Clinical Review

OCs, breakthrough bleeding, and patients’ need to know

OBG Manag. 2007 April;19(4):49-63

References

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Multiphasic OC regimens were developed with the intention of decreasing breakthrough bleeding by mimicking the rising and falling pattern of estrogen and progesterone in the normal menstrual cycle.²⁸ After the introduction of the biphasic pill, an increase in breakthrough bleeding was noted, which led to the development of the triphasic pill.²⁹ Though the multiphasic hypothesis is physiologically plausible, recent reviews of the literature have found the evidence for its efficacy too limited and methodologically flawed to draw any definitive conclusions about a decrease in breakthrough bleeding.^30,31

Patient behaviors are contributory

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 6,676 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.

TABLE 2

What to review with patients who are starting a combination OC

Breakthrough bleeding is common in the initial months after starting OCs Breakthrough bleeding, if experienced, usually diminishes over the first 3 months of OC use and abates by the 4th cycle Skipping even 1 pill can result in breakthrough bleeding Avoidance of breakthrough bleeding can be aided by taking your pill at the same time every day; you may find it helpful to make pill-taking part of another daily routine such as tooth brushing Tell me about other medications you are taking, including over-the-counter preparations and herbal supplements If you smoke, the chances of breakthrough bleeding are increased If bleeding continues beyond the 4th cycle, there are diagnostic tests available to explore possible underlying causes If bleeding continues without adequate explanation and despite adherence to the regimen, we can try switching you to a different formulation to see if that helps

Breakthrough bleeding is common in the initial months after starting OCs
Breakthrough bleeding, if experienced, usually diminishes over the first 3 months of OC use and abates by the 4th cycle
Skipping even 1 pill can result in breakthrough bleeding
Avoidance of breakthrough bleeding can be aided by taking your pill at the same time every day; you may find it helpful to make pill-taking part of another daily routine such as tooth brushing
Tell me about other medications you are taking, including over-the-counter preparations and herbal supplements
If you smoke, the chances of breakthrough bleeding are increased
If bleeding continues beyond the 4th cycle, there are diagnostic tests available to explore possible underlying causes
If bleeding continues without adequate explanation and despite adherence to the regimen, we can try switching you to a different formulation to see if that helps

When an electronic device was used to monitor pill ingestion, as many as 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 undermine 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 than 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 and 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 or moderate depression, is associated with CYP450 induction. It has been shown to increase the incidence of breakthrough bleeding and probably ovulation in women taking an OC.³⁷

Smoking is associated with such anti-estrogenic effects as early menopause, osteoporosis, and menstrual abnormalities.³⁸ these effects may be related to induction of hepatic estrogen and progesterone metabolism by 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.

Bleeding is sometimes pathologic

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 what appears to be breakthrough bleeding may actually represent bleeding in early pregnancy.