Higher Anabolic Hormone Levels Predict Lower Risk of Worsening Frailty in Men: Prospective Results from the European Male Ageing Study

Presentation Number: SUN 425
Date of Presentation: April 2nd, 2017

Agnieszka Swiecicka*1, Mark Lunt1, Tomas Ahern1, Terence W. O'Neill1, Gyorgy Bartfai2, Felipe F Casanueva3, Gianni Forti4, Aleksander Giwercman5, Thang S Han6, Krzysztof Kula7, Michael E. J. Lean8, Neil Pendleton1, Margus Punab9, Dirk M. Vanderschueren10, Ilpo T. Huhtaniemi11, Frederick C. W. Wu1 and Martin K. Rutter1
1University of Manchester, Manchester, United Kingdom, 2Albert Szent-György Medical University, Szeged, Hungary, 3Universidad de Santiago de Compostela, Santiago de Compostela, Spain, 4University of Florence, Florence, Italy, 5Malmo University Hospital, Malmo, Sweden, 6Royal Holloway University of London (ICR2UL) and Ashford and St Peter's NHS Foundation Trust, Surrey, United Kingdom, 7Medical University of Łódź, Łódź, Poland, 8University of Glasgow, Glasgow, United Kingdom, 9Tartu University Hospital, Tartu, Estonia, 10Katholieke Universiteit Leuven, Leuven, Belgium, 11Imperial College London, London, United Kingdom


Background: Frailty is described as a state of reduced homeostatic reserve associated with adverse outcomes such as disability, falls and death. The pathophysiology of frailty is not well understood but has been linked with declining levels of anabolic hormones [IGF-1, DHEAs, 25-hydroxyvitamin D (25OHD)]. The evidence, derived from cross-sectional studies, is conflicting, and prospective data are largely lacking.

Aims: We aimed to determine the associations between anabolic hormones and 4-year change in frailty status in community-dwelling older men using longitudinal data from the European Male Ageing Study.

Methods: This was a prospective, observational cohort study of 3369 men aged 40-79 years from 8 European centres followed for a median of 4.3 years. Men with known adrenal or pituitary disease and/or using medication affecting anabolic hormone levels were excluded. Frailty status was determined using frailty phenotype (FP, n=2114) and frailty index (FI, n=2458). Logistic regression was used to assess relationships between baseline levels of IGF-1, IGF-1 binding protein 3 (IGFBP3), DHEAs, 25OHD and PTH (standardised as Z scores) and 4-year change in FP (worsening or improving), and negative binomial regression to assess relationships between hormonal predictors and follow-up FI; all models were adjusted for age, centre and baseline FP or FI, as appropriate.

Results: Men whose frailty status deteriorated (n=459), compared to those whose frailty status did not change (n=1443), were older (mean±SD: 61±11 vs 57±10 years, p<.001), had lower BMI (27±4 vs 28±4 kg/m2, p=0.035) and a higher prevalence of diabetes (8% vs 5%, p=0.001).

The risk of worsening FP and FI decreased with each standard deviation increase in IGF-1, IGFBP3 and 25OHD in multivariable-adjusted models [IGF-1: OR (95%CI) for worsening FP: 0.82 (0.73, 0.93); β (95%CI) for change in FI: -0.04 (-0.06, -0.02), IGFBP3: OR 0.84 (0.74, 0.94); β -0.04 (-0.06, -0.01), 25OHD: OR 0.86 (0.76, 0.97); β -0.05, (-0.07, -0.02)].

Higher levels of DHEAs were also associated with a lower risk of worsening FP and FI; however statistical significance was lost after age-adjustment. In secondary analysis, higher DHEAs was associated with a lower risk of worsening FP in men >70 years old [OR: 0.57 (0.35, 0.92)] but not in younger men. None of the baseline hormones predicted improvement or recovery from frailty.

Conclusions: In this prospective study, higher levels anabolic hormones predicted a lower risk for worsening frailty in ageing men. Baseline anabolic hormone levels did not predict improvement in either FP or FI. These data support the hypothesis that anabolic hormones have a causal role in the development of frailty. Further basic research and clinical trials are called for to clarify mechanisms of action and to assess the potential clinical risks and benefits of therapeutic intervention.


Disclosure: ITH: Consultant, Ferring Pharmaceuticals, Consultant, Novartis Pharmaceuticals. FCWW: Consultant, Bayer Schering Pharma, Consultant, Eli Lilly & Company, Consultant, Besins Healthcare, Advisory Group Member, Bayer Schering Pharma, Advisory Group Member, Eli Lilly & Company, Advisory Group Member, Besins Healthcare, Teacher, Bayer Schering Pharma, Teacher, Besins Healthcare, Clinical Researcher, Bayer Schering Pharma. MKR: Advisory Group Member, GlaxoSmithKline, Consultant, GlaxoSmithKline, Recipient Award, Novo Nordisk, Recipient Award, Merck & Co.. Nothing to Disclose: AS, ML, TA, TWO, GB, FFC, GF, AG, TSH, KK, MEJL, NP, MP, DMV