Misakian Aaron L, Kelley Carly E, Sullivan Erika A, Chang Julia J, Singh Gagandeep, Kokosa Sarah, Avila Jonathan, Cooper Holly, Liang Jane W, Botzheim Bren, Quint Meg, Jeevananthan Athavi, Chi Ellenor, Harmer Madison, Hiatt Laurel, Kowalewski Michaela, Steinberg Benjamin, Tausinga Telisha, Tanner Hannah, Ho Tiffany F, Mark Bayarmaa, Zenger Brian, Hu Sophia, Gebregzabheir Amanuail, Penny Justin M, Loeb Danielle F, Strickland Tyler, Iwamoto Sean J, Rothman Micol S, Hamnvik Ole-Petter R, Ariel Danit
Division of Pediatric Endocrinology and Diabetes, Stanford University School of Medicine, Stanford, CA 94304, USA.
Division of Endocrinology, Metabolism, and Nutrition, Duke University Medical Center, Durham, NC 27710, USA.
J Clin Endocrinol Metab. 2025 Aug 7;110(9):e2898-e2907. doi: 10.1210/clinem/dgaf015.
Guidelines for use of injectable estradiol esters (valerate [EV] and cypionate [EC]) among transgender and gender-diverse (TGD) individuals designated male at birth vary considerably, with many providers noting supraphysiologic serum estradiol concentrations based on current dosing recommendations.
This work aimed to 1. determine the dose of injectable estradiol (subcutaneous [SC] and intramuscular [IM]) needed to reach guideline-recommended estradiol concentrations for TGD adults using EC/EV; 2. describe the relationship between estradiol concentration relative to timing/dose of last estradiol injection and other covariates; and 3. determine dosing differences between IM/SC EV/EC.
A cross-sectional retrospective study was conducted across 6 US medical centers including TGD adults on same-dose injectable estradiol for more than 75 days, with confirmed timing of estradiol concentration relative to last injection, from January 1, 2019 to December 31, 2023. Descriptive statistics were used to describe patient characteristics and weighted linear mixed models to evaluate relationship between various covariates and estradiol concentration.
Data from 562 patients were included. Among those injecting every 7 days who reached the guideline-recommended estradiol concentration (n = 131, 27.5%), the median estradiol dose was 4.0 mg (interquartile range, 3.0-5.0 mg). Among all patients, the majority reached supraphysiologic estradiol concentrations (>200 pg/mL [>734 pmol/L]) while dose and timing in the injection cycle were significant covariates for the estradiol concentration. There were no significant dosing differences between IM/SC EV/EC.
Injectable estradiol esters effectively reach guideline-recommended estradiol concentrations but at lower doses than previously recommended. Estradiol concentrations are best interpreted relative to timing of last injection. Route of administration and type of ester do not significantly affect estradiol concentrations.
对于出生时被认定为男性的跨性别者和性别多样化（TGD）个体，注射用雌二醇酯（戊酸酯[EV]和环戊丙酸酯[EC]）的使用指南差异很大，许多医疗服务提供者指出，根据当前的给药建议，血清雌二醇浓度高于生理水平。
这项研究旨在：1. 确定使用EC/EV使TGD成年人达到指南推荐的雌二醇浓度所需的注射用雌二醇（皮下[SC]和肌肉内[IM]）剂量；2. 描述雌二醇浓度与末次雌二醇注射时间/剂量及其他协变量之间的关系；3. 确定IM/SC EV/EC之间的给药差异。
在2019年1月1日至2023年12月31日期间，对美国6家医疗中心的TGD成年人进行了一项横断面回顾性研究，这些患者接受相同剂量的注射用雌二醇治疗超过75天，且确认了雌二醇浓度相对于末次注射的时间。采用描述性统计描述患者特征，采用加权线性混合模型评估各种协变量与雌二醇浓度之间的关系。
纳入了562例患者的数据。在每7天注射一次且达到指南推荐雌二醇浓度的患者中（n = 131，27.5%），雌二醇剂量中位数为4.0毫克（四分位间距，3.0 - 5.0毫克）。在所有患者中，大多数人达到了高于生理水平的雌二醇浓度（>200 pg/mL [>734 pmol/L]），而注射周期中的剂量和时间是雌二醇浓度的显著协变量。IM/SC EV/EC之间没有显著的给药差异。
注射用雌二醇酯能有效达到指南推荐的雌二醇浓度，但所需剂量低于先前推荐的剂量。雌二醇浓度最好根据末次注射时间来解释。给药途径和酯的类型对雌二醇浓度没有显著影响。
