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. 2022 Sep 20:13:885617.
doi: 10.3389/fendo.2022.885617. eCollection 2022.

Duration of oral contraceptive use relates to cognitive performance and brain activation in current and past users

Isabel Asar Noachtar  1 , Esmeralda Hidalgo-Lopez  1 , Belinda Pletzer  1
Affiliations

Duration of oral contraceptive use relates to cognitive performance and brain activation in current and past users

Isabel Asar Noachtar et al. Front Endocrinol (Lausanne). .

Abstract

Previous studies indicate effects of oral contraceptive (OC) use on spatial and verbal cognition. However, a better understanding of the OC effects is still needed, including the differential effects of androgenic or anti-androgenic OC use and whether the possible impact persists beyond the OC use. We aim to investigate the associations of OC use duration with spatial and verbal cognition, differentiating between androgenic and anti-androgenic OC. Using functional magnetic resonance imaging (MRI), we scanned a group of 94 past and current OC-users in a single session. We grouped current OC users (N=53) and past OC users with a natural cycle (N=41) into androgenic and anti-androgenic user. Effects of OC use duration were observed for current use and after discontinuation. Duration of OC use was reflected only in verbal fluency performance but not navigation: The longer the current OC use, the less words were produced in the verbal fluency task. During navigation, deactivation in the caudate and postcentral gyrus was duration-dependent in current androgenic OC users. Only during the verbal fluency task, duration of previous OC use affects several brain parameters, including activation of the left putamen and connectivity between right-hemispheric language areas (i.e., right inferior frontal gyrus and right angular gyrus). The results regarding performance and brain activation point towards stronger organizational effects of OCs on verbal rather than spatial processing. Irrespective of the task, a duration-dependent connectivity between the hippocampus and various occipital areas was observed. This could suggest a shift in strategy or processing style with long-term contraceptive use during navigation/verbal fluency. The current findings suggest a key role of the progestogenic component of OCs in both tasks. The influence of OC use on verbal fluency remains even after discontinuation which further points out the importance of future studies on OC effects and their reversibility.

Keywords: androgenicity; brain activation and connectivity; duration of OC use; navigation; oral contraceptives (OC); progestins; sex hormones; verbal fluency.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Negative association between verbal fluency performance and duration of OC use (in years) in current androgenic users. (B) Negative association between verbal fluency performance and duration of OC use (in years) in current anti-androgenic users.
Figure 2
Figure 2
Association between duration of current OC use [in years] and BOLD-response in the bilateral caudate in androgenic (A) and anti-androgenic (B) OC-users during navigation.
Figure 3
Figure 3
Negative association between duration of OC use and left postcentral gyrus activation during navigation in current androgenic OC users.
Figure 4
Figure 4
Negative association between duration of OC use and right superior occipital gyrus and right calcarine cortex deactivation during navigation in current OC users.
Figure 5
Figure 5
Positive association between duration of OC and left putamen activation during verbal fluency in past OC users.
Figure 6
Figure 6
Positive association between duration of current OC use and connectivity between left and right caudate during navigation in current users.
Figure 7
Figure 7
Positive association between duration of OC use and connectivity between left hippocampus and right cuneus, lingual gyrus, superior occipital gyrus in current users during navigation.
Figure 8
Figure 8
Negative association between duration of OC use and connectivity between left hippocampus and right angular gyrus in current users during navigation.
Figure 9
Figure 9
Positive association between duration of OC use and connectivity between left hippocampus and bilateral posterior cingulate gyrus, left cuneus and right lingual gyrus in current users during verbal fluency.
Figure 10
Figure 10
Positive association between duration of OC and connectivity between right IFG and right angular gyrus in past users during verbal fluency.
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