Scientists have found a possible link between using oral contraceptives and changes in parts of the brain that process fear. The findings may help explain fear-related mechanisms that disproportionately affect women.
Hormonal changes during a menstrual cycle are currently understood to affect the fear circuitry in the brain. So Canadian researchers looked into the effects of combined oral contraceptive (COC) use to learn more about the relationship between sex hormones our bodies make naturally and synthetic versions of those hormones.
Over 150 million people use oral contraceptives, with COCs (containing synthetic versions of estrogens and progestogens) being highly popular. The study found that a brain region called the ventromedial prefrontal cortex (vmPFC) was thinner in women who currently use COCs compared to men.
This effect appeared to be reversible. A comparison with those who stopped using contraceptives or those who had never used contraceptives indicated this physiological change didn't seem to be lasting.
To be clear, these are just associations, and there are no known negative effects linked to the change in size of certain brain regions. But the authors think it could be worth exploring further.
"This part of the prefrontal cortex is thought to sustain emotion regulation, such as decreasing fear signals in the context of a safe situation," explains Alexandra Brouillard, a physiologist at the University of Quebec in Montreal.
"Our result may represent a mechanism by which combined OCs could impair emotion regulation in women."
Brouillard and colleagues studied healthy adults aged 23 to 35, including 139 women: 62 who were currently using COCs, 37 who had previously used only COCs, and 40 who had never used any hormonal contraceptives. The total sample also included 41 men.
Because women are more likely than men to have anxiety and stress disorders, researchers compared these groups to see if COC use was linked to short-term or long-term changes in the brain and if there are differences between sexes.
The scientists measured levels of natural and synthetic sex hormones in participants' saliva and used magnetic resonance imaging ( MRI) to scan their brains, specifically looking at regions involved in processing fear.
They found levels of both natural and synthetic sex hormones were linked to changes in the size and thickness of the vmPFC compared to the same anatomy in men. However, only women who were currently using oral contraceptives had a thinner vmPFC than that in men.
The researchers also found the structure in a fear-promoting brain region – the dorsal anterior cingulate cortex (dACC) – varied between men and women. This was noticeable regardless of COC use, emphasizing one way naturally-produced sex hormones can influence brain structure.
"Given our results that men have smaller dACC volume than women and thicker vmPFC than COC users, these findings may represent structural vulnerabilities to psychopathologies that predominantly affect women," the team writes.
"Specifically, a larger dACC could represent a female predisposition to fear promotion, whereas COC use could exacerbate this vulnerability by potentially inducing a thinning of a fear-inhibiting region such as the vmPFC."
Notably, the researchers found that this effect seemed to go away when COC use stopped, though they emphasize that more research is needed to delve into the impacts. Just because a brain region changes in size doesn't necessarily mean there are negative effects. We can't draw firm conclusions about an individual's emotions or behavior based on the findings about brain structure.
Ongoing exclusion of women from animal and human research contributes to the gap in our understanding of why women are more likely than men to have anxiety and stress-related disorders.
This underrepresentation of women is primarily due to a perception that changes in sex hormones would make results more variable. The bias towards studying men has led to some pretty grave consequences.
"When prescribed COCs, girls and women are informed of various physical side effects, for example that the hormones they will be taking will abolish their menstrual cycle and prevent ovulation," Brouillard explains.
"The objective of our work is not to counter the use of COCs, but it is important to be aware that the pill can have an effect on the brain."
The study has been published in Frontiers.