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Family Practice THE JOURNAL OF FAMILY PRACTICE Patricia A. Lohr, MD, and Oral contraceptives Mitchell D. Creinin, MD Department of Obstetrics, Gynecology and Reproductive and breakthrough bleeding: Sciences, University of Pittsburgh, Pittsburgh, PA What patients need to know Managing expectations is as important as adjusting formulations Practice recommendations Understandable concern, embarrass- T Lack of adherence is a common cause of ment, and annoyance lead these women to 1,2 breakthrough bleeding.® Dowden Focus counseling Healthabandon Media OCs. What they often don’t on ensuring that patients understand and know, though, is that breakthrough bleed- can follow pill-taking instructions before ing generally is greatest in the first 3 to 4 Copyrightswitching pillsFor or method personal (A). use onlymonths after starting OCs,3 and it steadily declines and stabilizes by the end of the T If breakthrough bleeding extends beyond fourth cycle.4 Timely counsel could enable 4 cycles and a woman wish to continue many of these women to cope with the using oral contraceptives, consider switch- bleeding and stick with an effective contra- ing to a pill with a higher ethinyl estradiol ceptive method. Additional incentives are (EE):progestin ratio, either by increasing noncontraceptive benefits of OCs: improved the EE dose or decreasing the relative menstrual regularity and decreased menstru- progestin dose (C). al blood loss, dysmenorrhea, and risk of T Breakthrough bleeding may be due to ovarian and endometrial cancer. progestin type; switching from an estrane Women who discontinue OCs on their to a gonane may reduce it (C). own switch to less effective methods of 1,2 T Women who have breakthrough bleeding birth control or use no method. after having well-controlled menstrual Consequences may be unexpected preg- 5 cycles on oral contraceptives should be nancies and increased abortion rates. assessed for for causes not related to With patients who are using OCs, it would their birth control pills, such as pregnancy, be appropriate to ask periodically whether cervicitis, smoking, or interactions with they are satisfied with OC use. medications (A). In this review we discuss the mecha- nisms and management of breakthrough n 1982, more than 20% of women bleeding in women taking OCs, and pro- surveyed in a nationally representative vide tips for counseling that may help C O RRESPON D ENC E I sample had discontinued oral contra- decrease the risk of discontinuation due to Patricia A. Lohr, MD, University ceptives (OCs) on their own or at the menstrual abnormalities in the initial of Pittsburgh, Magee-Womens recommendation of their physician due to months of use. Hospital, 300 Halket Street, 1 Pittsburgh, PA 15213-3180. bleeding or spotting. Sadly, the percentage Breakthrough bleeding in this review E-mail: [email protected] today has not decreased much. refers to either unplanned spotting or 872 VOL 55, NO 10 / OCTOBER 2006 THE JOURNAL OF FAMILY PRACTICE For mass reproduction, content licensing and permissions contact Dowden Health Media. Oral contraceptives and breakthrough bleeding L bleeding, regardless of requirement for How is irregular bleeding defined? protection—unless defined otherwise by a specific study under discussion. or the purpose of performing studies, unplanned bleeding is F classified by the World Health Organization into 2 categories: 1) breakthrough bleeding, which requires sanitary protection, and 2) T 4 factors contribute 6 to breakthrough bleeding spotting, which does not require sanitary protection. Despite this formal classification, trials have varied in their terminology and Breakthrough bleeding may be due to method of recording menstrual irregularities, making comparisons any the following factors: 1) physiologic between studies difficult. In addition, there is wide variation among effects of OCs on the endometrium, 2) women in tolerance to bleeding abnormalities, perceptions of OC-related parameters, including dose, heavy vs light bleeding, as well as the need for protection.3 formulation, and regimen, 3) patient Nevertheless, menstrual abnormalities are consistently cited as behavior, including compliance, using a common reason for discontinuing OCs. A prospective US study concomitant medications, and smoking, of 1657 women performed in the 1990s reported that 37% of OC and 4) benign or malignant pathology. users had stopped taking OCs by 6 months after starting a new prescription because of side effects.2 Irregular bleeding was the OCs and the endometrium: Estrogen- most common cause; cited by 12% of women, followed by nausea, progestin balance significant weight gain, and mood changes, which ranged from 5% to 7%. Progestin and estrogen in combination OCs have profound effects on the endometrium, which, though not con- containing 30 µg or 35 µg EE have not tributing to contraception, do lead to a been very useful for judging breakthrough predictable pattern of bleeding or such bleeding rates because the products often problems as breakthrough bleeding or lack also vary in the phasing and type of prog- of withdrawal bleed. estin. Some studies show more break- Normally, estrogen causes the through bleeding with 20 µg EE pills,9–11 endometrium to proliferate. Progesterone but others show equal or improved cycle stabilizes the growing uterine lining. Since control with the lower EE dose. the introduction of OCs in 1960, the trend Estrogen-progestin balance is more FAST TRACK in formulation has been to use the least important than absolute level of estrogen. Low-level estrogen amount of hormone necessary to inhibit Endrikat et al12 conducted a study to ovulation. Given that the progestin is pri- compare two 20 µg EE pills containing in combination marily responsible for the contraceptive different progestins, and to compare 2 with a progestin efficacy of OCs, the risk of pregnancy is levonorgestrel-based formulations with is excellent for not altered with decreases in the estrogen differing EE amounts. An OC of 20 µg component. However, significantly lower- EE/100 µg levonorgestrel was compared contraception but ing the estrogen in OCs may account for with a preparation of 20 µg EE/500 mg may not sustain breakthrough bleeding. Unplanned bleed- norethisterone. A 30 µg EE/150 mg lev- endometrial ing, though, is not dependent solely on the onorgestrel pill was used as a standard integrity in estrogen component as variations in the reference preparation. progestin can contribute to breakthrough Overall, the 30 µg EE preparation some women bleeding.7 showed a lower cumulative incidence of Most OC users in the US take low- breakthrough bleeding compared with the dose formulations, so designated because 20 µg EE/100 µg levonorgestrel and 20 µg the estrogen component is <50 µg. This EE/500 µg norethisterone pills over 13 level of estrogen in combination with a cycles (1.0% vs 4.1% vs 11.7%, respec- progestin provides excellent contraceptive tively). However, the 20 µg EE/500 µg efficacy, but may be insufficient to sustain norethisterone pills consistently had higher endometrial integrity in some women.8 breakthrough bleeding rates than the 20 µg Studies that have compared OCs contain- EE/100 µg levonorgestrel pill. This suggests ing 20 µg ethinyl estradiol (EE) with those that, although the higher EE component www.jfponline.com VOL 55, NO 10 / OCTOBER 2006 873 THE JOURNAL OF FAMILY PRACTICE T ABLE 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 mg 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) Drospirinone (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) Drospirinone (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 mcg) 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 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
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