Lopez Laureen M, Grimes David A, Schulz Kenneth F, Curtis Kathryn M
Clinical Sciences, FHI, P.O. Box 13950, Research Triangle Park, North Carolina, USA, 27709.
Cochrane Database Syst Rev. 2011 Jul 6(7):CD006033. doi: 10.1002/14651858.CD006033.pub4.
Steroidal contraceptive use has been associated with changes in bone mineral density in women. Whether such changes increase the risk of fractures later in life is not clear. Osteoporosis is a major public health concern. Age-related decline in bone mass increases the risk of fracture, especially of the spine, hip, and wrist. Concern about bone health influences the recommendation and use of these effective contraceptives globally.
To evaluate the effect of using hormonal contraceptives before menopause on the risk of fracture in women
We searched for studies of fracture or bone health and hormonal contraceptives in MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS, as well as ClinicalTrials.gov and ICTRP. We wrote to investigators to find additional trials.
Randomized controlled trials (RCTs) were considered if they examined fractures, bone mineral density (BMD), or bone turnover in women with hormonal contraceptive use prior to menopause. Interventions could include comparing a hormonal contraceptive with a placebo or another hormonal contraceptive or could compare providing a supplement versus a placebo.
We assessed all titles and abstracts identified through the literature searches. Mean differences were computed using the inverse variance approach. For dichotomous outcomes, the Mantel-Haenszel odds ratio (OR) was calculated. Both included the 95% confidence interval (CI) and used a fixed-effect model. Due to different interventions, no trials could be combined for meta-analysis.
Of the 16 RCTs we found, 2 used a placebo and 1 used a non-hormonal method as the comparison, while 13 compared two hormonal contraceptives. No trial had fracture as an outcome. Most measured BMD and several assessed bone turnover. Depot medroxyprogesterone acetate (DMPA) was associated with decreased bone mineral density. The placebo-controlled trials showed BMD increases for DMPA plus estrogen supplement and decreases for DMPA plus placebo. Combination contraceptives did not appear to negatively affect bone health, but none were placebo-controlled. For implants, the single-rod etonogestrel group showed a greater BMD decrease versus the two-rod levonorgestrel group. However, results were not consistent across all implant comparisons.
AUTHORS' CONCLUSIONS: Whether steroidal contraceptives influence fracture risk cannot be determined from existing information. Many trials had small numbers of participants and some had large losses to follow up. Health care providers and women should consider the costs and benefits of these effective contraceptives. For example, injectable contraceptives and implants provide effective, long-term birth control yet do not involve a daily regimen. Progestin-only contraceptives are considered appropriate for women who should avoid estrogen due to medical conditions.
使用甾体类避孕药与女性骨矿物质密度变化有关。这种变化是否会增加晚年骨折风险尚不清楚。骨质疏松是一个主要的公共卫生问题。与年龄相关的骨量下降会增加骨折风险，尤其是脊柱、髋部和腕部骨折。对骨骼健康的担忧影响了全球对这些有效避孕药的推荐和使用。
评估绝经前使用激素避孕药对女性骨折风险的影响。
我们在MEDLINE、POPLINE、CENTRAL、EMBASE和LILACS以及ClinicalTrials.gov和ICTRP中检索了关于骨折或骨骼健康与激素避孕药的研究。我们写信给研究人员以寻找其他试验。
如果随机对照试验（RCT）研究了绝经前使用激素避孕药的女性的骨折、骨矿物质密度（BMD）或骨转换情况，则予以考虑。干预措施可包括将一种激素避孕药与安慰剂或另一种激素避孕药进行比较，或比较提供补充剂与安慰剂。
我们评估了通过文献检索确定的所有标题和摘要。使用逆方差法计算平均差异。对于二分结局，计算Mantel-Haenszel比值比（OR）。两者均包括95%置信区间（CI）并使用固定效应模型。由于干预措施不同，无法将试验合并进行荟萃分析。
在我们找到的16项RCT中，2项使用安慰剂，1项使用非激素方法作为对照，而13项比较了两种激素避孕药。没有试验将骨折作为结局。大多数测量了BMD，有几项评估了骨转换。醋酸甲羟孕酮长效注射剂（DMPA）与骨矿物质密度降低有关。安慰剂对照试验显示，DMPA加雌激素补充剂时BMD增加，DMPA加安慰剂时BMD降低。复方避孕药似乎不会对骨骼健康产生负面影响，但均未设安慰剂对照。对于植入剂，单棒依托孕烯组的BMD下降幅度大于双棒左炔诺孕酮组。然而，所有植入剂比较的结果并不一致。
现有信息无法确定甾体类避孕药是否会影响骨折风险。许多试验的参与者数量较少，一些试验的失访率较高。医疗保健提供者和女性应考虑这些有效避孕药的成本和益处。例如，注射用避孕药和植入剂可提供有效、长期的避孕效果，且无需每日服药。仅含孕激素的避孕药被认为适用于因医疗状况应避免使用雌激素的女性。
