Over 85 percent of women, and more than 300 million people worldwide at any given moment, use hormonal contraceptives for a minimum of five years in their lifetime. While these contraceptives are primarily used for birth control, many individuals also rely on them to manage various menstruation-related symptoms, including cramps, acne, and mood swings. However, in up to 10 percent of women, hormonal contraceptives can heighten the risk of depression. Hormones like estrogen and progesterone play an essential role in brain health. So, how does altering hormone levels with these contraceptives impact mental well-being? I am a researcher focusing on the neuroscience of stress and processes related to emotions. I also examine sex differences in vulnerability and resilience to mental health disorders. Understanding the impact of hormonal contraceptives on mood can assist researchers in predicting who might experience positive or negative effects.
In the United States and other Western nations, the most prevalent form of hormonal contraceptive is “the pill,” which contains a synthetic estrogen and a synthetic progesterone, both involved in the regulation of the menstrual cycle, ovulation, and pregnancy. Estrogen orchestrates the timely release of other hormones, while progesterone supports pregnancy maintenance. This might seem counterintuitive—why do hormones essential for pregnancy also prevent it? And why does taking a hormone decrease its level? Hormone cycles are meticulously regulated by the hormones themselves. When progesterone levels rise, processes in cells are triggered that stop further production of progesterone, known as a negative feedback loop. The estrogen and progesterone in a daily pill, or in other common contraceptive forms like implants or vaginal rings, prompt the body to produce less of these hormones, bringing them down to levels seen outside the fertile window of the cycle. This disrupts the carefully timed hormonal cycle necessary for ovulation, menstruation, and pregnancy. Hormonal contraceptives affect more than the ovaries and uterus.
The brain, specifically a region called the hypothalamus, manages the synchronization of ovarian hormone levels. Although they are referred to as “ovarian hormones,” receptors for estrogen and progesterone exist throughout the brain. Estrogen and progesterone have wide-ranging effects on neurons and cellular processes that are unrelated to reproduction. For instance, estrogen is involved in processes that control memory formation and protect the brain from damage, while progesterone aids in regulating emotion. By altering hormone levels in the brain and body, hormonal contraceptives may influence mood—for better or worse. Estrogen and progesterone also regulate the stress response, the body’s “fight-or-flight” reaction to physical or psychological challenges. The main hormone involved in the stress response—cortisol in humans and corticosterone in rodents, both shortened to CORT—is primarily a metabolic hormone, meaning that raising blood levels of these hormones during stress results in more energy mobilized from fat stores. The interaction between stress systems and reproductive hormones forms a key connection between mood and hormonal contraceptives, as energy regulation is extremely crucial during pregnancy.
So, what happens to someone’s stress response when they use hormonal contraceptives? When faced with a mild stressor, such as placing an arm in cold water or delivering a public speech, women using hormonal contraceptives exhibit a smaller increase in CORT than those not using them. Researchers observed a similar effect in rats and mice—when treated daily with hormone combinations that mimic the pill, female rats and mice also displayed a suppressed stress response. Do hormonal contraceptives raise the risk of depression? In short, it varies from person to person. But for most, probably not. It’s important to point out that neither increased nor decreased stress responses directly correlate with risk or resilience against depression.
However, stress is closely tied to mood, and prolonged stress significantly elevates the risk for depression. By altering stress responses, hormonal contraceptives change the risk of depression following stress, offering “protection” against depression for many, but an “increased risk” for a minority. Over 9 in 10 people who use hormonal contraceptives won’t experience mood reduction or depression symptoms, while many will notice improved mood. Yet, researchers are still unsure who might face an increased risk. Genetic factors and past stress experiences contribute to depression risk, and similar factors seem to influence mood changes associated with hormonal contraception.