Sex Hormones and Frailty in Older Men: The Osteoporotic Fractures in Men (MrOS) Study
Open accessAbstract
CONTEXT: As men age, the prevalence of frailty increases whereas levels of androgens decline. Little is known about the relation between these factors. OBJECTIVE: The aim of this study was to assess cross-sectional and longitudinal associations of estradiol, bioavailable estradiol, testosterone, bioavailable testosterone (bioT), and SHBG with frailty status. DESIGN AND SETTING: The Osteoporotic Fractures in Men (MrOS) study was conducted at six U.S. clinical centers. PARTICIPANTS: A total of 1469 community-dwelling men at least 65 yr old with baseline data participated; 1245 men had frailty status reassessed 4.1 yr later. MAIN OUTCOME MEASURE: Proportional odds models estimated the likelihood of greater frailty status. Frail men had at least three of the following: weakness, slowness, low activity, exhaustion, and shrinking/sarcopenia; intermediate men had one or two criteria; and robust men had none. At follow-up, death was included as an additional ordinal outcome. Sex hormones were assayed by spectrometry/chromatographic methods. RESULTS: In cross-sectional analyses, men in the lowest quartile of bioT had 1.39-fold (95% confidence interval, 1.02, 1.91) increased odds of greater frailty status compared to men in the highest quartile after adjustment for covariates including age, body size, health status, and medical conditions. In age-adjusted longitudinal analyses, men in the lowest quartile of bioT had 1.51-fold (95% confidence interval, 1.10, 2.07) increased odds of greater frailty status 4.1 yr later. This association was largely attenuated by adjustment for covariates. No other hormones were associated in a cross-sectional or longitudinal manner with frailty status after adjustment. CONCLUSIONS: Low levels of bioT were independently associated with worse baseline frailty status. Frailty status should be considered as an outcome in trials of testosterone supplementation.
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Multiple studies report a correlation between SHBG levels and fractures in elderly men.
“Multiple studies report a correlation between SHBG levels and fractures in elderly men as well [153–155].”
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 [153]
Low bioavailable T is independently associated with increased frailty risk (1.39-fold for lowest vs highest quartile).
“After multivariate adjustment, men in the lowest quartile of bioavailable T were subject to a 1.39-fold increased risk of greater frailty compared to men in the highest quartile [153].”
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 [153]
Testosterone levels have been linked to frailty, but this may reflect a sensitive marker rather than a causal mechanism.
“Although an association between testosterone levels and frailty has been identified (44) this may be a sensitive marker rather than a pathological mechanism (45).”
From Frailty in elderly people (2013) · cites this paper as [44]
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- Authors
- Cawthon, P. M., Ensrud, K. E., Laughlin, G. A., Cauley, J. A., Dam, T.-T. L., Barrett-Connor, E., Fink, H. A., Hoffman, A. R., Lau, E., Lane, N. E., Stefanick, M. L., Cummings, S. R., Orwoll, E. S., & for the Osteoporotic Fractures in Men (MrOS) Research Group
- Affiliations
- California Pacific Medical Center (US)
- University of Minnesota (US)
- University of California San Diego (US)
- University of Pittsburgh (US)
- Columbia University (US)
- VA Palo Alto Health Care System (US)
- Center for Health and Medical Research (E.L.), Hong Kong, China
- University of California Davis Medical Center (US)
- Stanford Medicine (US)
- Oregon Health & Science University (US)
- Corresponding author
- Cawthon, Peggy M.
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2009-10-01
- Volume
- 94
- Issue
- 10
- Pages
- 3806-3815
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC2758722
- OpenAlex
- W2096777479
- Cited by
- 157
- References
- 5
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 6 · 2023: 3 · 2022: 6 · 2021: 6 · 2020: 10 · 2019: 7 · 2018: 8 · 2017: 12 · 2016: 11 · 2015: 9 · 2014: 8 · 2013: 12 · 2012: 12
- FWCI
- 11.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (U01-AG-18197, U01AG018197, U01AG027810, U01AG042140)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (U01AR45614, U01-AR45632, U01 AR45647, U01AR045583, U01 AR-45583, U01-AR-45654, U01AR045580, U01AR045632, U01AR045654, K24AR048841, U01AR045614, U01AR045647, U01AR066160, U01AR45580)
- National Center for Research Resources (UL1RR024140)
- 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, sex hormones, testosterone, bioavailable testosterone, estradiol, sex hormone-binding globulin, older men, androgen decline, sarcopenia, mortality, testosterone supplementation, MrOS study
- MeSH terms
- Aged, Aged, 80 and over, Biological Availability, Cross-Sectional Studies, Estradiol, Follow-Up Studies, Fractures, Spontaneous, Humans, Male, Osteoporosis, Residence Characteristics, Sex Hormone-Binding Globulin, Testosterone, Absorptiometry, Photon, Prevalence, Odds Ratio, Frail Elderly, Fractures, Bone
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