Key Takeaways: Hormones and Mental Health: A Bio-Psycho-Social Perspective Hormones play a significant and often under-recognized role in mental health, particularly during perimenopause and menopause, when fluctuations in estrogen and progesterone can directly impact mood, anxiety, sleep, and cognitive functioning. A bio-psycho-social framework is essential for understanding mental health symptoms in a whole-person context. Biological factors such as hormonal changes must be considered alongside psychological and social influences to support accurate assessment and effective treatment. Hormone replacement therapy (HRT), when appropriately prescribed and monitored, can reduce a range of mental health symptoms, including depression, irritability, anxiety, and sleep disturbances, while also improving overall quality of life. HRT also offers important physical health benefits, including support for bone density, cardiovascular health, and symptom relief during the menopausal transition. Emerging research suggests that untreated or undertreated hormonal changes may contribute to increased mental health vulnerability, including elevated suicide risk in midlife women, highlighting the importance of timely assessment and intervention. Despite its benefits for many patients, HRT remains underutilized in clinical practice, often due to outdated perceptions or limited provider education. Integrating hormonal assessment and education into routine psychiatric and primary care can improve diagnostic accuracy, expand treatment options, and lead to more effective, individualized care. Optimal outcomes are achieved when providers adopt a whole-person approach that includes consideration of therapy, sleep, nutrition, movement, and medication—including HRT when clinically appropriate.