The combined hormonal contraceptive pill, commonly known as the birth control pill, is the second most popular form of contraception in the United States, following condoms. The pill has been a staple in preventing unwanted pregnancies for the past 60 years, and one of its key components has been ethinyl estradiol, a synthetic estrogen. Researchers have recently discovered that rats given this hormone exhibited more behaviors associated with anxiety, as compared to a more natural estrogen used in a newer form of the contraceptive pill.
In a recent study presented at ENDO 2024, researchers found that rats given synthetic estrogens displayed increased signs of anxiety compared to those given natural estrogens. The findings revealed that synthetic estrogens were associated with lower steroid hormone levels when compared to their natural counterparts. The natural estrogen used in the study is similar to the one found in NOMAC-E2, a combined oral contraceptive known as Zoely, produced by Merck. On the other hand, the synthetic estrogen commonly used in most combined hormonal contraceptive pills is a highly potent synthetic estrogen called ethinyl estradiol.
Abigail Hegwood, MS, the study author, aimed to investigate the differences in side effects between natural and synthetic estrogens in hormonal contraceptives. Three groups of female rats were given ethinyl estradiol, estradiol valerate, or a control, and their spatial awareness and anxiety levels were tested. The results showed that rats given the synthetic estrogen exhibited different behaviors in the maze test, indicating anxiety-like behaviors. Furthermore, both types of estrogen reduced circulating testosterone levels in the rats.
According to Alesia Prakapenka, PhD, the supervisor of the study, synthetic ethinyl estradiol caused circulating estrogen levels to fall below the detection limit in many rats. This suggests that there may be changes within the feedback loop affecting the behavior of the rats. The research highlights the need to further study the behavioral effects of hormonal contraceptives and to develop tailored options that minimize side effects.
Jonathan Schaffir, MD, who was not involved in the research, believes that while hormonal contraceptives can influence mood and behavior to some extent, the impact on most women is usually small. He emphasized the importance of examining the components of medications, particularly hormonal treatments, and developing new medications with better responses and fewer side effects. It is crucial to consider individual differences in medication responses and to aim for optimal physiological effects in each person.
