The effects of serum testosterone, estradiol, and sex hormone binding globulin levels on fracture risk in older men - PubMed (original) (raw)

The effects of serum testosterone, estradiol, and sex hormone binding globulin levels on fracture risk in older men

Erin S LeBlanc et al. J Clin Endocrinol Metab. 2009 Sep.

Abstract

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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Figures

Figure 1

Figure 1

Case-cohort design for the MrOS sex steroids and fracture study. *, Subcohort consisted of 1436 randomly selected non-Hispanic white men and all 446 minority men. Weighting was used in analyses to account for stratified sampling by race.

Figure 2

Figure 2

HRs and 95% CIs for risk of nonvertebral fractures by quartiles of sex steroids (adjusted for age, race, BMI). A, Bioavailable estradiol. B, Bioavailable testosterone. C, SHBG. To convert bioavailable estradiol to picomoles per liter, the conversion factor is 3.671; to convert bioavailable testosterone to nanomoles per liter, the conversion factor is 0.0347.

Figure 3

Figure 3

Spline models for the detection of any nonlinear relationships between sex steroids or SHBG and nonvertebral fracture risk. A, bioE2. B, bioT. C, SHBG. To convert bioavailable estradiol to picomoles per liter, the conversion factor is 3.671; to convert bioavailable testosterone to nanomoles per liter, the conversion factor is 0.0347.

Figure 4

Figure 4

Combinations of sex steroids and SHBG and risk of nonvertebral fracture. A, bioT and SHBG. B, bioT, bioE2, and SHBG. There were 1079 men in the high bioT, low SHBG category; 397 men in the high bioT, high SHBG category; 392 men in the low bioT, low SHBG category; and 110 men in the low bioT, high SHBG category. □, Low SHBG; •, high SHBG.

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