Hormone Therapy For Trans Women Shifts Dozens Of Proteins To Align With Their Gender Identity

A new study highlights just how flexible the human body can be by demonstrating that in adult transgender women receiving gender-affirming hormone therapy, several key proteins became altered to more closely match their forms in cisgender women. As well as changing the way someone’s body looks on the surface, the results show that feminizing hormones have impacts at a molecular level, with implications for susceptibility to various health conditions. 

The rest of this article is behind a paywall. Please sign in or subscribe to access the full content.

The study, led by scientists at the Murdoch Children’s Research Institute (MCRI) in Victoria, Australia, included 40 adult trans women receiving one of two common forms of gender-affirming hormone treatment: estradiol, coupled with either cyproterone acetate or spironolactone. 

A suite of 5,279 blood proteins was examined before starting treatment and after six months. The proteins from the participants were also compared against data from cisgender women taken from the UK Biobank, a long-running study of 500,000 people. 

What the researchers discovered was that over time, receiving hormones caused protein changes in the trans women that made them more closely align with those in cisgender women. Of the top 100 proteins that normally differ between males and females, 36 and 22, respectively, shifted towards the “female” form in the trans women after either hormone regimen. 

The results were similar to what is seen in menopausal women who receive hormone replacement therapy. 

“For transgender women we found gender affirming hormone therapy alters the levels of many protein biomarkers that reflect what happens clinically,” explained senior author and MCRI Associate Professor Boris Novakovic in a statement.

“This may go onto impact the risk of allergic and autoimmune diseases, which tend to affect more females, but decrease the risk of heart disease, more commonly seen in males. This highlights that human biology is malleable and that even in adulthood, our bodies respond to sex hormone changes.”

As well as decreases in some protein biomarkers linked to male reproduction, there were also increases in proteins involved in body fat, breast development, immune function, and good heart health.

The decrease in proteins linked to sperm formation was particularly notable in the group receiving cyproterone, which was put down to the fact that this particular combination treatment causes a greater drop in testosterone. 

The findings could have implications for how transgender people receiving hormones are monitored over the long term. Novakovic said that as well as considering aspects of health that are unique to trans women, it’s important that providers recognize that trans women may also face similar health challenges to cisgender women. 

Equally, these findings could help optimize hormone therapy itself.

“Studying proteins could help with the development of personalised treatment approaches by monitoring the effectiveness of gender affirming hormone therapy in trans women and help us with early detection of potential side-effects on heart health or immune function,” explained co-author Professor Ada Cheung. 

This study was relatively small and only looked at feminizing gender-affirming hormones, so more research will be needed to assess whether similar changes may be seen in transgender men or non-binary individuals receiving masculinizing hormones. 

It’s been established that biological sex affects the risk of certain diseases – females are more prone to autoimmune conditions, but males are more susceptible to a range of infectious diseases, for example. Gender-affirming hormone therapy is an important treatment for many trans and non-binary people experiencing gender dysphoria, so a better understanding of how it impacts the body – even down to the molecular level – is vital to protect the long-term health of this patient population. 

The study is published in Nature Medicine.