ESPE Abstracts

Background: Turner syndrome (TS) is a chromosomal disorder characterized by ovarian dysgenesis, short stature, and other congenital abnormalities. This condition arises from a complete or partial loss of one X chromosome in females, often leading to delayed diagnosis and thus missing critical opportunities for timely treatment. Estrogen Replacement Therapy (ERT) and Growth Hormone Replacement Therapy (GHRT) are standard treatments, yet their long-term impacts remain insufficiently understood.

Methods: This retrospective longitudinal cohort study utilized anonymized electronic health records from the TriNetX Global Collaborative Network. TS patients who received either ERT or GHRT monotherapy for ≥2 years were included. Propensity score matching (1:1) was performed using the built-in TriNetX tool, adjusting for 30 covariates (demographics, comorbidities, medications, renal function, CRP), with successful matching indicated by Standardized Mean Difference <0.1. Cox proportional hazards models calculated hazard ratios (HRs) and 95% confidence intervals for 20-year outcomes. Kaplan-Meier method estimated survival probability. Subgroup analyses examined risk variations by age. Outcomes included all-cause mortality, hospitalizations, thyroid complications, cardiovascular conditions, autoimmune diseases, and biochemical indices (compared using Student's t-test). Statistical significance was set at P <0.05.

Findings: In the cohort of 2,592 TS patients undergoing ERT, 20-year hazard ratios (HR) showed a decrease in overall mortality (HR 0.43, 95% CI 0.29-0.65) and hospitalizations (HR 0.46, 95% CI 0.38-0.54). However, there were increases in incidences of thyroiditis (HR 1.64, 95% CI 1.10-2.44) and ovarian dysfunction (HR 4.66, 95% CI 3.57-6.08). Additionally, the risk of Type 2 diabetes was reduced (HR 0.55, 95% CI 0.38-0.78). Among 1,606 patients treated with GHRT, there was an elevated risk of mortality (HR 1.67, 95% CI 1.09-2.54), despite reductions in both hypothyroidism (HR 0.70, 95% CI 0.50-0.97) and hyperthyroidism (HR 0.34, 95% CI 0.14-0.81). Biochemical profiles remained largely consistent. Further, subgroup analysis indicated variations in outcomes dependent on age.

Interpretation: This extensive study delineates the complex array of risks and benefits associated with ERT and GHRT in managing Turner syndrome over two decades, underscoring the need for intensified monitoring. While ERT contributes to reduced mortality, morbidity, and metabolic issues, it may heighten risks related to ovarian dysfunction and susceptibility to autoimmune thyroiditis. Conversely, GHRT presents a dual effect; it aids in height improvement but could possibly escalate mortality risks. These insights are critical for refining clinical approaches to optimize treatments while meticulously monitoring for specific long-term adverse effects.