* Corrections were made to this chart following its publication in print.
TABLE 2
Progestins used in oral contraceptive formulations
| ESTRANES | GONANES | SPIROLACTONES |
|---|---|---|
| Norethindrone | Norgestrel | Drospirenone |
| Norethindrone acetate | Levonorgestrel | |
| Ethynodiol diacetate | Norgestimate | |
| Gestodene | ||
| Desogestrel |
Patient behavior contributing to breakthrough bleeding
Skipping a pill is a common cause of breakthrough bleeding.5 Compliance with any OC regimen is crucial to achieving a regular and predictable bleeding pattern. Of 6676 women surveyed retrospectively, 19% reported missing 1 or more pills per cycle, and 10% reported missing 2 or more pills per cycle.32 Prospective studies have found even higher rates of inconsistent use.
When an electronic device was used to monitor pill ingestion, up to 81% of women were found to miss at least 1 pill per cycle and up to 51% missed 3 or more pills per cycle.33
Other side effects also adversely affect adherence. For example, women experiencing nausea may skip pills, which leads to breakthrough bleeding and, ultimately, discontinuation.34 Patients need to understand the impact of skipping pills. Women who report irregular bleeding are 1.6 to 1.7 times more likely as those not reporting this side effect to miss 2 or more pills per cycle.5 Even 1 missed pill can increase the risk of bleeding irregularities.35
Failure to take the pill at the same time every day, as well as poor comprehension of pill-taking instructions, are other strong predictors of inconsistent use and breakthrough bleeding.32
Taking some prescription and over-the-counter medications, as well as herbal supplements, may interfere with the activity of OCs to alter bleeding patterns and contraceptive efficacy.36 Medications that induce the cytochrome P-450 system (CYP450) in the liver increase the metabolism of OCs. Anticonvulsants, the antituberculosis agent rifampin, and antifungals such as griseofulvin, can increase the clearance of steroid hormones and thus lead to breakthrough bleeding. The herbal supplement St. John’s Wort, commonly used for mild to moderate depression, is associated with CYP450 induction. It has been shown to increase the incidence of breakthrough bleeding and probably ovulation in women taking OCs.37
Smoking is associated with such anti-estrogenic effects as early menopause, osteoporosis, and menstrual abnormalities.38 These effects may be related to the induction of hepatic estrogen and progesterone metabolism by cigarette smoking.39,40
Before receiving OCs, women are made aware of the relationship between smoking, OCs, and an increased risk of myocardial infarction, stroke, and venous thromboembolism.41 They should also understand that the anti-estrogenic effect of smoking may lower estrogen levels and lead to breakthrough bleeding, even in women who are reliable pill-takers.42,43
Smoking appears to have a dose-response relationship with breakthrough bleeding. Increasing levels of smoking have been associated with an increased risk of spotting or bleeding in each cycle.44 The difference in cycle control between smokers and nonsmokers appears to be more pronounced with each cycle. Smokers demonstrate a 30% elevation in the risk of bleeding irregularities compared with nonsmokers in the first cycle of use, which rises to an 86% increased risk by the sixth cycle.
Reports conflict regarding the relationship between smoking and contraceptive efficacy, suggesting that confounding factors like compliance may be more important than the antihormonal effect of cigarettes.45 Nevertheless, women who smoke should be informed of this potential complicating factor to OC use and as yet another reason to encourage smoking cessation.
Pathologic causes of breakthrough bleeding
When a woman experiences difficult cycle control after the first 3 to 4 months of OC use, consider the possibility of benign and malignant growths, including endometrial polyps, submucous myomas, and cervical or endometrial cancer.46 Additionally, contraceptive failure must always be a consideration and that what appears to be breakthrough bleeding may actually represent bleeding in early pregnancy.
Cervicitis is an important but largely unrecognized source of unplanned bleeding in women using OCs. Causative organisms include chlamydia, gonorrhea, and trichomonas.22 Intermenstrual bleeding in women previously well controlled on OCs is particularly suggestive of asymptomatic chlamydia cervicitis.
Krettek et al37 found that 29.2% of women who had been taking OCs for more than 3 months and presented with intermenstrual spotting had a positive test for Chlamydia trachomatis. By comparison, chlamydia cervicitis was found in 10.7% of matched controls taking OCs without spotting who were screened for symptoms of vaginitis or high-risk sexual behavior, and in just 6.1% of women undergoing routine screening before the initiation of contraception.