Effects of oral contraceptives on spatial cognition depend on pharmacological properties and phase of the contraceptive cycle
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The central nervous system effects of oral contraceptives (OCs) are not well-documented. In a set of 3 studies, we investigated a specific cognitive function, mental rotation, in healthy women currently using OCs for contraceptive purposes (n = 201) and in medication-free controls not using OCs (n = 44). Mental rotation was measured using a well-standardized and extensively validated psychometric test, the Vandenberg Mental Rotations Test (MRT). In an initial study (Study 1), current OC users (n = 63) were tested during the active or inactive phases of the contraceptive cycle in a parallel-groups design. Studies 2 and 3 were based on an archival dataset (n = 201 current OC users) that consisted of data on the MRT collected in real-time over a 30-year period and compiled for purposes of the present work. The OCs were combined formulations containing ethinyl estradiol (10-35 ug/day) plus a synthetic progestin. All 4 families of synthetic progestins historically used in OCs were represented in the dataset. Cognitive performance was evaluated during either active OC use (‘active phase’) or during the washout week of the contraceptive cycle (‘inactive phase’) when OC steroids are not used. The results showed a significant phase-of-cycle (POC) effect. Accuracy on the MRT was mildly diminished during the active phase of OC use, while scores on verbal fluency and speeded motor tasks were modestly improved. The POC effect was most evident in women using OCs that contained first- or second-generation progestins (the estrane family of progestins or OCs containing levonorgestrel), but not in women using OCs containing recently developed progestins and lower doses of ethinyl estradiol. Using independently established ratings of the estrogenic, androgenic, and progestogenic intensities of the different OC formulations, each brand of OC was classified according to its distinct endocrine profile. Multiple regression revealed that the effects of OC use on the MRT could be predicted based on the estrogenic strength of the contraceptives used. Estrogenic potency, not androgenic or anti-androgenic effects of the OC pill, may underlie the effects of OC usage on spatial cognition.
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Several papers detail that oral contraceptive use and type influences CAT performance on verbal and spatial tasks.
“several papers detail oral contraceptive use and type influences CAT performance on verbal and spatial task (Griksiene & Ruksenas, 2011;Hampson et al., 2022)”
From Factors Related to Mean Score Group Differences on Cognitive Ability Tests: A Systematic Review (2025) · cites this paper as Hampson et al., 2022
Study 1 Results report differences across contraceptive-cycle phases on spatial and verbal-fluency tasks, and the paper examines how contraceptive formulations relate to spatial performance. It does not establish that contraceptive type influences verbal performance; the General Discussion also cautions that its observational design cannot conclusively establish causation. The reported tests are not identified as CAT. (LLM, conf=0.85)
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- Authors
- Hampson, E., Morley, E. E., Evans, K. L., & Fleury, C.
- Affiliations
- Western University (CA)
- Corresponding author
- Hampson, Elizabeth
- ORCID
- Hampson, Elizabeth
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2022-09-06
- Volume
- 13
- Pages
- 888510-888510
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC9487179
- OpenAlex
- W4294763259
- Cited by
- 17
- References
- 83
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 4 · 2023: 2 · 2022: 1
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Scholarship@Western (Western University) (submittedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada (#2020-04989 , #2015-03662, #138017)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Physical Sciences › Engineering › Automotive Engineering › Spatial Cognition and Navigation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- oral contraceptives, spatial cognition, mental rotation, ethinyl estradiol, progestins, levonorgestrel, estrogenic potency, androgenic effects, antiandrogenic effects, women
- MeSH terms
- Cognition, Contraceptives, Oral, Estranes, Ethinyl Estradiol, Female, Humans, Progestins, Levonorgestrel, Progesterone Congeners
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