Reproductive Hormone Levels Predict Changes in Frailty Status in Community-Dwelling Older Men: European Male Ageing Study Prospective Data

Agnieszka Swiecicka, Robert J A H Eendebak, Mark Lunt, Terence W O'Neill, György Bartfai, Felipe F Casanueva, Gianni Forti, Aleksander Giwercman, Thang S Han, Jolanta Slowikowska-Hilczer, Michael E J Lean, Neil Pendleton, Margus Punab, Dirk Vanderschueren, Ilpo T Huhtaniemi, Frederick C W Wu, Martin K Rutter, European Male Ageing Study Group, Agnieszka Swiecicka, Robert J A H Eendebak, Mark Lunt, Terence W O'Neill, György Bartfai, Felipe F Casanueva, Gianni Forti, Aleksander Giwercman, Thang S Han, Jolanta Slowikowska-Hilczer, Michael E J Lean, Neil Pendleton, Margus Punab, Dirk Vanderschueren, Ilpo T Huhtaniemi, Frederick C W Wu, Martin K Rutter, European Male Ageing Study Group

Abstract

Context: Clinical sequelae of androgen deficiency share common features with frailty. Evidence supporting the role of androgens in the development of frailty is limited and conflicting.

Objective: To determine associations between male reproductive hormones and prospective changes in frailty status.

Design/setting: A 4.3-year prospective cohort study of community-dwelling men participating in the European Male Ageing Study.

Participants: A total of 3369 men aged 40 to 79 from eight European centers.

Intervention: None.

Main outcome measure: Frailty status was determined using frailty index (FI; n = 2278) and frailty phenotype (FP; n = 1980).

Results: After adjusting for baseline frailty, age, center, and smoking, the risk of worsening FI decreased with higher testosterone (T), free T, and dihydrotestosterone (DHT) [percentage change (95% confidence interval) in FI associated with 1 standard deviation higher hormone level: -3.0 (-5.9, -1.0) for total T; -3.9 (-6.8, -2.0) for free T; and -3.9 (-6.8, -2.0) for DHT]. After further adjustment for body mass index, only free T remained a significant predictor of FI change. In fully adjusted models, higher luteinizing hormone and follicle-stimulating hormone were positively related to worsening FI only in men <60 years, and higher estradiol predicted lower likelihood of improving FP [odds ratio: 0.68 (0.52, 0.88)].

Conclusions: These prospective data support the hypothesis that higher androgen levels may protect elderly men from worsening frailty. However, the causal nature of these relationships requires further investigation. Whereas raised gonadotropins in men <60 years might be an early marker of frailty, the role of estradiol in frailty needs further clarification.

