Abstract
BackgroundDespite the widespread use of oral contraceptives (OCs), and the well-documented influence of estrogens, notably 17β-estradiol (E2), on cognition, research relating OCs to working memory is limited and mixed. Two factors may contribute to these mixed findings: 1) pharmacokinetics of oral contraceptives, which drive fluctuations in synthetic hormone levels; and 2) genetic polymorphisms related to dopamine degradation and working memory, which interact with E2. This research investigated whether the pharmacokinetics of oral contraceptives, in concert with the single nucleotide polymorphism (Val158Met; rs4680) of the catechol-o-methyltransferase gene (COMT), influence working memory performance.MethodsUniversity-age women taking and not taking OCs were tested for working memory and genotyped for COMT. If they were not taking OCs (n = 62), sessions occurred in the early follicular (low E2) and late follicular (high E2) phase. If they were taking OCs (n = 52), sessions occurred 1–2 hours after (high ethinyl estradiol, EE) and ~24 hours after (low EE) pill ingestion. Working memory was tested using the N-back, AX-CPT, Digit Span, and Digit Ordering Tasks. Data were analyzed using multilevel models with estrogen condition, COMT, and group as predictors, controlling for mood and practice effects.ResultsFor women taking OCs, time of pill ingestion did not influence performance. However, the subgroup with COMT val/val (low dopamine) were less accurate on 2-back lure trials than those with COMT met/met (high dopamine). For women not taking OCs, cycle phase moderated COMT’s influence on lure accuracy. When compared, women taking OCs had higher AX-CPT proactive control indices than those not taking OCs.ConclusionThese findings suggest that oral contraceptives are not detrimental for young women’s working memory and that they may increase proactive control. The more pronounced effects of COMT in women taking OCs suggests that, in women taking OCs, suppressed endogenous E2–not fluctuating EE levels–may be more relevant for working memory. Future studies are needed to differentiate effects of endogenous versus synthetic estrogens on working memory.
Highlights
Oral contraceptives (OCs), a widely used form of hormonal birth control, are often prescribed for treating endometriosis and polycystic ovarian syndrome, and managing symptoms related to the menstrual cycle [1,2]
Dopamine-dependent working memory is influenced by COMT genotype, but not time of oral contraceptive ingestion degrades dopamine at synapses in the prefrontal cortex (PFC; [21]), interacts with E2 levels to mediate working memory performance [22]
There were no effects of pill ingestion time in the present study, this does not mean other cognitive domains may not be sensitive to daily estradiol https://doi.org/10.1371/journal.pone.0252807.g001 (EE) fluctuations, or that the pharmacokinetics of Dopamine-dependent working memory is influenced by COMT genotype, but not time of oral contraceptive ingestion other hormonal contraceptives with differing routes of administration may not influence cognition
Summary
Oral contraceptives (OCs), a widely used form of hormonal birth control, are often prescribed for treating endometriosis and polycystic ovarian syndrome, and managing symptoms related to the menstrual cycle [1,2]. Premenopausal women with pharmacologically induced E2 suppression show working memory deficits [11] With these pronounced effects of E2 on women’s memory, it stands to reason that pharmacologically influencing estrogen with OCs could likewise influence women’s memory. Despite the widespread use of oral contraceptives (OCs), and the well-documented influence of estrogens, notably 17β-estradiol (E2), on cognition, research relating OCs to working memory is limited and mixed. Two factors may contribute to these mixed findings: 1) pharmacokinetics of oral contraceptives, which drive fluctuations in synthetic hormone levels; and 2) genetic polymorphisms related to dopamine degradation and working memory, which interact with E2. This research investigated whether the pharmacokinetics of oral contraceptives, in concert with the single nucleotide polymorphism (Val158Met; rs4680) of the catechol-o-methyltransferase gene (COMT), influence working memory performance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
