Hormonal contraception and cognition: Considering the influence of endogenous ovarian hormones and genes for clinical translation

•Hormonal contraception cognitive studies use mixed delivery modes: oral, vaginal, intrauterine.•Oral contraceptives may exert dose-dependent effects on the brain and cognition.•No studies disentangle the effects of exogenous and endogenous hormones.•Accounting for day of pill ingestion improves understanding of cognitive changes.•Consideration of gene-contraception interactions in larger cohorts is needed. Despite the well-known influence of ovarian hormones on the brain and widespread use of hormonal contraception (HC) since the 1960s, our knowledge of HC’s cognitive effects remains limited. To date, the cognitive findings have been inconsistent. In order to establish what might make HC studies more consistent, we surveyed the literature on HCs and cognition to determine whether studies considered HC formulation, phase, pharmacokinetics, duration, and gene interactions, and assessed whether oversight of these factors might contribute to variable findings. We found that synthetic HC hormones exert dose-dependent effects, the day of oral contraceptive (Pill) ingestion is critical for understanding cognitive changes, and gene-cognition relationships differ in women taking the Pill likely due to suppressed endogenous hormones. When these factors were overlooked, results were not consistent. We close with recommendations for research more likely to yield consistent findings and be therefore, translatable.