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Cited by 45Hormonal and reproductive studiesFrailty in Older AdultsNutrition and Health in Aging

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

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Swiecicka, Agnieszka, Eendebak, Robert J A H, Lunt, Mark, O’Neill, Terence W, Bartfai, György, Casanueva, Felipe F, Forti, Gianni, Giwercman, Aleksander +10 more·2018·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2017-01172PMC PMC5800832
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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.

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  • Low calculated free T, but not total T, is associated with greater likelihood of frailty after adjustment for age, smoking, BMI, and comorbidities.

    “In both cases, after adjusting for age, smoking, BMI and other comorbidities, low levels of calculated free T and not total T concentrations were associated with a greater likelihood of frailty [231].”

    From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [231]

    The Results (Hormonal predictors of worsening frailty; page unavailable) report that only free T remained a significant predictor of worsening frailty index after adjustment for BMI, whereas total T did not. But free T was not significant for worsening frailty phenotype after age adjustment, so the finding does not hold for both frailty measures. The Methods (Statistical analysis; page unavailable) list the study’s adjustments as baseline frailty, age, center, smoking, and BMI—not comorbidities. (LLM, conf=0.88)

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Authors
Swiecicka, A., Eendebak, R. J. A. H., Lunt, M., O’Neill, T. W., Bartfai, G., Casanueva, F. F., Forti, G., Giwercman, A., Han, T. S., Slowikowska-Hilczer, J., Lean, M. E. J., Pendleton, N., Punab, M., Vanderschueren, D., Huhtaniemi, I. T., Wu, F. C. W., Rutter, M. K., & European Male Ageing Study Group
Affiliations
  • Andrology Research Unit, Division of Diabetes, Endocrinology, and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
  • Manchester Academic Health Science Centre (GB)
  • Department of Obstetrics, Gynaecology, and Andrology, Albert Szent-Györgyi Medical University, Szeged, Hungary
  • Complejo Hospitalario Universitario de Santiago (ES)
  • University of Florence (IT)
  • Lund University (SE)
  • Royal Holloway University of London (GB)
  • Department of Andrology and Reproductive Endocrinology, Medical University of Lodz, Lodz, Poland
  • University of Glasgow (GB)
  • University of Manchester (GB)
  • Tartu University Hospital (EE)
  • KU Leuven (BE)
  • University of Turku (FI)
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2017-11-24
Volume
103
Issue
2
Pages
701-709
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2017-01172
PMC
PMC5800832
OpenAlex
W2766529636
Cited by
45
References
5
Citations by year
2026: 2 · 2025: 10 · 2024: 2 · 2023: 5 · 2022: 6 · 2021: 4 · 2020: 3 · 2019: 10 · 2018: 2
FWCI
3.24
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion, other-oa)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
  • Lirias (submittedVersion, other-oa)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
National Institute for Health Research
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Keywords
frailty, male reproductive hormones, androgen deficiency, testosterone, free testosterone, dihydrotestosterone, luteinizing hormone, follicle-stimulating hormone, estradiol, frailty index, Fried frailty phenotype, community-dwelling older men, European Male Ageing Study
MeSH terms
Frailty, Adult, Aged, Aging, Europe, Humans, Male, Middle Aged, Prognosis, Cohort Studies, Geriatric Assessment, Frail Elderly, Gonadal Hormones, Independent Living

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