Mellströ D et al. (2008) Older men with low serum estradiol and high serum SHBG have an increased risk of fractures. J Bone Miner Res 23: 1552–1560

Previous studies on the influence of androgen and estrogen levels on fracture risk in elderly men have produced conflicting results. A new prospective study that used gas chromatography–mass spectrometry to measure sex hormone levels in men aged 69–80 years has shown that low estradiol and high sex-hormone-binding globulin (SHBG) levels are independent predictors of fracture risk.

The study cohort comprised 3,014 men from three Swedish cities, who were followed for an average of 3.32 years after enrolment. Serum testosterone, dihydrotestosterone and estradiol were measured by gas chromatography–mass spectrometry, and SHBG was measured by immunoradiometric assay. Free testosterone and free estradiol levels were calculated from these values. Age and fracture risk were positively associated with SHBG levels, and inversely associated with levels of all sex steroids. Estradiol and testosterone levels were correlated, and the association with fracture risk was stronger for free than for total hormone levels. Age-adjusted regression models suggested that levels of free estradiol (but not free testosterone) were independently associated with fracture risk (hazard ratio 1.36 per 1 SD decrease). SHBG levels also independently predicted fracture risk (hazard ratio 1.32 per 1 SD increase). Both associations remained significant after adjustment for height, weight, femoral neck BMD and grip strength. The relationship between estradiol and fracture risk was nonlinear: threshold estradiol levels below which fracture risk increased were 16 pg/ml for total estradiol and 0.27 pg/ml for free estradiol.