A new Danish study has found that testosterone therapy significantly reduces the risk of death in men with Klinefelter syndrome (KS), a common but often undiagnosed genetic condition. The research, led by scientists at Aarhus University and Aarhus University Hospital, suggests that testosterone treatment not only improves quality of life but also extends lifespan, bringing mortality rates closer to those of the general population.
Despite these findings, more than half of all men with KS remain undiagnosed, and among those who are diagnosed, only half receive testosterone therapy. Researchers say this study highlights the urgent need for early identification and treatment of the condition.
“This is a significant discovery because it means that we can save lives by providing the right treatment,” said Dr. Simon Chang, lead author of the study. “Today, only half of diagnosed men with KS receive the necessary testosterone therapy.”
Klinefelter Syndrome and Its Health Risks
Klinefelter syndrome is the most common sex chromosome disorder in men, affecting approximately one in 600 male births. It occurs when a male is born with an extra X chromosome, leading to lower testosterone production.
Low testosterone levels increase the risk of multiple health conditions, including cardiovascular disease, type 2 diabetes, and osteoporosis. Prior research has established that men with KS have a significantly higher risk of developing these diseases, but the extent to which testosterone therapy could mitigate these risks was previously unknown.
The new study is the first large-scale research effort to document the clinical impact of testosterone treatment in KS patients. The findings confirm that testosterone therapy does not increase the risk of serious cardiovascular diseases, heart attacks, or strokes. However, researchers did observe a slight increase in the risk of heart failure among men undergoing treatment.
“It is important to emphasize that the benefits far outweigh the potential drawbacks,” Dr. Chang noted. “The reduction in mortality is so significant that it outweighs concerns about a potential increased risk of heart failure.”
How Testosterone Therapy Improves Health Outcomes
While researchers do not yet fully understand why testosterone therapy leads to a substantial reduction in mortality, they suggest several possible explanations.
Testosterone plays a crucial role in metabolism, muscle development, and fat distribution. By increasing muscle mass and reducing body fat, the hormone may help lower the risk of metabolic disorders such as diabetes and heart disease. Additionally, researchers suspect testosterone may have positive effects on immune function, bone health, and even cognitive abilities.
These findings reinforce the need for early diagnosis. A simple screening test at birth could identify KS through routine blood samples, yet most affected individuals remain undiagnosed throughout their lives.
“More than half of those born with KS are never diagnosed, even though a simple screening test at birth could identify the syndrome,” Dr. Chang emphasized.
Impact on Future Treatment Guidelines for Testosterone Therapy
Currently, international guidelines for KS treatment are under development and are expected to be published in 2027. The study’s findings are likely to play a key role in shaping these recommendations.
“We expect the new guidelines to recommend initiating testosterone treatment as soon as the diagnosis is made,” Dr. Chang concluded.
With growing evidence of testosterone therapy’s life-extending benefits, researchers hope that more men with KS will receive timely diagnoses and access to treatment that could significantly improve—and potentially save—their lives.
Reference: Simon Chang, Lars Pedersen, Anne Skakkebæk, Agnethe Berglund, Claus H. Gravholt. Cardiovascular risk and mortality in men receiving testosterone replacement therapy for Klinefelter syndrome in Denmark: a retrospective cohort study. The Lancet Regional Health – Europe, 2025.
