16 Apr 2018

Fransplaining Science: Antibiotics won't stop your pill from working

12:57 pm on 16 April 2018

In our new weekly column, Fransplaining Science,  biochemist Dr Frances-Rose Schumacher explains science.


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For most of my life I’ve been trying not to get pregnant. 

I’ve been on the contraceptive pill since I first started university and have fastidiously followed the guidelines; take the pill at the same time, avoid grapefruit, observe the “seven-day rule” (by using other forms of contraception for seven days) if I vomit or have diarrhoea, or if I take antibiotics. These rules are ingrained in my brain and have been there for well over a decade. 

So when I was recently prescribed antibiotics from my GP I told her smugly not to worry about giving me the spiel - I knew to observe the seven-day rule. But then she dropped a bombshell: The vast majority of antibiotics - including doxycycline (the one I was being prescribed) - do not interfere with modern contraceptive pills. 

This was news to me, I’m a biochemist and I like to think I know a lot about the drugs I choose to take. How could I have missed this update? Did all my friends on the pill know this and no one had told me? Was my GP even correct? Could I trust the research she had read and the advice she had given me? I wanted to understand how this advice could have changed so dramatically since 2001.
So like any intrigued biochemist would, I started reading up, researching the science behind the advice my GP gave me. And she was right, only a couple of specific antibiotics interfere with the contraceptive pill, the majority do not! 

Understanding the reasons behind changes in medical advice is valuable. Many of my friends feel they “can’t trust scientists or medical doctors” because they’re forever changing their minds, a classic example of this is the reversal on the advice regarding a high fat intake being inherently “bad for us”. But it also emcompasses what I’m writing about today.  

Considering the advice our GPs provide is based on the evidence-based hypotheses of the time, we should be happy to learn that this advice is constantly refined, altered and updated to reflect a better understanding of how our bodies work.  Such refinement, or even a complete change in advice, suggests that scientists have tested their hypotheses with an open mind and have been willing to admit their original thinking did not stand true. 

While there are differences in how modern contraceptive pills specifically function, they all contain synthetic forms of female hormones. By taking a controlled daily dose of these hormones a woman’s “natural” monthly fertility cycle is suppressed, preventing the release of mature eggs from the ovaries, so you don’t get pregnant.  

What’s interesting to me as a scientist is how medical advice - like telling women on the pill to avoid grapefruit or take extra precautions when taking antibiotics - is derived. Is it based clear scientific research and rationale? Is the message simplified to make a clear message easily understood by the masses? Why does it change?

As we’ve learnt more about the precise biochemistry of how our cells function and how pharmaceuticals work, medical advice has evolved.  In the case of the contraceptive pill, the dose of female hormone has been decreased and altered to reduce negative side effects, while still providing effective contraception.  The advice to avoid grapefruit when on the pill stands.  Eating a grapefruit at the same time as you take your pill will likely render your pill ineffective. Grapefruit contains furocoumarins, enzymes known to inhibit drug metabolising enzymes, and prevent your body from absorbing the daily dose of your pill.  The “grapefruit advice” has always been based on a specific biochemical rationale.  We’ve understood enough about the pathways that enable drugs to be metabolised that we can rationalise, test and confirm that when consumed, the level of furocoumarins in grapefruit juice are sufficient to render your pill ineffective. 

In the instance of antibiotics and the pill though, the medical advice was generalised and based in historical fact, with a conservative viewpoint.  
Aside from a few specific classes of the drugs, antibiotics work by targeting bacteria through non-enzyme inducing means.  Then there are the Rifamycin class of antibiotics such as rifampicin, which are enzyme-inducing antibiotics that do interfere with the pill.  Similar to the furocoumarins in grapefruit, this class of antibiotics alter drug metabolism and so decrease absorption. It’s seems likely to me, that given this known interaction with one class of antibiotics, medical advice was simplified to encompass all antibiotics and ensure a clear public health message.  

But as more research has been carried out and as we understand more of the ‘how’ behind the effectiveness of antibiotics and contraception, the advice medical doctors now give to patients has changed.  Such turn-abouts can seem bizarre if we think of the science behind the advice as being based on hard facts. But it is not always.  Advice medical doctors give their patients is based on ‘best-practice’ at a given time.  As we learn more about how drugs act and how our body works, the medical advice evolves.  

Scientists are taught to think in terms of hypotheses; “proposed explanations made on the basis of limited evidence as a starting point”.  Medical advice, based on the strongest and best hypotheses of the time, is therefore bound to change as we understand more of the science underlying the biological system in question.  In the case of antibiotics and contraceptive effectiveness, much has been learnt and, as such, the advice has changed.  

The pill used to contain nearly double the amount of female hormone as it does today.  With the older generational pill, research showed a decrease in female hormone in the bloodstream that coincided with women taking antibiotics.  In the context of these observations, it really was best practice to advise women that contraceptive would be ineffective if they took antibiotics while on the pill. 

But the pill that most of us take today contains nearly half the amount of synthetic hormone than earlier forms and we now know, through more-controlled research, that this lower dose is sufficient to suppress the release of mature eggs.  We also know that when taken in this lower dose, there is no detectable decrease in active hormone in the bloodstream when non-enzyme-inducing antibiotics are taken.  That is why my GP confidently advised me that my contraceptive pill would remain effective while taking a seven-day course of doxycycline.  

When considering research in all areas of science, looking retrospectively can be enlightening.  The reasons for the drop in female hormone at a higher dose and reported levels of contraceptive failure when taking antibiotics is possibly due to the side-effects of the antibiotics and not the antibiotics per se.  Many antibiotics cause patients to have diarrhoea or vomiting, and when we’re unwell many of us alter our daily routines.  These things are known to impact contraceptive effectiveness and were maybe in the past incorrectly assumed to be due to the action of the antibiotic rather than the flow-on effects of taking it. 

There is no doubt that as we learn more, much of the medical advice we receive will be different to what it is today.  An increasingly refined approach, including the personalisation of healthcare based on understanding our genetic variability, will lead to reduced side-effects and more effective care. 

Let’s celebrate these advice-changes as proof scientists are making progress in understanding the complex intricacies of the human form.