How does the brain react to the birth control pill? One researcher scanned herself 75 times to find out

How does the brain react to the birth control pill? One researcher scanned herself 75 times to find out

Chicago, Illinois

No more morning coffee and meditation: For about 75 days over the course of a year, neuroscientist Carina Heller's morning ritual included diving into her university's brain scanner at 7:30 a.m. and lying perfectly still for an hour and a half - without falling asleep. According to her estimate, she is the most scanned woman in science.

But it wasn't the title she wanted. Heller's goal was to catalog how her brain functions during her menstrual cycle both with and without oral contraceptives changed. Their findings suggest that brain structure and connections change daily in natural cycles and are influenced by birth control pills, according to preliminary results presented at this year's annual meeting of the Society for Neuroscience.

Heller is one of a group of women's health researchers who are tired of poor data chronically under-researched area and who took matters into their own hands by climbing into a brain imaging machine. More data could give women and their doctors more agency to "make more informed decisions about whether or not to take the drug" and which specific formulations are best, said Heller, who is at the University of Minnesota in Minneapolis.

“She underwent rigorous self-experimentation and dedication to science,” says Emily Jacobs, a neuroscientist at the University of California, Santa Barbara, who works with Heller. “And as a result, we now have a better understanding of the human brain.”

Research gaps

Oral contraceptives often contain synthetic versions of one or two hormones that the body produces naturally: progesterone and estrogen. These hormones prevent pregnancy in several ways, including by stopping the ovaries from releasing an egg.

U.S. regulators approved the first oral contraception in 1960. Within two years, more than a million people were taking “the pill,” as it became known. Today, more than 150 million people of childbearing age worldwide take oral contraceptives, making them the most widely used medications in the world. Many take the pill for reasons unrelated to conception, such as to fight acne, regulate the menstrual cycle, or relieve menstrual symptoms and migraines.

Decades of data on these drugs suggest that they are generally safe, but their effects on the brain have not been adequately studied. For example, some people report experiencing reduced depression and anxiety, while others find these symptoms worsening - and it remains unclear why this is.

Many people start taking the pill during puberty, a crucial time for brain maturation. That's why it's important to understand how it affects neurocognitive development, says Kathryn Lenz, a behavioral neuroscientist at Ohio State University in Columbus.

The adaptable brain

Most neuroimaging experiments use magnetic resonance imaging (MRI) to scan the brains of 10 to 30 participants only once or twice, which is costly. However, this approach does not account for daily variations in brain structure and connections.

A growing number of neuroimaging studies are instead using a technique called dense sampling ", in which researchers repeatedly scan a single or a few participants to create a high-resolution data set. Dense sampling captures observations that might otherwise be missed, but the small sample size results in limited generalizability of the results to larger populations.

Still, by comparing data sets between participants — particularly those who have different reactions to the pill — researchers could figure out what drives different side effects.

Using this approach, Heller scanned herself 25 times over a 5-week period, capturing images at different stages of her natural menstrual cycle. A few months later, she started taking oral contraceptives and then waited 3 months before scanning herself another 25 times in 5 weeks. At that point, Heller stopped taking the pill, waited another 3 months, and scanned himself one final time 25 times over 5 weeks. She also had blood drawn and completed a mood survey after each scan.

Heller found a rhythmic pattern of changes in brain volume and connectivity between brain regions over the course of her menstrual cycle, with volume and connectivity decreasing slightly while taking oral contraceptives. (Higher brain volume or connectivity does not necessarily mean improved brain function and vice versa.)

This pattern largely returned to its previous state after she stopped the medication, showing that the brain is "very adaptable," says Laura Pritschet, who did her graduate work with Jacobs and is now a cognitive neuroscientist at the University of Pennsylvania in Philadelphia.

A growing network

Heller was inspired by a study in which Pritschet scanned her own brain for 30 days during her natural menstrual cycle and another 30 days while taking oral contraceptives. This was part of a project Pritschet calls 28andMe: the name is a reference to the Southern California consumer genetics company 23andMe and the 28 days in a classic menstrual cycle.

Data from Pritschet's project showed that higher estrogen levels stimulate certain key brain networks to become more functionally connected 1. One of these was the “Default Mode Network,” which is active during daydreaming and is involved in memory processes. Progesterone had the opposite effect. Pritschet also scanned her husband over 30 consecutive days in a spin-off project called 28andHe to understand the effects of hormone fluctuations in the male brain 2.

Next, Heller plans to compare her data with that of a woman with endometriosis, a painful condition that affects up to 10% of women of childbearing age, to understand whether hormone fluctuations in the brain might be driving the condition.

These data sets will “give us a really fascinating insight into the relationship between hormonal status and subtle changes in brain structure and behavioral functions,” says Lenz.

1. Pritschet, L. et al. Neuroimage 220, 117091 (2020).

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2. Grotzinger, H. et al. J. Neurosci. 44, e1856232024 (2024).

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