How birth control pills affect the brain

Birth control pills quite literally changed the course of history, giving women unprecedented control of their fertility and thus more freedom of choice in education, work, and family matters. But the most used form of hormonal contraception was developed before scientists understood the myriad functions hormones play in the body and brain—and some recent findings are highlighting how much is not yet known.

“As a global population we’ve been taking this pill as a natural experiment, as we’ve been simultaneously discovering that the impact of estrogen and progesterone is way beyond just pregnancy,” said Caitlin Taylor, PhD, a senior scientist at the University of California, Santa Barbara (UCSB), who studies changes in brain structure and function across periods of hormonal transition, including puberty and the menstrual cycle.

Amid growing evidence that links birth control pills with changes in stress responses, cognition, libido, and mood—including an increased risk for depression in adulthood if taken during adolescence—researchers are calling for more attention to the issue.

“We lack basic, mechanistic information about how women’s bodies and brains work, and how synthetic hormones interact with normal biological processes,” said Summer Mengelkoch, PhD, a postdoctoral fellow in psychology at the University of California, Los Angeles, who studies women’s stress responses. “Psychologists have a great opportunity to contribute here,” she added, because they are adept at designing experiments to identify both clinical and subclinical effects.

One of the most pressing issues is to understand how synthetic estrogen and progesterone affect brain development, Taylor said, because these drugs were developed and tested with adults but are often given to teenage girls. They are prescribed for reasons other than pregnancy prevention, too, such as to treat dysmenorrhea (heavy, painful periods), polycystic ovary syndrome, and even acne in teenagers.

Research generally does not suggest that the pill is dangerous. For women in many parts of the world, including much of the United States, where reproductive freedom is under threat, its benefits still far outweigh potential negative side effects. But age, mental health history, pill formulation, and other factors can lead to significant variability in how people respond.

“Hormonal contraceptives continue to be an incredibly safe and incredibly effective family planning method for many people,” said Frances Chen, PhD, a professor of psychology at the University of British Columbia who studies how hormones shape social and emotional health, particularly during adolescence. “But a subset of people may be more vulnerable to their negative side effects. These people deserve a good knowledge base, based on high-quality research, to make informed decisions about their health.”

A large and robust literature shows that sex hormones, including estrogen and progesterone, have widespread effects throughout the body and brain, far beyond sex and pregnancy. They play a role in nearly all the body’s systems, influencing everything from cardiovascular and immune function to emotion regulation, executive function, and appetite.

“It’s only very recently that people have started to ask the question: What does this mean for birth control pills? And since we started asking it, we’ve begun to find some peculiar things,” said Sarah E. Hill, PhD, a professor of psychology at Texas Christian University who studies the role of women’s hormones in relationships and health and authored the book This Is Your Brain on Birth Controlopens in new window.

One troubling finding: Taking hormonal contraceptives during adolescence is linked to a higher risk of developing major depressive disorder in adulthood, according to research by Chen and her postdoc, Christine Anderl, PhD (The Journal of Child Psychology and Psychiatry, Vol. 61, No. 2, 2020opens in new window; The Journal of Child Psychology and Psychiatry, Vol. 63, No. 3, 2022opens in new window).

“That suggests there may be a long-term effect of these synthetic hormones on the way the brain develops during adolescence—that it’s not just about the side effects happening when these drugs are currently in your system,” Chen said.

To investigate that link, Chen is now collecting baseline data from teenage girls before they start taking birth control pills, between ages 13 and 15, then tracking them for several years. She and others are also conducting mechanistic studies to start teasing out the biological processes that underlie the newfound association.

A leading theory is that the increased risk for depression stems from an altered stress response among birth control pill users. Studies indicate that women on the pill have a blunted cortisol response: In acute stress tasks, they have a slow rise and a gradual fall of cortisol rather than the classic spike that signifies a healthy stress response. Despite the cortisol differences, these women report feeling at least as much stress as non–pill takers (Sharma, R., et al., Hormones and Behavior, Vol. 124, 2020opens in new window).

