Antibiotic use with hormonal contraception linked to 7x higher risk of unwanted pregnancy

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The combined use of broad-spectrum antibiotics and hormonal birth control was associated with a higher risk of unintended pregnancy, MedPageToday reports researchers found. Individuals who used antibiotics while taking hormonal contraceptives – such as the pill, patch, or ring – were nearly seven times as likely to get pregnant (odds ratio 6.7, 95% CI 2.9-16.0), according to Dr Jeffrey Aronson, of Oxford University, and Dr Robin Ferner of the University of Birmingham.

Enzyme-inducing medications, which have known effects on the efficacy of hormonal birth control, were associated with 13 times the risk of unintended pregnancy (OR 13.0, 95% CI 5.5-31.0), the team reported.

The researchers suggested that unintended pregnancy may occur by a few different mechanisms, including the effects of antibiotics on increasing hepatic metabolism of hormones, altering gastrointestinal function, and changing physio-chemical factors in the gut that may affect the absorption of synthetic oestrogen and progesterone.

Ferner that the findings should encourage physicians to tell their patients that “it’s safest to take extra precautions to avoid unintended pregnancy.”

“We don’t know from our data how many unplanned pregnancies occur as a result of broad-spectrum antibiotics,” he said. “But for some women, even a 1:1,000 chance of an unintended pregnancy would be too much.”

The researchers recommended that individuals who do not wish to get pregnant either stop having sex, or use a condom in addition to hormonal birth control while taking antibiotics and for 7 days after completing the course.

For the study, Aronson and Ferner conducted a database review of Yellow Card reports to the UK’s Medicines and Healthcare Products Regulatory Agency, including all reports that mentioned unintended pregnancy.

The researchers looked at three different kinds of medications: non-enzyme-inducing antibiotics, enzyme-inducers, and commonly used control medicines, including ibuprofen and citalopram. Non-enzyme-inducing medications included amoxicillin, ampicillin, cephalexin, ciprofloxacin, erythromycin, metronidazole, nitrofurantoin, oxytetracycline, and trimethoprim.

The primary outcome of the study was unintended pregnancy. The researchers also assessed for congenital abnormalities, cardiac arrhythmias, and headaches, and looked at diarrhoea as a potential confounding factor.

In the analysis of 173,073 spontaneous reports, the investigators found that patients who took enzyme-inducing medications had the highest rate of unintended pregnancy (119 per 100,000, 95% CI 81-156). The rate of unintended pregnancy was 62 per 100,000 among those who took antibiotics (95% CI 44-79), and 6 per 100,000 among those in the control group (95% CI 2-16).

The risk of congenital abnormalities was higher among individuals who took enzyme-inducing medications, but not among the cohort who took broad-spectrum antibiotics. Diarrhoea was not a confounding factor.

Aronson and Ferner acknowledged that the research is limited based on the use of adverse reports, so the actual number of unintended pregnancies and combined users of hormonal contraceptives and antibiotics is thus unknown. In addition, it was not possible to calculate absolute risk.

Background: Enzyme-inducing antibacterial drugs can impair the efficacy of hormonal contraceptives. Suspicion that other antibiotics might do likewise led to advice that extra contraceptive precautions should be taken during a course of antibiotics. However, current advice is that the purported interaction does not occur, based on small studies observing few pregnancies, assuming that all women are susceptible, and without measuring unbound hormone concentrations.
Objective: To test the null hypothesis that antibiotics do not impair the effectiveness of oral contraceptives.
Design: A database review of Yellow Card reports to the UK’s Medicines and Healthcare products Regulatory Agency.
Data: Spontaneous reports of suspected adverse drug reactions in people taking antibacterial drugs (n=74 623), enzyme-inducing medicines (n=32 872), or control medicines (n=65 578).
Main outcome measures: Reports of the primary outcome—unintended pregnancies; reports of cardiac arrhythmias and headaches (control events); reports of congenital abnormalities (positive control events); and reports of diarrhoea (a possible confounding factor).
Results: Compared with control medicines, unintended pregnancies were seven times more commonly reported with antibiotics and 13 times more commonly reported with enzyme inducers (the positive controls). Congenital abnormalities were reported seven times more often with enzyme inducers but were not more common with antibiotics. Diarrhoea was not a confounding factor.
Conclusion: This study provides a signal that antibacterial drugs may reduce the efficacy of hormonal contraceptives. Women taking hormonal contraceptives should be warned that antibiotics may impair their effectiveness. Extra precautions can be taken during a course of antibiotics; an unintended pregnancy is a life-changing event.

Jeffrey K Aronson, Robin E Ferner


Full MedPageToday report


BMJ Evidence Based Medicine abstract

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