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The combined use of broad-spectrum antibiotics and hormonal birth control was associated with a higher risk of unintended pregnancy, 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 Jeffrey Aronson, DPhil, of Oxford University, and Robin Ferner, MD, of the University of Birmingham, both in England.

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 online in .

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 physiochemical factors in the gut that may affect the absorption of synthetic estrogen and progesterone.

Ferner told 麻豆传媒 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 in an email. "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.

Asked for her perspective, Carrie Cwiak, MD, MPH, director of the family planning division at Emory University School of Medicine in Atlanta, said that while the research suggests an association between unintended pregnancy and antibiotic use, "it doesn't seem to fit with some of the studies early on."

Cwiak added that some mechanisms of unintended pregnancy suggested by the investigators need further clarification, such as the possibility that antibiotic use might affect levels of ethinylestradiol -- i.e., synthetic estrogen -- in certain patients.

"Ethinylestradiol is in fact not the main driver of contraceptive effect in hormonal contraceptives," Cwiak told 麻豆传媒. "It is the level of synthetic progesterone in the medication that you're using that provides the majority of contraceptive effect."

She noted that although the CDC for the combined use of hormonal birth control methods and broad-spectrum antibiotics, the study indicates an opportunity to further explore the interaction of these two medications.

For the study, Aronson and Ferner conducted a database review of to the U.K.'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 diarrhea 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. Diarrhea 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.

Cwiak stated that although further research is needed about the drug interactions of antibiotics and hormonal birth control, it is important to emphasize the need to counsel patients to keep using their chosen contraceptive method. When taking the medications in question, dual protection is the safest choice, she noted.

"We hear too many negative messages about birth control overall, and the benefits by far outweigh the risks," Cwiak said. "At the end of the day, our message has to be birth control positive."

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