Glaucoma is the leading cause of irreversible blindness and is projected to affect 112 million people worldwide by 2040. Unfortunately, Veterans have a 2-fold higher prevalence of developing glaucoma compared to the general US population. While the exact cause of glaucoma is unknown, recent evidence has shown that early menopause, mutations in estrogen receptors, and polymorphism mutations along the estrogen metabolic pathway are linked to developing glaucoma. These data highlight that menopause, and particularly estrogen, may play a role in the development of this disease. However, there is a gap in our knowledge of quantifying if menopause, regardless of age, is related to the onset of glaucoma. It is vital to understand this relationship, as 59% of the glaucomatous population are women and the number of female Veterans has doubled over the last ten years. In addition, nearly 43% of female Veterans are younger than 45 years old and will experience menopause (average age at 51 years) within the next decade. The evidence of 1) a higher prevalence of glaucoma in Veterans, 2) the increasing number of female Veterans, and 3) the aging of female Veterans will make glaucoma a major health issue in the future for this population. The VA formed the Women’s Veterans Health Research Network (WVHRN) to help focus attention on research and treatments for this portion of the Veteran population, and this proposal aims to understand the association between menopause, a major life event for women, and glaucoma. In this proposal, we hypothesize that menopause is related to the onset of glaucoma and will use the power of the national VA database to perform a retrospective study to address this hypothesis. We will examine medical records from female U.S. Veterans in the corporate data warehouse (VINCI – VA Informatics and Computing Infrastructure) between 2000-2019. Previous studies summarized the impact of age of menopause on developing glaucoma in the general population. However, this has not been confirmed in the Veteran population where glaucoma is more prevalent. In addition, no study has directly assessed whether there is a direct relationship between menopause and the onset of glaucoma. The VA database is a unique resource that can provide longitudinal care records of patients that will allow us to understand the relationship between the onset of menopause and glaucoma and the overall incidence of glaucoma in female and male Veterans. Although glaucoma can occur at any level of intraocular pressure (IOP), elevated IOP remains clinically relevant as a major causal risk factor for developing this disease. Several studies have shown that postmenopausal women taking hormone replacement therapy (HRT) containing estrogen had a lower IOP compared to postmenopausal women not taking HRT. This has led researchers to suggest that estrogen-based therapies may be a potential treatment for glaucoma. Based on our work and others, we hypothesize that hormone replacement th...