More than 60 years after the FDA first approved birth control, 151 million reproductive-aged women across the world are on the pill, according to a 2019 report by the United Nations. In recent years, efforts to widen the accessibility of birth control have resulted in the FDA’s approval of the first over-the-counter hormonal birth control called the Opill.
However, even decades after the pill first came out, researchers are only beginning to understand how the hormones affect various body systems. A new study published Tuesday in the journal Frontiers in Endocrinology looked at how the synthetic hormones in oral contraceptives affect the brains of individuals assigned female at birth.
Researchers in Canada found that the pill may change parts of the brain that deal with fear. Thankfully, these changes didn’t appear to be lasting: If an individual discontinued the drug, these brain circuits seemed to bounce back to normal over time. The researchers also noticed that certain types of pills, like those with lower doses of a hormone called ethinyl estradiol (a synthetic form of estrogen), might make these fear-related brain areas shrink, while slightly higher-dose oral contraceptives do the opposite.
These findings are a big deal because these fear-handling brain circuits are involved in conditions like anxiety and PTSD, which are more common in women. Understanding how both natural hormones and the ones in the pill mess with these circuits could help us figure out why these conditions happen in certain individuals, offering better methods of addressing one’s unique mental health needs.
“[These findings] can help in trying to understand how the pill could impair emotional regulation,” Alexandra Brouillard, the study’s first author and a graduate student at the Université du Québec à Montréal, tells Inverse.
This is your brain on hormones
Since the 1930s, scientists have studied female reproductive hormones and their effects on physiology and behavior. One key insight in recent decades is that rhythmic fluctuations of hormones like estrogen and progesterone over a typical month-long cycle are associated with corresponding restructuring in areas involved in memory and learning, like the hippocampus and white and gray matter connectivity. These changes aren’t necessarily detrimental to cognitive function; on the contrary, they could offer a cognitive boost or more flexibility in thinking.
Regarding the brain’s neural pathways involved in fear, Brouillard says it’s well-known that endogenous sex-related hormones — namely, the ones our bodies naturally produce — can affect our ability to learn and unlearn stimuli provoking fear, stress, or anxiety. These structures are located deep in the brain. The amygdala (a small, almond-shaped cluster of neurons in the brain's temporal lobe responsible for processing and regulating emotions, especially fear, and pleasure), the nucleus accumbens (plays a central role in the reward circuit, associated with pleasure, reinforcement learning, addiction, and motivation), the hippocampus (plays an essential role in consolidating memory and spatial navigation), and the hypothalamus (helps control your hormone system), to name a few.
Some studies have found that women with lower levels of estradiol — the main form of estrogen in the human body — may have a harder time unlearning fear, what’s called fear extinction.
“There’s a small body of research [looking into] the effects of endogenous sex hormones but also exogenous hormones, so the fact that we take synthetic hormones via hormonal contraception,” says Brouillard. “There is evidence that [hormone birth control] can impact the brain function and connectivity. But it’s still very novel, and there’s not a ton of research. We still don’t really know all the nuances with [taking the pill].”
Anatomical brain changes
For their study, Brouillard and her colleagues recruited 180 healthy adults — 139 individuals assigned female at birth and 41 men — between the ages of 25 and 35 years old. Participants were divided into three groups depending on whether they were currently on the pill for three months or more (62 volunteers), previously on the pill with the last use 12 months prior (37 volunteers), or had never taken hormonal contraceptives at all (40 volunteers). The men served as essentially a comparison group.
The participants had their brains scanned with a structural MRI to look for any underlying differences in brain anatomy between the groups, specifically looking at gray matter volumes and the thickness of the cortex. They also had a functional MRI to map brain activity detected by changes in blood flow, which indicates areas of the brain that are more active during specific tasks or at rest.
Ethinyl estradiol, the synthetic estrogen found in birth control, often in combination with synthetic progesterone, was also measured through a saliva test.
The brain scans showed that compared to the men, the three female groups appeared to have more gray matter (the brain’s processing units, kind of like a computer) in the dorsal anterior cingulate cortex. This isn’t a well-understood brain structure, but it may be important to cognitive control or our capacity to modify our actions and behavior in line with our goals and intentions rather than just reacting automatically to things around us.
But here's where it gets really interesting. For individuals currently on the pill, a part of their brain called the ventromedial prefrontal cortex — a spot associated with emotions and decision-making — appeared a bit thinner compared to the other groups. In contrast, the group who had never been on the pill had a thicker right anterior insular cortex — another brain region tied to emotions and self-awareness — compared to women who used to take the pill. This thickness was consistent regardless of where these individuals were in their menstrual cycle.
“We tried to understand what was going on in taking the pill that may be associated with this decrease in thickness,” says Brouillard. “We found it was related to the dose of synthetic [estrogen] and not the progestin [the synthetic form of progesterone]. Only women currently using a low dose of 10 to 25 micrograms — so a very low dose of ethinyl estradiol — had a thinner ventromedial prefrontal cortex compared to the men.”
More research is needed
How these anatomical differences in brain structure are related functionally to behavior and, ultimately, clinical significance isn’t yet known, says Brouillard. Uncovering part of the puzzle is part of ongoing research other colleagues in her lab are working on, the findings of which they hope to publish in the near future.
It does seem that over the long run, comparing the brain scans of current and former pill users, the brain changes appear to be reversible. But as this study involved healthy adults, it's hard to say whether what Brouillard and her colleagues saw is generalizable to other individuals, especially those with preexisting neurological or mental health conditions.
But she hopes that studies like this raise awareness that synthetic hormones from birth control do have an impact on the brain, encouraging more scientific and clinical dialogue around the use of hormonal birth control, especially with respect to younger birth control users taking the pill during a critical period of brain development.
This doesn’t mean hormonal birth control is harmful as it remains among the only reliable options to prevent pregnancy, says Brouillard. “It’s too early to make any decisions based on [this research]. But I’m pretty sure that in a few years, we will know so much more, and it will help us make better decisions.”
