OR31-01 The Dose-dependent Effect Of Estrogen On Bone Mineral Density In Trans Girls

Disclosure: L.S. Boogers: None. M.A. van der Loos: None. C.M. Wiepjes: None. A. van Trotsenburg: None. M. den Heijer: None. S.E. Hannema: None. Introduction: Treatment in transgender girls can consist of puberty suppression with Gonadotrophin-releasing hormone agonists (GnRHa) followed by estrogen treatment. A decrease in bone mineral density (BMD) Z-scores is a known effect of GnRHa. After initiation of estradiol BMD Z-scores remain relatively low, even after several years of treatment. It has been hypothesized that the estradiol dosage may be insufficient, explaining the persistently low Z-scores. Some trans girls are treated with a higher dosage of estradiol or ethinylestradiol in order to limit growth. This provides the opportunity to evaluate if a higher estradiol dosage results in a greater increase in BMD Z-scores. Methods: Trans girls diagnosed with gender dysphoria were included if they were treated with GnRHa for a minimum of one year prior to treatment with estradiol. Estradiol was increased to the regular dosage (2 mg), or high growth-reductive dosages of estradiol (6 mg) or ethinyl estradiol (100-200 μg (EE)) before the age of 18 years. BMD was assessed using DXA scans performed regularly during GnRHa and estrogen treatment. Z-scores of the lumbar spine were adjusted for height, and the development over time was compared between the different treatment groups. Results: A total of 100 trans girls were included with a mean duration of GnRHa treatment of 2.3±0.7 years. Mean BMD Z-score of the lumbar spine at start of PS was -0.26±0.84. During PS, Z-scores decreased in all three treatment groups to a mean Z-score of -0.99±0.86. After two years of estrogen treatment, Z-scores increased by 0.15 (95% CI 0.00 to 0.30) in the 2 mg estradiol group (n=65) versus 0.35 (95%CI 0.08 to 0.62) in individuals treated with 6 mg estradiol (n=21), and 0.74 (95%CI 0.27 to 1.21) in the EE group (n=14). Compared with 2 mg estradiol, the increase in trans girls treated with EE was significantly higher (0.59, 95% 0.10 to 1.08). There was no difference in individuals treated with 2 mg or 6 mg estradiol (0.20 , 95%CI -0.11 to 0.51). After three years of estrogen treatment, only in the individuals treated with EE, Z-scores were not significantly different from start of GnRHa (-0.01, 95%CI -0.38 to 0.36). Conclusion: When compared to the regular 2 mg dosage of estradiol, a higher estradiol dose, and especially treatment with EE resulted in a greater increase in BMD Z-scores in the lumbar spine in trans girls. This might indicate that 2 mg estradiol is insufficient as a maintenance dose during adolescence and that a higher adult dose is required to optimise BMD. Presentation: Sunday, June 18, 2023