Copyright © 2017 Endocrine Society

References

    1. Zaslavsky O, Cochrane BB, Thompson HJ, Woods NF, Herting JR, LaCroix A. Frailty: a review of the first decade of research. Biol Res Nurs. 2013;15(4):422–432.
    1. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA; Cardiovascular Health Study Collaborative Research Group . Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–M156.
    1. Reiner AP, Aragaki AK, Gray SL, Wactawski-Wende J, Cauley JA, Cochrane BB, Kooperberg CL, Woods NF, LaCroix AZ. Inflammation and thrombosis biomarkers and incident frailty in postmenopausal women. Am J Med. 2009;122(10):947–954.
    1. Barzilay JI, Blaum C, Moore T, Xue QL, Hirsch CH, Walston JD, Fried LP. Insulin resistance and inflammation as precursors of frailty: the Cardiovascular Health Study. Arch Intern Med. 2014;167(7)635–641.
    1. O’Donnell AB, Travison TG, Harris SS, Tenover JL, McKinlay JB. Testosterone, dehydroepiandrosterone, and physical performance in older men: results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2006;91(2):425–431.
    1. Krasnoff JB, Basaria S, Pencina MJ, Jasuja GK, Vasan RS, Ulloor J, Zhang A, Coviello A, Kelly-Hayes M, D’Agostino RB, Wolf PA, Bhasin S, Murabito JM. Free testosterone levels are associated with mobility limitation and physical performance in community-dwelling men: the Framingham Offspring Study. J Clin Endocrinol Metab. 2010;95(6):2790–2799.
    1. Hyde Z, Flicker L, Almeida OP, Hankey GJ, McCaul KA, Chubb SA, Yeap BB. Low free testosterone predicts frailty in older men: the health in men study. J Clin Endocrinol Metab. 2010;95(7):3165–3172.
    1. Cawthon PM, Ensrud KE, Laughlin GA, Cauley JA, Dam TT, Barrett-Connor E, Fink HA, Hoffman AR, Lau E, Lane NE, Stefanick ML, Cummings SR, Orwoll ES; Osteoporotic Fractures in Men (MrOS) Research Group . Sex hormones and frailty in older men: the osteoporotic fractures in men (MrOS) study. J Clin Endocrinol Metab. 2009;94(10):3806–3815.
    1. Lee DM, O’Neill TW, Pye SR, Silman AJ, Finn JD, Pendleton N, Tajar A, Bartfai G, Casanueva F, Forti G, Giwercman A, Huhtaniemi IT, Kula K, Punab M, Boonen S, Vanderschueren D, Wu FC; EMAS study group . The European Male Ageing Study (EMAS): design, methods and recruitment. Int J Androl. 2009;32(1):11–24.
    1. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30(6):473–483.
    1. Washburn RA, Smith KW, Jette AM, Janney CA. The Physical Activity Scale for the Elderly (PASE): development and evaluation. J Clin Epidemiol. 1993;46(2):153–162.
    1. National Child Traumatic Stress Network—Child Trauma Home. Beck Depression Inventory Second Edition (BDI-II). Available at: . Accessed 11 October 2015.
    1. Bosch JL, Hop WC, Kirkels WJ, Schröder FH. The International Prostate Symptom Score in a community-based sample of men between 55 and 74 years of age: prevalence and correlation of symptoms with age, prostate volume, flow rate and residual urine volume. Br J Urol. 1995;75(5):622–630.
    1. Reuben DB, Siu AL. An objective measure of physical function of elderly outpatients. The Physical Performance Test. J Am Geriatr Soc. 1990;38(10):1105–1112.
    1. Tinetti ME, Williams TF, Mayewski R. Fall risk index for elderly patients based on number of chronic disabilities. Am J Med. 1986;80(3):429–434.
    1. Osterrieth PA, Osterrieth PA. Le test de copie d’une figure complexe: contribution a l’étude de la perception et de la memoire. Arch Psychol. 1944;1944(30):286–356.
    1. Warrington E. The Camden Memory Tests: Topographical Recognition Memory Test. East Sussex, UK: Psychology Press; 1996.
    1. Uiterwijk JM. WAIS-III-NL/V. Lisse, Netherlands: Swets & Zeitlinger; 2001.
    1. Searle SD, Mitnitski A, Gahbauer EA, Gill TM, Rockwood K. A standard procedure for creating a frailty index. BMC Geriatr. 2008;8(1):24.
    1. O’Connell MDLO, Tajar A, O’Neill TW, Roberts SA, Lee DM, Pye SR, Silman AJ, Finn JD, Bartfai G, Boonen S, Casanueva FF, Forti G, Giwercman A, Han TS, Huhtaniemi IT, Kula K, Lean ME, Pendleton N, Punab M, Vanderschueren D, Wu FC. Frailty is associated with impaired quality of life and falls in middle-aged and older European men. J Frailty Aging. 2013;2(2):77–83.
    1. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84(10):3666–3672.
    1. Swiecicka A, Lunt M, Ahern T, O’Neill TW, Bartfai G, Casanueva FF, Forti G, Giwercman A, Han TS, Lean MEJ, Pendleton N, Punab M, Slowikowska-Hilczer J, Vanderschueren D, Huhtaniemi IT, Wu FCW, Rutter MK; EMAS Study Group . Nonandrogenic anabolic hormones predict risk of frailty: European male ageing study prospective data. J Clin Endocrinol Metab. 2017;102(8):2798–2806.
    1. Travison TG, Nguyen A-H, Naganathan V, Stanaway FF, Blyth FM, Cumming RG, Le Couteur DG, Sambrook PN, Handelsman DJ. Changes in reproductive hormone concentrations predict the prevalence and progression of the frailty syndrome in older men: the concord health and ageing in men project. J Clin Endocrinol Metab. 2011;96(8):2464–2474.
    1. Sinha-Hikim I, Artaza J, Woodhouse L, Gonzalez-Cadavid N, Singh AB, Lee MI, Storer TW, Casaburi R, Shen R, Bhasin S. Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy. Am J Physiol Endocrinol Metab. 2002;283(1):E154–E164.
    1. Auyeung TW, Lee JSW, Kwok T, Leung J, Ohlsson C, Vandenput L, Leung PC, Woo J. Testosterone but not estradiol level is positively related to muscle strength and physical performance independent of muscle mass: a cross-sectional study in 1489 older men. Eur J Endocrinol. 2011;164(5):811–817.
    1. Baumgartner RN, Waters DL, Gallagher D, Morley JE, Garry PJ. Predictors of skeletal muscle mass in elderly men and women. Mech Ageing Dev. 1999;107(2):123–136.
    1. Barzilay JI, Blaum C, Moore T, Xue QL, Hirsch CH, Walston JD, Fried LP. Insulin resistance and inflammation as precursors of frailty: the Cardiovascular Health Study. Arch Intern Med. 2007;167(7):635–641.
    1. Finkelstein JS, Lee H, Burnett-Bowie S-AM, Pallais JC, Yu EW, Borges LF, Jones BF, Barry CV, Wulczyn KE, Thomas BJ, Leder BZ. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013;369(11):1011–1022.
    1. Schaap LA, Pluijm SMF, Smit JH, van Schoor NM, Visser M, Gooren LJ, Lips P. The association of sex hormone levels with poor mobility, low muscle strength and incidence of falls among older men and women. Clin Endocrinol (Oxf). 2005;63(2):152–160.
    1. Gielen E, O’Neill TW, Pye SR, Adams JE, Wu FC, Laurent MR, Claessens F, Ward KA, Boonen S, Bouillon R, Vanderschueren D, Verschueren S. Endocrine determinants of incident sarcopenia in middle-aged and elderly European men. J Cachexia Sarcopenia Muscle. 2015;6(3):242–252.
    1. Arnal JF, Scarabin PY, Trémollières F, Laurell H, Gourdy P. Estrogens in vascular biology and disease: where do we stand today? Curr Opin Lipidol. 2007;18(5):554–560.

Source: PubMed

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