A new UCLA Health study provides insights into how hormonal contraceptive pills may influence women's stress responses and their risk for inflammation-related illnesses.
Published in the journal Brain, Behavior, and Immunity, the study is the first to directly compare the psychological and immune responses to social stress in hormonal contraceptive users and non-users.
Researchers from the UCLA Department of Psychiatry and Biobehavioral Sciences’ Laboratory for Stress Assessment and Research found that users and non-users of hormonal contraceptives process stress differently at a molecular level. Contraceptive users also reported a more negative psychological response to stress compared to non-users.
Lead author Summer Mengelkoch believes these findings could help uncover the mechanisms linking birth control pills, stress responses, and inflammation. This understanding could improve health outcomes for the hundreds of millions of women worldwide who use birth control pills.
Mengelkoch, a UCLA postdoctoral fellow, expressed hope that this research will pave the way for a precision medicine approach to hormonal contraceptive use, enabling women and their doctors to make better-informed health decisions. She emphasized the need for basic science research to explore how both endogenous sex steroid hormones and exogenous hormones from contraceptives impact stress processing, inflammation, and the risk of inflammation-related disorders.
Despite the safe use of hormonal contraceptives by over 300 million women globally (as reported in a 2019 United Nations study), there has been limited research on their long-term physiological and behavioral effects.
Previous research has suggested that hormonal contraceptive pills may increase the risk of chronically elevated inflammation, which can lead to illnesses such as cancer, cardiovascular disease, autoimmune disorders, and mood disorders like depression. However, the mechanisms behind this association remain unclear.
Earlier studies have shown that hormonal contraceptive users have higher levels of C-reactive protein (CRP), a marker of systemic inflammation, compared to non-users. However, no differences were found in the basal levels of other inflammation markers, such as cytokines, between users and non-users. Cytokines are proteins that increase inflammation in response to stress and can contribute to systemic inflammation over time. Mengelkoch and her team, including UCLA faculty mentor Dr. George Slavich, aimed to investigate differences in proinflammatory cytokines in response to stress between hormonal contraceptive users and non-users.
The study involved nearly 130 women—60 using hormonal contraceptive pills and 67 naturally cycling, or not using hormonal contraceptives. Participants provided saliva samples and rated their mood and stress levels. They then underwent a stress test involving a five-minute speech about their dream job to a non-responsive researcher, followed by a mental math task. Afterward, participants provided another saliva sample and rated their mood and stress levels again.
Results showed that contraceptive users had higher levels of an inflammatory cytokine called TNF-alpha before and after the stress test. This cytokine may be linked to a more "male-typical" stress response. In contrast, naturally cycling women had a more "female-typical" stress response, with higher levels of the cytokine interleukin-6 and increases in cortisol.
Different synthetic hormones in contraceptives bind to different receptors in the body. Mengelkoch suggested that synthetic hormones in some contraceptives, which bind more to androgen receptors (where testosterone usually binds), may cause differences in inflammatory stress responses.
The study also found that contraceptive users reported a more negative emotional response to stress as their cortisol levels—a hormone that helps reduce inflammation—rose.
"Cortisol often gets a bad reputation, but it helps the body manage stress," Mengelkoch said. "If women on the pill experience increases in cortisol but also a worsening mood, it might mean the pill is hindering their ability to recover from stress."
