Study Shows “Novel Associations” Between Anabolic Hormone Levels and Frailty in Old Age

Defining frailty as “a reduced state of homeostatic reserve” related with old age, including loss of mobility and potential falls, Angieszka Swiecicka, MD, of the University of Manchester (pictured) spoke about the actual pathology of what has always just been seen as an inevitable outcome of aging. Her team hypothesized that anabolic hormones with a known role in muscle physiology would be related to worsening frailty in aging men.

The results of their study were presented at the 99^th Annual Meeting of the Endocrine Society in Orlando, Florida. The study included a cohort of 3,369 men aged 40 to 79 who took part in the European Male Aging Study (EMAS). The participants had hormone levels measured and frailty status assessed on two scales, both at baseline and at 4-year follow-up. The assessments included the Fried frailty phenotype, which explores muscle mass and function, exhaustion, weakness, and physical activity, and another 39-point index that included psychological and cognitive factors.

Insulin-like growth factor-1 (IGF-1) and associated binding protein 3 (IGFBP3) were the non-androgenic anabolic hormones that the team investigated for the study. Vitamin D, parathyroid hormone, and DHEA-S were also measured at baseline and follow-up.

Ultimately, 2114 men had their frailty assessed by phenotype and 2,444 had their frailty assessed by index. At baseline, 24% of participants were deemed “pre-frail” or “frail” at baseline: that number increased 10% at follow-up. Status deteriorated in 459 men and improved in 206.

“We found that higher baseline levels of IGF-1 and IGFBP 3 were associated with lower likelihood of worsening frailty status at 4 years, as assessed by both frailty phenotype and frailty index,” Swiecicka said. The associations were independent of age, body mass index, and comorbidities. IGF-1 level was not independently associated with lower risk, however, when IGFBP3 level was taken into account.

Higher vitamin D levels were also associated with reduced risk in both models, again independently of factors like age and BMI. DHEA-S as well associated with lower risk of worsening frailty, but only in men older than 70.

“We know that growth hormone IGF1 affects muscle growth and repair across the human lifespan,” Swiecicka said, “but despite all documented effects of IGF-1 in muscle physiology, human studies have demonstrated conflicting results concerning associations with muscle mass and physical performance. Specific studies in frail men are lacking.”

She went on to detail how such associations are suspected for DHEA-S and vitamin D as well, but that clinical studies to establish cause were lacking and will be needed in the future. The study concludes that its findings “enhance our understanding of the etiology of frailty and the role of the endocrine system” and suggests that trials should explore if supplementing such hormones could prevent progression of frailty.

“We showed novel associations between anabolic hormone levels and changes in frailty levels in aging men,” Swiecicka said in a press release.