FROM THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM

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 .

In an interview, Steve Borst, PhD, of the University of Florida, questioned the study’s approach because it looks only at baseline hormone levels. “What would be much more interesting to study would be changes in hormone levels vs. changes in frailty,” he said.

Dr. Borst added that researchers already know that “the relationship between testosterone and frailty is both large in magnitude and causal in nature.”

He pointed to his group’s research that linked testosterone injections to an increase in muscle strength, and he said others have linked testosterone administration to an increase in bone density. “While these measures are not exactly the same as frailty index,” he said, “it is well established that lower body muscle strength keeps older people in an independent living state and that the changes in bone mineral density are enough to account for protection against fracture.”

John Morley, MBBCh, of Saint Louis University, said in an interview that testosterone has a role in combating frailty. “But it’s not like it’s going to turn people into super people,” he said.

He added that “we shouldn’t say ‘Let’s do testosterone before we do exercise.’ It’s better to do resistance exercise than it is to take testosterone. But most older males are loath to do any physical work to make themselves better. That’s just human nature.”

The study was funded by various European research-based organizations. The study authors reported multiple disclosures. Dr. Morley reports no disclosures.

cenews@frontlinemedcom.com

SOURCE: Swiecicka A et al. J Clin Endocrinol Metab. 2018 Feb;103(2):701-9 .

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