce it ods of birth control or use no method. y Type of progestin z Women who have breakthrough bleed- Consequences may be unexpected preg- ing after having well-controlled menstrual nancies and an increased abortion rate.5 affects bleeding cycles on an oral contraceptive should be With patients who are using an OC, it Page 56 assessed for causes not related to their would be appropriate to ask periodically y How patients birth control pills, such as pregnancy, cer- whether they are satisfied with OC use. contribute to vicitis, smoking, or interactions with medi- In this review, we discuss the mecha- cations. nisms and management of breakthrough the problem bleeding in women taking OCs, and pro- Page 58 n 1982, more than 20% of women vide tips for counseling that may help surveyed in a nationally representa- decrease the risk of discontinuation due Itive sample had discontinued oral con- to menstrual abnormalities in the initial traceptives (OCs) on their own or at the months of use. recommendation of their physician due to Breakthrough bleeding in this review bleeding or spotting.1 Sadly, the percent- refers to either unplanned spotting or age today has not decreased much. bleeding, regardless of requirement for Understandable concern, embarrass- protection—unless defined otherwise by ment, and annoyance lead these women a specific study under discussion. CONTINUED

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in the estrogen component. However, sig- How is irregular bleeding nificantly lowering the estrogen in OCs may account for breakthrough bleeding. defined? Unplanned bleeding, though, is not de- For the purpose of performing studies, unplanned bleeding is pendent solely on the estrogen compo- classified by the World Health Organization into 2 categories: nent, as variations in the progestin can 1) breakthrough bleeding, which requires sanitary protection, and contribute to breakthrough bleeding.7 2) spotting, which does not require sanitary protection.6 Despite Most OC users in the US take low- this formal classification, trials have varied in their terminology dose formulations, so designated because and method of recording menstrual irregularities, making compar- the estrogen component is <50 μg. This isons between studies difficult. In addition, there is wide variation level of estrogen in combination with a among women in tolerance to bleeding abnormalities, perceptions progestin provides excellent contracep- of heavy vs light bleeding, as well as the need for protection.3 tive efficacy, but may be insufficient to Nevertheless, menstrual abnormalities are consistently cited as a common reason for discontinuing OCs. A prospective sustain endometrial integrity in some 8 US study of 1,657 women performed in the 1990s reported that women. Studies that have compared 37% of OC users had stopped taking OCs by 6 months after OCs containing 20 μg ethinyl estradiol starting a new prescription because of side effects.2 Irregular (EE) with those containing 30 μg or bleeding was the most common cause, cited by 12% of women, 35 μg EE have not been very useful for followed by nausea, weight gain, and mood changes, which judging breakthrough bleeding rates ranged from 5% to 7%. because the products often also vary in the phasing and type of progestin. Some studies show more breakthrough bleed- Four causes of bleeding ing with 20 μg ee pills,9–11 but others Breakthrough bleeding may be due to show equal or improved cycle control any the following variables: 1) physiolog- with the lower EE dose. ic effects of OCs on the endometrium, 2) Estrogen-progestin balance is more im- OC-related parameters, including dose, portant than absolute level of estrogen. formulation, and regimen, 3) patient be- Endrikat et al12 conducted a study to fast track havior (including compliance, using con- compare two 20 μg EE pills containing Low-level estrogen comitant medications, and smoking), and different progestins, and to compare 2 4) benign or malignant pathology. levonorgestrel-based formulations with in combination differing EE amounts. An OC of 20 μg with a progestin OCs and the endometrium: Estro- EE/100 μg levonorgestrel was