Estrogen and the Brain: The Long Term Cognitive Effects of Estrogen Therapy in Older Trans Women

Estrogen therapy is commonly prescribed by physicians to transgender women who chose to undergo gender confirmation surgery(ies). Estrogens are a versatile group of hormones with a variety of roles in the human body, one of them being involved in cognitive processes such as memory. So, do trans women’s cognitive abilities change as they take estrogen therapy? While scientists have researched cognitive side-effects of short-term hormone therapy use, cognitive effects of long-term usage have not been studied. Luckily, a larger project in the Einstein Lab, the Trans Cognition Project, encompasses this question and is looking into just that. To fill the gap in the literature, previous undergraduate students Ava Ma de Sousa and Leah Velikonja examined memory changes associated with long term estrogen therapy use in older trans women. The Older Trans Women project was undertaken because a trans activist stopped into Dr. Einstein’s office and said, “You’re study the effect of estrogens on the brain; why aren’t you studying us?!”

Ma de Sousa, who is currently a M.Sc. student in Brain and Cognitive Science at the University of Amsterdam, piloted the Older Trans Women project in her fourth and final undergraduate year after returning from a year abroad in the Netherlands. “I was interested in this project because it was something that I hadn’t seen research about, and because of that, it felt all the more important.” The Einstein Lab had previously run a project on cognition in trans men taking testosterone therapy. Therefore, Ma De Sousa got the idea to research the effects of estrogen therapy on older trans women. “Back then there was no research on older trans populations,” she explains. “There might have been one paper discussing blood clots and other physiological mechanisms resulting from hormone therapy in general, but nothing about cognitive effects.”

In that year, Ma de Sousa worked very closely with Dr. Gillian Einstein – the principle investigator of the Einstein lab of Cognitive Neuroscience, Gender, and Health – to foster a relationship with women in the trans community. “The women that I tested were so happy that we were doing this research and were so helpful,” Ma de Sousa recalls. “One of the things I took away from the project was the [conversation] I had with every person I tested. They told me about the effects the therapies were having on them, not necessarily on their cognition, and it got me interested in social neuroscience. I thought it was crazy that these tiny neurotransmitters could be doing so much for their emotional and social lives.”

A year later, Velikonja worked on the project in her final undergraduate year as well. Velikonja – who is now a M.Sc. Student in Anatomical Sciences student at Queen’s University – was keen to continue Ma de Sousa’s project. “I saw the important impact of her work and wanted to continue it by doing something similar,” she says. As part of the project, Velikonja looked at the visuospatial ability, associative memory, working memory, verbal memory, and language performance of trans women above the age of 50 who had been taking hormone therapy for at least five years. “I administered several different [neuropsychological] tasks covering each of those five domains, because with such a lack of research, I wanted to be able to cover as many aspects of cognition as possible,” she reiterates.

The Study

Velikonja and Ma de Sousa together recruited trans women above the age of fifty who had been taking hormone therapy for at least five years. The study also included cis women over the age of fifty who had been taking hormone therapy for the same length of time and cis men as comparator groups.  “One thing I learned a lot about was how to create inclusive environments for the participants,” Velikonja recalls. “As a researcher, this is very important to consider both for the participants’ and the study’s sakes.” Velikonja herself administered seven different cognitive tasks with the whole process to around two hours.

The work is still very preliminary because it only currently includes 8 trans women, 7 cis women taking hormone therapy, 11 cis women who were not taking hormone therapy, and 3 cis men all above the age of fifty. In this small population, there was a suggestion that long term hormone therapy in trans women might affect verbal memory even when compared to cis women who had been taking hormone therapy for the same period of time. These preliminary data beg for further study to determine the long term effects on verbal memory, in particular.

Research Philosophy and Implications

Ma de Sousa talks about the philosophy she adopted when starting her research, which to her, was as integral as the research itself. “As a scientist in the health sciences, you have to acknowledge your positionality,” she details. “I remember discussing this in lab meetings, and meetings just between me and [Dr. Einstein]. You have to acknowledge who you are as a researcher and what you bring to the table. While the earliest research on trans men was devised and carried out by a trans undergraduate, no one who has worked on the Older Trans Women project up till now has been a member of the trans community, which is a shame,” she says. “Hopefully that will change. Sometimes it’s hard to do work from outside the community, and we all feel strongly about, ‘no research about us without us.’ We did, however, have a community advisory group who helped us think through the importance of the study and guided us throughout.  In terms of the terminology, sometimes the women we worked with did correct us. I’m very grateful to have had participants who were so engaged and willing to help, because without their guidance, we could not have conducted this research.”

Velikonja goes on to mention the motivation behind the participants’ willing participation in the study. “Many of them want to have inclusive healthcare in the future, which is a big part of this project and why it’s so important to me,” she explains. “As a researcher, you always want to answer your questions, but the women [we were testing] also wanted to know because their health was on the line. They’re going to be taking these hormone therapies for the rest of their lives and they want to be comfortable taking them. They wanted to know whether the therapies were safe, and ultimately to know more about themselves and their future.”

When commenting on her research, Ma de Sousa mentions that it was these interactions with participants that really stood out for her. “Even though I was researching verbal and spatial memory, what really popped out were the social aspects [of the study] and the fact that your biology can influence your emotional life and your social interactions and how you feel about other people so profoundly, and I thought that was really amazing,” she recalls. “And self-esteem, of course,” she adds.” Because in a way, those are the things that people notice. And those are the things that that really affect people.”

The Older Trans Women study is an ongoing project of the Einstein Lab. The work by Ma de Sousa and Velikonja laid the groundwork for future researchers to add into this research, and produce complete findings that will later be beneficial for the participants they test. The study is supported by the Women’s Brain Health Initiative Foundation.

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