December 4, 2019

expert reaction to conference abstract looking at brain regions in women taking the contraceptive pill

A conference abstract, presented at the annual meeting of the Radiological Society of North America (RSNA) in Chicago, reports differences in brain structure in women who take contraceptive pills, when compared to those that do not. 

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

“This study is a small one and the abstract does not provide enough information to be able to assess it fully.  However it is clear that the clinical meaning is uncertain for a number of reasons in addition to the limited numbers studied.  Small studies which find “dramatic differences” should be treated extremely cautiously – it is likely that the play of chance in the findings has been underestimated.  Women who are using oral contraceptives and those who are not differ in many ways that do not relate to their oral contraceptive use.  It is not clear how similar the users and non-users of oral contraceptives were in regards to age, education, smoking, alcohol use or potentially many other factors, and it seems to be unknown if these affect the MRI results.

“Oral contraceptives are among the most carefully studied medicines and their adverse and beneficial effects are very well known.  Many of the psychiatric effects that have been postulated have been based on weak evidence and the overall quality of evidence of this type of harm is poor.

“While investigation of effects seen on MRI may be worth pursuing, this study should not be used to change any woman’s oral contraceptive use or planned use.”

Dr Ali Abbara, Clinical Senior Lecturer in Reproductive Endocrinology, Imperial College London, and member of the Society for Endocrinology, said:

“The birth control pill works in part by reducing the normal secretion of reproductive hormones from the hypothalamus, thus this finding is not surprising and would likely spontaneously reverse following cessation of the pill.  Women on the oral contraceptive pill should not be at all concerned by the findings presented in this abstract.”

Prof Derek Hill, Professor of Medical Imaging, UCL, said:

“Brain scanning can be used to precisely measure the volume of anatomical structures, provided the way the scans are collected and analysed is carefully controlled.  In this study, a group of 50 women, 21 of whom were on the contraceptive pill, had suitable brain scans which were analysed with dedicated software.  It was found that a particular structure in the centre of the brain (the hypothalamus) is smaller in those women taking the pill.

“Results like this are intriguing but must be treated with caution.  Firstly, small studies like this are susceptible to ‘false positives’ – that is random findings that would disappear in a larger study.  Secondly, it isn’t clear from this work whether the authors only studied the hypothalamus, or examined many brain structures and this one was significantly different between the group, which could increase the chance of false positive findings.  Thirdly, even if the difference in volume is real, it doesn’t mean that the contraceptive pill has damaged the brain.  A study like this tells us about associations between factors, not causation.  And even if a drug does make a part of the brain smaller that could be due to a change in fluid in that region rather than any damage to the brain cells themselves.

“In order for these results to more conclusive, it would be necessary to undertake further research on more women, including looking at the same women before and after they take the pill, and after they come off the pill, to look for some evidence of whether the change is caused by the medicine, and whether or not it is reversible.”

Prof Christopher Petkov, Professor of Comparative Neuropsychology, Newcastle University, said:

“I would be very careful about concluding that oral contraceptive use is associated with smaller hypothalamic volumes from this preliminary work being presented at a scientific meeting for the authors to discuss with the scientific community as they work towards completing their study.

“First, such meeting presentations are not peer-reviewed, nor intended to be a report that occurs when a study completes.  Thus preliminary results and impressions can change as the project goes towards completion.  Also these presentations are for the scientific community to provide feedback for the authors.

“At this stage the basis for this association between oral contraceptive use and smaller hypothalamic volumes cannot support the conclusion drawn.  The authors will no doubt seek to rule out alternative explanations, such as whether an unintended bias was introduced by the researchers doing the tracing of this region if they were aware of whether the scans came from one of the two groups (contraceptive use and not); the authors do not state if they were blind to the conditions and whether automatic segmentation would have been possible as a more objective analysis.

“More importantly, it may be that there is self-selection influencing the results, whereby individuals who happen to have smaller hypothalamus volumes also happen to take oral contraceptives, so causality cannot be assumed or established and the work is thus exploratory.

“I would be very concerned if these preliminary impressions are used to discourage oral contraceptive use, at this stage, which could have other ramifications that could otherwise be avoided if the scientific work is allowed to complete with a peer-reviewed published paper, and the authors or scientific community may determine that further science may be needed after their study completes.”  

Abstract title: ‘Oral Contraceptive Use Is Associated with Smaller Hypothalamic Volumes in Healthy Women’ by Michael Lipton.

This is a conference abstract from the annual meeting of the Radiological Society of North America (RSNA) and was published on Wednesday 4 December 2019.

There is no paper as this is not published work.

Declared interests

Prof Stephen Evans: “No conflicts of interest.”

Dr Ali Abbara: “No conflicts of interest.”

Prof Derek Hill: “No conflicts.”

None others received.