Retrospective Study of 260 Women Finds Hormone Therapy Cut Severe Mood Symptoms from 62% to 25%

The single-center chart review examined women starting systemic estrogen with or without progestogen. Clinicians recorded mood via standardized scales at baseline and follow-up visits; sleep disturbance was tracked as a secondary outcome. Absolute reduction in severe mood burden reached 37.7 percentage points, with largest gains among those entering with the highest symptom scores. Response rates showed no interaction with prior psychiatric diagnosis, age at initiation, or concurrent antidepressant use.

Prior randomized trials of estrogen for perimenopausal depression produced inconsistent results, often limited by short duration and narrow eligibility. This observational design captured longer real-world exposure and broader racial and socioeconomic representation, yet lacked a control arm and relied on routine clinical documentation rather than blinded outcome assessment. Socioeconomic factors known to amplify symptom burden were not fully adjusted.

The findings align with mechanistic data linking estrogen repletion to cortical perfusion and serotonergic function but cannot distinguish treatment effects from regression to the mean or concurrent lifestyle changes. Next required evidence is a pragmatic randomized trial stratifying by baseline severity and race, with validated mood instruments and at least 12-month follow-up.