2026 ECNP Congress

PS01-1064

Cognitive flexibility and hormonal contraceptive use: a cross-sectional study in healthy women

Janika Fortunato — S.V. Larsen, P.M. Fisher, V.G. Frøkjær, V.H. Dam · Copenhagen University Hospital- Rigshospitalet, Neurobiology Research Unit, Copenhagen, Denmark

2026 ECNP Congress

Background

Hormonal contraception is used by ∼400 million women worldwide for family planning. Therefore, improving our understanding of potential brain-related effects is essential to ensure safe use and informed choices for women. In recent years, the use of hormonal contraceptives has been associated with increased risk for depression [1], suggesting that exogenous hormones influence brain systems may be involved. Cognitive dysfunction is a core feature of depression [2], however, the contributions of hormonal contraceptives remain poorly understood. In particular, their impact on cognitive flexibility, i.e., the ability to adapt to changing demands, has been understudied. Given that demands in daily life are highly dynamic, cognitive flexibility is essential for adaptive human functioning. This study aims to investigate the effects of hormonal contraceptive use on cognitive flexibility in healthy women.

Methods

In this cross-sectional study from the Cimbi database [3], we included data from 113 healthy women (naturally cycling women = 68; hormonal contraceptive users = 45). Within the hormonal contraceptive users, 20 women were using combined oral contraceptives (COC), 21 women used hormonal intrauterine device (IUD), and 4 women used other types of hormonal contraceptives. Cognitive flexibility was measured using errors on the three-dimensional intradimensional/extradimensional set-shifting (IDED3D) task, where higher error rates indicate lower cognitive flexibility [4]. We compared naturally cycling women to i) hormonal contraceptive users and ii) COC users only, by using multiple linear regression models on log-transformed error rates adjusted for age and education level.

Results

COC users showed lower cognitive flexibility compared to naturally cycling women (β = 0.3, p = 0.009, 95% CI = 0.08–0.53). When pooling COC with other hormonal contraceptive users, the group difference was substantially smaller, and we found no statistically significant difference between naturally cycling women and hormonal contraceptive users (β = 0.06, p = 0.50, 95% CI = -0.11–0.23).

Discussion:Our findings show that COC use is associated with reduced cognitive flexibility in healthy women, whereas no such association was observed when all hormonal contraceptive users were pooled together. This pattern suggests that the cognitive effects of hormonal contraceptives may be more pronounced for combined estrogen/progestogen products relative to progestogen-only products. The results from our study provide essential initial effect estimates that can guide the selection of relevant samples for future investigation on these differences in better-powered cohorts. In addition, it is worth highlighting that the functional implications of the observed differences in cognitive flexibility remain unclear, as the study population consists of healthy individuals, and the effects may be different, e.g., in individuals at high risk for depression. Overall, the study contributes to growing literature on the cognitive effects of hormonal contraceptive use and highlights the need for future research. Future studies should clarify how specific types of contraceptives influence cognitive functioning and whether these changes, followed by hormonal contraceptive use, have a positive or negative impact on individuals’ mental health, to enable people to make informed choices on hormonal contraceptive use.

References

  1. Johansson, T., Vinther Larsen, S., Bui, M., Ek, W.E., Karlsson, T., Johansson, Å., 2023. Population-based cohort study of oral contraceptive use and risk of depression. Epidemiol Psychiatr Sci. 2023;32:e39, this issue, http://doi.org/10.1017/S2045796023000525.
  2. Gabrys, R.L., Tabri, N., Anisman, H., Matheson, K., 2018. Cognitive control and flexibility in the context of stress and depressive symptoms: The cognitive control and flexibility questionnaire. Frontiers in Psychology, this issue, http://doi.org/10.3389/fpsyg.2018.02219.
  3. Knudsen, G.M., Jensen, P.S., Erritzoe, D., Baare, W.F.C., Ettrup, A., Fisher, P.M., Gillings, N., Hansen, H.D., Hansen, L.K., Hasselbach, S.G., Henningsson, S., Herth, M.M., Holst, K.K., Iversen, P., Kessing, L.V., Macoveanu, J., Madsen, K.S., Mortensen, E.L., Nielsen, F.Å., Paulson, O.B., Strother., Frokjaer, V.G., 2016. The Center for Integrated Molecular Brain Imaging (Cimbi) database. NeuroImage, this issue, http://doi.org/10.1016/j.neuroimage.2015.04.025.
  4. Rogers, R.D., Blackshaw, A.J., Middleton, H.C., Matthews, K., Hawtin, K., Crowley, C., Hopwood, A., Wallace, C., Deakin, J.F.W., Sahakian, B.J., Robbins, T.W., 1999. Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour. Psychopharmacology, this issue, http://doi.org/10.1007/pl00005494.