CHICAGO (FRONTLINE MEDICAL NEWS) Declining androgen levels are associated with deteriorating physical function and increased frailty in aging men, according to a study presented at the annual meeting of the Endocrine Society.

The findings provide more evidence of the relationship between function and lower levels of androgens such as testosterone and introduce the possibility of using hormones to offset frailty in older patients.

“The decline in total and free [testosterone] and DHEA-S [dehydroepiandrosterone sulfate] was significantly associated with small deteriorations in physical function and worsening frailty,” according to presenter Frederick C. Wu, MD, an endocrinologist at the University of Manchester (England). “The present results are consistent with and support our hypothesis that the decline in these hormones can contribute to a worsening physical function and frailty in the elderly.”

Investigators gathered data on 2,278 men from eight centers across Europe to conduct an observational study of their physical functions.

Patients were all men, an average of 58 years old, and had an average body mass index of 27.6 kg/m2 and average free testosterone and DHEA-S levels at 16.9 nmol/L and 4.7 micromol/L, respectively.

At follow-up, which was on average conducted 4.4 years later, average age was 63 years, and average testosterone and DHEA-S levels had dropped to 287.3 nmol/L and 4 micromol/L respectively, which Dr. Wu described as a moderate drop.

Decreases of free testosterone or DHEA-S by one standard deviation – 86.8 nmol/L and 2.6 micromol/L, respectively – accounted for 11%-17% of the average rate of deterioration of physical function, according to Dr. Wu.

Patients with lower levels of free testosterone and DHEA-S experienced worsening 15-meter walk time, five chair-stands, physical quality of life, and overall worsening of frailty phenotypes at follow up.

Dr. Wu and his colleagues measured frailness in patients by looking for the presence of frailty phenotypes, which include slowness, sarcopenia, exhaustion, low activity, and weakness.

If one-two of these criteria were present, patients would be considered “prefrail,” and if three or more were present, patients would be deemed “frail.”

Patients experienced an average 2.5% increase in frailty per year during the time between baseline and follow up, Dr. Wu told attendees.

Investigators used the mean of 60 years old to adjust for age, Dr. Wu explained in response to a question from the audience; however, this may have been an overadjustment as free testosterone and DHEA-S are age dependent, Dr. Wu admitted.

Investigators also incorporated a frailty index of 39 health deficits – 16 physical or cognitive, 11 comorbidities, and 12 clinical – measuring on a 0-1 scale in order to measure different levels of frailty.

While the link between these androgens and frailty are evident, the potential benefits of hormonal intervention in elderly men are still in the air and demand further study.

“The decline in androgen levels in the physiological range, because of the modest degree of change, is unlikely to be the single greatest cause of deterioration in the majority of aging men in the population,” said Dr. Wu. “Therefore, the possible therapeutic roles of androgens in improving physical health may be limited to a minority of men with very low levels of testosterone.”

Dr. Wu is on the advisory board of Bayer-Schering, Eli Lilly, and Besins Healthcare. Dr. Wu is a research supporter or consultant for Repros Therapeutics, Merck Serono, and Mereo Biopharma. Investigators reported no additional relevant financial disclosures.

SOURCE: Wu F C et al. ENDO 2018, Abstract OR15-1 .


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