Birth control pills reduce the brain’s functional individuality

A new neuroimaging study suggests that oral contraceptive pills may alter how the brain is functionally organized. Researchers found that oral contraceptives reduce the individuality of brain network patterns and may influence connectivity in circuits associated with emotional regulation. The findings, published in the journal Human Brain Mapping, add to a growing body of research examining how hormonal contraceptives affect the brain.

Oral contraceptive pills are used by over 150 million people worldwide and represent one of the most common forms of hormonal contraception. These pills typically contain synthetic versions of the hormones estrogen and progestin, which work together to prevent pregnancy by suppressing ovulation, thickening cervical mucus, and altering the uterine lining. In doing so, they effectively interrupt the natural hormonal cycles that regulate reproductive function.

While they are widely regarded as safe and effective, their influence extends beyond the reproductive system. Because sex hormones also interact with brain regions involved in emotion, cognition, and reward, researchers have raised questions about whether oral contraceptives may alter brain function more broadly.

Some users report emotional side effects such as irritability, sadness, or mood instability, particularly during the first few months of use. In other cases, oral contraceptives are associated with mood improvements, especially for those with pre-existing hormonal mood sensitivity. Despite these individual differences, researchers still do not fully understand why some people are more vulnerable to adverse emotional effects while others are not.

Previous brain imaging studies have suggested that oral contraceptives may alter brain structure and connectivity, including in regions related to emotional regulation, memory, and social processing. However, these studies have often yielded conflicting results. Many relied on observational designs or small, cross-sectional samples, which limits the ability to draw conclusions about causality.

To address these gaps, a research team led by Gino Haase of the University of Cambridge and Nicole Petersen of UCLA conducted a randomized, double-blind, placebo-controlled crossover trial to assess whether oral contraceptive pills produce measurable changes in brain network activity and mood within individuals.

The researchers recruited 26 women between the ages of 20 and 33 who reported past negative mood symptoms when using hormonal contraceptives. Each participant completed two study arms: one in which they took oral contraceptive pills (30 µg ethinyl estradiol and 0.15 mg levonorgestrel) for 18–21 days, and one in which they took a matched placebo. A full menstrual cycle washout period separated the two arms. During both phases, participants underwent resting-state functional magnetic resonance imaging (fMRI) scans and provided daily self-reports of mood using the Daily Record of Severity of Problems (DRSP).

Blood samples confirmed that hormone levels were suppressed during the oral contraceptive phase. The researchers then analyzed brain imaging data to examine functional connectivity—patterns of synchronized activity between different brain regions over time. Unlike structural connectivity, which refers to the physical wiring of the brain through anatomical pathways, functional connectivity reflects how different regions dynamically coordinate with one another, even in the absence of an explicit task.

The research team first attempted to replicate specific findings from three prior studies that had identified changes in connectivity between brain regions such as the amygdala, dorsal anterior cingulate cortex, and putamen during oral contraceptive use. These regions are commonly involved in emotion regulation and reward processing.

The current study largely failed to replicate those findings. For instance, it did not observe a previously reported increase in connectivity between the amygdala and ventromedial prefrontal cortex. It also did not find expected changes in the dorsal anterior cingulate or parahippocampal connectivity. One partial exception was an increase in connectivity between the putamen and a region of the middle frontal gyrus, though this occurred in the opposite hemisphere compared to earlier findings.

The researchers suggest that methodological differences—including sample size, hormonal formulation, or analytic strategies—may account for the lack of replication. These inconsistencies led the team to explore broader, whole-brain effects of oral contraceptive use.

To investigate whether oral contraceptives had more diffuse effects on brain networks, the researchers applied a technique known as functional connectome fingerprinting. This method identifies patterns of connectivity that are unique to each individual and can detect changes in those patterns under different conditions.

The analysis revealed that oral contraceptive pills caused participants’ brain connectivity profiles to become more similar to one another, reducing between-person variability. While each participant’s brain pattern remained identifiable across conditions, the overall distinctiveness of each person’s functional connectome was lower during oral contraceptive use. This effect was strongest in networks involved in executive control, somatomotor processing, salience detection, and the default mode.

This convergence suggests that oral contraceptive pills may exert a normalizing or dampening effect across the brain’s functional architecture. Rather than targeting specific regions, the influence appears to be more global—altering how entire networks are configured and reducing the brain’s functional individuality.

In addition to these network-wide shifts, the researchers also found evidence linking brain changes to self-reported mood symptoms. Participants experienced more negative affect during the oral contraceptive phase, as measured by the DRSP. The researchers identified 13 specific connections between brain regions that significantly correlated with increases in negative mood.

These connections involved areas such as the frontal pole, superior frontal gyrus, posterior cingulate cortex, and precuneus—all regions known to play roles in emotional processing, self-referential thought, and regulation of internal states. The findings suggest that oral contraceptive-related changes in these circuits may underlie the mood symptoms reported by some users.

Rather than pointing to a single brain region responsible for these effects, the results support the idea of a distributed, hormone-sensitive network that may be involved in emotional changes during hormonal transitions—such as menstruation, postpartum periods, or contraceptive use.

But the study, like all research, has limitations. The sample size was relatively small (26 participants), which may limit generalizability and increase the likelihood of false positives or missed effects. Only one formulation of oral contraceptive pills was tested, so the results may not apply to other hormonal combinations. The study measured brain activity at rest, meaning it did not capture how oral contraceptives affect the brain during emotional or cognitive tasks.

Additionally, the intervention lasted only a few weeks. It remains unknown whether longer-term use would amplify, reduce, or change the nature of these connectivity shifts. Finally, although associations between brain connectivity and mood were observed, the study cannot establish a definitive causal pathway linking them.

Despite these limitations, the study suggests that oral contraceptive pills can produce measurable and widespread changes in brain connectivity. These changes are not limited to isolated regions but span across multiple major brain networks. The results also suggest that oral contraceptive pills may reduce the uniqueness of individual brain network patterns, a finding with implications for both research and clinical care.

The researchers propose that future studies could build on these findings by enrolling larger and more diverse samples, testing additional formulations, and using multivariate tools like connectome fingerprinting to better understand how hormonal contraceptives interact with brain function and behavior. They also suggest that the network of brain regions identified in this study could serve as a candidate for investigating mood changes across different hormone-sensitive conditions.

The study, “Effects of Oral Contraceptive Pills on Brain Networks: A Conceptual Replication and Extension,” was authored by Gino Haase, Jason Liu, Timothy Jordan, Andrea Rapkin, Edythe D. London, and Nicole Petersen.