Scoping Review Finds Lisdexamfetamine Reduced Self-Reported ADHD Symptoms in Perimenopausal Women but Showed No Benefit on Objective Cognitive Tests

The review examined small trials of lisdexamfetamine and atomoxetine in perimenopausal and postmenopausal participants whose last menstrual period fell within the prior decade. Researchers tracked changes in self-reported executive-function scales and a limited set of standardized cognitive tests. Declining estrogen is known to alter prefrontal dopamine and norepinephrine signaling, producing subjective complaints that overlap with ADHD symptoms. Because the included studies were short, unblinded at follow-up, and relied heavily on self-report, the signal remains vulnerable to placebo effects and reporting bias.

Cardiovascular monitoring data were sparse, yet both agents carry documented risks of increased heart rate and blood pressure that could compound age-related vascular changes. Off-label prescribing for menopausal brain fog is already occurring in clinical practice, often after patients fail to meet full ADHD diagnostic criteria. This pattern echoes earlier expansions of stimulant use for fatigue syndromes where subjective benefit preceded rigorous outcome validation.

Larger randomized controlled trials with predefined objective endpoints, longer safety follow-up, and stratification by estrogen-receptor genotype are required before any guideline recommendation. Regulatory review would also need to address whether perceived cognitive relief constitutes a clinically meaningful benefit distinct from placebo response.