Mengelkoch has found that women on the pill also tend to show differences in their inflammatory stress response, which occurs just before the cortisol spike. During a lab-based stress task, the inflammatory response of naturally cycling women was dominated by one cytokine, IL-6, while the response of women on the pill was dominated by another cytokine, known as TNF-alpha. The rise in TNF-alpha was also linked to a decrease in positive mood (Brain, Behavior, and Immunity, Vol. 115, 2024opens in new window).

“It could be the case that hormonal contraceptive use is causing women to have an atypical inflammatory response to stress, which may be related to their depression risk down the line,” Mengelkoch said. She is now planning a prospective study of women before they start taking the pill to investigate possible changes in stress-related gene expression.

Understanding how contraception affects mood involves teasing apart subtle changes in affect. Most of what’s known so far comes from studies of women with severe premenstrual syndrome and premenstrual dysphoric disorder, who experience high levels of negative affect in the last week of their cycle. When taking the pill, these women report better moods during that week. But Mengelkoch’s review of the literature (in press with the Open Access Journal of Contraception) suggests a hidden downside: Some women on the pill also experience a small but statistically significant decrease in positive affect earlier in their cycles (Lundin, C., et al., Psychoneuroendocrinology, Vol. 76, 2017opens in new window).

“It hasn’t had as much light shined on it because a decrease in positive affect doesn’t sound as bad as an increase in negative affect,” Mengelkoch said. “But things may feel very different for these women when they go on the pill, and changes in positive affect might not be showing up in studies because we aren’t looking for them.”

While the science on adolescence remains unclear, research suggests that for adult women, depression risk is particularly a concern during the first 2 years of pill use (Johansson, T., et al., Epidemiology and Psychiatric Sciences, Vol. 32, 2023opens in new window).

Brain scanning research further supports the idea that hormone-driven biological changes could underlie the psychological side effects of birth control. Taylor, her supervisor Emily Jacobs, PhD, an associate professor of psychological and brain sciences at UCSB, and their colleagues have shown that hormones are even linked to daily changes in the structure of a woman’s brain.

The group collected brain scans from a woman for 30 consecutive days during a natural menstrual cycle, finding fluctuations in the volume of her hippocampus that correlated with changes in progesterone (NeuroImage, Vol. 220, 2020opens in new window).

“We then collected scans while she was on the birth control pill and saw no volume differences across the 30 days we scanned her. That suggests that the pill’s control of her hormone levels was quashing the natural fluctuations of the brain,” said Taylor, who is now conducting a similar analysis of the whole brain.

It is no surprise, then, that researchers have documented a broad range of psychological changes linked to birth control use. In addition to changes in stress response and depression risk, hormonal contraceptives can lower libido and impact sexual attraction.

Pill use may also alter spatial reasoning, according to research by Adriene Beltz, PhD, an associate professor of psychology at the University of Michigan who studies gendered cognition. In a study that compared men, naturally cycling women, and users of two types of birth control pills, one group of pill users performed slightly better on a 3D mental rotation task than naturally cycling women (Hormones and Behavior, Vol. 74, 2015opens in new window).

“The effects were present but small. We expect to see small effects because we’re studying highly complex behaviors that vary among people for so many different reasons,” Beltz said.

Another key takeaway from the study: When Beltz ran the analysis without separating hormonal contraceptive users by pill formulation, she found no effects. Not all birth control pills are the same—some use synthetic progestins derived from progesterone, others from testosterone, for example, which can have varying effects throughout the body. Individual factors, such as the number of receptors a woman has for a given hormone, can also lead to different outcomes.

“Studying biology is already really messy, and then adding the idiosyncrasies of these different exogenous hormones makes it even messier,” Hill said. “We need to move beyond looking at the mean because averaging all pill users may not tell us anything.”

Those complexities were long seen as a reason to exclude women from psychological and biomedical research. Though more studies now include women, researchers often ignore the effects of hormones (lumping all women together regardless of cycle stage or pill use) or minimize them (enrolling women at the start of their menstrual cycles, when they are hormonally most similar to men). Neither of those approaches really captures the complexity of the issue, Hill said.

