Endrikat J, Mih E, Düsterberg B, Land K, Gerlinger C, Schmidt W, Felsenberg D
Schering AG, Müllerstrasse 178, D-13342 Berlin, Germany.
Contraception. 2004 Mar;69(3):179-87. doi: 10.1016/j.contraception.2003.10.002.
In this first prospective, double-blind, randomized, parallel-group study we evaluated the influence of two combined oral contraceptives on bone mineral density (BMD) and metabolic bone parameters. One dose-reduced preparation contained 20 microg ethinylestradiol (EE) in combination with 100 microg levonorgestrel (LNG) (20/100) was compared with the reference preparation which contained 30 microg EE in combination with 150 microg LNG (30/150). Data from 48 volunteers aged 20-35 years were obtained over an observation period of 36 treatment cycles. The direction of the change (increase or decrease) in all investigated bone-related variables was similar in both treatment groups. As compared to baseline, bone mineral density decreased by 0.4% in the 20/100 group and by 0.8% in the 30/150 group after 36 treatment cycles. These changes were not significantly different between the two treatment groups (p = 0.902). For bone-specific alkaline phosphatase, we measured a mean increase of 55.4% (20/100 group) and of 113.2% (30/150 group) after 36 treatment cycles. The two treatments did not differ statistically significantly (p = 0.522). With respect to cross-linked N-telopeptides (NTx), we detected a decrease of the mean NTx urine concentrations of 21.1% (20/100) and of 13.4% (30/150). These changes also did not significantly differ between the two treatments (p = 0.613). Both study treatments were safe and well-tolerated by all volunteers participating in the study. In conclusion, BMD did not change during the 3-year observation period. Thus, both trial preparations containing either 20 or 30 microg EE in combination with LNG were capable of maintaining BMD in young fertile women. There is no reason to assume that the EE dose reduction had any negative impact on BMD. Because there were no differences in BMD between the treatment groups, it can be assumed that even lower dosages than 20 microg EE might be sufficient for bone protection. Biochemical markers provided evidence for a reduced bone resorption.
在这项首个前瞻性、双盲、随机、平行组研究中，我们评估了两种复方口服避孕药对骨矿物质密度（BMD）和代谢性骨参数的影响。一种低剂量制剂含有20微克炔雌醇（EE）与100微克左炔诺孕酮（LNG）（20/100），将其与含有30微克EE与150微克LNG的参比制剂（30/150）进行比较。在36个治疗周期的观察期内获取了48名年龄在20至35岁志愿者的数据。两个治疗组中所有研究的骨相关变量的变化方向（增加或减少）相似。与基线相比，在36个治疗周期后，20/100组的骨矿物质密度下降了0.4%，30/150组下降了0.8%。这两个治疗组之间的这些变化无显著差异（p = 0.902）。对于骨特异性碱性磷酸酶，在36个治疗周期后，我们测得20/100组平均升高55.4%，30/150组平均升高113.2%。两种治疗在统计学上无显著差异（p = 0.522）。关于交联N-端肽（NTx），我们检测到20/100组平均NTx尿浓度下降了21.1%，30/150组下降了13.4%。这两种治疗之间的这些变化也无显著差异（p = 0.613）。参与研究的所有志愿者对两种研究治疗均耐受良好且安全。总之，在3年观察期内BMD未发生变化。因此，两种分别含有20或30微克EE与LNG的试验制剂均能够在年轻有生育能力的女性中维持BMD。没有理由认为EE剂量降低会对BMD有任何负面影响。由于治疗组之间BMD无差异，可以假定甚至低于20微克EE的剂量可能也足以保护骨骼。生化标志物提供了骨吸收减少的证据。
