Analysis of the contribution of dydrogesterone to bone turnover changes inpostmenopausal women commencing hormone replacement therapy

Although gestagens have been reported to influence bone metabolism, whether these contribute to the beneficial effects of hormone replacement therapy (HRT) on the skeleton of postmenopausal women is currently unclear. To addr ess this question, we compared changes in bone turnover markers after comme ncing HRT in 26 postmenopausal women randomized to receive 8 weeks of treat ment with 2 mg estradiol daily or 2 mg estradiol plus 10 mg dydrogesterone daily. Serum and second morning void urine samples were obtained at baselin e (twice) and after 1, 2, 4, and 8 weeks. Serum estradiol was measured by R IA, urinary total deoxypyridinoline (DPD) excretion by high pressure liquid chromatography, and serum osteocalcin and C-terminal procollagen peptide b y enzyme-linked immunosorbent assay. The increase in serum estradiol after treatment with estradiol alone was slightly, but significantly, greater tha n that in the combination group (P = 0.04). Although estradiol suppressed u rinary DPD excretion to a greater extent when given alone (P = 0.02), osteo calcin levels were significantly higher in this group than in women receivi ng combination therapy (P = 0.04). To assess the effect of dydrogesterone o n the balance between formation and resorption in more detail, we subsequen tly compared the ratio between formation and resorption markers in the two treatment groups. We found that osteocalcin/DPD and C-terminal procollagen peptide/DPD ratios were significantly higher in women treated with estradio l alone (P < 0.0001 and P = 0.002, respectively), suggesting that dydrogest erone may reduce formation relative to resorption. These results suggest th at gestagens may reduce estrogen's beneficial effects on the skeleton of po stmenopausal women, as assessed over the first 8 weeks of replacement thera py.