Imagine this: you’re standing in front of a group of stone-faced researchers and a camera, giving a speech on why you deserve your dream job. They look on as you talk, instructing you to continue your speech for at least five minutes—even if you run out of things to say. As soon as your speech is over, you must verbally count down from the number 1022, skip-counting by 13s. Yes, 13s. And if you make a mistake? Start over.
Is your heart rate quickening and are your palms sweating at the mere thought of this stressful experience? Good, because that’s exactly what’s supposed to happen! This is the Trier Social Stress Test (TSST), and it’s been proven to induce stress in a laboratory setting. A recent study out of the University of California, Los Angeles (UCLA) utilized the TSST in order to answer one question [1]: What is the difference between how women on or off hormonal birth control react to acute stress?
This UCLA study was co-authored by Summer Mengelkoch, Jeffery Gassen, George M. Slavich, and Sarah E. Hill (Hill also authored This is Your Brain on Birth Control). Lead researcher Mengelkoch told UCLA Health: “I hope this research is the beginning of work that can advance a precision medicine-based approach to hormonal contraceptive use… To do this, we need basic science research that investigates how both endogenous sex steroid hormones that women already have in their bodies and exogenous sex steroid hormones from contraceptives impact their stress processing, inflammation, and risk for inflammation-related disorders.”
Research participants were young, healthy women
The participants in this study were 153 healthy women, and most were university students. Researchers studied 78 women on combination oral contraceptive pills (meaning birth control with both synthetic estrogen and progestin), and 75 women who were not on birth control (who therefore experienced their natural menstrual cycles). The naturally cycling women were studied only during their luteal phase, because past research has indicated that the greatest difference between naturally cycling women’s stress response and that of women on birth control occurs during the luteal phase of the menstrual cycle [2].
All participants were tested for their glucocorticoid, inflammatory, and psychological responses to acute stress. ‘Glucocorticoid response’ refers to cortisol (i.e., the “stress hormone”) levels. ‘Inflammatory response’ refers to cytokine levels. Cytokines are ”small proteins that are crucial in controlling the growth and activity of other immune system cells and blood cells,” and high levels of different cytokines represent inflammation in the body. Both the glucocorticoid (cortisol) and inflammatory (cytokine) responses were measured via the participants’ saliva samples. Finally, ‘psychological response’ refers to the participants’ mood, which was measured via questions before and after the previously described TSST.
What researchers expected to happen
Researchers expected to observe blunted cortisol levels and higher cytokines in the participants who were birth control users, indicating more inflammation. This is because past research found that taking birth control dysregulates the HPA-axis and blunts the body’s natural response to acute stress. Normally, the body would respond to acute stress with a spike in cortisol, followed by a decline [3]. As a rough example, if you trip while walking but catch yourself right away, your heart rate spikes for just a second. But once the “danger” has passed, it returns to normal within seconds.
In her book, This is Your Brain on Birth Control, Dr. Sarah E. Hill says that women on the Pill have an “HPA-axis function [that] looks suspiciously similar to that of someone who has experienced chronic stress, suggesting that the Pill might actually cause the HPA-axis to go into overdrive, requiring it to take coordinated action to blunt itself.”
As regards inflammation, while women on the Pill are known to be more likely than naturally cycling women to suffer chronic inflammation and inflammation-related disorders—ranging from cardiovascular disease to depression—past research has found that their baseline levels of proinflammatory cytokines were similar to those of naturally cycling women [4][5][6][7]. Dr. Hill, along with her team, wanted to further understand this mechanism by testing the women’s inflammatory responses (via their cytokine levels) when faced with an acutely stressful situation.
What the researchers learned about birth control, inflammation, and stress instead
The UCLA researchers found differences in cortisol response, cytokine response, and reports of mood between naturally cycling women and women on oral contraceptives. The UCLA study found that women on birth control actually had a more marked cortisol response to acute stress than naturally cycling women, rather than a blunted one. Women on the Pill also had different cytokine responses, suggesting that they experienced more inflammation than naturally cycling women. The naturally cycling women reported significantly better moods throughout the stress test experience, and their moods “bounced back” more quickly after the test was over than their peers on birth control did.
The researchers summed up, “Together, these results suggest that HC [hormonal contraceptive] use impacts women’s glucocorticoid, inflammatory, and psychological responses to psychosocial stress, potentially contributing to observed differences in these women’s mental and physical health.”
They wrote, “Together, these findings suggest that [hormonal contraceptive] users may differ from non-users in terms of both their inflammatory response to acute stress and in how their inflammatory activity, cortisol, and mood are interrelated in such conditions.”
Did the COVID-19 pandemic influence study results?
Though the UCLA study gives us another piece of the puzzle in fully understanding how birth control affects women, it has a few limitations. Researchers cite the timing of the study to be a potential factor in how participants responded to the test: trials were completed from August 2021 to April 2022, when researchers believe all participants may have had increased chronic stress due to the covid-19 pandemic. They believe this level of chronic stress might have been responsible for the less robust cortisol response in the naturally cycling women (as compared to the women on the Pill), as this aspect of the data contradicted prior research [2].
Birth control-influenced inflammation could have long-term consequences
The UCLA study has far greater implications for birth control users than increased sweating during public speaking or greater difficulty performing mathematical tasks, as the TSST measured. Researcher Mengelkoch commented, “This study provides the first evidence that beyond impacting cortisol responses to stress, hormonal contraceptive use also impacts inflammatory responses to stress.” Learning more about the role of inflammation in stress response of women on hormonal birth control is also crucial in painting a fuller picture of the harms of the Pill, as excess inflammation can cause a host of mental and physical health disorders—impacting women’s health in myriad ways.
Additional Reading:
The Pill and stress: How hormonal contraception might make it harder for you to cope
New book explores how hormonal birth control affects women’s brains
What does birth control do to women’s ability to process fear?
How hormonal birth control affects your brain
‘Adrenal fatigue’ may not be real, but HPA axis dysregulation definitely is
