经皮用雌二醇凝胶预防绝经早期骨丢失的三年探索性观察

目的 探索经皮用雌二醇（E2）凝胶在中国妇女中预防绝经早期骨丢失的用法。方法 将60例身体健康、绝经1－5年的妇女，开放随机分为4组，每组15例，采用周期联合方法分别予含0．75或1．5mgE2的经皮17β-E2凝胶（E2凝胶）与100mg微粉化天然黄体酮（MP）或2mg醋甲羟孕酮（MPA）口服，每日睡前应用，每月连用25d，停药5d。用单光子吸收法测前臂皮质骨骨密度；定量CT法测腰椎松质骨骨密度；双能X线吸收法测腰椎与髋部骨密度。在治疗0、6、12、18、24与36个月时分别测量骨密度、骨代谢生化指标，行绝经症状评分。结果 59例（98％）完成1年；56例（93％）完成2年，51例（85％）完成3年。治疗6个月时，4个组症状缓解率平均约80％；2年时腰椎松质骨骨密度升高平均为4．3％－7．5％；3年时第2－4腰椎骨密度升高4．2％－6．2％；股骨颈骨密度升高1．6％－3．8％。与治疗前相比，差异均有显著性（P＜0．05）；4组间比较，骨密度的改善差异无显著性（P＞0．05）。阴道出血率1．5mgE2凝胶＋2mgMPA治疗者、0．75mgE2凝胶＋2mgMPA治疗者较高，其他两组较低。结论 每日0．75mg与1．5mgE2凝胶可有效缓解绝经相关症状，预防绝经早期骨丢失。雌孕激素补充治疗3年，可连续增加腰椎骨密度，增加并维持股骨上端骨密度。

Observation of preventing of bone loss during early postmenopause by percutaneous estradiol in Chinese postmenopausal women

OBJECTIVE: To investigate the optimal regimen for application of percutaneous estradiol gel in preventing bone loss in Chinese postmenopausal women. METHODS: A 3-year open randomized clinical study was designed. The percutaneous estradiol gel was used in a cyclic regimen combined with micronized progesterone (MP) or medroxyprogesterone acetate (MPA). Sixty healthy women (naturally menopause for 1 to 5 years) were recruited and divided into four groups according to estrogen dosage and two kinds of progestin. All were given for 25 d/month. The cortical bone mineral density (BMD) of right radius was measured by single photon absorptiometry. The trabecular BMD in lumbar vertebrae was measured by quantitative CT. The spine and hip BMD were also measured by dual energy X-ray absorptiometry at baseline, 6, 12, 18, 24 and 36 months, respectively. The bone metabolic markers, scores of menopausal symptoms were also evaluated. RESULTS: Fifty-nine patients (98%) completed 1 year and 56 patients (93%) 2 years, 51 (85%) 3 years of study. The symptoms were alleviated by 80% after 6 months treatment on average. By the end of 24 month, the mean increases of BMD ranged from 4.3% to 7.5% in trabecular bone, and by the end of 36 month 4.2% to 6.2% in the lumbar (L) 2-4, 1.6% to 3.8% in the femur neck, with significant differences (P < 0.05). Comparing the 4 groups with each other, no significant differences (P > 0.05) were found in improvement of symptoms, bone markers and BMD. CONCLUSIONS: Both daily estrogen containing 0.75 mg and 1.5 mg E2 are effective to prevent the early postmenopausal bone loss and improve the menopausal symptoms. During 3 years treatment, the BMD of lumbar increased continuously and the BMD of hip increased in the first 2 years and then plateau.