2026 ECNP Congress

PS02-2071

A framework for evaluating effects of hormonal contraception on hippocampal volume and its relation to memory function in healthy women

Sonja Sofie Hvitved — A. Fuglsang-Damgaard, V.G. Frokjaer, S.V. Larsen · Rigshospitalet, Neurobiology Research Unit, Copenhagen, Denmark

2026 ECNP Congress

Background

Hormonal contraceptives (HC) contain primarily synthetic sex steroids, which can suppress endogenous ovarian hormone production and potentially affect brain regions sensitive to sex hormones. The hippocampus, which contains a high density of sex hormone receptors, plays a central role in several cognitive processes, particularly in episodic and spatial memory. Hippocampal volume has been shown to vary across the menstrual cycle, during which sex hormones levels naturally fluctuate [1-3]. However, current literature reports inconsistent effects of HC use on hippocampal structure, why potential HC-induced effect on hippocampus warrants further investigation, and in particularly its relationship with memory function. Therefore, we here present a study framework aimed at investigating possible HC-associated structural brain effects and their relationship with memory function.

Aims

Primarily, this study framework is aimed at evaluating whether HC use is associated with hippocampal volume; secondarily at evaluating potential hippocampal volume differences across users of different HC types (i.e. combined hormonal contraception vs progestogen-only contraception vs natural cycling women); and lastly, at evaluating the association between hippocampal volume and memory function and whether it depends on HC use.

Hypotheses

We hypothesise reduced hippocampal volume in HC users compared to naturally cycling women and that this difference may be more pronounced between HC-types. Further, we hypothesise that the postulated hippocampal volume reduction in HC users will map onto a decreased memory performance.

Methods

This study will leverage data from the Cimbi database [4], where approximately 250 women have undergone structural magnetic resonance imaging (MRI). A majority of the participants have also completed neuropsychological testing including the Verbal Affective Memory Task 24 (VAMT-24), the Verbal Affective Memory Task 26 (VAMT-26), Taylor Complex Figure Task (TCFT), or Reys Complex Figure Task (RCFT).

The association between 1) HC use and 2) HC type and hippocampal grey matter volume will be evaluated using multiple linear regression models adjusted for age, BMI, intracranial volume, and MR scanner. Further, we will construct a “global verbal memory performance” and “global visuospatial memory performance” by using latent variable models where the global memory performance will be estimated by a latent variable across immediate, short-term and long-term recall scores, adjusted for age, BMI, and HC use. We will test the association between the latent variable and hippocampal volume adjusted for age, BMI, intracranial volume, MR scanner, and HC use. In an alternative model, we will test if the association between hippocampal volume and global memory performance depends on HC use.

Based on the mean and standard deviation from a prior study on healthy women [4], with a sample size of 250, we are able to capture a difference of 3% with a 5% significance and 80% power.

Expected impact

Given the potential influence of HC use on brain structure and its relevance for reproductive mental and cognitive health, this study may contribute to a better understanding of the underlying neurobiological mechanism and inform future treatment and prevention strategies in women’s mental health.

References

  1. Lisofsky, N., Riediger, M., Gallinat, J., Lindenberger, U., Kühn, S., 2016. Hormonal contraceptive use is associated with neural and affective changes in healthy young women. NeuroImage 134, 597–606.
  2. Pletzer, B., Harris, T., Hidalgo-Lopez, E., 2018. Subcortical structural changes along the menstrual cycle: beyond the hippocampus. Sci. Rep. 8 (1), 16042.
  3. Zsido, R.G., et al., 2023. Ultra-high-field 7T MRI reveals changes in human medial temporal lobe volume in female adults during menstrual cycle. Nat. Ment. Health 1, 761–771.
  4. Knudsen GM, Jensen PS, Erritzoe D, Baaré WFC, Ettrup A, Fisher PM, et al. The Center for Integrated Molecular Brain Imaging (Cimbi) database. Neuroimage. 2016; 124:1213–9.