Impact of hormone therapy on mood in a real-world clinical setting: a retrospective observational study

Mood disturbances-including depressed mood, irritability, anxiety, and mental exhaustion-are common during the menopause transition, affecting up to 68% of women. While menopausal hormone therapy (HT) is FDA-approved for vasomotor and genitourinary symptoms, its role in managing mood symptoms remains less well understood. This retrospective, comparative study evaluated the impact of systemic HT on mood in a cohort of HT-naive individuals.

We included 260 patients presenting to an urban, academic menopause center between 2023 and 2025 who completed the Menopause Rating Scale (MRS) before and after initiating systemic HT for FDA-approved indications. MRS psychological subdomain scores covering depressive mood, irritability, anxiety, and mental exhaustion were analyzed. Most patients (96.5%) received transdermal estradiol, had an average age of 52.1 years, and a mean follow-up of 4.5 months. Notably, 51% had a history of anxiety or depression, and 24% were on antidepressant therapy at baseline.

Results showed a significant reduction in MRS psychological subdomain scores from baseline to follow-up (P<0.001). The proportion of patients with severe mood symptoms (score ≥7) decreased from 62.3% to 24.6%. Improvement was greatest in those with severe baseline symptoms (mean change: -3.85, SE: 0.223). Treatment response did not differ by psychiatric history, age, menopausal stage, or antidepressant use.

These findings suggest systemic HT may improve mood symptoms in midlife, especially among those with elevated baseline severity, independent of prior mental health diagnosis, antidepressant use, or menopause stage. These findings support further investigation of HT's impact on mood in midlife women.