 Framed within a diathesis-stress model, the primary objective of this research is to determine the pathophysiological mechanisms of estradiol E2 in the clinical anxiety and anhedonia seen in the menopause transition MT. Specifically whether E2 variability or E2 levels predict exaggerated hypothalamic-pituitary-adrenal HPA axis reactivity and impaired recovery to stress and, in turn, deficits in behavioral indices of threat responsivity and approach motivation and symptoms of anxiety and anhedonia. The secondary objective of the research is to use a hormonal manipulation as a mechanistic probe to stabilize E2 variability in premenopausal ranges and determine if: a HPA axis reactivityrecovery represents a biomarker of behavioral and symptom responses to E2 stabilization; b whether recent severe life stress predicts the HPA axis response to hormone stabilization. 