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Accepted manuscript

Differences in Verbal Memory, Visuospatial Ability, and Cognitive Inhibition Among Young Women Using Drospirenone and Ethinyl Estradiol Oral Contraceptives Versus Naturally Cycling Controls

Published online by Cambridge University Press:  02 January 2026

Natalia Lagunas Open the ORCID record for Natalia Lagunas [Opens in a new window] ,
Laura Sánchez-Giraldo ,
Daniela Grassi ,
Teresa Diéguez-Risco  and
Alejandro de la Torre-Luque
Natalia Lagunas*
Affiliation:
Department of Legal Medicine, Psychiatry and Pathology, School of Medicine, Complutense University of Madrid, Ciudad Universitaria, 28040, Madrid, Spain. Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029, Madrid, Spain.
Laura Sánchez-Giraldo
Affiliation:
Independent Researcher
Daniela Grassi
Affiliation:
Department of Anatomy, Histology and Neuroscience, School of Medicine, Autonomous University of Madrid, 28029, Madrid, Spain. Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029, Madrid, Spain. Neuroactive Steroids Lab, Cajal Institute, CSIC, Avenida Doctor Arce 37, 28002 Madrid, Spain.
Teresa Diéguez-Risco
Affiliation:
Departament of Social, Work and Differential Psychology, School of Psychology, Complutense University of Madrid, Somosaguas Campus, 28223, Madrid, Spain
Alejandro de la Torre-Luque
Affiliation:
Department of Legal Medicine, Psychiatry and Pathology, School of Medicine, Complutense University of Madrid, Ciudad Universitaria, 28040, Madrid, Spain. Centro de Investigación Biomédica en Red en Salud Mental (CIBERSAM), Instituto de Salud Carlos III, 28029, Madrid, Spain.
*
*Correspondence: Natalia Lagunas, llagunas@ucm.es
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Abstract

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Objective:

this study aimed to investigate the differences on cognitive performance across four cognitive domains—verbal memory, language fluency, visuospatial ability, and cognitive inhibition— between drospirenone and ethinyl estradiol (DRSP/EE) users and naturally cycling women in the luteal phase (LP). The goal was to determine whether hormonal suppression associated with DRSP/EE use is linked to domain-specific cognitive alterations.

Methods:

a total of 48 young adult women were assessed: 23 using DRSP/EE (with pharmacologically suppressed endogenous hormonal levels) and 25 naturally cycling during the LP. Participants completed standardized neuropsychological tasks measuring verbal memory, language fluency, visuospatial ability, and cognitive inhibition. Group comparisons analyses were conducted.

Results:

Significant group differences were observed in verbal memory, visuospatial ability, and cognitive inhibition, while no significant group differences were found in language fluency. Women using DRSP/EE showed significantly lower performance in verbal memory (U = 165, p = 0.009, r = 0.38) and visuospatial ability (U = 155, p = 0.006, r = 0.40) tasks compared to naturally cycling women. In contrast, they demonstrated higher performance in cognitive inhibition, quantified by a significantly higher Stroop interference score (t(46) = 2.710, p = 0.009, d = 0.783).

Conclusion:

The present findings suggest that the use of DRSP/EE oral contraceptives is associated with differences across specific cognitive domains compared to naturally cycling women in the LP. The observed pattern -lower performance in hippocampus-related domains (verbal memory and visuospatial ability) paired with higher performance on a frontal-lobe-dependent task (cognitive inhibition)- is consistent with existing evidence suggesting that suppression of endogenous ovarian hormones may differentially influence cognitive functions. These behavioral associations underscore the need for further domain-specific research into the long-term cognitive implications of combined oral contraceptives.

Keywords

Verbal MemorySpatial AbilityExecutive FunctionMenstrual CycleCombined-Oral-Contraceptives

Information

Type
Original Article
Information
Acta Neuropsychiatrica , Accepted manuscript , pp. 1 - 21
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
Copyright
© The Author(s), 2026. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology