Gibson J H, Mitchell A, Reeve J, Harries M G
British Olympic Medical Centre, Harrow, Middlesex, UK.
Osteoporos Int. 1999;10(4):284-9. doi: 10.1007/s001980050228.
There is considerable concern about the adverse effects on the skeleton of loss of menstrual function as a result of athletic activity, as well as uncertainty as to how it should be managed clinically. In a pilot intervention study 34 elite middle and long-distance runners, aged 18-35 years, with menstrual irregularity due to their athletic activity were randomized to three groups: (A) to receive hormone replacement therapy (HRT) and 1000 mg calcium per day (n = 10), (B) to receive 1000 mg calcium per day (n = 14), (C) a control group who received no treatment (n = 10). Bone mineral density (BMD) was measured in the left hip and lumbar spine (L2-4) using dual-energy X-ray absorptiometry. Results were first analyzed according to whether menstruation returned, either naturally or secondary to HRT (EU), and compared with those from subjects who remained amenorrheic (AM). During the first year BMD increased in the EU group in Ward's triangle (3.8%) and the lumbar spine (4.1%; both P < 0.05). BMD fell in the AM group in all regions and the between-group differences were 5.6% (p < 0.02) in Ward's triangle, 5.8% (p < 0.02) in L2-4 and 3.9% in the trochanter (p < 0.05). An 'intention to treat' analysis was then performed. It was found that the mean relative improvement at 1 year in spinal BMD was only 1.5%, due to return of menses in some of the controls and withdrawals from treatment in the treatment group. In consequence, a trial designed to show, with 80% power and 5% significance, a measurable benefit in lumbar spine BMD resulting from allocation to HRT treatment would require about 1150 athletes with amenorrhea or oligomenorrhea. These numbers could be reduced substantially to 380 subjects by confining the trial to completely amenorrheic athletes, who in this study were less likely to regain menses. For these and other logistical reasons, an HRT trial in amenorrheic athletes could only be successfully organized through international collaboration. This study illustrates the major effects of treatment withdrawals and instability of menstrual status on the design of longitudinal studies on the bony effects of menstrual dysfunction prior to menopause.
人们非常关注体育活动导致月经功能丧失对骨骼的不良影响，以及临床上应如何处理这一问题。在一项试点干预研究中，34名年龄在18至35岁之间、因体育活动导致月经不规律的精英中长跑运动员被随机分为三组：（A）接受激素替代疗法（HRT）和每日1000毫克钙（n = 10），（B）每日接受1000毫克钙（n = 14），（C）对照组不接受治疗（n = 10）。使用双能X线吸收法测量左髋和腰椎（L2 - 4）的骨密度（BMD）。结果首先根据月经是否自然恢复或继发于HRT（月经恢复组）进行分析，并与仍闭经的受试者（闭经组）的结果进行比较。在第一年，月经恢复组的Ward三角区骨密度增加了3.8%，腰椎骨密度增加了4.1%（均P < 0.05）。闭经组所有区域的骨密度均下降，组间差异在Ward三角区为5.6%（P < 0.02），L2 - 4为5.8%（P < 0.02），转子区为3.9%（P < 0.05）。然后进行了“意向性治疗”分析。结果发现，由于一些对照组月经恢复以及治疗组退出治疗，1年后脊柱骨密度的平均相对改善仅为1.5%。因此，一项旨在以80%的检验效能和5%的显著性水平表明分配接受HRT治疗能使腰椎骨密度有可测量益处的试验，大约需要1150名闭经或月经过少的运动员。通过将试验局限于完全闭经的运动员，这些数字可大幅减少至380名受试者，在本研究中这些运动员恢复月经的可能性较小。由于这些以及其他后勤方面的原因，闭经运动员的HRT试验只能通过国际合作才能成功组织。这项研究说明了治疗退出和月经状态不稳定对绝经前月经功能障碍骨骼影响的纵向研究设计的主要影响。
