Intrauterine Device Use: A New Frontier for Behavioral Neuroendocrinology.

Intrauterine devices (IUDs) are the most-used reversible contraceptive method for women in the world, but little is known about their potential modulation of brain function, cognition, and behavior. This is disconcerting because research on other hormonal contraceptives, especially oral contraceptives (OCs), increasingly shows that exogenous sex hormones have behavioral neuroendocrine consequences, especially for gendered cognition, including spatial skills. Effects are small and nuanced, however, partially reflecting heterogeneity. The goal of this paper is to introduce IUD use as a new frontier for basic and applied research, and to offer key considerations for studying it, emphasizing the importance of multimodal investigations and person-specific analyses. The feasibility and utility of studying IUD users is illustrated by: scanning women who completed a functional magnetic resonance imaging mental rotations task; taking an individualized approach to mapping functional connectivity during the task using network analyses containing connections common across participants and unique to individual women, focusing on brain regions in putative mental rotations and default mode networks; and linking metrics of brain connectivity from the individualized networks to both mental rotations task performance and circulating hormone levels. IUD users provide a promising natural experiment for the interplay between exogenous and endogenous sex hormones, and they are likely qualitatively different from OC users with whom they are often grouped in hormonal contraceptive research. This paper underscores how future research on IUD users can advance basic neuroendocrinological knowledge and women's health.