The effects of serum testosterone, estradiol, and sex hormone binding globulin levels on fracture risk in older men
Open accessAbstract
CONTEXT: The relationship between sex steroids and fracture is poorly understood. OBJECTIVE: The objective of the study was to examine associations between nonvertebral fracture risk and bioavailable estradiol (bioE2), bioavailable testosterone (bioT), and SHBG. DESIGN: This was a case-cohort study. SETTING: The Osteoporotic Fractures in Men Study (MrOS) was conducted in a prospective U.S. cohort in 5995 community-dwelling men 65 yr old or older. PARTICIPANTS: Participants included a subcohort of 1436 randomly chosen white men plus all 446 minorities and all those with incident hip and other nonvertebral fractures. MAIN OUTCOME MEASURES: Baseline testosterone and estradiol were measured by mass spectrometry (MS) and SHBG by RIA. RESULTS: Men with the lowest bioE2 (<11.4 pg/ml) or highest SHBG (>59.1 nm) had greater risk of all nonvertebral fractures [adjusted hazard ratio (HR) [95% confidence interval]: 1.5 (1.2-1.9) and 1.4 (1.1-21.8), respectively]. Men with the lowest bioT (<163.5 ng/dl) had no increased fracture risk after adjustment for bioE2 [adjusted HR 1.16 (0.90-1.49)]. A significant interaction between SHBG and bioT (P = 0.03) resulted in men with low bioT and high SHBG having higher fracture risk [HR 2.1 (1.4-3.2)]. Men with low bioE2, low bioT, and high SHBG were at highest risk [HR 3.4 (2.2-5.3)]. CONCLUSIONS: Older men with low bioE2 or high SHBG levels are at increased risk of nonvertebral fracture. When SHBG levels are high, men with low bioT levels have higher risk. The strongest association occurred when all measures were considered in combination.
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Low testosterone levels are associated with reduced bone mineral density and with increased fracture risk.
“Low testosterone levels are associated with reduced bone mineral density (44) and with increased fracture risk (45).”
From A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holistic Management (2017) · cites this paper as [45]
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- Authors
- LeBlanc, E. S., Nielson, C. M., Marshall, L. M., Lapidus, J. A., Barrett-Connor, E., Ensrud, K. E., Hoffman, A. R., Laughlin, G., Ohlsson, C., Orwoll, E. S., & for the Osteoporotic Fractures in Men Study Group
- Affiliations
- Oregon Health & Science University (US)
- University of California San Diego (US)
- University of Minnesota (US)
- Stanford University (US)
- Department of Internal Medicine (C.O.), Center for Bone Research at the Sahlgrenska Academy, SE-416 85 Göteborg, Sweden
- Corresponding author
- Orwoll, Eric S.
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2009-09-01
- Volume
- 94
- Issue
- 9
- Pages
- 3337-3346
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC2741717
- OpenAlex
- W2162115101
- Cited by
- 240
- References
- 54
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 9 · 2023: 8 · 2022: 12 · 2021: 11 · 2020: 19 · 2019: 11 · 2018: 13 · 2017: 16 · 2016: 12 · 2015: 12 · 2014: 18 · 2013: 24 · 2012: 17
- FWCI
- 14.81
- 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, AR049828, U01 AR-45583, U01-AR-45654, R01AR049828, U01AR045580, U01AR045632, U01AR045654, 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 › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- testosterone, estradiol, sex hormone-binding globulin, non-vertebral fractures, hip fracture, older men, osteoporosis, sex steroids, fracture risk, bioavailable testosterone, bioavailable estradiol
- MeSH terms
- Aged, Estradiol, Humans, Male, Prospective Studies, Risk, Sex Hormone-Binding Globulin, Testosterone, Cohort Studies, Bone Density, Fractures, Bone
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