Does Hormonal Contraception Affect the Brain?

‘When using hormonal contraception, it is often believed that this method only affects the reproductive system. The possibility that its effects may be systemic and have an impact on the entire body is often not even considered. Therefore, the main question of our study is: what is the effect on the brain, given that it contains a large number of hormone receptors and that hormonal balance changes?’ explained Prof. Ramunė Grikšienė.

Researchers from the Life Sciences Center of Vilnius University – Prof. Ramunė Grikšienė, Dr Rimantė Gaižauskaitė, and Dr Ingrida Zelionkaitė – have analysed the links between hormonal contraception and brain activity. Their research shows that contraception is not merely a matter of gynecology: when hormonal balance is altered, it is essential to consider not only the reproductive system but also how hormonal changes affect emotion processing, attention, and cognitive functions – all intrinsically linked to brain activity.

How are hormones related to the brain? 

To understand why hormonal contraception is not solely associated with reproduction, it is vital to recall a fundamental biological principle: hormones circulate in the bloodstream and act at their receptors. Hormones produced by the sex glands reach various tissues, and the brain is no exception.

Prof. Grikšienė pointed out that the brain has receptors for the main sex hormones: ‘Many of these receptors are found in the hippocampus, a brain structure associated with memory, spatial orientation, and emotions. Studies show that it contains receptors for estrogen, progesterone, and androgens.’

In addition to the hippocampus, hormone receptors are also found in the prefrontal cortex – the brain region responsible for decision-making, predicting consequences, working memory, and the conscious evaluation of emotions. Hormone receptors are also abundant in the hypothalamus, which regulates reproduction as well as the stress response, growth, and metabolic rate. They are also present in the amygdala, which is associated with emotions and automatic emotional responses.

Hormonal rhythm: what changes with contraception?

The natural menstrual cycle is a constantly changing hormonal system. ‘During the natural cycle, hormone levels fluctuate: in some phases they are low, in others high,’ said Prof. Grikšienė. According to the researcher, these fluctuations are essential not only for the reproductive system but for the body’s overall hormonal balance.

In scientific research, cycle phases are carefully selected to compare different hormonal states. For example, the early follicular phase (menstruation and a few days after) is characterised by low levels of estrogen and progesterone. ‘Therefore, this phase is often used as a control phase. If a study includes women but does not aim to analyse the cycle in detail, it is safest to choose this phase, which is easy to determine, as it is directly linked to the first day of menstruation – during this time, the levels of the main sex hormones are relatively stable and low,’ explained Prof. Grikšienė.

This cycle changes when hormonal contraception is used. ‘If hormones fluctuate during the natural cycle and affect the entire body and brain, then with hormonal contraception, which suppresses ovarian activity, natural hormone levels remain consistently low. When a woman takes synthetic hormones – usually as a once-daily tablet – their levels fluctuate differently: after the tablet is ingested, hormone levels rise, then fall, and the pattern repeats. These are not natural fluctuations and do not correspond to the natural cycle,’ the researcher noted.

Contraception affects women differently

Hormonal contraception is classified, according to its composition, as combined or progestin-only. ‘The most common form of combined hormonal contraception is the tablet, which contains two types of hormones: a synthetic estrogen and a progestin. The latter is a synthetic compound that mimics the effects of natural progesterone,’ the researcher explained.

The researchers emphasise that differences exist not only in the form of contraception (such as tablets or intrauterine devices), but also in the active ingredients. This is why women’s experiences with contraception can be highly diverse: ‘Progestins differ from one another. These differences are reflected in how they interact with receptors for natural hormones: some may be up to ten times more potent than natural progesterone, resulting in significantly stronger effects,’ said Prof. Grikšienė. According to her, another reason why understanding the effects of progestins is essential is that they can interact not only with progesterone receptors: ‘Progestins can also interact with receptors for other hormones and neurotransmitters, such as androgens, estrogens, glucocorticoids (cortisol), and serotonin, thereby further expanding their effects on the body and brain.’

