Dingding Hu

If you think your contraception is making you anxious or depressed, you’re not imagining things. Evolutionary psychologist Sarah E. Hill explains what happens to your brain on birth control.

Most women know at least one or two other women who have had a bad reaction to the pill. In fact, the question that many of us have about the pill: “Why does the pill make me crazy?”

Before I get into what the research says about all this, let me just address the elephant in the room — the whole thing about women’s sex hormones influencing mood. Which they do. This might be the world’s oldest cliché about women, but that doesn’t make it any less true. Women’s sex hormones influence women’s moods. Men’s sex hormones affect men’s moods. It would be impossible for them not to.

Back to the question. To start with, all of us feel a little crazy sometimes. Life is hard and can make anyone feel anxious and overwhelmed at times. For some women, being on the pill can magnify these feelings, leading to anxiety disorders and depression. But if these things happen to you, it doesn’t mean you’re crazy; it just means you’re on the wrong pill.

Mood-related issues like anxiety and depression are super-common among women on the pill. Almost half of all women who go on the pill stop using it within the first year because of intolerable side effects, and the one most frequently cited is unpleasant changes in mood. Sometimes it’s intolerable anxiety; other times, it’s intolerable depression; or maybe both simultaneously. And even though some women’s doctors may tell them that those mood changes aren’t real or important, a growing body of research suggests otherwise.

The Scandinavian nation of Denmark is home to a number of nationwide registers, collections of data from its citizens on different health and social issues. Because all Danish citizens have a unique personal identification number, researchers have been able to link individual people’s data across different registers, giving them access to tons of information about patterns of health and social behavior in a whole population.

From these registers, we’ve learned valuable lessons about the powerful effects that the birth control pill can have on mood. In the first of these studies, the researchers looked at the records of all the healthy, nondepressed women living in Denmark between the ages of 15 and 34. They then followed the prescription and mental health records of these women (more than a million of them) for 14 years to see whether going on hormonal contraceptives influenced the likelihood of later being diagnosed with depression or being prescribed antidepressants.

The researchers found that women on hormonal contraceptives were 50 percent more likely to be diagnosed with depression six months later, compared with women who were not prescribed hormonal contraceptives during this time. They also found the women on hormonal contraceptives were 40 percent more likely to be prescribed an antidepressant than were women who weren’t prescribed hormonal contraceptives during this time. The results of this study, as well as others, suggest the pill can increase some women’s risk of depression. This seemed particularly true for non-oral products (such as a patch, vaginal ring or hormonal IUD) and for young women (ages 15 to 19), whose brains are not yet done developing and may be more prone to the influence of hormonal signaling.

As a scientist, I’m obliged to point out we don’t know for sure that the pills caused this increase. Correlation doesn’t equal causation. It’s possible the researchers found pill taking and depression to be related because they were each related to some other third variable. For instance, women who seek medical interventions to prevent pregnancy might be more likely to seek medical interventions for depression. Or, getting into a new sexual relationship (which can prompt a pill prescription) could be what’s increasing women’s depression risk.

However, the researchers statistically tested for the influence of a number of third variables, and each of these tests found that hormonal contraceptives predicted depression risk even after statistically controlling for these third variables. Even though this wasn’t a double-blind, placebo-controlled experiment, the researchers took great care with their study design and data analysis and the results were published in the New England Journal of Medicine, the top medical journal in the US.

More recently, the same team looked at whether hormonal contraceptives might increase women’s risk of suicide. Researchers tracked hormonal contraceptive usage and suicide attempts and deaths in all Danish women who’d turned 15 between 1996 and 2013. (As in their prior study, they did not include any women who had previously diagnosed psychological problems or who had used antidepressants. They also didn’t include women already on hormonal contraceptives when they entered the study.) They followed the women for an average of eight years and then compared the likelihood of having attempted or successfully committed suicide among the women who were prescribed hormonal contraceptives and those who were not.

The women on hormonal contraceptives were twice as likely to have attempted suicide during this time than the women not on hormonal contraceptives. But the risk of successful suicide attempts was actually higher: It was triple that of women not on hormonal contraceptives. As with depression risk, the biggest negative impact of hormonal contraceptives on suicide risk was found for young women (ages 15 to 19) on non-oral products.

When it comes to why the pill can mess with your mood, the two systems that shoulder most of the blame are the HPA axis and some of our neurotransmitter systems. First, the HPA axis (or hypothalamic-pituitary-adrenal axis). It’s made up of three systems working together — the hypothalamus, the pituitary gland, the adrenal glands — and plays a central role in the body’s stress response. The type of blunting of the HPA axis we tend to see in pill-taking women is a known contributor to mental health problems, including the types of mood disturbances characteristic of PTSD. Because lacking the biological tools necessary to deal with stress literally harms your ability to cope, having a broken stress response might be a key player in the development of anxiety and depression. It could also harm emotional well-being in indirect ways through its negative impact on our ability to absorb emotionally meaningful events from our environments.

The second piece is the role that neurotransmitter systems play in making women feel lousy on the pill. Before I explain, I need you to know three quick things.

Quick Thing 1: Neurotransmitters are chemicals that the brain uses to communicate with itself and the rest of the body.
Quick Thing 2: Excitatory neurotransmitters tell your brain cells to get ready for action, making them more likely to fire off messages to other brain cells.
Quick Thing 3: Inhibitory neurotransmitters tell your brain cells to slow their roll, making them less likely to fire off messages to other cells in the brain.

