Hormone Therapy Timing and Chronic Disease Incidence in Primary Ovarian Insufficiency: A National Cohort Study

OBJECTIVE: To estimate hormone therapy (HT) use among women with primary ovarian insufficiency (POI) and to explore whether HT initiation timing is associated with differential long-term health outcomes. DESIGN: Retrospective cohort study. SETTING: Population-based using the South Korean National Health Insurance Service database. POPULATION: 105 830 South Korean women from 2005 and 2015. METHODS: Women with POI with ICD-10 code E283 in the database were compared to a 1:4 propensity score-based matching controls. MAIN OUTCOME MEASURES: Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for major chronic diseases. RESULTS: The study compared 21 166 women with POI and 84 664 controls. POI was associated with higher risks of major chronic diseases, including thyroid disease, metabolic disorders, cardiovascular disease and osteoporosis. Within the POI cohort, HT exposure was associated with lower risks of type 2 diabetes mellitus (T2DM) (IRR 0.82, 95% CI 0.76-0.88) and dyslipidaemia (IRR 0.87, 95% CI 0.84-0.91). In the landmark analysis, on-time HT initiation within 1 year was associated with lower risks of thyroid disease (IRR 0.69, 95% CI 0.62-0.76), T2DM (IRR 0.77, 95% CI 0.64-0.93) and dyslipidaemia (IRR 0.71, 95% CI 0.65-0.78) compared with delayed initiation. CONCLUSIONS: The current study suggests that an on-time HT initiation strategy within 1 year of POI diagnosis is associated with more favourable long-term cardio metabolic outcomes, supporting the clinical importance of early management in POI.