SUN-139 A Case Series Examining the Use of Subcutaneous Estradiol for Feminization

Abstract Disclosure: R. Lassalle Klein: None. R. Feinn: None. P. Phulwani: None. Guidelines list oral estrogen tablets, transdermal patches, and intramuscular (IM) injections as acceptable modalities to offer patients who desire feminization using estrogen.1 Data suggests a higher risk of liver enzyme elevation and thrombotic events with oral estrogen versus other modalities, presumably due to the first pass effect.2 Side effects of other therapies are barriers to satisfactory treatment. The aim of this study was to examine the efficacy and safety of self-administered weekly subcutaneous (SC) injections of estradiol in a retrospective case series of adult transgender women. 40 patients who met 6 inclusion criteria were assessed: age ≥18 years old, received diagnosis ICD10 F64.0 (gender dysphoria/incongruence), prescribed estrogen formulation was solely SC estradiol cypionate or estradiol valerate, visited Hartford Healthcare Endocrinology between January 1, 2020 and March 7, 2023, completed at least two lab visits to establish baseline and also after initiation of therapy, and had at least one clinic visit to assess satisfaction. RedCAP was used to collect, de-identify, and analyze data from patient charts on retrospective review. The majority (N=27, 67.5%) achieved the target-range estradiol (100-300 pg/uL) using SC estradiol cypionate or valerate within the study period. With respect to the in-range patients who were using estradiol cypionate (N=6) the commonest dose was 2.5 mg/week (mean= 3.2 ± 1.1). No patients at or below dosages of estradiol cypionate of 1 mg/week or estradiol valerate 2 mg/week achieved target-range. With respect to the in-range patients who were using estradiol valerate (N=21), the commonest dose was 4 mg/week (mean 5.38 ± 2.0). Remaining patients out of range at the conclusion of the study continued dose titration. Blood estradiol level correlation with AST/ALT was analyzed using a two-tailed t-test. The correlation between estradiol level and AST was r = 0.156 (p=0.414) and correlation between estradiol level and ALT was r = 0.088 (p=0.644), which were both small and not statistically significant. In this study, including in patients with high estradiol levels (estradiol range: 21-991 pg/uL), no elevated liver enzymes or adverse events occurred in relation to therapy. Although this is a small, retrospective, and short duration study, it highlights that SC estradiol is likely a safe option for estrogen replacement for gender affirming hormone therapy and has potentially broader applications for all conditions that require estrogen. 1. Hembree WC et al. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017 Nov 1;102(11):3869-3903. 2. Getahun D et al. Cross-sex Hormones and Acute Cardiovascular Events in Transgender Persons: A Cohort Study. Ann Intern Med. 2018 Aug 21;169(4):205-213. Presentation: Sunday, July 13, 2025