# Idiosyncrasy and generalizability of contraceptive- and hormone-related functional connectomes across the menstrual cycle

## TL;DR

This study explores how brain connectivity changes with hormone fluctuations during the menstrual cycle and how these patterns vary between individuals.

## Contribution

The study reveals idiosyncratic and generalizable brain connectivity patterns linked to hormones and contraceptive use.

## Key findings

- Common and individual-specific factors similarly influence brain network organization.
- Hormonal contraceptive use is associated with widespread connectivity changes.
- Estradiol and progesterone show sparser, hormone-related connectivity patterns.

## Abstract

Neuroendocrinology has received little attention in human neuroscience research, resulting in a dearth of knowledge surrounding potent and dynamic modulators of cognition and behavior, as well as brain structure and function. This work addresses one such phenomenon by studying functional connectomics related to ovarian hormone fluctuations throughout the adult menstrual cycle. To do so, we used fMRI and hormone assessments from two dense, longitudinal datasets to assess variations in functional connectivity with respect to endogenous and exogenous endocrine factors throughout the menstrual cycle. First, we replicated prior findings that common, group-level, and individual-specific factors have similar relative contributions to functional brain network organization. Second, we found widespread connectivity related to hormonal contraceptive (HC) use, in addition to sparser estradiol- and progesterone-related connectivity. Differential generalizability of these connectivity patterns suggests progestin-specific impacts on functional brain organization in HC users. These results provide novel insight into within-individual changes in brain organization across the menstrual cycle and the extent to which these changes are shared between individuals, illuminating understudied phenomena in reproductive health and important information for all neuroimaging studies that include participants who menstruate.

Endocrine modulation of brain function across the menstrual cycle is poorly understood. Human neuroimaging research on the menstrual cycle has long relied on group differences and/or coarse, within-individual cycle stage differences, overlooking considerable individual differences in brain organization, the menstrual cycle, and hormone concentrations. Here, we take a multidataset approach to identify the idiosyncratic contraceptive- and hormone-related functional connectivity from within-individual neuroendocrine dynamics and then test the generalizability of this connectivity to other individuals. In doing so, we identified idiosyncratic hormone-responsive functional connectivity that is somewhat generalizable to other individuals, although this generalizability is complicated by hormonal contraceptive use, potentially reflecting differential connectivity between contraceptive formulations. Thus, this work illuminates individual similarities and differences in neuroendocrine dynamics across the menstrual cycle.