Distinct and Convergent Beneficial Effects of Estrogen and Insulin on Cognitive Function in Healthy Young Men

Context: Systematic investigations into the cognitive impact of estradiol and insulin in male individuals are sparse, and it is unclear whether the 2 hormones interact to benefit specific cognitive functions in humans. Objective: We investigated the acute effect of estradiol and insulin and of their combined administration on divergent (creative) and convergent (arithmetical) thinking as well as short-term and working verbal memory in healthy young men. Methods: According to a 2 x 2 design, 2 groups of men (each n = 16) received a 3-day transdermal estradiol (100 mu g/24 h) or placebo pretreatment and on 2 separate mornings were intranasally administered 160 IU regular human insulin and, respectively, placebo before completing a battery of cognitive tests; we also determined relevant blood parameters. Results: Estrogen compared with placebo treatment induced a 3.5-fold increase in serum estradiol and suppressed serum testosterone concentrations by 70%. Estrogen in comparison to placebo improved creative performance, that is, verbal fluency and flexibility, but not arithmetical thinking, as well as verbal short-term memory, but not visuospatial memory. The combination of estrogen and insulin enhanced recognition discriminability at delayed verbal memory recall; insulin alone remained without effect. Conclusion: Estrogen specifically enhances core aspects of creativity and verbal memory in young male individuals; delayed recognition memory benefits from the combined administration of estradiol and insulin. Our results indicate that insulin's acute cognitive impact in young men is limited and not robustly potentiated by estradiol. Estradiol per se exerts a beneficial acute effect on creative and verbal performance in healthy young men.