Abstract
BACKGROUND: The relationship between menopausal hormone therapy (MHT) and risk of Parkinson's disease (PD) remains controversial. OBJECTIVE: This nationwide population-based cohort study investigated the association between MHT and PD development. METHODS: Data from the National Health Insurance System of South Korea from 2007 to 2020 were used. The MHT group included women who underwent MHT for the first time between 2011-2014, while the non-MHT group included women who visited a healthcare provider for menopause during the same period but never received hormonal therapy. We used propensity score matching (1 : 1) to adjust for potential confounders, and Cox regression models to assess the association between MHT and PD. RESULTS: We selected 303,260 female participants (n = 151,630 per MHT and non-MHT groups). The median age of the participants was 50 (48-54) years, and the follow-up period lasted 7.9 (6.9-8.9) years. Cox regression analysis revealed an increased risk of PD with MHT (hazard ratio [HR] 1.377, 95% confidence interval [CI] 1.184-1.602), particularly with tibolone (HR 1.554, 95% CI 1.297-1.861) and estrogen alone (HR 1.465, 95% CI 1.054-2.036). Tibolone and estrogen alone were linked to PD within three years; however, no association was observed after three years. In contrast, the use of combined estrogen-progesterone was linked to a higher risk of PD, which increased with the duration of MHT (HR 1.885, 95% CI 1.218-2.918 for over five years). CONCLUSIONS: This study demonstrated that the MHT is closely associated with the risk of PD in a regimen- and duration-specific manner.