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Abstract
The growing aging population underscores the need to preserve cognitive health and quality of life. Gonadal and adrenal steroids, including estradiol (E2), testosterone (T), and dehydroepiandrosterone (DHEA), influence memory but decline with age. While DHEA shows promise in animal models, human trials report minimal cognitive benefit. Using postmenopausal rhesus macaques, this research examined hormone supplementation effects on memory and hormone pathways. Findings reveal intracrine conversion of DHEA to E2 in the brain declines with age, limiting efficacy. Significant sex-dependent interactions between adrenal and gonadal systems suggest that multi-hormone strategies, rather than single-hormone therapy, may better restore endocrine balance and support cognition.