Do we need to start worrying about the pill?

Science HeaderThe first ever method of birth control was used by the Ancient Egyptians. They used cotton, dates, honey and acacia as a suppository, which coincidentally worked as fermented acacia, which is proven to have spermicidal properties. There was very little development in the field of contraceptives until, thankfully, science finally stepped up its game in the 1900s. In 1951, Carl Djerassi, a chemist working in Mexico City, synthesised the first viable “birth control” hormones in his lab. This sparked a race amongst scientists to create the first human safe product, and by the year 1957, the FDA has approved the first ever oral contraceptive pill (albeit only for use in severe menstrual disorders). In 1960 the first ever human pill for the prevention of unwanted pregnancy was approved and by 1962, over 1.2 million American women are using it. Within one year, this figure doubled.

Since Djerassi’s work, the popularity of birth control pills has increased exponentially, making it the leading choice from female contraception in the world. Although there has been some controversy about the dangerous side effects of the pill in previous years, these claims tended to be specific to one brand or compound only. However, a research group at the University of Salzberg has linked certain classes of the pill to changes in grey matter volume in the brain.

All contraceptive pills contain progestogens, but there are three main sub-classes of the contraceptive pill termed ‘generations’. First generation pill contain progestogens such as norethisterone. Second generation compounds contain molecules such as levenorgestrel and norgestrel, while third generation tablets tend to have desogestrel and similar chemicals in their dosage. Second generation compounds are the most common as they have less side effects that first generation and are much cheaper than the third. These pills are mostly either androgenic or antiandrogenic, which tells you roughly what their metabolism is and to which receptors they attach in the body.


The study, carried out by Belinda Pletzer et al. at the Centre for Neurocognitive Research in the University of Salzburg, involved 50 women undergoing a series of non-invasive neurological testing. Within the subject group, there were 20 naturally cycling women, 18 women taking androgenic contraceptives and 22 women taking antiandrogenic contraceptives. Magnetic Resonance Imaging (MRI) scans of the subjects brains revealed that the participants taking the antiandrogenic pills had significantly larger volumes of grey matter compared to naturally cycling women. Conversely, the women taking androgenic pills were shown to have much lower grey matter volumes in the brain when compared to naturally cycling women. The regions in the brain affected were the hippocampus, related to function and memory, and the fusiform face area (FFA), thought to be related to facial recognition.

A sample group were then subjected to a memory and recognition test. All 50 women were shown 30 photos of different faces for a period of 30 seconds, and asked to memorise them. After the time had been elapsed, they were presented with 60 facial photos and asked to pick out the 30 that they were previously asked to memorise. The results agreed with the MRI scans conducted.“Face recognition performance was significantly better in users of anti-androgenic progestins compared to the other groups,” Dr. Pletzer has written in the abstract of the published study.

When one considers the MRI study and the facial recognition study, there is strong evidence that the nature of the oral contraceptive can alter the brains structure.  In Brain Research¸the renowned scientific journal, Dr. Pletzer explains what the findings can tell scientists about the brain. “Morphological differences between active and inactive pill phase were observed in users of androgenic progestins,” she writes. “These findings suggest differential effects of androgenic and anti-androgenic progestins on human brain structure.” At a glance, this study and its findings provide conclusive evidence the antiandrogenic pills reduce grey matter volume.


But there are indications that the findings of this study could be statistically flawed. The University of Salzburg researchers failed to screen for two key factors: the length of time for which an individual was taking that dosage of oral contraceptive, and the age of the participant. These two characteristics could have had a monumental effect of the findings of the study. It is possible that the reason for some individuals having altered brain structure was not due to the nature of the contraceptive at all, but the time for which the individual was actually taking the pill – any effects would only increase to a measurable rate after a lot of exposure.

With regard to not screening for age, the brain develops in both size and volume until at least the mid-20s according to research conducted at Massachusetts Institute of Technology. If any of the participants were aged less than 30, it is possible that their brain wasn’t fully developed and any anomalies in grey matter volume could be due to age rather than the pill.One of the more damaging flaws of this study was the sample size. With only 50 participants involved, biologists and statisticians have claimed that the changes in brain volume could be attributed to genetic inheritance or a coincidence rather than any medication.

In a preliminary survey conducted by Trinity News of 52 students attending Irish colleges such as Trinity College Dublin, National College of Art and Design  (NCAD) and Dublin Institute of Technology (DIT), 37% of participants (19 responses) were using an androgenic pill. Of this 37% ,only five students reported any noticeable change in facial recognition ability or memory retention, having taken the pill for more than one year but less than five. In the remaining group of 33 students who did instead take antiandrogenic or neither type of contraceptive, only one respondent reported having experienced any sort of memory loss in the two years she had been taking the pill. The participants were not told what the survey was about to avoid the introduction of any bias and there was plenty of room for explanation of answers. Although this survey only serves purpose as a very rough approximation of the truth, the statistics are insignificant with reference to the claims of the study.

Should consumers worry?

Before everyone starts changing their medication or trying out the ancient Egyptian method, you should be aware that studies of hormonal metabolism are still in very early stages. The brain still holds many mysteries in its functionality and pathways, and although this study may shed some light on the possible unknown side effects of oral contraceptives it is not yet known whether there is anything to actually be worried about in terms of reducing brain volume.

Illustration: Sarah Larragy

Dylan Lynch

Dylan is an SF Medicinal Chemist studying at Trinity College Dublin, and is the Science & Technology Editor.