Animal models of hormonal contraceptives: Understanding drug-specific and user-specific variables

This manuscript reviews findings from the symposium "Hormonal Contraceptives and the Brain: A Focus on Rodent Models," presented at the 2024 meeting for Steroids and the Nervous System in Turin, Italy. Hormonal contraceptives (HCs) are widely used by over 300 million women globally, yet their neurobiological and behavioral impacts have only recently gained extensive research attention. This review emphasizes the importance of animal models in studying these effects due to the practical and ethical limitations of human studies. By distinguishing drug-specific variables (e.g., dosage, chemical composition, routes of administration) from user-specific variables (lifestyle factors, genetic predispositions), researchers can better understand HC-related outcomes. Here, we emphasize the utility of animal models for uncovering putative mechanisms underlying the effects of HCs observed in human studies. Moreover, the authors reflect on the design of the animal models of HC used in their experiments, past and present. We also discuss current research related to user-specific variables which highlight the vulnerability of adolescents to the adverse effects of HCs, exposure to stressors, and the compounded risks of HC when combined with substances like cannabinoids and nicotine. This review underscores the value of animal models in advancing our understanding of the broader neurobiological and behavioral impacts of HCs in humans. These studies are crucial for developing personalized medicine approaches and optimizing contraceptive regimens to mitigate risks.