Menstrual cycle modulates the effect of BDNF Val66Met variant on category learning.

Overview

1. Department of Psychology, University of Toronto,Toronto, ON M5S 3G3 Canada

Abstract

Background: Both brain-derived neurotrophic factor (BDNF) and ovarian hormones are powerful neuromodulators, yet evidence of their impact on human cognition remains mixed. As prior work has studied them in isolation, examining their interacting effects presents a key empirical opportunity for explicating their effects on cognition.

Methods: We genotyped participants for the BDNF Val66Met single nucleotide polymorphism, which is associated with less efficient activity-dependent BDNF secretion and altered hippocampal function, and examined their performance on a complex learning task at two points in the menstrual cycle: early follicular (characterized by low levels of ovarian hormones) and late follicular (characterized by high estradiol).

Results: While met carriers showed advantages during the early follicular timepoint, val homozygotes outperformed them at the late follicular timepoint. Furthermore, effects in met carriers were largely driven by increased sensitivity to both absolute levels and changes in levels of estradiol.

Conclusions: The current findings provide the first evidence of BDNF Val66Met interacting with the menstrual cycle to predict cognition, demonstrate nuanced genotype- and hormone-specific outcomes, and underscore the importance of studying effects of interacting biological systems on human cognition.

Supplementary Information: The online version contains supplementary material available at 10.1186/s13293-026-00856-2.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Code, as well as data necessary to reproduce the main analyses will be made available on OSF upon publication: [https://osf.io/wfecv/](https:/osf.io/wfecv) Demographic data will not be shared in order to ensure that no sensitive genotype or hormone information can be linked to individual participants.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 3 authors, 5 keywords, 10 MeSH terms, 3 funders, 111 references.

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This paper

Perović, M., Hou, J., & Mack, M. L. (2026). Menstrual cycle modulates the effect of BDNF Val66Met variant on category learning. Biology of sex differences, 17(1), 65. https://doi.org/10.1186/s13293-026-00856-2

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