Ovarian hormones: a long overlooked but critical contributor to cognitive brain structures and function

Cognitive neuroscience research has traditionally overlooked half of the population. Arguing that variability in ovarian hormones confounds empirical findings, girls and women have been excluded from research for decades. But times are changing. This review summarizes historical trends that have led to a knowledge gap in the role of ovarian hormones in neuroscience, synthesizes recent findings on ovarian hormone contributions to cognitive brain structures and function, and highlights areas ripe for future work. This is accomplished by reviewing research that has leveraged natural experiments in humans across the life span that focus on puberty, the menstrual cycle, hormonal contraceptive use, menopause, and menopausal hormone therapy. Although findings must be considered in light of study designs (e.g., sample characteristics and group comparisons versus randomized crossover trials), across natural experiments there is consistent evidence for associations of estradiol with cortical thickness, especially in frontal regions, and hippocampal volumes, as well as with frontal regions during cognitive processing. There are also emerging investigations of resting state connectivity and progesterone along with exciting opportunities for future work, particularly concerning biopsychosocial moderators of and individual differences in effects in novel natural experiments. Thus, delineating complex ovarian hormone contributions to cognitive brain structures and function will advance neuroscience.