Estrogen Effects on ADHD and Cognition

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Females with Attention-Deficit/Hyperactivity Disorder (ADHD) remain dramatically understudied, even though they exhibit increased impairment beginning around puberty. Estrogen rises rapidly at puberty and exerts important effects on dopamine and cognition in both humans and animals. Both animal and human work suggest that cognition and ADHD symptoms may be sensitive to hormonal effects, particularly in highly impulsive females. Yet, the effect of estrogen on ADHD symptoms in young adult women remains virtually unstudied. Our pilot data in 33 naturally-cycling young women suggest that among women with greater ADHD symptoms, within-person declines in estrogen, particularly in the context of rising levels of progesterone, just post-ovulation, are associated with clinically significant increases in ADHD symptoms. Yet, no published empirical work has directly examined the role of circulating estrogen in relation to ADHD symptoms and cognitive mechanisms in women with ADHD. The current study would pioneer a new stage of work by being the first to utilize a rigorous quasi-experimental design that involves intensive longitudinal measurement across the menstrual cycle in order to examine within-person estrogen effects on ADHD and cognitive mechanisms in young women with ADHD. A sample of 120 young women ages 18 to 25 with inattention, overactivity, or impulsivity problems will be recruited from the university health center and local ADHD clinic, psychology department, and through social media. Participants will be comprehensively assessed for ADHD and exclusion criteria (e.g., use of hormone-based medication or hormonal conditions). Female participants will complete well-established assessment measures of ADHD and other psychopathological symptoms and diagnoses and cognition and provide saliva samples of hormones in the laboratory during a baseline laboratory visit within the first few days of the start of their menstrual cycle (i.e., during the mid-follicular phase, characterized by stable low estrogen). Then, they will provide daily saliva samples for hormone assay each morning and complete short daily assessments of ADHD and cognition every evening for up to 2 full menstrual cycles. They will also complete laboratory cognitive testing of inhibition and working memory targeted to key cycle phases characterized by declining estrogen (post-ovulatory, perimenstrual) and a cycle phase characterized by stable high estrogen levels (midluteal), based on menses onset and ovulation test results. Multi-level modeling will evaluate the clinical significance of within-person estrogen associations with ADHD and cognition with consideration of progesterone as an interactive factor. Effects of comorbid disorders and affect will also be explored. Study results have the potential to shift our understanding of ADHD in women by consideration of dynamic hormone influences. In addition, results will change clinical practice by indicating the need to account for cycle phase in ADHD evaluations in women, as well as suggest personalized approaches to treatment targeted to cycle phase or hormone levels.