Long-term use of hormone therapy, particularly testosterone for transgender men and estrogen for transgender women, has been linked to notable changes in body composition, including increased fat accumulation and shifts in muscle mass.
Published Nov 30, 2024 | 7:00 AM ⚊ Updated Nov 30, 2024 | 7:00 AM
Hormone therapy, a fundamental aspect of gender-affirming care for transgender individuals, helps facilitate the transition by inducing physical changes that align with one’s gender identity.
While it is essential for promoting well-being and mental health, long-term use of hormone therapy, particularly testosterone for transgender men and estrogen for transgender women, has been linked to notable changes in body composition, including increased fat accumulation and shifts in muscle mass.
These changes, combined with altered cholesterol levels and liver fat, raise important concerns about cardiovascular health, highlighting the need for ongoing medical monitoring to manage potential risks effectively.
New research from Sweden’s Karolinska Institutet, published in the Journal of Internal Medicine on the long-term effects of sex hormone therapy in transgender individuals, reveals significant changes in body composition and cardiovascular health, particularly in transgender men, and emphasises the importance of monitoring these effects to mitigate potential health risks.
The research followed 33 adults — 17 transgender men undergoing testosterone therapy and 16 transgender women on estrogen therapy — over a six-year period.
Using magnetic resonance imaging (MRI) and blood tests, the researchers tracked changes in muscle mass, fat distribution, and metabolic risk factors at several intervals: Before treatment, after one year, and after five to six years.
Key findings in transgender men
The study found that testosterone therapy led to notable physical changes in transgender men.
Muscle volume increased by an average of 21% within the first year, continuing to rise over six years.
After starting testosterone therapy, muscle mass increased significantly in the first year, with the most noticeable changes in muscle size. However, this increase slowed down and plateaued after about a year, with no major changes after the first five years.
Testosterone caused a significant increase in certain types of fat, especially visceral fat (fat around internal organs) and liver fat.
These changes continued throughout the study. This is important because visceral fat is linked to higher risks of metabolic problems like diabetes and heart disease.
Liver fat levels also rose, along with higher levels of LDL cholesterol (commonly referred to as “bad” cholesterol), which is linked to plaque buildup in arteries and an increased risk for heart disease.
“This highlights the need for long-term health monitoring in transgender men to assess and manage cardiovascular risk,” said Dr. Tommy Lundberg, author of the research paper from Karolinska Institutet, in a statement.
Transgender women receiving estrogen therapy experienced more modest changes.
Muscle volume decreased by 7% over five years, but muscle strength remained largely stable. For those on estrogen, there were only small changes in muscle mass, with no significant increase over five years.
Fat volume increased, but abdominal fat accumulation was notably less pronounced than in transgender men. Estrogen caused an increase in fat overall, but the increase in visceral fat (the fat around organs) was less noticeable compared to transgender men. This aligns with the expected feminising effects of estrogen.
The study underscores that while the feminising effects of estrogen were less dramatic than the masculinising effects of testosterone, the long-term metabolic changes still warrant attention.
Health risks associated with hormone therapy have been observed, particularly in transgender men undergoing testosterone therapy.
“One of the key concerns is the increase in unhealthy cholesterol levels, such as LDL (low-density lipoprotein) and triglycerides, which can develop over the years. LDL, often referred to as “bad” cholesterol, can build up plaque in the arteries, raising the risk of heart disease,” Hyderabad based physician Dr Sai Kiran Chilukuri told South First.
The study found that transgender men on testosterone therapy experienced increased levels of LDL cholesterol and triglycerides, both of which contribute to artery blockages and increase the likelihood of developing atherosclerosis (hardening of the arteries). This, in turn, raises the risk of heart attacks, strokes, and other cardiovascular issues.
“Another major concern is the accumulation of visceral fat, the fat stored around internal organs like the liver and heart. This type of fat is particularly harmful as it is linked to a higher risk of heart disease and metabolic disorders. The study showed a significant increase in visceral fat in transgender men over time, which is concerning as it is associated with insulin resistance, type 2 diabetes, and cardiovascular diseases,” said Dr Chilukuri.
Fatty liver disease, which occurs when fat accumulates in the liver, also poses risks to heart health. The study found that testosterone therapy led to increased liver fat, raising concerns about long-term metabolic health and its impact on the heart. Fatty liver disease is linked to metabolic syndrome, a group of conditions such as high blood pressure, high blood sugar, high triglycerides, and excess abdominal fat, all of which increase the risk of heart disease, stroke, and diabetes.
“Insulin resistance, which happens when the body becomes less responsive to insulin, is another significant risk factor. Insulin resistance is strongly associated with an increase in visceral fat and can lead to type 2 diabetes and high blood pressure, both of which are major contributors to cardiovascular disease,” Dr Chilukuri said.
Lastly, while the study did not find immediate changes in blood pressure or arterial stiffness, these factors are known to increase the risk of heart disease over time.
Arterial stiffness, in particular, occurs when blood vessels lose their flexibility, making it harder for blood to flow. Long-term exposure to high levels of testosterone could contribute to these risks as transgender men age, emphasising the importance of monitoring heart health in this population.
The study’s findings underscore the necessity for long-term monitoring of transgender individuals undergoing hormone therapy to assess and manage potential health risks, including cardiovascular disease.
Previous studies have often been limited to short-term assessments (up to two years), but this research provides a broader perspective on the lasting effects of hormone treatment.
Tissue samples from muscle, fat, and skin were also collected, with future research aimed at understanding the interaction between genetic sex and sex hormones, particularly how hormone therapy affects skeletal muscle gene expression and the mechanisms behind changes in adipose tissue (fat storage).
“We aim to explore how sex hormones affect tissue at the molecular level to better understand the broader health implications,” said Dr. Lundberg.
While the study provides essential insights into the masculinising and feminising effects of hormone therapy, it also cautions against expecting dramatic, long-term transformations.
Dr. Lundberg emphasises the need for personalised healthcare approaches to ensure the overall well-being of transgender individuals undergoing hormone therapy, particularly as the long-term health effects continue to be explored.
(Edited by Rosamma Thomas).
