Integrating the Impacts of Ovarian Hormones on Brain and Behavior: Implications for Women’s Wellbeing

Abstract: Hormones exert significant control over brain functions. Hormonal fluctuations during the menstrual cycle are one of the most systematic and recurring changes experienced by half of human populations. However, findings on the impacts of these hormones are disconnected and often contradictory. This may be due to differences in methodologies, the opposite pattern of fluctuations in these hormones, their widespread neuronal effects, and brain homeostatic mechanisms. To overcome these shortcomings, this review combines findings across synaptic and cellular, systems, cognitive, behavioral, social level to examine how hormonal changes affect the nervous system and behavior more holistically. To that end, it also investigates the effect of exogenous hormone exposure caused by contraceptive usage, which disturbs the interdependent fluctuations. This analysis reveals that estradiol and progesterone have strong effects at the cellular and systems levels, but the impacts on cognition and behavior are inconsistent and limited, partially due to the brain’s homeostatic mechanisms and counteractive effects of the two hormones. As a result, behavioral stability should be considered separately when interpreting hormonal effects. This idea is further supported by studies showing clear effects of contraceptives on cognition and behavior. These findings highlight the importance of integrative approaches in investigating hormonal effects on the brain and can be used to fight against the dogma that the menstrual cycle and hormonal changes extensively affect behavior. Future research should combine hormone measurements, neuroimaging techniques, and behavioral testing across the cycle to better understand the above interactions and provide a clinical perspective for hormonal health.