INITIAL EVALUATION OF SAFETY AND EFFICACY OF ADMINISTRATION OF ESTRADIOL (E2) BY SUBCUTANEOUS (SC) INJECTIONS TO MALE-TO-FEMALE (MTF) TRANSGENDER PATIENTS

Abstract

The primary aim of this study was to determine if SC injection of E2 valerate could produce serum E2 levels within our clinic’s target therapeutic range for MTF patients (75-200 pg/mL) without causing significant adverse effects. Secondary aims were to assess: 1) if SC E2 can suppress serum total testosterone (T) levels (<50 ng/dL) as effectively as oral (PO) E2 , 2) if SC administration has less of a hepatic effect than PO, 3) if serum E2 levels remain within the target range between weekly injections and 4) if SC E2 is acceptable to patients. Retrospective chart review of MTF patients treated in Maine Medical Center Reproductive Endocrinology clinic. All charts of MTF patients seen from 2011-2020 were reviewed. Patients were allowed to choose PO, SC or transdermal (TD) administration. Inclusion criteria were age 18-79 years, PO or SC E2 therapy, and serum E2 and T levels measured by LabCorp (Calabasas CA). E2 valerate was injected SC using a 5/8’ 25g needle. 17β-E2 was administered orally. Serum E2, T, estrone (E1), and sex hormone binding globulin (SHBG) levels and fasting lipid panels were measured in SC and PO patients and values compared by Mann Whitney U test. Peak and nadir serum E2 concentrations were measured in a subgroup of SC patients. Serum sex steroid concentrations were measured by liquid chromatography/mass spectrometry. Local and systemic adverse effects were assessed by history and physical exam. The study was approved by the Maine Medical Center IRB. 102 charts were reviewed. Of 65 patients who were offered PO, TD or SC therapy (the SC option became available in May 2017), 23 choose SC. 61 patients were included in the final analysis, 23 in the SC group and 38 in the PO group. Median dose of E2 for the PO group was 4 mg/day [full range=1-12]; for SC E2 it was 4 mg/week [full range=2-6]. For the SC and PO groups the median E2 were 155.5 [75-291] (n=18) and 122 [76-208] pg/mL (n=38) respectively. Median and range of serum T levels in the SC and PO groups were 16 [4.5-82] (n=14) and 13 [4.8-515] (n=38) ng/dL respectively. E1 serum levels in the SC and PO groups were 49.0 [31.0-104.0] (n=10) and 495 [198-926] (n=12) pg/mL (p=0.003). SHBG and lipid levels did not vary significantly between the two groups (not shown). In a subgroup of SC patients, the median serum E2 decreased from 212 [158-245] to 112 [87-150] pg/mL from the day after to the day before an injection (n=12). 22/23 patients in the SC group chose to continue this method, 0/23 patients experienced a systemic reaction and 1/23 experienced a local site reaction. These preliminary data suggest that SC E2 injection is a safe and effective option for administration of E2 that appears to be well accepted by patients. It is well absorbed with minimal adverse effects and suppresses serum T levels as effectively as PO E2. SC E2 has less hepatic effect as reflected by serum E1 levels (but not SHBG or lipids in this small sample size). Serum E2 levels decrease between weekly injections and additional studies are required to refine dosing to maintain E2 values within the target range. Additional pharmacodynamic studies are also indicated.