compared is excellent for gen-progestin balance significant with a preparation of 20 μg EE/500 μg contraception but Progestin and estrogen in combination norethisterone. A 30 μg EE/150 μg levo- may not sustain OCs have profound effects on the endo- norgestrel pill was used as a standard ref- metrium that, although not contributing erence preparation. endometrial integrity to contraception, do lead to a predictable Overall, the 30 μg ee preparation in some women pattern of bleeding or such problems as showed a lower cumulative incidence of breakthrough bleeding or lack of with- breakthrough bleeding compared with drawal bleed. the 20 μg EE/100 μg levonorgestrel and Normally, estrogen causes the en- 20 μg EE/500 μg norethisterone pills over dometrium to proliferate. Progesterone 13 cycles (1.0% vs 4.1% and 11.7%, re- stabilizes the growing uterine lining. spectively). However, the 20 μg EE/500 Since the introduction of OCs in 1960, μg norethisterone pills consistently had a the trend in formulation has been to use higher breakthrough bleeding rate than the least amount of hormone necessary the 20 μg EE/100 μg levonorgestrel pill. to inhibit ovulation. Given that the pro- This suggests that, although the higher gestin is primarily responsible for the EE component in the 30 μg pill was im- contraceptive efficacy of OCs, the risk of portant when comparing 2 formulations pregnancy is not altered with decreases with the same progestin, the difference in

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progestins of the two 20 μg EE pills was do not account for the effects of missed most likely responsible for the differing pills, use of concomitant medications, or rates of breakthrough bleeding. smoking. The percentage of women who This study highlights the ability to experience breakthrough bleeding in a achieve greater cycle control by titrating given cycle varies widely even in differ- the ee component of an OC in a bal- ent trials of the same formulation. anced ratio with the same progestin, but Pay attention to progestin level. Conven- suggests that the absolute quantity of tional wisdom holds that OCs with the EE in a given pill may be less important lowest doses of EE (<20 μg) are associ- than maintaining a balance between the ated with more breakthrough bleeding.11 2 hormones or less important than the However, even moderately low doses of impact of different progestins on break- either EE or progestin can increase the in- through bleeding rates. cidence of breakthrough bleeding. For ex- The delicate balance between estro- ample, when 3 pills with the same estrogen gen and progesterone supplementation and progestin (50 μg EE/100 μg norethin- required for contraception may also lead drone; 35 μg ee/100 μg norethindrone; to progestin-induced decidualization and and 35 μg EE/50 μg norethindrone) were endometrial atrophy, which can result in compared in 192 women over 8 cycles, asynchronous, erratic bleeding.7,13 this the pill containing the lowest amount of has been primarily studied in long-act- norethindrone (35 μg EE/50 μg norethin- ing progestin-only contraceptives such drone) caused the highest rates of break- as implants. alterations in angiogenic through bleeding (decreasing to approxi- factors14 may play a role. Hysteroscop- mately 50% by cycle 8 as compared with ic studies have shown abnormalities in 35% in the 35 μg ee/100 μg norethin- superficial endometrial blood vessels in drone pill and 25% in the 50 μg EE /100 terms of size, proliferation, and fragility μg norethindrone pill).21 in women using Norplant.13,15,16 Abnor- In addition, the number of inter- malities in endothelial cells and extracel- menstrual bleeding days plateaued more fast track lular matrix proteins,17 tissue factor,18 slowly as the amount of both hormones Regardless of the and endometrial lymphoid cells19 may in the OC formulations decreased. This contribute to breakthrough bleeding in underscores the importance of the rela- type of progestin or progestin-dominant environments. tive proportion of estrogen and proges- amount of estrogen, tin contained in combination OCs and breakthrough OC formulations, doses, regimens its impact