5158 Estrogen for Feminizing Gender Affirming Hormone Therapy: Understanding the Influence of Route of Administration and Dose on Serum Estradiol and Testosterone Levels
Authors: Slack Daniel J , Via Ioschpe Anais Di , Saturno Michael , Kihuwa-Mani Sky , Amakiri Uchechukwu , Karim Subha , Guerra Dan , Safer Joshua David 
Published: October 2024

Abstract
Disclosure: D.J. Slack: None. A. Di Via Ioschpe: None. M. Saturno: None. S. Kihuwa-Mani: None. U. Amakiri: None. S. Karim: None. D. Guerra: None. J.D. Safer: None.
For feminizing gender affirming hormone therapy (GAHT), the Endocrine Society and WPATH SOC 8 suggest targeting testosterone (T) levels below 50 ng/dL and estradiol (E2) levels in the range of 100-200 pg/mL. Exogenous estrogen may be given via several routes of administration (ROA) and at a variety of doses, but little is known about how ROA and dose influence T and E2 levels. We sought to investigate the relationship between estrogen dosage, ROA, and hormonal profiles in trans feminine individuals. We conducted a chart review of patients in the Mount Sinai Health System and included all patients who had active prescriptions for feminizing GAHT with both T and E2 levels recorded (n = 585), excluding those with a history of orchiectomy. For oral (PO) estrogen, there was a negative correlation between dose and serum T (p &lt; .01), LH (p &lt; .05), and FSH (p &lt; .05), but no correlation with E2. For transdermal (TD) estrogen, dose did not correlate with serum T, E2, LH, or FSH. For intramuscular (IM) estrogen, there was a positive correlation with serum E2 (p &lt; .05), LH (p &lt; .05), and FSH (p &lt; .01), but no correlation with T. Individuals were then stratified into groups of T and E2 ranges that were determined via bell-curve frequency distributions. Within each group, the relative proportion of users of a given ROA, their mean dose of estrogen given via that ROA, and their resulting mean T and E2 levels were calculated. For users of IM estrogen, a significantly higher proportion of individuals had T &lt; 50 ng/dL as opposed to T &gt;= 50 ng/dL. IM users also much more frequently exhibited E2 &gt;= 200 pg/mL than E2 &lt; 200 pg/mL. For users of PO estrogen, a higher proportion of individuals had T &gt;= 100 ng/dL compared to T &lt; 50 ng/dL, with the proportion of those with T 50-99 ng/dL not differing from either group. A higher proportion of users of PO estrogen had E2 50 - 199 pg/mL compared to E2 &lt; 25 ng/dL and E2 &gt; 200 pg/mL, with the proportion of those with E2 25-49 pg/mL not differing significantly from either. For users of TD estrogen, there was a higher proportion of those with T 50 - 99 ng/dL compared to &lt; 50 ng/dL and &gt;= 200 ng/dL, with the proportion of those with T 100 - 199 ng/dL not differing from either group. A higher proportion of users of TD estrogen had E2 25 - 49 pg/mL compared to E2 100 - 199 pg/mL and E2 &gt; 300 pg/mL, while the frequency of those with E2 &lt; 25 pg/mL, 50 - 99 pg/mL, or 200 - 299 pg/mL did not differ significantly. Our results indicate a propensity for users of IM estrogen to achieve T suppression and to overshoot E2 targets, while users of PO estrogen were most likely to have E2 levels at-target but less likely to achieve T suppression. Users of TD estrogen appear least likely to achieve either target. While further research is needed to confirm and expand upon our findings, our data are an important step forward in providing clinicians with some predictive capability as to the serum E2 and T levels they might expect with the use of exogenous estrogen at a given dose and ROA.
Presentation: 6/2/2024