Estrogen is the key regulator of bone metabolism in both men and women. Menopause and the accompanying loss of ovarian estrogens are associated with declines in bone mineral density (BMD): 10-year cumulative loss was 9.1% at the femoral neck and 10.6%, lumbar spine. Estradiol concentrations also predict fractures. Total estradiol levels, <5 pg/ml were associated with a 2.5-fold increase in hip and vertebral fractures in older women, an association that was independent of age and body weight. Similar associations were found in men. Despite the lower BMD and higher fracture risk in hypogonadal men, there is little association between circulating testosterone, fracture and bone loss. Nevertheless, the combination of any low sex steroid hormone and 25-hydroxyvitamin D was associated with an increased fracture risk. Menopausal hormone therapy has been shown to reduce hip and all fractures in the Women's Health Initiative with little difference between the estrogen-alone and the estrogen plus progestin trials. The risk reductions were attenuated in both trials post intervention; however, a significant hip fracture benefit persisted over 13 years for women assigned to the combination therapy. Clinical trials of testosterone replacement in older men give tantalizing but inconclusive results. The results suggest that testosterone treatment probably improves BMD, but the results are less conclusive in older versus younger men. The Testosterone Trial is designed to test the hypothesis that testosterone treatment of men with unequivocally low serum testosterone (<275 ng/dL) will increase volumetric BMD (vBMD) of the spine. Results of the Testosterone Trials are expected in 2015.