Warming L, Ravn P, Christiansen C
Center for Clinical and Basic Research A/S, Ballerup Byvej 222, DK-2750 Ballerup, Denmark.
Maturitas. 2005 Feb 14;50(2):78-85. doi: 10.1016/j.maturitas.2004.03.016.
To evaluate the efficacy and safety of a new transdermal continuous combined hormone replacement therapy (HRT) for the prevention of postmenopausal osteoporosis.
212 osteopenic (lumbar spine and/or hip (femoral neck) bone mineral density (BMD) between -1.0 and -2.5 S.D. of the premenopausal mean value) postmenopausal women aged 45-65 years participated in a 2-year prospective study. Treatments were 45 microg 17beta-estradiol combined with 30 (n = 69) or 40 microg (n = 72) levonorgestrel daily or placebo (n = 71) given as a 7-day patch. All received a daily supplement of 500 mg calcium. BMD at lumbar spine (L2-L4), hip and total body, as well as blood and urinary biochemical markers of bone turnover (serum osteocalcin (sOC), serum bone-specific alkaline phosphatase (sBSAP), urinary calcium (uCa) and urinary CrossLaps (uCTX)) were measured regularly.
BMD at the lumbar spine, hip and total body increased by 8, 6 and 3% (P < 0.001), respectively, in the hormone groups versus placebo. The bone markers all decreased accordingly (sOC: 37%, sBSAP: 34% and uCTX: 65% from baseline (all P < 0.001)), except for uCa that did not change significantly. No significant dose-related effect of levonorgestrel was found. Vaginal bleeding/spotting decreased from 48 to 25% of the HRT-treated women during the study period. Skin tolerance was good in 84% of the women with no difference between the study groups. No incidences of endometrial hyperplasia, uterine or mammary cancer occurred.
The transdermal combination of 17beta-estradiol and levonorgestrel has a positive effect on BMD in an osteopenic postmenopausal population. Furthermore, a high safety profile was observed.
评估一种新型经皮连续联合激素替代疗法（HRT）预防绝经后骨质疏松症的疗效和安全性。
212名年龄在45 - 65岁之间的绝经后骨质减少（腰椎和/或髋部（股骨颈）骨密度（BMD）在绝经前平均值的 -1.0至 -2.5标准差之间）女性参与了一项为期2年的前瞻性研究。治疗方法为每日给予45微克17β - 雌二醇联合30微克（n = 69）或40微克（n = 72）左炔诺孕酮，或安慰剂（n = 71），以7天贴片形式给药。所有受试者每日补充500毫克钙。定期测量腰椎（L2 - L4）、髋部和全身的骨密度，以及骨转换的血液和尿液生化标志物（血清骨钙素（sOC）、血清骨特异性碱性磷酸酶（sBSAP）、尿钙（uCa）和尿交联C末端肽（uCTX））。
与安慰剂组相比，激素组的腰椎、髋部和全身骨密度分别增加了8%、6%和3%（P < 0.001）。除尿钙无显著变化外，所有骨标志物均相应下降（sOC：较基线下降37%，sBSAP：下降34%，uCTX：下降65%（均P < 0.001））。未发现左炔诺孕酮有显著的剂量相关效应。在研究期间，接受HRT治疗的女性阴道出血/点滴出血发生率从48%降至25%。84%的女性皮肤耐受性良好，各研究组之间无差异。未发生子宫内膜增生、子宫或乳腺癌事件。
17β - 雌二醇和左炔诺孕酮经皮联合应用对绝经后骨质减少人群的骨密度有积极影响。此外，观察到其安全性良好。
