Tobias J H, Clarke S, Mitchell K, Robins S, Amer H, Fraser W D
Rheumatology Unit, University of Bristol Division of Medicine, Rowett Research Institute, Aberdeen, United Kingdom AB21 9SB.
J Clin Endocrinol Metab. 2001 Mar;86(3):1194-8. doi: 10.1210/jcem.86.3.7321.
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 address this question, we compared changes in bone turnover markers after commencing HRT in 26 postmenopausal women randomized to receive 8 weeks of treatment with 2 mg estradiol daily or 2 mg estradiol plus 10 mg dydrogesterone daily. Serum and second morning void urine samples were obtained at baseline (twice) and after 1, 2, 4, and 8 weeks. Serum estradiol was measured by RIA, urinary total deoxypyridinoline (DPD) excretion by high pressure liquid chromatography, and serum osteocalcin and C-terminal procollagen peptide by enzyme-linked immunosorbent assay. The increase in serum estradiol after treatment with estradiol alone was slightly, but significantly, greater than that in the combination group (P = 0.04). Although estradiol suppressed urinary DPD excretion to a greater extent when given alone (P = 0.02), osteocalcin levels were significantly higher in this group than in women receiving combination therapy (P = 0.04). To assess the effect of dydrogesterone on the balance between formation and resorption in more detail, we subsequently 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 estradiol alone (P < 0.0001 and P = 0.002, respectively), suggesting that dydrogesterone may reduce formation relative to resorption. These results suggest that gestagens may reduce estrogen's beneficial effects on the skeleton of postmenopausal women, as assessed over the first 8 weeks of replacement therapy.
尽管有报道称孕激素会影响骨代谢，但目前尚不清楚这些是否有助于激素替代疗法（HRT）对绝经后女性骨骼产生有益影响。为了解决这个问题，我们比较了26名绝经后女性开始接受HRT后的骨转换标志物变化，这些女性被随机分为两组，一组每天接受2mg雌二醇治疗8周，另一组每天接受2mg雌二醇加10mg地屈孕酮治疗8周。在基线（两次）以及1、2、4和8周后采集血清和次日晨尿样本。血清雌二醇通过放射免疫分析法测定，尿总脱氧吡啶啉（DPD）排泄量通过高压液相色谱法测定，血清骨钙素和I型前胶原C端肽通过酶联免疫吸附测定法测定。单独使用雌二醇治疗后血清雌二醇的升高幅度略高于联合治疗组，但差异有统计学意义（P = 0.04）。尽管单独使用雌二醇时对尿DPD排泄的抑制作用更大（P = 0.02），但该组的骨钙素水平显著高于接受联合治疗的女性（P = 0.04）。为了更详细地评估地屈孕酮对骨形成和骨吸收平衡的影响，我们随后比较了两个治疗组中骨形成和骨吸收标志物的比值。我们发现，单独使用雌二醇治疗的女性中骨钙素/DPD和I型前胶原C端肽/DPD比值显著更高（分别为P < 0.0001和P = 0.002），这表明相对于骨吸收，地屈孕酮可能会降低骨形成。这些结果表明，在替代治疗的前8周评估中，孕激素可能会降低雌激素对绝经后女性骨骼的有益影响。
