Gordon Catherine M, Grace Estherann, Emans S Jean, Feldman Henry A, Goodman Elizabeth, Becker Kelly A, Rosen Clifford J, Gundberg Caren M, LeBoff Meryl S
Division of Adolescent/Young Adult Medicine, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.
J Clin Endocrinol Metab. 2002 Nov;87(11):4935-41. doi: 10.1210/jc.2002-020545.
Young women with anorexia nervosa (AN) have subnormal levels of dehydroepiandrosterone (DHEA) and estrogen that may be mechanistically linked to the bone loss seen in this disease. The purpose of this study was to compare the effects of a 1-yr course of oral DHEA treatment vs. conventional hormonal replacement therapy (HRT) in young women with AN. Sixty-one young women were randomly assigned to receive oral DHEA (50 mg/d) or HRT (20 micro g ethinyl estradiol/0.1 mg levonorgestrel). Anthropometric, nutrition, and exercise data were acquired every 3 months, and bone mineral density (BMD) and body composition were measured by dual energy x-ray absorptiometry (DXA) every 6 months over 1 yr. Serum samples were obtained for measurements of hormones, proresorptive cytokines, and bone formation markers, and urine was collected for determinations of bone resorption markers at each visit. In initial analyses, total hip BMD increased significantly and similarly (+1.7%) in both groups. Hip BMD increases were positively correlated with increases in IGF-I (r = 0.44; P = 0.030) and the bone formation marker, bone-specific alkaline phosphatase increased significantly only in the DHEA treatment group (P = 0.003). However, both groups gained significant amounts of weight over the year of therapy, and after controlling for weight gain, no treatment effect was detectable. There was no significant change in lumbar BMD in either group. Both bone formation markers, bone-specific alkaline phosphatase and osteocalcin, increased transiently at 6-9 months in those subjects receiving DHEA compared with the estrogen-treated group (P < 0.05). Both DHEA and HRT significantly reduced levels of the bone resorption markers, urinary N-telopeptides (P < 0.05). There was a positive correlation between changes in IGF-I and changes in weight, body fat determined by DXA, and estradiol for both groups. In addition, patients receiving DHEA exhibited improvement on three validated psychological instruments (Eating Attitudes Test, Anorexia Nervosa Subtest, and Spielberger Anxiety Inventory). Both DHEA and HRT had similar effects on hip and spinal BMD. Over the year of treatment, maintenance of both hip and spinal BMD was seen, but there was no significant increase after accounting for weight gain. Compared with HRT, DHEA appeared to have anabolic effects, evidenced by the positive correlation between increases in hip DXA measurements and IGF-I and significant increases in bone formation markers. Both therapies significantly decreased bone resorption. Replicating results from studies of the elderly, DHEA resulted in improvements in specific psychological parameters in these young women.
患有神经性厌食症（AN）的年轻女性体内脱氢表雄酮（DHEA）和雌激素水平低于正常水平，这可能在机制上与该疾病中出现的骨质流失有关。本研究的目的是比较为期1年的口服DHEA治疗与传统激素替代疗法（HRT）对患有AN的年轻女性的影响。61名年轻女性被随机分配接受口服DHEA（50mg/天）或HRT（20μg炔雌醇/0.1mg左炔诺孕酮）。每3个月获取人体测量、营养和运动数据，在1年的时间里，每6个月通过双能X线吸收法（DXA）测量骨矿物质密度（BMD）和身体成分。每次就诊时采集血清样本以测量激素、促吸收细胞因子和骨形成标志物，并收集尿液以测定骨吸收标志物。在初始分析中，两组的全髋BMD均显著且相似地增加（+1.7%）。髋部BMD的增加与胰岛素样生长因子-I（IGF-I）的增加呈正相关（r = 0.44；P = 0.030），并且骨形成标志物骨特异性碱性磷酸酶仅在DHEA治疗组中显著增加（P = 0.003）。然而，两组在治疗的一年中体重均显著增加，在控制体重增加后，未检测到治疗效果。两组的腰椎BMD均无显著变化。与雌激素治疗组相比，接受DHEA的受试者在6 - 9个月时，骨特异性碱性磷酸酶和骨钙素这两种骨形成标志物均短暂增加（P < 0.05）。DHEA和HRT均显著降低了骨吸收标志物尿N-端肽的水平（P < 0.05）。两组中IGF-I的变化与体重、DXA测定的体脂以及雌二醇的变化之间均呈正相关。此外，接受DHEA治疗的患者在三项经过验证的心理测试工具（饮食态度测试、神经性厌食症子测试和斯皮尔伯格焦虑量表）上表现出改善。DHEA和HRT对髋部和脊柱BMD的影响相似。在治疗的一年中，观察到髋部和脊柱BMD均得以维持，但在考虑体重增加后没有显著增加。与HRT相比，DHEA似乎具有合成代谢作用，这表现为髋部DXA测量值的增加与IGF-I之间的正相关以及骨形成标志物的显著增加。两种疗法均显著降低了骨吸收。与对老年人的研究结果一致，DHEA使这些年轻女性的特定心理参数得到改善。
