Objective: To compare the serum sclerostin levels in premenopausal and postmenopausal women and evaluate its related influencing factors. Methods: Eligible premenopausal and postmenopausal women were enrolled. And their serum sclerotin levels, related blood biochemical indicators, sex hormone levels and bone turnover biomarkers were detected. Bone mineral density (BMD) of femoral neck, lumbar spine and hip were measured by dual energy X-ray. Results: The levels of estradiol (P<0.01), estrogen (P=0.01), free estrogen index (P=0.01) and bone mineral density at all sites in postmenopausal women were lower than those in premenopausal women; the sclerotin levels in postmenopausal women were higher than those in premenopausal women (P=0.02). Since most of the premenopausal women taken oral contraceptives, subsequent analyses were limited to postmenopausal women. The serum sclerosing hormone levels in postmenopausal women were negatively correlated with the levels of free estrogen index (r=0.57, P=0.01), parathyroid hormone (r=0.48, P=0.03), and femoral neck bone mineral density (r=0.49, P=0.01). Multiple regression analysis showed that the levels of free estrogen index (β=−0.63, P=0.01), and parathyroid hormone (β=−0.56, P=0.01) were found to be the independent risk factors of sclerostin levels in postmenopausal women. Conclusion: The level of serum sclerotin in postmenopausal women is higher than that in premenopausal women. Serum sclerosing hormone levels may be regulated by estrogen and parathyroid hormones.