Background Female athletes might develop reduced bone mineral density (BMD) and amenorrhoea due to low energy intake. Objective To systematically review the literature of randomised controlled trials (RCTs) assessing the effect of oestrogen oral contraceptives (OCP), conjugated oestrogens (CE) and transdermal estradiol (TE) on BMD in premenopausal women with functional hypothalamic amenorrhoea (FHA) due to weight loss, vigorous exercise and/or stress. Methods A comprehensive literature search in PubMed, MEDLINE, Cochrane Library, Ovid and CINAHL from inception to 1 October 2020. Data extraction and synthesis Two authors independently extracted data. When possible, the data were pooled in a random-effects meta-analysis. Main outcomes Difference in BMD (g/cm2) at the lumbar spine. Results Nine RCTs comprising 770 participants met the inclusion criteria; five studies applied OCP, two CE and two TE. Four RCTs (two OCP, two TE) found an increased BMD in premenopausal women with FHA, and five (three OCP, two CE) found a decreased BMD compared with controls. A meta-analysis showed no difference in BMD between the treatment and control groups, (standardised mean difference (SMD) 0.30, 95% CI −0.12 to 0.73). A secondary analysis for change scores from baseline to first assessment point, showed a similar overall result (SMD 0.17, 95% CI −0.16 to 0.51). No serious adverse events were reported. Conclusion The literature suggests that TE might increase lumbar BMD in premenopausal women with FHA, but pooled results revealed no effect of the intervention. The findings do not support oestrogen therapy to improve BMD in these patient groups.

中文翻译：

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口服和透皮雌激素治疗对功能性下丘脑闭经骨密度的影响：系统评价和荟萃分析

背景 女运动员可能会因能量摄入低而出现骨矿物质密度 (BMD) 降低和闭经。目的 系统回顾评估雌激素口服避孕药 (OCP)、结合雌激素 (CE) 和透皮雌二醇 (TE) 对因体重导致功能性下丘脑闭经 (FHA) 的绝经前妇女 BMD 影响的随机对照试验 (RCT) 文献损失、剧烈运动和/或压力。方法 从开始到 2020 年 10 月 1 日，在 PubMed、MEDLINE、Cochrane Library、Ovid 和 CINAHL 进行全面的文献检索。数据提取和合成两位作者独立提取数据。在可能的情况下，将数据汇总到随机效应荟萃分析中。主要结果 腰椎 BMD (g/cm2) 的差异。结果 包含 770 名参与者的 9 项 RCT 符合纳入标准；五项研究应用了 OCP、两项 CE 和两项 TE。与对照组相比，四项 RCT（两项 OCP，两项 TE）发现绝经前 FHA 女性的 BMD 增加，五项（三项 OCP，两项 CE）发现 BMD 降低。一项荟萃分析显示治疗组和对照组之间的 BMD 没有差异（标准化平均差 (SMD) 0.30, 95% CI -0.12 至 0.73）。从基线到第一个评估点的变化分数的二次分析显示了相似的总体结果（SMD 0.17，95% CI -0.16 至 0.51）。没有报告严重的不良事件。结论 文献表明，TE 可能会增加 FHA 绝经前妇女的腰椎 BMD，但汇总结果显示干预没有效果。