Spatial and verbal performance do not differ between active pill intake and pill pause.

Androgenic COC-users demonstrate better orientation accuracy than anti-androgenic COC-users.

Longer duration of COC-use relates to subtle shifts in spatial and verbal performance.

Ovarian hormones and testosterone have been related to verbal and spatial processing. Oral contraceptives are taken by approximately 150 million women worldwide often for extended time periods. To date, the literature on long-term effects of COCs on cognition is sparse, and results and methodology are inconsistent.

In this manuscript we examined whether verbal and spatial performance changed (i) during short-term hormonal withdrawal as during the monthly pill pause and (ii) related to the duration of COC-use. We assessed the moderating effects of progestin type (androgenicity) and task complexity.

180 participants (60 androgenic COC-users, 60 anti-androgenic COC-users and 60 non-users with a menstrual cycle) were tested once during their active pill phase/luteal phase and once during their pill pause/menses. We compared mental rotation, navigation and verbal fluency performance between the pill pause and active intake phase in COC users and assessed how the differences compared to fluctuations along the menstrual cycle in naturally cycling women.

No differences between active pill intake and pill pause were found in mental rotation, navigation or verbal fluency in long-term users. Irrespective of COC-phase, androgenic COC-users demonstrated higher orientation accuracy compared to anti-androgenic COC-users and non-users. Longer pill duration was associated with better orientation accuracy and decreased phonemic word and switching production in COC-users independent of the pill's androgenicity.

The association of verbal and spatial performance to COC use duration in the absence of short-term changes during the pill-free interval may hint at cumulative effects of long-term COC-use on spatial and verbal processing.

Combined oral contraceptive

Verbal fluency

Mental rotation

Navigation

Pill duration

Androgenicity

Pill pause

© 2025 The Authors. Published by Elsevier Inc.