U-shaped association of plasma testosterone, and no association of plasma estradiol, with incidence of fractures in men

Yeap, Bu B., Alfonso, Helman, Chubb, S.A. Paul, Center, Jacqueline R., Beilin, Jonathan, Hankey, Graeme J., Almeida, Osvaldo P., Golledge, Jonathan, Norman, Paul E., and Flicker, Leon (2020) U-shaped association of plasma testosterone, and no association of plasma estradiol, with incidence of fractures in men. Journal of Clinical Endocrinology and Metabolism, 105 (5). pp. 1-12.

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Purpose: Whether androgens, distinct from estrogen, maintain bone health during male aging has implications for understanding osteoporosis. We assessed associations of different sex hormones with incidence of any bone fracture or hip fracture in older men.

Participants and methods: Analysis of 3307 community-dwelling men aged 76.8 +/- 3.5 years, median follow-up period of 10.6 years. Plasma testosterone (T), dihydrotestosterone (DHT), and estradiol (E2) assayed by mass spectrometry, sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) using immunoassay. Incident fractures determined via data linkage. We analyzed probability of fracture and performed Cox regression adjusted for age, medical comorbidities, and frailty.

Results: Incident fractures occurred in 330 men, including 144 hip fractures. Probability plots suggested nonlinear relationships between hormones and risk of any fracture and hip fracture, with higher risk at lower and higher plasma T, lower E2, higher SHBG, and higher LH. In fully adjusted models, there was a U-shaped association of plasma T with incidence of any fracture (Quartile 2 [Q2] versus Q1: fully adjusted hazard ratio [HR] = 0.69, 95% confidence interval [CI] 0.51-0.94, P = .020; Q3: HR 0.59, 95% CI 0.42-0.83, P = .002) and hip fracture (Q2 versus Q1: HR 0.60, 95% CI 0.37-0.93, P = .043; Q3: HR 0.52, 95% CI 0.31-0.88, P = .015). DHT, E2, and LH were not associated with fracture. Higher SHBG was associated with hip fracture (Q4 versus Q1: HR 1.76, 95% CI 1.05-2.96, P = .033).

Conclusions: Midrange plasma T was associated with lower incidence of any fracture and hip fracture, and higher SHBG with increased risk of hip fracture. Circulating androgen rather than estrogen represents a biomarker for hormone effects on bone driving fracture risk.

Item ID: 63014
Item Type: Article (Research - C1)
ISSN: 1945-7197
Keywords: testosterone, estradiol, sex hormone-binding globulin, fracture, osteoporosis, male aging
Copyright Information: © Endocrine Society 2020. All rights reserved.
Funders: National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NHMRC 279408, NHMRC 379600, NHMRC 403963, NHMRC 634492, NHMRC 1045710, NHMRC 1060557, NHMRC 1121548
Date Deposited: 06 May 2020 07:30
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320199 Cardiovascular medicine and haematology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 100%
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