In a recent study published in the journal Frontiers in Neuroendocrinology, researchers assessed the impact of hormonal contraceptives (HC) on the brain and stress.
Hormonal contraceptives have enabled unprecedented levels of reproductive control and several health benefits, including reducing premenstrual symptoms and protecting against certain cancers. These alterations, including those in mood, are often benign or even beneficial. However, hormonal contraceptives cause symptoms of depression or anxiety in 4-10% of users or up to 30 million people at any given time. Extensive research is needed to understand how hormonal contraceptives affect these reactions or who is most vulnerable to the negative consequences.
Hormonal contraceptives, stress and the brain: the critical need for animal models. Image credit: Africa Studio/Shutterstock
Need for animal models
In the present study, the team discussed research on the use of hormonal contraceptives in humans and described how laboratory animal models of hormonal exposure to contraceptives will be a crucial tool for expanding knowledge of the precise mechanisms by which hormonal contraceptives affect brain, stress responses. , and risk of depression.
The use of rat and mouse models is crucial to determine the precise cellular, molecular, and circuit-level mechanisms of hormonal effects on behavior and the brain. In laboratory animals, researchers can systematically vary HC formulations, age at which HC exposure begins, history of stress exposure, and interactions between stress and use of HC. Furthermore, the function of individual variations in stress or hormonal response can be determined by specific genotypes, including various strains and transgenic animals.
In addition, researchers can investigate how HCs affect psychological processes using behavioral models that represent anxiety- and depression-like behaviors and cognitive processes. To determine the precise causative processes by which HCs alter the brain, researchers can directly monitor stress hormone levels in laboratory animals and perform pharmacological manipulations and molecular, invasive surgical, and imaging approaches.
Hormonal effects on the brain
Studies of women and free-ranging female rodents and exogenous interventions provide ample evidence for the physiological effects of estrogen and progesterone on the brain beyond sexual behaviors. For example, in rats and mice, there is significant hormone-dependent regulation of gene expression and chromatin, dendritic spines, plasticity, and cognitive processes such as memory, as well as behaviors such as motivation, anxiety, fear and impulsivity throughout the estrous cycle. Similar changes in prefrontal and hippocampal activity, as well as in affective states such as anxiety and cognitive tasks such as fear extinction, are caused by the menstrual cycle in humans.
Therefore, the study’s findings that hormonal changes affect a number of measures are constant throughout the human menstrual cycle and the estrous cycle of rodents. This supports the validity of using animals as models to study the mechanisms underlying the effects of hormones, including HC, on the brain. Future mouse models exposed to contraceptive hormones will rely on the use of animal models to study specific hormone-mediated effects on the brain.
Effects of HC on mood, anxiety, and depression
Whether contemporary HCs influence mood swings and increase risks or rates of anxiety, panic attacks, or depression is still a matter of debate. On the one hand, most people claim that the rates or risk of these diseases have not changed; on the other hand, many believe that using HC has helped their mood, especially around menstruation. People stop using HC mainly because of unpleasant emotional effects and mood swings. Depression and suicide are some of the serious side effects that people experience when using HC.
Understanding the mechanisms behind the effects of HC on mood and the causality of the effects of HC found in human studies would require animal models. However, the impact of HCs during adolescence, how androgenic versus antiandrogenic progestins affect the risk of depression-like behaviors, and how known risk factors for depression, such as prior exposure to stress, modify the risk of depression while using HCs, are questions that these models are particularly well suited to address.
Hormonal contraceptives and the stress response
Most studies of HC users showed a blunted stress response, while some had altered basal cortisol levels, providing an indirect mechanism by which HCs could modulate mood. spirit, motivation and cognition. To fully understand the advantages and disadvantages of HCs in the brain, it is essential to consider their role in controlling the HPA axis. Animal models of HC exposure are well equipped to determine how HCs mediate these effects, as well as the molecular mechanisms involved in these alterations, both in the periphery and in the brain.
Overall, the study highlighted that animal models are essential to address the issues raised by studies of HC users and to prompt new questions that human studies can subsequently answer. As a result, animal models will be crucial for understanding the risk factors, variability, and processes by which HCs influence the brain, formulating plans for more individualized approaches to HC prescription and providing a basis for research on new and evolving HCs.