 A total of 170 women in the early or late MT who are eligible for the hormonal probe will be recruited to reflect the full continuum of anxiety and anhedonia symptoms based on self-report to the State-Trait Anxiety Inventory and the Snaith-Hamilton Pleasure Scale, respectively. However, the investigators will over-represent the clinically impairing end of the anxious and anhedonic phenotype 75 of the sample. Over an 8-week baseline, anxiety and anhedonia symptoms and serum E2 measured by liquid chromatography-tandem mass spectrometry LC-MSMS will be assessed on a weekly basis. At baseline week 8, HPA axis plasma cortisol and ACTH response to the Trier Social Stress Test and behavioral measures of threat responsivity via Dot-Probe task and approach motivation Effort Expenditure for Rewards Task EEfRT will be determined. Using transdermal E2 as a pharmacological probe to stabilize variability of E2 in premenopausal ranges, women will then be randomized to transdermal E2 0.10 mg or placebo for 16 weeks. This is not a clinical efficacy trial. The investigators will use an randomized control trial RCT design with a hormonal manipulation in order to investigate the pathophysiologic role of E2 variability or E2 levels in HPA axis dysregulation and, in turn, threat responsivity and approach motivation. Serum E2 will be assessed weekly during weeks 9-16, and HPA axis reactivity to stress and behavioral responses to the Dot-Probe and EEfRT tasks will be assessed every four weeks during the 16 week probe. 