Immediate Testosterone Therapy Curbs Gender Dysphoria in Transgender Adults

Testosterone therapy significantly reduced gender dysphoria, depression, and suicidality among transgender and gender-diverse adults seeking masculinization compared with no treatment, a randomized trial showed.

Among 64 participants, those randomized to immediate initiation of testosterone therapy had a decrease in gender dysphoria as measured by the Gender Preoccupation and Stability Questionnaire compared with those randomized to a standard care waiting list of 3 months (mean difference -7.2 points, 95% CI -8.3 to -6.1, P<0.001), reported Ada Cheung, MBBS, PhD, of the University of Melbourne in Australia, and co-authors.

Patients in the intervention group also experienced a clinically significant decrease in depression, as demonstrated by a 5-point drop in the Patient Health Questionnaire-9 (mean difference -5.6 points, 95% CI -6.8 to -4.4, P<0.001), and a significant decrease in suicidality, as measured by the Suicidal Ideation Attributes Scale (mean difference -6.5 points, 95% CI -8.2 to -4.8, P<0.001), they noted in JAMA Network Open.

Additionally, suicidality resolved in 11 study participants who received immediate testosterone therapy compared with one participant who received standard care (P=0.002).

"The implications [of the study results], for me, are this works," co-author Brendan Nolan, MBBS, also of the University of Melbourne, told MedPage Today. "So, we need to try and do things to promote earlier access to hormones and try and reduce some of the barriers to initiation of hormone treatment."

Nolan explained that earlier studies of testosterone therapy were mainly observational, and of those that had a comparator group, a totally different population, such as cisgender women, was used.

"So, the difference with this study is, it's the first randomized study, and it's the first one that has a control group of trans people who want to be on testosterone, but are not yet on testosterone," he said.

However, he also pointed to the 3-month study duration as a limitation, since that meant the window for follow-up was narrow.

"The downside of that is we didn't capture ongoing changes in some of these mental health parameters over time," Nolan noted.

Gender dysphoria, for example, did not decline by a "clinically significant amount," which the Gender Preoccupation and Stability Questionnaire defines as 11 points or more, he said. "We didn't reach that 11-point change in 3 months, but previous research has demonstrated that there are ongoing improvements over time."

For Joshua Safer, MD, executive director of the Mount Sinai Center for Transgender Medicine and Surgery in New York City, the main take-away was clear.

"People who get the medication they require feel better," he told MedPage Today. "Testosterone therapy is quite safe. That people feel better when treated with the correct medication should not be surprising."

"There are potential interesting studies for the future to extend our understanding of testosterone action on various tissues," noted Safer, who was not involved in the study. "But there isn't much more to say about the safety of testosterone and that we can measure that trans-masculine people feel better when appropriately treated."

This 3-month open-label trial was conducted at endocrinology outpatient clinics and primary care clinics that provide care to transgender and gender-diverse patients in Melbourne from November 2021 through July 2022. Median age of study participants was 22.5.

All participants completed questionnaires to assess gender dysphoria, depression, and suicidality at baseline and at 3 months.

The control group initiated testosterone therapy at the end of 3 months, which is on par with the typical wait lists at clinics in the study, Nolan explained, adding that the advisory group of people with lived experience that the researchers consulted cautioned against randomizing people to placebo, as they did not feel that was ethical.

As for side effects, seven participants reported injection site pain or discomfort and one reported a transient headache 24 hours after receiving testosterone undecanoate. None of the participants developed polycythemia.

Nolan said that he and his colleagues are also examining the impact of treatment on quality of life and they plan to study different dosages of testosterone, as well as initiation of estradiol.

If you or someone you know is in crisis or has had thoughts of suicide, call the 988 Suicide & Crisis Lifeline.

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