Hormonal dynamics shape brain structure in women with and without endometriosis

2281 

Abstract Submission 

Carina Heller¹, Christian Gaser², Lejla Colic², Nooshin Javaheripour², Feliberto de la Cruz², Philine Rojczyk³, Carina Koeppel¹, Habib Ganjgahi⁴, Ann-Christine Buck¹, Michael Kiehntopf², Laura Pritschet⁵, Emily Jacobs⁵, Zora Kikinis⁶, Martin Walter², Ilona Croy¹, Daniel Güllmar²

¹Friedrich Schiller University Jena, Jena, Germany, ²Jena University Hospital, Jena, Germany, ³Ludwig-Maximilians-University, Munich, Germany, ⁴University of Oxford, Oxford, United Kingdom, ⁵University of California Santa Barbara, Santa Barbara, CA, ⁶Harvard Medical School, Boston, MA

Carina Heller  
Friedrich Schiller University Jena
Jena, Germany

Christian Gaser  
Jena University Hospital
Jena, Germany

Lejla Colic  
Jena University Hospital
Jena, Germany

Nooshin Javaheripour  
Jena University Hospital
Jena, Germany

Feliberto de la Cruz  
Jena University Hospital
Jena, Germany

Philine Rojczyk  
Ludwig-Maximilians-University
Munich, Germany

Carina Koeppel  
Friedrich Schiller University Jena
Jena, Germany

Habib Ganjgahi  
University of Oxford
Oxford, United Kingdom

Ann-Christine Buck  
Friedrich Schiller University Jena
Jena, Germany

Michael Kiehntopf  
Jena University Hospital
Jena, Germany

Laura Pritschet  
University of California Santa Barbara
Santa Barbara, CA

Emily Jacobs  
University of California Santa Barbara
Santa Barbara, CA

Zora Kikinis  
Harvard Medical School
Boston, MA

Martin Walter  
Jena University Hospital
Jena, Germany

Ilona Croy  
Friedrich Schiller University Jena
Jena, Germany

Daniel Güllmar  
Jena University Hospital
Jena, Germany

As an endocrine organ, the brain is intricately influenced by gonadal hormones, particularly endogenous estradiol and progesterone (1,2). Recent advances in neuroscience have shifted the paradigm from cross-sectional analyses to longitudinal tracking (e.g. 3), also recognizing the rhythmic nature of gonadal hormone production (e.g. 4). To expand our understanding how gonadal hormones impact brain structure, it is essential to broaden the scope beyond individuals with typical menstrual cycles. Including those with endocrine disorders such as endometriosis, which features a unique hormonal profile (5–7) and affects approximately 10% of women in the reproductive years (8), will enhance our understanding of the complex interplay between gonadal hormones and their influence on brain structure.

The current study densely-sampled three females who underwent extensive brain imaging and venipuncture over the full menstrual cycle (Fig. 1, Panel A). First, we densely sampled a healthy woman with a typical menstrual cycle. Here, a healthy female underwent majority weekday testing for five consecutive weeks while freely cycling, resulting in n = 25 test sessions, referred to as 'natural cycle.' We compared this dataset of one woman to the densely-sampled open-access 28andMe dataset of another woman (4), referred to as '28andMe (natural) cycle.' The healthy female participant underwent testing for n = 30 consecutive days while freely cycling. We repeated these procedures in a female participant diagnosed with endometriosis. A female participant underwent testing from Monday to Friday for five consecutive weeks while freely cycling, resulting in n = 25 test sessions, referred to as 'endometriosis cycle.' Estradiol and progesterone levels were assessed daily and T1w images were preprocessed with the CAT12 toolbox (9) using the longitudinal pipeline. Singular Value Decomposition (SVD) extracted spatiotemporal patterns from the three-dimensional image sets for each participant separately. Spatial patterns represent the regions of the brain that share a similar temporal pattern, while temporal dynamics describe local volume changes of these regions over time. The time-pattern explaining the highest variance (40%,endometriosis cycle; 45%, natural cycle, 54%, 28andMe (natural) cycle) was selected for further analysis (Fig. 2, Panel A), revealing overlapping brain regions (thalamus, pallidum, putamen, and caudate) across the three participants (Fig. 2., Panel B). Linear regression analysis assessed the relationship between spatiotemporal patterns and gonadal hormones in each participant separately.

In the natural cycle and the 28andMe (natural) cycle, the linear regression with estradiol as a predictor did not yield significant results. Conversely, progesterone (28andMe (natural) cycle: p < 0.001; natural cycle: p = 0.013) and the progesterone/estradiol ratio (28andMe (natural) cycle: p < 0.001; natural cycle: p = 0.009) emerged as significant predictors, indicating a linear association between these hormones and the brain structural time-pattern. For the endometriosis cycle, the linear regression revealed estradiol as a statistically significant predictor of the brain structural time-pattern (p = 0.010). In contrast, progesterone and the progesterone/estradiol ratio were insignificant (Fig. 1, Panel B).

Extensive brain imaging and venipuncture across typical and endometriosis menstrual cycles reconfirmed that brain volume fluctuates during the menstrual cycle. Gonadal hormones, particularly estradiol and progesterone, led to short-term changes in brain structures, particularly in areas with increased estradiol and progesterone receptor distributions. The associations between hormones and brain structure differed between the natural menstrual cycles and the cycle with endometriosis, highlighting the importance of considering individual hormonal dynamics in understanding brain structural plasticity.

Cortical Anatomy and Brain Mapping

Subcortical Structures ²

Neuroanatomy Other

Anatomical MRI ¹

ADULTS

Data analysis

Design and Analysis

DISORDERS

STRUCTURAL MRI

Sub-Cortical

Thalamus

Other - gonadal hormones