According to Dr Gaižauskaitė, androgenic and anti-androgenic progestins are also important: ‘Androgenic progestins can bind to androgen (testosterone) receptors and activate them, whereas anti-androgenic progestins also bind to these receptors but inhibit androgenic activity.’ Such differences explain why some types of oral contraceptives are more commonly associated with specific effects on the skin or hair growth, while others are not. This diversity of active compounds becomes particularly important when evaluating not only bodily responses but also the potential differential effects on brain activity.

Researchers studied working memory, spatial thinking, and emotions

To understand how hormonal contraception may affect the brain, researchers from Vilnius University adopted an approach that integrates both behavioural measures and brain responses. Across several studies, they compared women in different phases of their natural menstrual cycle, women using oral hormonal contraceptives, and women with hormonal intrauterine devices; a group of men was also included for comparison.

Participants completed cognitive tasks assessing spatial thinking and working memory, as well as emotion-related tasks designed to evaluate emotional processing and regulation. In addition to task performance, the researchers recorded further indicators, including brain activity and eye movements. This allowed them to examine not only the final responses but also how the information was processed: where attention was directed, how participants responded to emotional stimuli, and how much effort was required to regulate emotions.

The researchers assessed working memory using a change-detection task: participants were briefly shown three or four letters, and, after a short delay, the letters were presented again – either identical or slightly altered. The participants’ task was to determine whether the second set of letters matched the first. ‘We did not observe an overall group effect, but differences emerged when memory load increased,’ said Dr Gaižauskaitė.

The difference became apparent when participants had to memorise four letters: women in the early follicular phase performed worse than those using oral hormonal contraception. ‘One possible interpretation is that hormonal background may be more closely related to working memory performance precisely when the task becomes more complex and approaches the limits of human working memory capacity,’ the researcher noted. 

The conditions of the experiment are no less important than the results

One of the most prominent gender stereotypes about cognitive abilities is the belief that men are better at spatial orientation. In scientific research, this question is often examined using spatial tasks, one of the most classic being the so-called mental rotation task. In this task, participants are presented with two three-dimensional shapes: one is shown upright, and the other is rotated at a certain angle. ‘The participant’s task is to determine whether the shapes are identical or mirror images of one another. As the angle of rotation increases, the task becomes progressively more difficult,’ explained Dr Gaižauskaitė.

Results from this task have consistently revealed sex differences in previous research. ‘Sex differences (with men typically performing better), as well as differences related to women’s hormonal background (with lower performance observed at higher levels of estrogen and/or progesterone), have been reported fairly consistently in the scientific literature for this task,’ stated Dr Gaižauskaitė. However, studies by the researchers have shown that outcomes may depend on how a person perceives the task and the strategy they choose. 

In most studies, the task is presented with fairly explicit instructions: participants are told to ‘rotate the shape in their mind’ and then decide whether the shapes are identical. In one study conducted by the research team, the task condition was modified: ‘We did not provide explicit instructions to ‘rotate the shape’ mentally; instead, we allowed participants to choose spontaneously how to solve the task,’ said researcher Dr Gaižauskaitė. ‘Interestingly, no significant differences emerged: the patterns were very similar regardless of gender or hormonal status – whether women were using oral contraception, had a hormonal intrauterine device, or were in a natural menstrual cycle, their performance was comparable. This suggests that the differences between genders, or between women with different hormonal backgrounds observed in previous studies, may not be due to differences in spatial ability, but rather to differences in how task instructions are interpreted or implemented before performing the task.’

Contraception and emotions

Researchers assess emotions from multiple perspectives. It is important not only how individuals describe their emotional state, but also how they perform tasks and how their brains respond to emotional stimuli. Dr Zelionkaitė explains that in this study, emotions were evaluated at several levels. First, psychological traits were assessed using questionnaires measuring anxiety, depression, alexithymia, and the use of emotion regulation strategies in daily life. 