on breakthrough bleeding. bleeding generally More than 30 formulations of combina- Similarly, a large comprehensive decreases with tion OCs are available in the US, with study in 1,991 women compared 7 dif- different doses and types of estrogen and ferent formulations of combination successive cycles 20 progestin (see Table 1, on page e52). OCs containing different dose combina- Approved OCs have been studied in clini- tions of ee and norgestimate—20/250, cal trials to assess contraceptive efficacy 50/250, 35/125, 20/60, 50/60, 30/90, and cycle control; however, comparisons 25/125.22 Total intermenstrual bleeding between studies regarding bleeding phe- was more frequent at lower doses of ei- nomena are impaired by inconsistent ter- ther estrogen or progestin. However, as minology.3 long as a similar estrogen-progestin ra- Whereas some studies describe tio was maintained, bleeding rates were breakthrough bleeding and spotting ac- considered acceptable (approximately cording to their recognized definitions, 10% of days per cycle with bleeding). others simply refer to intermenstrual The authors also noted that in the low- bleeding or use spotting to refer to any dose range of OCs, small changes in the unexpected bleeding. In addition, cycle absolute amount of either EE or norges- control studies of OC users frequently timate might result in noticeable changes CONTINUED

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table 1

Available OCs by formulation and regimen Trade Name Generic Name(s) Estrogen (dose) Progestin (dose) MONOPHASIC Alesse, Levlite Aviane, Lessina Ethinyl estradiol (20 μg) Levonorgestrel (0.1 mg) Mircette Kariva Ethinyl estradiol (20 μg x 21 days + Desogestrel (0.15 mg) 10 μg x 5 days during placebo week) Loestrin FE Microgestin FE 1/20, June FE 1/20 Ethinyl estradiol (20 μg) Norethindrone acetate (1 mg)

Yaz Ethinyl estradiol (20 μg) Drospirenone (3 mg) Levlen, Nordette Levora, Portia Ethinyl estradiol (30 μg) Levonorgestrel (0.15 mg) Lo/Ovral Low-ogestrel, Cryselle Ethinyl estradiol (30 μg) Norgestrel (0.3 mg) Desogen, Ortho-cept Apri Ethinyl estradiol (30 μg) Desogestrel (0.15 mg) Loestrin 21 1/5/30 Microgestin, Junel Fe Ethinyl estradiol (30 μg) Norethindrone acetate (1.5 mg) Yasmin Ethinyl estradiol (30 μg) Drospirenone (3 mg) Ovcon 35 Ethinyl estradiol (35 μg) Norethindrone (0.4 mg) Ortho-Cyclen Mononesessa, Sprintec Ethinyl estradiol (35 μg) Norgestimate (0.25 mg) Brevicon, Modicon Nortrel, Necon 0.5/35 Ethinyl estradiol (35 μg) Norethindrone (0.5 mg) Demulen 1/35 Zovia 1/35 Ethinyl estradiol (35 μg) Ethynodiol diacetate (1 mg) Ortho-Novum 1/35, Necon 1/35, Nortrel Ethinyl estradiol (35 μg) Norethindrone (1 mg) Norinyl 1+35 Ortho-Novum 1/50 Necon 1/50 Ethinyl estradiol (50 μg) Norethindrone (1 mg) Ovral Ogestrel Ethinyl estradiol (50 µg) Norgestrel (0.5 mg) Ovcon 50 Ethinyl estradiol (50 μg) Norethindrone (1 mg) Demulen 1/50 Zovia 1/50 Ethinyl estradiol (50 μg) Ethynodiol diacetate (1 mg) Norinyl 1/50 Mestranol (50 μg) Norethindrone (1 mg) BIPHASIC Ortho-Novum 10/11, Necon 10/11, Nelova 10/11 Ethinyl estradiol (35 μg) Norethindrone (0.5 mg x 10 days, Jenest 1 mg x 11 days) TRIPHASIC Ortho Tri-Cyclen Lo Ethinyl estradiol (25 μg) Norgestimate (0.18 mg x 7 days, 0.215 mg x 7 days, 0.25 mg x 7 days) Cyclessa Velivet Ethinyl estradiol (25 μg) Desogestrel (0.1 mg x 7 days, 0.125 mg x 7 days, 0.15 mg x 7 days) Triphasil, Tri-Levlen Trivora, Enpresse Ethinyl estradiol (30 μg x 6 days, Levonorgestrel (0.05 mg x 6 days, 40 μg x 5 days, 30 μg x 10 days) 0.075 mg x 5 days, 0.125 mg x 10 days) Tri-Norinyl Ethinyl estradiol (35 μg) Norethindrone (0.5 mg x 7 days, 1 mg x 9 days, 0.5 mg x 5 days) Ortho Tri-Cyclen Tri-Sprintec, TriNessa Ethinyl estradiol (35 μg) Norgestimate (0.18 mg x 7 days, 0.215 mg x 7 days, 0.25 mg x 7 days) Ortho-Novum 7/7/7 Nortrel 7/7/7, Necon 7/7/7 Ethinyl estradiol (35 μg) Norethindrone (0.5 mg x 7 days, 0.75 mg x 7 days, 1 mg x 7 days) Estrostep FE Ethinyl estradiol (20 μg x 5 days, Norethindrone acetate (1 mg) 30 μg x 7 days, 35 μg x 9 days) EXTENDED CYCLE Seasonale Ethinyl estradiol (30 μg x 84 days Levonorgestrel (0.15 mg) followed by 7 placebo pills) Seasonique Ethinyl estradiol (30 μg x 84 days Levonorgestrel (0.15 mg) followed by 10 μg x 7 days)

