From the Journals

Free testosterone linked to frailty in older men



A new study provides more evidence of a link between lower free testosterone levels and higher levels of frailty in older men, but a researcher says proof of a causal connection remains elusive.

“Our study demonstrates clear associations between testosterone and frailty progression, and, although causality and directionality of the hormone/frailty relationships require clarification, the results presented here make a strong case for large interventional trials of testosterone therapy in frail men to determine whether such treatment would be beneficial,” lead author Agnieszka Swiecicka, MD, of the andrology research unit in the division of diabetes, endocrinology, and gastroenterology at the University of Manchester (England), said in an interview.

As Dr. Swiecicka noted, “in men, testosterone levels decline with age, and it has been suggested that this phenomenon might play a role in the development of frailty.”

However, evidence is limited, and studies have offered conflicting results Dr. Swiecicka said.

For the new study, the researchers prospectively tracked 3,369 community-dwelling men aged 40-79 years from eight European centers. Hundreds were excluded for various reasons or lost to follow-up, and 2,278 men were ultimately included.

The average age was 58 years, and the average body mass index was 28 kg/m2.

Hormone measurements were performed, and frailty was tracked via frailty status (FS, n = 2,278) and frailty phenotype (FP, n = 1,980).

After adjusting their statistics to account for various factors, the researchers were able to link only free testosterone – and not testosterone or dihydrotestosterone – to changes in frailty index (FI). They linked each standard deviation improvement in free testosterone level at baseline to a –2.8% change in FI over 4 years (95% confidence interval, –4.9 to –0.3, P = .030).

“Higher free testosterone levels were associated with a lower risk of worsening frailty status. The direction of this association was consistent regardless of the frailty construct used (FI and FP),” Dr. Swiecicka said. “Higher androgen remained significantly associated with improving frailty status, as assessed by FI, despite age adjustment, suggesting that these relationships cannot be explained by age-related differences in androgen levels.”

Overall, “sex hormones are associated with the development/worsening of frailty in middle-aged and older men, but these relationships vary between different constructs of frailty assessment,” Dr. Swiecicka said. “In light of the findings, a therapeutic role for testosterone in the context of physical frailty prevention or alleviation remains an attractive possibility that should be further explored.”

The study was published in the Journal of Clinical Endocrinology and Metabolism.


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