When it comes to positive and negative affect, Beltz’s research shows that daily variations do not differ substantially between men, naturally cycling women, and women on three types of birth control pills. She administered surveys each day for 75 days and found virtually no differences between the groups tested (Scientific Reports, Vol. 11, 2021opens in new window).

“This doesn’t mean that hormones don’t matter for emotions. Hormones may contribute to variation for some people in some contexts, but not more so—at least systematically—than folks’ emotional lives vary from day to day anyway,” she said. “And certainly not enough to exclude naturally cycling women or hormonal contraceptive users from scientific research.”

When women stop using the pill, most find that their cycles regularize and sex drive rebounds within about 3 months. More research is needed to understand whether the same is true for side effects related to mood and stress response, Mengelkoch said.

At a time when reproductive freedom is at risk in the United States and many women worldwide still lack access to reliable contraception, those who study birth control side effects say they worry that their findings will be taken out of context. Last year, the Washington Post reported that social media misinformationopens in new window about hormonal birth control, promoted in some cases by anti-abortion groups, had swayed women to opt for less reliable forms of contraception, such as cycle tracking.

On the other hand, public discourse about birth control can provide women with the knowledge and confidence they need to approach their doctors about side effects that have long been dismissed.

“For a long time, these complaints have been written off as ‘pesky women’s issues,’” Mengelkoch said. “Even if these are not life-threatening side effects, or side effects that outweigh those of pregnancy, we should still talk about them.”

That disconnect between patients and providers is reflected in research. In a survey of 188 patients conducted by Allison B. Deutch, MD, a reproductive psychiatrist at the New York University (NYU) Langone School of Medicine, and NYU medical student Sarah Martell, 83% reported that their doctor did not mention potential psychological side effects during contraception counseling (Contraception and Reproductive Medicine, Vol. 8, No. 9, 2023opens in new window).

Women also reported having their complaints dismissed by their providers, being discouraged from switching to a different form of birth control, or feeling that their providers were playing a “guessing game” about which pill would have the fewest side effects. That’s due in part to rushed provider visits, but it is also due in part to a dearth of research that can inform nuanced decision-making about contraception, Deutch said.

“We want patients to feel comfortable talking to their providers and we want providers to feel comfortable talking to their patients,” she said. “How do we navigate that in a place where there’s so much gray?”

One promising development: digital contraceptive decision aids, which can help with personalization and patient education, typically before or after a doctor’s appointment. Mengelkoch, Hill, and their colleagues conducted a trial of one such tool, Tuune, finding that women who used it had better knowledge of contraception and greater self-efficacy around their reproductive health than those who did not use the tool (BMC Digital Health, Vol. 1, No. 36, 2023opens in new window).

So much about women’s biology remains unknown. Securing funding for this work can be challenging, Mengelkoch said, because it often does not map onto a particular disease category and has long been undervalued. Former President Biden’s 2024 White House Initiative on Women’s Health Research, led by psychologist Carolyn Mazure, PhD, of Yale School of Medicine, offered a beacon of hope, but its future is now in question with a new administration in power.

As psychologists and other researchers forge ahead, Hill suggests a three-pronged approach to expanding research in the field. First: Understanding how synthetic hormones impact development is vital and urgent.

“It’s absolutely critical that the research gets done on what happens to young girls when we put them on hormonal birth control, before we make it de rigueur for doctors to be prescribing it,” Hill said.

Next, women need more information about the side effects of pill alternatives, such as intrauterine devices (IUDs), as well as new and better contraception options. Finally, understanding variability—both among contraceptives and the people who use them—will pave the way for a precision medicine approach. For example: Which women are more vulnerable to negative side effects on the pill? How can providers tailor recommendations to a woman’s individual hormonal profile?

“Converging findings in the field suggest that variability matters,” Beltz said. “We need to map that variability well so we can help maximize the benefits and minimize the negatives for those who want to use hormonal contraception.”