The most prevalent and frequently used inhibitory neurotransmitter in the brain is GABA. It’s often on the scene in a big way when your brain is trying to slow itself down. GABA gets released when you’re relaxing in your PJ pants, and it’s also released when doing things like meditation and yoga.

Interestingly, you can get a relaxed GABA-rific experience from other things that stimulate GABA receptors, such as alcohol and benzodiazepines like Xanax. And our bodies actually produce compounds that work much like alcohol and Xanax. One of the most powerful is allopregnanolone, a neurosteroid. It gets synthesized when progesterone is broken down in the body and has the effect of kick-starting action by your GABA receptors.

Unfortunately for women on the pill, the artificial progestins in the pill don’t seem to offer this same benefit. In fact, research suggests that women on the pill may have lower levels of these natural sedatives relative to what’s observed in its absence, regardless of the point in the cycle.

This can mean bad news for women’s mental health. When GABA receptors aren’t properly stimulated, it’s known to make people feel anxious, overwhelmed and depressed. A number of mental-health-related issues, including panic disorder, depression, bipolar disorder and the mood-related symptoms of PMS, are characterized by lower-than-average levels of GABAergic activity. Lack of such activity can also increase a person’s risk of alcohol dependence.

Research suggests that changes in dopamine and serotonin signaling may also play a role in mood-related changes seen on the pill. Dopamine and serotonin, like GABA, are neurotransmitters. These chemicals come on the scene when we’re spending time with people we love, eating hot fudge sundaes, falling in love, having sex and having orgasms.

Not surprisingly, these neurotransmitter systems change what they do in response to women’s cyclically changing sex hormones. In particular, the research finds that estrogen makes rewarding things feel even more rewarding than they do in its absence and that progesterone attenuates these effects. Estrogen makes sex feel sexier, chocolate taste yummier, and getting status boosts feel boost-ier.

Given that the pill keeps estrogen levels low across the cycle and stimulates progesterone receptors, it’s possible the pill might have the effect of dampening reward processing in the brain. And if the world seems unrewarding, this makes us feel depressed. One hallmark symptom of depression is that people no longer find pleasure in things that they used to find pleasure in. So it’s also possible that the pill might increase a person’s risk of depression by making pleasure less pleasurable. Consistent with this idea, research finds that pill-taking women — when compared with their naturally cycling counterparts — have a blunted positive emotional response to happy things and don’t experience activity in the reward centers of their brains when looking at pictures of their romantic partners.

It seems pretty clear from the research that the pill can cause some women some pretty serious problems with their mental health, but the science isn’t yet at a point where we can make strong predictions about exactly what’s going to happen to whom, and on what.

However, according to the research, you might have a greater risk of experiencing negative mood effects on the pill if:

These bullet points can give you a starting point to initiate a conversation with your doctor about any mental health concerns. They aren’t your fate, though. Even if you’re an 18-year-old with a family history of depression and you’re on the birth control patch, if you aren’t experiencing signs of troubled mental health, the chances are incredibly low that you’re going to suddenly develop mood problems from birth control. This is especially true if you’ve been on it for a while and seem to be tolerating it well.

What’s more, while some women experience negative mood changes on the pill, some women experience the opposite reaction. They feel a whole lot better and mentally healthier on the pill than off it. Research also finds that the pill can offer huge mood-stabilizing benefits to women who have severe PMS.

The most critical thing about the pill’s effects will come from you: How do you feel on it?

Any time you start a new pill, please let someone close to you know about it. Ask them to make note and tell you if they notice any changes in your behavior that might suggest the onset of depression.

Because the hormones in the pill influence what the brain does, it’s almost impossible to separate out what the hormones are doing from who we are. We feel like the version of reality that is created by our brain on the pill is real. This can make it difficult to notice depression creeping in. Rather than feeling like the pill is messing with our mood, it just feels like our life is getting crappier or our job has gotten more stressful. If you tell your person that you are trying a new pill, they may be able to help you recognize problems that start to develop so that you can look for a new pill or an alternative means of protecting yourself from pregnancy.

On top of this, consider keeping a journal. If possible, start it before going on the pill so you have a log of how you were feeling before and after. Having hard evidence of your mood prior to the pill can be a good way for you to think about your past more objectively, making it easier to recognize any changes. In each entry, make note of your mood, energy level and well-being using some sort of scale (1=”I feel sad/anxious” and 10=”I feel great”). This will help you keep tabs on how things change for you (or not) when trying out a new pill.

If you’re already on the pill, it’s not too late to keep track of how you’re feeling. Make a note of your patterns. If you have more happy days than sad ones, that probably means everything’s on the right track. None of us feel happy all the time, but we should feel happier more often than sad when things in our lives are going well. If you have fewer happy days than you think you should, talk to your doctor. It could be time to try a new pill or address an issue with your mental health that you’ve let go too long.

Excerpted with permission from the new book This Is Your Brain on Birth Control: The Surprising Science of Women, Hormones, and the Law of Unintended Consequences by Sarah E. Hill PhD. Published by Avery, an imprint of Penguin Random House, LLC. © 2019 by Sarah E. Hill.

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