What are the findings of studies on the brains of transgender (trans) individuals?

From the Guidelines

Transgender individuals, particularly transfeminine people, may have a higher incidence of ischemic stroke compared to cisgender women, but not compared to cisgender men, when using gender-affirming hormone therapy (GAHT) 1.

Key Findings

• A cohort study of 2842 transfeminine people and 2118 transmasculine people found that transfeminine people using GAHT had a higher incidence of ischemic stroke compared with cisgender women, but not compared with cisgender men 1.
• The evidence suggests that interventions on known vascular risk factors, such as tobacco use and hypertension, would be effective at reducing stroke risk in this population, but specific intervention studies inclusive of transgender people are lacking 1.
• Brain structure and function in transgender individuals often more closely resemble those of their experienced gender rather than their assigned sex at birth, with key areas showing differences including the bed nucleus of the stria terminalis and white matter patterns 1.

Clinical Implications

• It is essential to consider the potential increased risk of stroke in transfeminine individuals taking GAHT and to monitor and manage known vascular risk factors accordingly.
• The interpretation of clinical data for transgender or gender-diverse individuals on GAHT should take into account the influence of GAHT on various laboratory values, such as red blood cell indices, liver enzymes, and electrolytes 1.
• Healthcare providers should be aware of the dynamic changes in laboratory values that depend on whether or not the individual is receiving GAHT at the time and use reference ranges for the affirmed gender when appropriate 1.

Limitations and Future Directions

• The observational design of the published studies and the lack of important details on hormone regimens, hormone levels, lifestyle factors, and external minority stress risk factors limit the interpretation of the findings 1.
• Further research is needed to fully understand the relationship between GAHT and stroke risk in transgender individuals and to develop specific intervention studies inclusive of transgender people.

From the Research

Studies of Trans Brains Summary

There are no research papers provided that directly study trans brains. However, the following studies relate to hormone therapy in transgender individuals:

• The study 2 investigates the use of injectable estradiol in transgender and gender diverse adults, finding that current guidelines may lead to supraphysiologic levels of estradiol.
• The study 3 examines the influence of the route of administration and dose of estradiol on serum estradiol and testosterone levels in feminizing gender-affirming hormone therapy, suggesting that intramuscular estradiol may be the most potent delivery method.
• The study 4 discusses the metabolic benefits of estradiol and testosterone in both sexes, highlighting their importance in maintaining bone and vascular health, as well as preventing excess visceral adiposity and promoting insulin sensitivity.

Key Findings

• Injectable estradiol preparations are recommended for feminizing gender-affirming hormone therapy, but optimal dosing and route of administration are unclear 2, 3.
• Estradiol and testosterone have similar metabolic benefits in both sexes, including maintaining bone and vascular health, and preventing excess visceral adiposity and promoting insulin sensitivity 4.
• Compounded bioidentical transdermal hormone therapy may offer a different risk/benefit profile for peri/postmenopausal women, with favorable effects on cardiovascular biomarkers, inflammatory factors, and health outcomes 5.

Hormone Therapy Considerations

• Clinicians should consider the individual needs and priorities of patients when recommending hormone therapy 6.
• The route of administration and dose of estradiol can impact serum estradiol and testosterone levels, and should be carefully considered in feminizing gender-affirming hormone therapy 3.
• Further study is needed to determine the optimal dosing and route of administration for injectable estradiol in transgender and gender diverse adults 2.