Estradiol Concentrations and Wellbeing in Trans People Using Estradiol Hormone Therapy.

Purpose: In trans people undergoing feminizing hormone therapy, optimal estradiol concentrations are unclear, and anecdotally, some individuals desire supraphysiologic estradiol concentrations. We aimed to assess associations between estradiol concentration and psychological distress, well-being, and dysphoria. Second, we aimed to explore relationships between estradiol concentration and the risk of medical conditions potentially associated with estradiol therapy.

Methods: This exploratory online cross-sectional study was conducted between June 2020 and March 2021, using a nonprobability snowball sampling method. Inclusion criteria included the following: (1) Currently living in Australia, (2) identification as transgender and using estradiol for gender affirmation purposes, and (3) 16 years of age or older. Estradiol concentrations were correlated with the Kessler Psychological Distress Scale (K10), the Personal Wellbeing Index (PWI-A), and gender dysphoria as measured by the Gender Congruence and Life Satisfaction Scale.

Results: There were 172 participants, and the median estradiol concentration was 420 pmol/L (interquartile range 269-614). No clinically significant association was found between estradiol concentration with psychological distress, wellbeing, or gender dysphoria. While there was a statistically significant lower K10 score and higher PWI-A General Life Satisfaction score with higher estradiol concentrations, the order of magnitude was small and not clinically significant. There was no association between estradiol concentration and thrombosis, malignancy, stroke, myocardial infarction, migraine, or hypertension.

Conclusions: Given no clear association between higher estradiol concentrations, psychological distress, wellbeing, or dysphoria, approaches to estradiol hormone therapy should be individualized. Further prospective research, with larger sample sizes, is required to more thoroughly investigate optimal feminizing hormone therapy regimens.