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in bleeding. experience more breakthrough bleeding Type of progestin may affect break- than those using a standard 28-day pill. through bleeding. All combination OCs However, in a 3-month cycle, there are contain either EE or mestranol. Howev- only 7 days of planned bleeding. this er, a variety of progestins have come into is in contrast to 28-day cycles during 3 use. The 2 most common contraceptive months in which there are 21 days of progestins are derived from 19-nortes- planned bleeding. tosterone, and are classified as gonanes Though women on extended-cycle or estranes.23 regimens may initially experience more Estranes include norethindrone and breakthrough bleeding than women its derivatives, norethindrone acetate using 28-day regimens, the total num- and ethinyodiol diacetate. Gonanes in- ber of planned and unplanned bleeding clude levonorgestrel, norgestrel, desoges- days may still decrease. Women using trel, gestodene, and norgestimate. a 3-month cycle OC (30 μg EE/150 μg Each progestin differs in half-life, levonorgestrel) experienced more un- estrogenic, progestogenic, and andro- scheduled bleeding than women using a genic properties, and these variations standard 28-day cycle OC of the same may explain differing rates of break- formulation and dose.26 The number of through bleeding among formulations.4 bleeding days decreased with each cycle. As shown by Endrikat et al,12 pills with Another study examined continuous OC the same quantity of ee but different use (20 μg ee/100 μg levonorgestrel) progestins can have marked differences over a period of 1 year, and reported a in breakthrough bleeding rates. decreasing number of bleeding days over Although gonanes have greater time.27 In the case of continuous use, all progestational activity, no trial has bleeding is unscheduled, and any bleed- determined which progestin has the best ing is considered breakthrough bleeding. bleeding profile. A recent Cochrane re- Multiphasic OC regimens were de- view comparing different progestins veloped with the intention of decreasing fast track did find that, compared with pills con- breakthrough bleeding by mimicking the Though a patient taining levonorgestrel, those containing rising and falling pattern of estrogen and gestodene may be associated with less in- progesterone in the normal menstrual cy- may experience termenstrual bleeding.24 cle.28 After the introduction of the biphasic more breakthrough Regardless of the progestin used or pill, an increase in breakthrough bleeding bleeding on an the quantity of EE, breakthrough bleed- was noted, which led to the development extended-cycle ing generally decreases with each succes- of the triphasic pill.29 Though the multi- regimen, the num- sive cycle. One study that compared 2 phasic hypothesis is physiologically plau- combination OCs composed of EE/nor sible, recent reviews of the literature have ber of planned and gestimate and EE/norgestrel demonstrat- found the evidence for its efficacy too unplanned bleeding ed bleeding rates of 11.3% and 10.6% limited and methodologically flawed to days may still during the first 6 cycles, which decreased draw any definitive conclusions about a decrease to 5.1% and 6.3% in cycles 13 to 24, decrease in breakthrough bleeding.30,31 respectively.25 additionally, all women using OCs can experience some cycles Patient behaviors are contributory without a withdrawal bleed—a menstru- Skipping a pill is a common cause of al abnormality that may be concerning to breakthrough bleeding.5 Compliance those who desire a menstrual period as with any OC regimen is crucial to achiev- confirmation that they are not pregnant. ing a regular and predictable bleeding Comparing regimens. OC regimens are pattern. Of 6,676 women surveyed ret- available as biphasic, triphasic, extend- rospectively, 19% reported missing 1 or ed-cycle, and continuous use. Women more pills per cycle, and 10% reported using extended-cycle contraceptives may missing 2 or more pills per cycle.32 Pro-

