Do oral contraceptives affect young women’s memory? Dopamine-dependent working memory is influenced by COMT genotype, but not time of pill ingestion

Abstract

Background 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. Methods University-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. Results For 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. Conclusion These 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.

Chronic treatment with hormonal contraceptives alters hippocampal BDNF and histone H3 post-translational modifications but not learning and memory in female rats

“…), different doses and type of progestin administered, and/or duration of treatment (Gogos et al, 2014;Pletzer and Kerschbaum, 2014;Warren et al, 2014). Moreover, genotype might be another important variable to consider when examining cognitive function in hormonal contraceptives' users (Gravelsins et al, 2021). Likewise, we cannot rule out the possibility that different doses or type of synthetic steroids used in hormonal contraceptives might alter cognitive abilities in rats; moreover, strain and/or species differences might also contribute to the actions of EE and LNG on cognition.…”

“…), type of progestin administered, different dose of EE used, and/or duration of treatment (Beltz et al, 2015;Gogos et al, 2014;Pletzer and Kerschbaum, 2014;Warren et al, 2014;Wharton et al, 2008). Either improvement (Gurvich et al, 2020;Plamberger et al, 2021;Rosenberg and Park, 2002), no difference (Gogos, 2013;Gravelsins et al, 2021;Islam et al, 2008;Mihalik et al, 2009;Mordecai et al, 2008;Rosenberg and Park, 2002), or deterioration (Griksiene et al, 2018;Griksiene and Ruksenas, 2011) in cognitive abilities, have been reported in hormonal contraceptives' users compared to naturally cycling women.…”

The Relationship Between the Menstrual Cycle, Oral Contraceptives, and Executive Function – Inhibition, Updating, and Shifting

“…In 7 studies, cognitive task performances were compared between OC and NC groups in different cycle phases: menses, follicular and luteal phases in 3 studies, menses and follicular phases in one study, luteal and menses phases in 2 studies, follicular, and luteal in one study. Only Mordecai et al (2008) indicated randomizing the test sessions depending on the phases of the menstrual cycle whereas Gravelsins et al (2021) counterbalanced the order of the sessions for both the OC and NC groups. Six studies tested for actual levels of hormones to ensure that the phases of the menstrual cycle were adequately defined and to compare levels of hormones between NC women and OC users.…”

Reduced threat avoidance but increased stress induced approach bias in women taking oral contraceptives

“…Conditions of OC intake. Previous research suggests that certain conditions of OC use, such as age at first use or whether OC were taken before or after the measurement, may be important (Anderl et al, 2022; Gravelsins et al, 2021). In our sample, participants did not differ in their approach and avoidance behaviors depending on whether they started taking OC as adolescents (aged younger than 18 years (N=42)) or as adults (aged older than 18 years (N=22)) (no interaction of stress x emotion x movement x onset: F (1,62) = 0.997, p = .322, η 2 ρ = 0.016), nor did the timing of daily intake (before or after measurement) make a difference (no interaction of stress x emotion x movement x time of OC intake: F (1,62) = 2.6674, p = .107, η 2 ρ = 0.041).…”