Authors: Dr Brendan Nolan and Dr Sav Zwickl.
Content Warning: Mention of depression, gender dysphoria and suicidality.
Trans Health Research recently published findings from our study on the impact of fast access to testosterone gender-affirming hormone therapy (GAHT) on mental health and wellbeing in the peer-reviewed journal, JAMA Network Open.
Reandron testosterone, which was used in this study.
Results showed significant reductions in gender dysphoria, depression, and suicidality after 3 months with early testosterone GAHT use compared to standard care. Remarkably, over half of the study participants receiving testosterone experienced resolution of "thoughts of hurting themselves or that they were better off dead".
Since these findings were first presented at ENDO 2023 several months ago, there had been a lot of media hype and community interest in the project, including articles by CNN, The Guardian, Healio, PinkNews, and Endocrine Society.
Aside from providing evidence of the strong positive impact of testosterone GAHT, a large part of why this research has drawn so much attention is that it is a randomised controlled trial (RCT).
What is an RCT and why are they so rare in trans health research?
In research, there are levels of evidence (or a hierarchy of evidence). As shown in the pyramid image below (Figure 1), this system is used to rank studies based on the quality and reliability of their designs, where the higher the position on the pyramid, the stronger the evidence.
A RCT is a type of study design that is rated highly in terms of quality and reliability. RCTs measure the impact of an intervention treatment and are prospective in nature, meaning that they start following people from when they are first given a treatment and while they are on the treatment, for a certain amount of time. As part of the RCT study design, research participants are randomly allocated to either the ‘intervention group’ (who receive the treatment) or the ‘no treatment’ (control) group. Random allocation of participants to either the intervention or no treatment group is important because it limits the amount of bias in the study and any known and unknown confounders (factors that might influence the measured outcomes) should be equally distributed between the two groups. This means that any differences observed between the two groups is a lot less likely to be related to these confounders, and a lot more likely to be due to the impact of the treatment.
Figure 1: The hierarchy of research evidence.
RCTs, as a higher quality of evidence, have been rare to non-existent in trans health research, with most research fitting into the bottom levels of the pyramid - cross-sectional surveys, case studies, and expert opinion. The main reason for this, is that it would be unethical to withhold GAHT from a group of people who desire it, given the existing evidence of its positive and often literally life-saving benefits. However, with this newly published study we found a work-around, which allowed for an ethical, short-term RCT.
How did we design an ethical RCT?
Although any general practitioner (family doctor), endocrinologist or sexual health specialist in Australia can prescribe GAHT under national treatment guidelines, many do not have the knowledge of trans health to confidently do so. This means that there are only a limited number of doctors who prescribe GAHT, often resulting in long waitlists for a first appointment with a prescribing doctor. In Melbourne, these waitlists are often more than 3 months, and a 6–12-month wait is not uncommon.
Based on these wait times to see a doctor to initiate GAHT, we designed a study to ensure that no trans people who consented to being part of the study would be waiting longer to commence GAHT than had they been on a regular waitlist.
The study involved 64 trans and gender-diverse adults seeking testosterone GAHT who were assessed to establish their capacity to initiate testosterone using the informed consent model of care. As shown in the diagram below (Figure 2), participants were randomly allocated to one of two groups – the ‘intervention group’ who started testosterone within a week of the first study visit, and the ‘no treatment’ group who received standard care which involved waiting 3 months before starting testosterone (like being on a waitlist to see a doctor who prescribes GAHT).
Figure 2: Diagram of the study design for our Testosterone RCT.
This design allowed for a 3-month period in which half the participants were using testosterone and half were not. All participants completed surveys at baseline (at the beginning of the study when no participants had started testosterone) and at the end of the study, when the intervention group had been on testosterone for 3 months and the no treatment group hadn’t yet started testosterone (but were about to).
While this study has garnered a lot of attention, it has its limitations. The most obvious is that we only followed participants for 3 months and it would be useful to have evidence of the longer-term impacts of GAHT on mental health and wellbeing using an RCT design. However, the issue with doing a longer RCT, is that the no treatment group would have to go without access to GAHT for longer. To place trans people who want to start GAHT in a position where they are having to wait longer than standard care wait times, would be unethical.