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table 2 and contraceptive efficacy.36 Medica- tions that induce the cytochrome P-450 What to review with patients who are starting a combination OC system (CYP450) in the liver increase the metabolism of OCs. anticonvulsants, • Breakthrough bleeding is common in the initial months after starting OCs the antituberculosis agent rifampin, and • Breakthrough bleeding, if experienced, usually diminishes over the first antifungals such as griseofulvin can in- 3 months of OC use and abates by the 4th cycle crease the clearance of steroid hormones and thus lead to breakthrough bleeding. • Skipping even 1 pill can result in breakthrough bleeding The herbal supplement St. John’s wort, • Avoidance of breakthrough bleeding can be aided by taking your pill at commonly used for mild or moderate the same time every day; you may find it helpful to make pill-taking part depression, is associated with CYP450 of another daily routine such as tooth brushing induction. It has been shown to increase • Tell me about other medications you are taking, including over-the-counter the incidence of breakthrough bleeding preparations and herbal supplements and probably ovulation in women tak- 37 • If you smoke, the chances of breakthrough bleeding are increased ing an OC. Smoking is associated with such anti- • If bleeding continues beyond the 4th cycle, there are diagnostic tests estrogenic effects as early menopause, available to explore possible underlying causes osteoporosis, and menstrual abnormali- • If bleeding continues without adequate explanation and despite adherence ties.38 these effects may be related to to the regimen, we can try switching you to a different formulation to see if induction of hepatic estrogen and pro- that helps gesterone metabolism by smoking.39,40 Before receiving OCs, women are made aware of the relationship between spective studies have found even higher smoking, OCs, and an increased risk of rates of inconsistent use. myocardial infarction, stroke, and venous When an electronic device was used thromboembolism.41 they should also to monitor pill ingestion, as many as 81% understand that the anti-estrogenic effect of women were found to miss at least 1 of smoking may lower estrogen levels and fast track pill per cycle and up to 51% missed 3 or lead to breakthrough bleeding, even in Skipping pills, more pills per cycle.33 women who are reliable pill-takers.42,43 Other side effects also undermine Smoking appears to have a dose-re- smoking, and adherence. For example, women expe- sponse relationship with breakthrough taking certain riencing nausea may skip pills, which bleeding. Increasing levels of smoking medications and leads to breakthrough bleeding and, have been associated with an increased herbal supplements ultimately, discontinuation.34 Patients risk of spotting or bleeding in each cy- are common causes need to understand the impact of skip- cle.44 The difference in cycle control be- ping pills. Women who report irregular tween smokers and nonsmokers appears of breakthrough bleeding are 1.6 to 1.7 times more likely to be more pronounced with each cycle. bleeding than those not reporting this side effect Smokers demonstrate a 30% elevation to miss 2 or more pills per cycle.5 Even 1 in the risk of bleeding irregularities com- missed pill can increase the risk of bleed- pared with nonsmokers in the first cycle ing irregularities.35 of use, which rises to an 86% increased Failure to take the pill at the same time risk by the sixth cycle. every day and poor comprehension of Reports conflict regarding the re- pill-taking instructions are other strong lationship between smoking and con- predictors of inconsistent use and break- traceptive efficacy, suggesting that con- through bleeding.32 founding factors like compliance may be Taking some prescription and over-the- more important than the antihormonal counter medications, as well as herbal effect of cigarettes.45 Nevertheless, wom- supplements, may interfere with the ac- en who smoke should be informed of tivity of OCs to alter bleeding patterns this potential complicating factor to OC

