Since its advent 50 years ago, the pill has helped revolutionize contraception and transform women’s lives. The pill is so popular today that over 100 million women worldwide currently use this method of contraception, and the majority of users report high levels of satisfaction.

Many women, however, experience unpleasant side effects, ranging from mood changes to androgenic effects, such as acne and unwanted hair growth. The latter are caused by the fact that some progestins (the synthetic versions of the hormone progesterone used in oral contraceptives) interact with androgen receptors. The androgens, such as testosterone, are steroid hormones that are responsible for male characteristics. Some progestins have high androgenic activity and therefore increase the chances of androgen-related side effects, but many more modern pills actually exert anti-androgenic effects.

Over the years, many studies have scrutinized these side effects, but the focus of the majority of these studies has been on metabolic and emotional effects. A few studies also looked at effects on cognitive tasks, and some found that the pill is associated with memory changes, enhancing verbal and recognition memory. The possible effects on brain structure and function, however, have been largely ignored, despite the fact that the steroid from which many progestins were derived has been demonstrated to induce changes in the brain.

A few years back, a study aimed to address this gap in our knowledge and discovered that users of oral contraceptives had larger volumes of gray matter (brain tissue consisting of nerve cell bodies) in certain areas of the brain. However, they failed to take into account the androgenic activity (androgenicity) of the progestin or control for age differences.

Building on this work, scientists from the University of Salzberg enrolled 60 women into a new study. 20 of the participants were naturally cycling, i.e. not taking oral contraceptives (OCs), 18 were using OCs containing androgenic progestins, and 22 were taking OCs containing anti-androgenic progestins.

As described in Brain Research, after controlling for age, MRI scans revealed that women using anti-androgenic progestins had significantly larger gray matter volumes in several brain regions when compared with naturally cycling women. These brain areas include the hippocampus, which is involved in learning and memory, and the fusiform face area (FFA), which is thought to be specialized for facial recognition. Furthermore, they found that volume increased with duration of use, i.e. the longer women had been taking the pill, the greater the gray matter volume in these areas. Women taking androgenic progestins, however, had smaller gray matter volumes in certain brain regions when compared with naturally cycling women.

Next, they asked women to participate in a facial recognition test, which revealed that these observed changes were related to task performance. For the task, women were presented with 30 faces, 15 male and 15 female, for 3 seconds, and asked to memorize them. Next, they were shown 60 photos, which included the 30 previous photos and 30 previously unseen photos, and asked to indicate which ones they had seen before.

The researchers found that women taking anti-androgenic progestins performed significantly better than members of the other two groups, and that performance was related to the gray matter volume in the FFA.

Taken together, this study suggests that androgenic and anti-androgenic progestins may exert differential effects on brain structure. However, this study is limited by the fact that a small sample size was used, and the fact that it is not possible to discern which compound in the combined oral contraceptive could be inducing these effects.