Background: Treatment in trans girls can consist of puberty suppression with 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 cause might be an insufficient estradiol dose. Some trans girls are treated with a higher dose of estradiol or ethinylestradiol in order to limit growth. This provides the opportunity to evaluate if a higher estradiol dose 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 dose (2mg), or high growth-reductive doses of estradiol (6mg) 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 107 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 -0.33±0.84. During PS, Z-scores decreased in all treatment groups to –1.11±0.77. After three years of estrogen treatment, Z-scores increased by 0.12 (95% CI -0.03 – 0.27) in the 2mg estradiol group (n=66) vs. 0.34 (95%CI 0.07 – 0.61) in individuals treated with 6mg estradiol (n=24), and 0.66 (95%CI 0.19 – 1.13) in the EE group (n=17). Compared with 2mg estradiol, the increase in trans girls treated with EE was significantly higher (0.53, 95%CI 0.04 – 1.03).

Conclusion: When compared to the regular dose 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 2mg estradiol is insufficient and that a higher adult dose is required to optimise BMD.