58 OBG M a n a g e m e n t • A p r i l 2 0 0 7 use and as yet another reason to encour- naire at the pharmacy while they wait- age smoking cessation. ed.48 Over one third (34.5%) reported they had not received counseling from Bleeding is sometimes pathologic their healthcare provider about break- When a woman experiences difficult cy- through bleeding. Furthermore, only cle control after the first 3 to 4 months of 28.3% of women who were counseled, OC use, consider the possibility of benign and 26.1% of women who were not and malignant growths, including endo- counseled, gave the optimal response to metrial polyps, submucous myomas, and breakthrough bleeding as defined in this cervical or endometrial cancer.46 addi- study (“continue taking pill and not call tionally, contraceptive failure must always my doctor”). be a consideration, and what appears to Lack of counseling can lead to poor be breakthrough bleeding may actually method satisfaction and significant cost represent bleeding in early pregnancy. expenditures because of visits and phone Cervicitis is an important but largely calls by women experiencing unexpected unrecognized source of unplanned bleed- bothersome side effects.5 Compared with ing in women using OCs. Causative or- women who reported the highest satis- ganisms include Chlamydia trachomatis, faction with the care they received from Neisseria gonorrhoeae, and Trichomon- their provider, those reporting the lowest as vaginalis.22 Intermenstrual bleeding scores were 1.6 to 2.2 times as likely to in women previously well controlled on be dissatisfied with the pill. OCs is particularly suggestive of asymp- Inform women that breakthrough tomatic chlamydial cervicitis. bleeding is common in the first 3 or 4 Krettek et al47 found that 29.2% cycles of OC use, that bleeding irregu- of women who had been taking OCs larities tend to decline with each succes- for more than 3 months and presented sive cycle, and that they should not dis- with intermenstrual spotting had a posi- continue pill use without discussing their tive test for C. trachomatis. By compari- concerns with you. Remind women to son, chlamydial cervicitis was found in keep sanitary protection with them dur- fast track 10.7% of matched controls taking OCs ing the first few months. Tell the patient that without spotting who were screened for The impact of poor counseling was symptoms of vaginitis or high-risk sexu- underscored in a study of women en- bleeding is common, al behavior, and in just 6.1% of women rolled in clinical trials of OCs, contra- and usually declines undergoing routine screening before the ceptive vaginal rings, and Depo-Provera. after 3 or 4 months initiation of contraception. Women taking an OC were the least likely to have been warned of menstrual irregularities and thus tended to Three-pronged management stop using that method more often than Managing breakthrough bleeding in- those using a ring or Depo-Provera.49 Of volves effective pretreatment; ongoing women who discontinue OCs, 47% use counseling and reassurance; and timely a less effective method and 19% use no and appropriate testing (Table 2). In method at all.1 some cases, pill-switching or other forms Give specific instructions for spe- of medical management may be helpful, cific regimens. Given the array of OC but these options are largely unproven. regimens available, make sure women know how to take them properly. This Counseling reduces anxiety, will help ensure contraceptive efficacy improves satisfaction, adherence and cycle control. Women who do not In a recent survey, 649 Canadian women understand pill-package instructions are who were picking up prescriptions for up to 2.8 times more likely to miss pills, OCs were asked to complete a question- which increases the risk of breakthrough