‘We aimed to evaluate these aspects because some studies suggest that women who use contraception are more likely to report negative emotional states. However, we did not obtain results indicating higher levels of depression or anxiety among women using contraception,’ said Dr Zelionkaitė. The researcher emphasised individual differences: some women are more sensitive to hormonal changes, while others are less affected; the age at which hormonal contraception is first taken and the duration of its use can also be significant.

Another part of the study focused on emotion regulation. Participants were shown emotional images and asked either to simply observe them or to regulate their emotions through cognitive reappraisal. ‘This is one of the most commonly used emotion regulation strategies in research because it is relatively easy to apply: essentially, it involves changing one’s interpretation of what is seen in the image,’ explained Dr Zelionkaitė.

Two aspects were evaluated in this task: how the participants themselves rated the images and how their brains responded to them. The subjective ratings did not differ between the groups – in other words, women with different hormonal profiles reported similar emotional experiences. However, differences emerged in the recorded electrical brain activity. 

‘The electrophysiological brain data showed that women who had a hormonal intrauterine device stood out the most,’ said Dr Zelionkaitė. Electroencephalography studies analyse specific components of brain signals that help determine how much attention and cognitive control are required to perform a task. It was observed that brain signals from women with a hormonal intrauterine device showed greater engagement of attention and control mechanisms, suggesting that regulating emotions required greater effort for them.

What do eye movements reveal?

Previous group studies had shown that women using oral contraceptives may exhibit reduced brain responses to negative emotional images. This raised the question of how to interpret such findings – whether they reflect differences in emotional reactivity or whether they may instead be related to the allocation of attention during passive viewing tasks. Prof. Grikšienė explains that this is how the idea for the eye movement study emerged: ‘When we observed in one study that women taking hormonal contraceptive tablets showed lower brain responses to negative emotional images, we began to consider what this might mean. Perhaps it is not solely a matter of emotional reactivity, but also of attention – whether women engage equally in passive viewing, look at the same areas of an image, or direct their attention to different elements. For this reason, we conducted an additional study involving eye movement tracking.’

The study analysed where participants directed their gaze, i.e what they looked at and for how long. ‘In negative images, the areas depicting injuries attracted the most attention across all groups,’ said Dr Zelionkaitė. However, differences emerged in responses to neutral and erotic images. Women taking contraceptive tablets spent less time looking at faces than women in a natural menstrual cycle, and their gaze behaviour was more similar to that of men in this respect. According to the researchers, these findings raise new questions about how social information is processed, what shorter gaze duration towards faces may indicate, and how this relates to the recognition and interpretation of social signals. 

From research to practical solutions

Prof. Grikšienė emphasises that the effects of hormonal contraception should be considered more broadly than solely through the lens of reproduction. ‘Hormonal contraception affects the entire body. And that is nothing unusual,’ she said. Therefore, if a woman notices clear changes in her well-being – for example, a deterioration in mood, increased anxiety, or other symptoms – such experiences may be linked to the effects of hormonal changes on the body.

The researchers note that in some cases, hormonal contraception is prescribed not only for pregnancy prevention but also as part of medical treatment, which is why decisions should be made only in consultation with a doctor. According to the researchers, what matters most is not a ‘one-size-fits-all’ approach, but informed choice and dialogue with a specialist: if noticeable changes in well-being occur, it is essential to discuss them, evaluate possible contributing factors, and, if necessary, review the chosen method together with a doctor.

‘The future direction of this research has clear practical implications: to better understand why certain hormonal solutions are suitable for some women while others experience challenges, what mechanisms underlie these differences, and how more individualised solutions can be found,’ said Prof. Grikšienė. According to the researchers, the more we know about the links between hormones and the brain, the less room there will be for speculation – and the greater the opportunity to rely on clear, well-reasoned decisions.