Authors: Dr Sav Zwickl and A/Prof Ada Cheung.
Content Warning: This article contains brief mentions of psychological distress, life satisfaction and gender congruence.
A transgender woman. Credit: Supitnan via Adobe Stock.
There is no consensus on optimal oestradiol levels for trans people using oestradiol gender-affirming hormone therapy (GAHT). International guidelines vary, suggesting goal oestradiol concentrations anywhere between 250 pmol/L and 1000 pmol/L, but these recommendations are based on expert opinion and the approximate range for cisgender women across the menstrual cycle, rather than clinical evidence.
Over the last few years, we have observed an increase in trans people in Australia seeking high doses of oestradiol, while their doctors understandably have reservations about prescribing oestradiol GAHT well above levels recommended in current Australian guidelines.
Prompted by the lack of robust research on optimal oestradiol levels to guide clinical care, Trans Health Research designed a study to explore associations between oestradiol levels, psychological distress, wellbeing and risk of certain health conditions.
Between June 2020 and March 2021, 162 trans women and 10 non-binary people using oestradiol GAHT provided us with a copy of their latest blood test results and completed a survey that asked about their mental health, satisfaction with their GAHT, and whether they had experienced any adverse effects from hormone therapy. This allowed us to compare their oestradiol blood levels, the oestradiol formulation they were using and the survey answers to look for any trends.
Do different oestradiol formulations result in different oestradiol levels?
We were able to calculate median oestradiol concentrations achieved with the most common formulations of oestradiol. As shown in the graph below, oestradiol implants achieved the highest median oestradiol concentration (628 pmol/L), followed by Sandrena gel (451 pmol/L), and Progynova tablet (380 pmol/L). Estradot patches achieved a median oestradiol concentration of 357 pmol/L. Other formulations achieved varying oestradiol concentrations, though as these groups involved very small numbers of people, it is hard to generalise from that data.
The image description can be expanded below.
A graph displaying the median oestradiol concentrations for the four most common formulations of oestradiol. The Implant formulation has a median oestradiol concentration of 628 pmol/L. The Sandrena formulation has a median oestradiol concentration of 451 pmol/L. The Progynova formulation has a median oestradiol concentration of 380 pmol/L. The Estradot formulation has a median oestradiol concentration of 357 pmol/L.
A transgender female couple. Credit: FG Trade via iStock.
Are higher oestradiol levels associated with better mental health and wellbeing?
In our survey, we asked participants ‘‘How satisfied are you with your current oestradiol therapy?’’ and ‘‘How satisfied are you with the overall physical effects from your hormone therapy?’’ (on a scale from 0 to 100). As shown in the table below, we found no significant differences in satisfaction based on oestradiol concentration, meaning that higher oestradiol levels weren’t associated with higher satisfaction.
We looked at experiences of psychological distress using the Kessler Psychological Distress Scale (K-10), a commonly used 10-item questionnaire (where a lower score indicates a lower level of distress), and found that for every 1 pmol/L increase in oestradiol concentration, there was a mean decrease (less psychological distress) of 0.003 in the K-10 score. For example, an oestradiol concentration of 1300 pmol/L would be associated with 3-point lower K10 score than an oestradiol concentration of 300 pmol/L. While this is statistically significant, it is unlikely to have much clinical significance.
We used the Personal Wellbeing Index (PWI-A) to measure wellbeing. The PWI-A produces a General Life Satisfaction score, based on response to the question, ‘‘Thinking about your own life and personal circumstances, how satisfied are you with your life as a whole?,’’ and a Subjective Wellbeing score, which assesses satisfaction across different life domains (standard of living, health, what they are currently achieving, personal relationships, safety, community connection, and future safety). It was found that for every 1 pmol/L increase in oestradiol concentration, there was a mean difference increase (greater satisfaction) of 0.009 for the PWI-A General Life Satisfaction measure. No associated was found between oestradiol concentration and the PWI-A Subjective Wellbeing measure.
Lastly, participants completed the Gender Congruence andLife Satisfaction Scale (GCLS) which assesses sense of gender identity, feelings of gender congruence, and quality of life across different areas of life. Like some of the other measures, there was a small but statistically significant association between oestradiol concentration and gender congruence and life satisfaction.
Association by oestradiol concentration
Satisfaction with current GAHT
Satisfaction with physical effects of GAHT
K10- Psychological distress
A higher oestradiol concentration was associated with a very small decrease in K10 score (less psychological distress)
PWI-A General Life Satisfaction
A higher oestradiol concentration was associated with a very small increase in PWI-A (greater life satisfaction)
PWI-A Subjective Wellbeing
GCLS- Gender Congruence and Life Satisfaction
A higher oestradiol concentration was associated with a very small increase in GCLS (greater gender congruence)
Table 1. Associations between oestradiol concentration and satisfaction and mental health measures, sourced from Ginger et al, Transgender Health (2023).
Are higher oestradiol levels associated with risk of certain medical conditions?
One of the biggest reservations doctors have when it comes to prescribing higher doses of oestradiol, is whether higher oestradiol concentrations will increase the risk of adverse effects, including potentially serious health conditions.
In this study we found no significant association between oestradiol concentrations and risk of thrombosis, cancer, stroke, myocardial infarction, or migraine. However, it is important to note that the people participating in our study were relatively young (a median age of 37.5 years), making it hard to draw conclusions about risk in older trans women and non-binary people using oestradiol. You can find out more information about risks and adverse effects of oestradiol here.
A transgender woman. Credit: Annie via Adobe Stock.
An individualised approach is best
Our findings indicate that higher oestradiol concentrations are associated with lower levels of psychological distress, greater life satisfaction and greater gender congruence. However, these associations are very small. A part of the reason we may not have seen a stronger association is because like with many medications, oestradiol works very differently for different people. Our research and the varying experiences of trans people using oestradiol, indicate there is no one-size-fits-all approach.
My oestradiol levels have been fairly low in comparison to other people I know…. My physical results on such low levels have been amazing, I have full b-cup breasts… and all the other physical changes have been amazing.
- Angela, 35 years old.
I feel better when my levels are higher, usually 800 [pmol/L] and above is best.
-Julie, 62 years old.
Decisions about oestradiol dose, formulation, and goal levels should be a shared decision between you and your doctor and consider your individual circumstances, including any risk factors. There may need to be some trial and error before you find what works best for you in terms of both oestradiol formulation and oestradiol concentration.
You can find more information about how to access to gender-affirming hormone therapy in Australia here. If you are interested in learning more about the effects and risks of oestrogen, progesterone, and anti-androgens you can check out our blog, the TransHub website, or refer to Australian and international treatment guidelines.
About the authors
Dr Sav Zwickl (they/them) is a non-binary researcher and educator who is passionate about improving the health and wellbeing of the trans community through research. They have a Masters degree in Sexology, a PhD in Gender, Sexuality and Diversity Studies, and experience working in peer support roles with LGBTIQA+ young people and sexual health education. Sav has been part of the Trans Health Research team since early 2019.
A/Prof Ada Cheung (she/her) is an Endocrinologist at Austin Health and a NHMRC & Dame Kate Campbell Research Fellow at The University of Melbourne. Driven by community need and working with the trans community, she established the Trans Health Research group and is an unwavering ally. She has won a number of national and international awards for research excellence and outstanding community leadership and is committed to training MD & PhD students and trans researchers.