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bleeding and impacts contraceptive effi- Aside from changing from a mul- cacy.5 Among women who were coun- tiphasic to a monophasic formulation, seled about the consequences of missed altering the progestin component is of- pills, 76% reported knowing what to ten a first step in trying to control break- do in response (“use another form of through bleeding.46 An OC with a gonane birth control that month”). Of women rather than an estrane progestin may be who received no such counseling, only beneficial as this class of progestins may 48% gave the appropriate response provide more consistent hormonal ef- (P<.001).48 fects on the endometrium. To improve adherence, advise wom- Choosing an OC with a higher quan- en to establish a routine for pill-taking: tity of EE may also help, particularly for taking the pill at the same time each day women using 20 μg pills. When possible, or linking pill ingestion with another the same progestin should be used. daily activity, such as tooth brushing. You may want to start a trial of con- Women without an established routine jugated estrogen, 1.25 mg, or estradiol, 2 were 3.6 times more likely to miss 2 or mg, administered for 7 days when bleed- more pills per cycle than women with a ing occurs. This can be repeated if neces- routine.5 sary; however, if breakthrough bleeding continues despite this treatment, con- Reassurance regarding efficacy sideration of a different pill or method Reassure users who take their pills rou- should be undertaken. n tinely that breakthrough bleeding and contraceptive efficacy are not linked.50 References Breakthrough bleeding is not a sign that 1. Pratt WF, Bachrach CA. What do women use when they stop using the pill? Fam Plann Perspect. 4 OCs are not working. On the other 1987;19:257–266. hand, approximately 1 million unintend- 2. Rosenberg MJ, Waugh MS. Oral contraceptive discontinuation: A prospective evaluation of frequency and ed pregnancies in the United States each reasons. Am J Obstet Gynecol. 1998;179:577–582. year are associated with misuse or discon- 3. Thorneycroft IH. Cycle control with oral contracep- fast track tinuation of OCs.51 tives: A review of the literature. Am J Obstet Gynecol. 1999;180:S280–S287. An OC user who still 4. Speroff L, Darney PD. A Clinical Guide for Contracep- When to consider diagnostic testing tion. 3rd ed. Philadelphia, Pa: Lippincott Williams & has bleeding For OC users who continue to experi- Wilkins; 2001. 5. Rosenberg MJ, Waugh MS, Burnhill MS. Compliance, after 3 or 4 cycles ence breakthrough bleeding beyond 3 counseling, and satisfaction with oral contraceptives: A prospective evaluation. Fam Plann Perspect. 1998; should have other to 4 cycles, other potential causes must 30:89–92,104. causes ruled out be ruled out using appropriate diagnos- 6. Belsey EM, Machin D, d’Arcangues C. The analysis tic tests. a pregnancy test, appropriate of vaginal bleeding patterns induced by fertility regu- with a pregnancy lating methods. World Health Organization Special testing for cervical infection, pelvic ultra- Programme of Research, Development and Research test, Pap smear, sonography, Pap smear, or endometrial Training in Human Reproduction. Contraception. 1986; 34:253–260. endometrial biopsy, biopsy may be warranted, depending on 7. ESHRE Capri Workshop Group. Ovarian and endo- clinical circumstances. metrial function during hormonal contraception. Hum or other test Reprod. 2001;16:1527–1535. 8. Kaunitz AM. Oral contraceptive estrogen dose consid- erations. Contraception. 1998;58(Suppl):15S–21S. Fall-back options 9. Preston SN. A report of a collaborative dose-response clinical study using decreasing doses of combination If breakthrough bleeding continues be- oral contraceptives. Contraception. 1972;6:17–35. yond 3 months, and other reasons, in- 10. Akerlund M, Rode A, Westergaard J. Comparative cluding poor adherence and pathologic profiles of reliability, cycle control and side effects of two oral contraceptive formulations containing 150 processes, are excluded, one option mcg desogestrel and either 30 mcg or 20 mcg ethinyl oestradiol. Br J Obstet Gynaecol. 1993;100:832– would be to provide the patient with es- 838. trogen or switch her to a different pill, 11. Gallo MF, Nanda K, Grimes DA, Schulz KF. Twenty mi- though no clinical trials support defini- crograms vs >20 microg estrogen oral contraceptives for contraception: a systematic review of randomized tive recommendations. controlled trials. Contraception. 2005;71:162–169. CONTINUED

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