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

Beltz AM1Moser JS2.

Ann N Y Acad Sci. 2019 Oct 22. doi: 10.1111/nyas.14255. [Epub ahead of print]



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.


Significant progress has been made in the understanding of ovarian hormone influences on cognitive brain structures and function in the past 5 years, ignited in part by calls for research on sex differences and technological advances in neuroimaging and biological data analysis. Particular insight has been afforded by studies of natural experiments, such as puberty, the menstrual cycle, hormonal contraceptive use, menopause, and MHT. Across studies, there is compelling evidence for estradiol effects on the structure and function (during verbal and memory tasks) of the hippocampus and PFC, emerging evidence for estradiol’s interplay with dopamine during reward processing, and suggestion of complex interactions among sex hormones (including progesterone and androgens). Although inferences are limited by heterogeneity across study designs and samples, there is incredible opportunity for future research, especially concerning individual differences and biopsychosocial modulators of neuroendocrine associations in women, which has implications for advancing cognitive neuroscience to the benefit of all.