It's still not clear why, but women taking antibiotics should be vigilant about unwanted pregnancies.
Women may need to use condoms or abstain from sex while taking antibiotics if they rely on hormonal contraception, as new research suggests antibiotics as a class increases unintended pregnancies.
Researchers already knew that some antibiotics induce enzymes that interfere with the metabolism of contraceptives, but studies linking this same effect with non-enzyme-inducing drugs have been small and the findings mixed.
Dr Jeffrey Aronson at the Centre for Evidence Based Medicine at the University of Oxford and his colleague decided to investigate this by reviewing the database of suspected adverse reactions published by the UK’s regulatory agency, covering the years from 1963 to 2018.
They analysed the number of unintended pregnancies reported when an individual was taking either enzyme-inducing antibiotics, non-enzyme-inducing antibiotics or one of nine non-antibiotic drugs. This control group included medication commonly used by women of child-bearing age that hasn’t been thought to affect the efficacy of oral contraceptives, such as ibuprofen and loperamide.
As expected, women taking the enzyme-inducing drugs known to interfere with oral contraceptives had a 13-fold higher risk of an unintended pregnancy and those in the control group were at no higher risk of an unintended pregnancy.
Surprisingly, those taking non-enzyme-inducing drugs such as amoxicillin, ampicillin and erythromycin had a seven-fold higher chance of an unintended pregnancy.
The authors did not have a record of who was taking contraception, and assumed for the study that all took hormonal contraception.
The findings, published in BMJ Evidence Based Medicine, challenge recommendations from the WHO and other international guidelines that there is no interaction, and no additional precautions need to be taken while on most broad-spectrum antibiotics.
Instead, Dr Alex Polyakov, a specialist in obstetrics, gynaecology and fertility, supported the authors’ recommendations to inform patients that antibiotic treatment may make their hormonal contraceptive less effective.
“If you want to avoid pregnancy really badly, I think extra precautions are warranted if you’re taking antibiotics of any description – not just rifampicin, which is known to cause contraceptive failure,” he said.
“It would be reasonable for GPs to advise women to use some sort of other form of contraception, either abstinence or a barrier contraception such as condoms, for the duration of antibiotic exposure.”
While the authors recommended using additional contraception for a week after completing the course of antibiotics, Dr Polyakov said this may be “overkill”.
More research is needed to understand why antibiotics may interfere with the pill.
The authors suggested that changes in gastrointestinal function may be responsible for altering the absorption of estrogens and progestogens.
It could also be that antibiotics change the number and type of microbes responsible for reabsorption of oestrogens in the lower small intestine, after being excreted in bile, they said.
Regardless, not all women will be affected in the same way.
“The risk will vary according to the timing of administration of the antibiotic in relation to the woman’s menstrual cycle,” they wrote. “It will also vary according to other factors, including the individual response to a fixed dose of the combined contraceptive hormones.
“It is highly unlikely that it will affect more than a subset of women.”
It’s also impossible to know what the magnitude of the risk is, said Dr Polyakov. “We simply don’t know – it could be one in 1000 or one in 10,000. Or it could be one in 10.”
This is because the incidence of unintended pregnancy found in the study is probably both underreported and overreported. Not all pregnancies will be reported by GPs to the regulator when they happen, but some unintended pregnancies may be attributed to antibiotics rather than to other factors such as forgetting the pill, he said.
“Unfortunately on the population level, it is impossible to say how strong this association is.”
More research will be needed to understand whether some of these antibiotics have more of an effect on hormonal contraceptives than others, Dr Polyakov added.
But medical director of Family Planning NSW, Dr Deborah Bateson, said the message risked muddying the waters and sowing unnecessary anxiety among patients taking the pill.
“The startling figure was that only 46 unintended pregnancies were reported [among women taking non-enzyme-inducing antibiotics] in that 55-year study period, which is extremely reassuring – even if they were underreported,” she said.
“These database reports can’t prove causality, and I would suggest that the paper doesn’t alter current advice around contraception.”
If a woman’s tolerance for the risk of pregnancy was especially low, she recommended a more reliable form of contraception than the oral contraceptive pill, such as a LARC, which wasn’t affected even by enzyme-inducing antibiotics.
