OBJECTIVE Treatment in transgender girls can consist of puberty suppression (PS) with a gonadotropin-releasing hormone agonist (GnRHa) followed by gender-affirming hormonal treatment (GAHT) with estrogen. Bone mineral density (BMD) Z-scores decrease during PS and remain relatively low during GAHT, possibly due to insufficient estradiol dosage. Some adolescents receive high-dose estradiol or ethinyl estradiol (EE) to limit growth allowing comparison of BMD outcomes with different dosages. DESIGN Retrospective study. METHODS Adolescents treated with GnRHa for ≥1 year prior to GAHT followed by treatment with a regular estradiol dose (gradually increased to 2 mg), 6 mg estradiol or 100-200 µg EE were included to evaluate height-adjusted BMD Z-scores (HAZ scores) on DXA. RESULTS Eighty-seven adolescents were included. During 2.3 ± 0.7 years PS, lumbar spine HAZ scores decreased by 0.69 [95% confidence interval (CI) -0.82 to -0.56)]. During 2 years HT, lumbar spine HAZ scores hardly increased in the regular group (0.14, 95% CI -0.01 to 0.28, n = 59) vs 0.42 (95% CI 0.13 to 0.72) in the 6 mg group (n = 13), and 0.68 (95% CI 0.20 to 1.15) in the EE group (n = 15). Compared with the regular group, the increase with EE treatment was higher (0.54, 95% CI 0.05 to 1.04). After 2 years HT, HAZ scores approached baseline levels at start of PS in individuals treated with 6 mg or EE (difference in 6 mg group -0.20, 95% CI -0.50 to 0.09; in EE 0.17, 95% CI -0.16 to 0.50) but not in the regular group (-0.64, 95% CI -0.79 to -0.49). CONCLUSION Higher estrogen dosage is associated with a greater increase in lumbar spine BMD Z-scores. Increasing dosage up to 2 mg estradiol is insufficient to optimize BMD and approximately 4 mg may be required for adequate serum concentrations.

中文翻译：

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雌激素对跨性别女孩骨矿物质密度的剂量依赖性影响。

目的 跨性别女孩的治疗包括使用促性腺激素释放激素激动剂 (GnRHa) 进行青春期抑制 (PS)，然后使用雌激素进行性别肯定激素治疗 (GAHT)。骨矿物质密度 (BMD) Z 分数在 PS 期间下降，并在 GAHT 期间保持相对较低，可能是由于雌二醇剂量不足。一些青少年接受高剂量雌二醇或乙炔雌二醇 (EE) 来限制生长，从而可以比较不同剂量的 BMD 结果。设计回顾性研究。方法 GAHT 前接受 GnRHa 治疗≥1 年，随后接受常规雌二醇剂量（逐渐增加至 2 mg）、6 mg 雌二醇或 100-200 µg EE 治疗，以评估身高调整 BMD Z 分数（HAZ） DXA 分数）。结果 87 名青少年被纳入其中。在 PS 2.3 ± 0.7 年期间，腰椎 HAZ 评分下降了 0.69 [95% 置信区间 (CI) -0.82 至 -0.56)]。在 2 年 HT 期间，常规组的腰椎 HAZ 评分几乎没有增加（0.14，95% CI -0.01 至 0.28，n = 59），而 6 mg 组 (n = 13) 的腰椎 HAZ 评分为 0.42（95% CI -0.13 至 0.72） ，EE 组 (n = 15) 为 0.68 (95% CI 0.20 至 1.15)。与常规组相比，EE治疗组的增加更高（0.54，95% CI 0.05至1.04）。HT 2 年后，接受 6 mg 或 EE 治疗的个体在 PS 开始时的 HAZ 评分接近基线水平（6 mg 组的差异为 -0.20，95% CI -0.50 至 0.09；EE 组的差异为 0.17，95% CI -0.16 至 0.50 ）但不在常规组中（-0.64，95% CI -0.79 至 -0.49）。结论 较高的雌激素剂量与腰椎 BMD Z 值的较大增加相关。将雌二醇剂量增加至 2 mg 不足以优化 BMD，可能需要大约 4 mg 雌二醇才能获得足够的血清浓度。