Testosterone Therapy Nearly Halves Mortality for Men With Klinefelter Syndrome

Testosterone therapy significantly reduces mortality in men with Klinefelter syndrome, potentially saving lives and influencing future treatment guidelines.

Over half of men with Klinefelter syndrome (KS) are unaware of their condition. Among those diagnosed, only around half receive the necessary treatment. A recent Danish study shows that testosterone therapy not only enhances quality of life but can also be life-saving ().

Klinefelter syndrome is the most common sex chromosome disorder in men, affecting approximately one in 600 male births. The condition results from being born with an extra X chromosome, leading to low testosterone production, which in turn increases the risk of cardiovascular disease, type 2 diabetes, and overall higher mortality rates.

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Health Risks of Klinefelter Syndrome

“Our previous studies have shown that men with KS have a significantly higher risk of developing a range of diseases. However, we did not know to what extent testosterone treatment could reduce this risk. Until now, no large studies have been able to document the actual clinical effects of treatment,” explains postdoc and M.D. Simon Chang from Aarhus University and Aarhus University Hospital, describing the motivation behind the study.

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Testosterone Treatment Reduces Mortality in Klinefelter Syndrome

This is the first study of its kind and shows that testosterone treatment nearly halves the mortality rate among men with KS. Male participants who received treatment lived significantly longer than untreated men, with their mortality rate approaching that of the general population.

“This is an extremely important discovery because it means that we can save lives by providing the right treatment. Today, only half of diagnosed men with KS receive the necessary testosterone therapy,” says Simon Chang.

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Unexplained Mechanisms Behind Testosterone’s Impact

Researchers cannot yet fully explain why the treatment leads to such a significant reduction in mortality. According to Simon Chang, the effect may be linked to improved metabolism, increased muscle mass, and reduced body fat as a result of testosterone therapy.

“Testosterone is a powerful hormone that affects nearly every function in the body. We also suspect that it may have positive effects on the immune system, bone health, and possibly even cognitive functions,” he explains.

The study, he adds, underscores the importance of identifying more men with KS who remain undiagnosed. More than half of those born with KS are never diagnosed, even though a simple screening test at birth could identify the syndrome through the routine blood sample taken from all newborns.

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Safety of Testosterone Therapy in Klinefelter Syndrome

The study confirms that testosterone therapy does not increase the risk of serious cardiovascular diseases, heart attacks, or strokes. However, there is a slightly increased risk of heart failure among men receiving treatment.

“It is important to emphasize that the benefits far outweigh the potential drawbacks. The reduction in mortality is so significant that it outweighs concerns about a potential increased risk of heart failure,” says Simon Chang.

New International Guidelines for Klinefelter Syndrome Treatment

International guidelines for the treatment of KS are currently in development and are expected to be presented in 2027. Simon Chang anticipates that the study’s results will directly influence these guidelines, potentially improving, prolonging, and saving lives for many men with KS.

“We expect the new guidelines to recommend initiating testosterone treatment as soon as the diagnosis is made,” he concludes.

Reference:

Cardiovascular risk and mortality in men receiving testosterone replacement therapy for Klinefelter syndrome in Denmark: a retrospective cohort study - (https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(25)00022-5/fulltext)

Source-Eurekalert