Hormonal contraceptive use in adolescence and cortical brain metrics: Insights from the ABCD Study
Poster No:
957
Submission Type:
Abstract Submission
Authors:
Carina Heller1, Elvisha Dhamala2, Katherine Bottenhorn3, Megan Herting3, Brain Bossé4, Jennifer De La Rosa5, Leslie Farland5, Alicia Allen5, Claudia Barth6, Nicole Petersen4
Institutions:
1University of Minnesota, Minneapolis, MN, 2Feinstein Institutes for Medical Research, Glen Oaks, NY, 3Keck School of Medicine of USC, Los Angeles, CA, 4UCLA, Los Angeles, CA, 5University of Arizona, Tucson, AZ, 6Diakonhjemmet Hospital, Oslo, Norway
First Author:
Co-Author(s):
Introduction:
Adolescence is a critical period in human development, marked by a dynamic cascade of changes in brain structure and function (1), driven by neuromaturational processes such as myelination and synaptic pruning which actively shape the brain (2). Pubertal increases in sex steroids, including estrogens, progesterone, and testosterone, play a key role in shaping neurodevelopmental trajectories crucial for cognitive and emotional maturation (3). During this time, 1 in 5 females initiate hormonal contraceptive (HC) use (4), primarily in the form of oral contraceptive pills (OCPs), for contraceptive or therapeutic reasons (5). HCs contain exogenous hormones (ethinyl estradiol and a progestin) that reduce endogenous progesterone (6) and estradiol (7) production. In adults, OCP use has been associated with cortical morphometric brain changes that include lower cortical thickness in regions of the salience and default-mode network (8). Despite widespread HC use and extensive safety testing (9), their impact on adolescent brain development remains largely unexplored.
Methods:
We analyzed cortical thickness, surface area, and volume in 1,234 female adolescents from the ABCD Study from the 4-year follow-up (HC+: n = 65; HC-: n = 1,169). Hormonal levels of estradiol, testosterone, and dehydroepiandrosterone (DHEA), a precursor to testosterone, were compared between HC+ and HC- users. Structural brain differences and associations between hormonal levels and brain measures were assessed.
Results:
Salivary levels of estradiol, testosterone, and DHEA were significantly lower in HC+ users, with testosterone showing the largest difference (T = 4.64, p = 0.000004). However, all three distributions overlapped considerably. Cortical thickness was significantly thinner in HC+ users in regions including the bilateral paracentral, superior frontal, medial orbitofrontal, and superior parietal, left precentral, posterior cingulate, lateral occipital, and inferior temporal gyri, as well as the right precuneus. After applying False Discovery Rate (FDR) correction (10) for multiple comparisons, only cortical thickness in the paracentral gyrus remained significantly thinner in HC+ participants than in HC- (left: pFDR = 0.0225; right: pFDR = 0.0137; Figure 1 Panel A). HC+ participants exhibited significantly less surface area only in the left postcentral gyrus, and smaller volumes in the bilateral precentral, postcentral, and paracentral gyri, as well as the left lingual gyrus relative to HC- participants. However, results no longer met the threshold of statistical significance after FDR correction. Total intracranial volume (TIV) did not differ between groups. Across all participants, levels of estradiol were negatively correlated with cortical thickness in the right precuneus and left precentral gyrus after adjusting for puberty stage and TIV (Figure 1 Panel B). Estradiol, testosterone, and DHEA levels were negatively correlated with volume in several regions, including the left pre- and postcentral gyri. Surface area of the left postcentral gyrus negatively correlated with levels of estradiol and DHEA. Correlations did not remain significant after applying FDR correction.
·Figure 1
Conclusions:
This work contributes to a growing body of literature examining the impact of HCs on brain structure, specifically addressing adolescence as a critical period for neurodevelopment. Our study identifies HC-related differences in childhood cortical morphology and highlights the need for continued research in this area across adolescent development. By elucidating impacts of HC-related hormonal suppression on brain structure and function, or lack thereof, we can better understand the potential risks and benefits associated with HC use during this critical period of brain maturation. Such insights are essential for informing clinical practice and public health policies aimed at optimizing adolescent reproductive, brain, and mental health.
Lifespan Development:
Early life, Adolescence, Aging 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Cortical Anatomy and Brain Mapping 2
Novel Imaging Acquisition Methods:
Anatomical MRI
Keywords:
Cortex
Development
MRI
Open Data
Other - Hormonal contraceptives
1|2Indicates the priority used for review
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