Jankowski Catherine M, Gozansky Wendolyn S, Kittelson John M, Van Pelt Rachael E, Schwartz Robert S, Kohrt Wendy M
Division of Geriatric Medicine, University of Colorado Denver, mail stop B179, Room 8111, 12631 East 17th Avenue, Aurora, Colorado 80045, USA.
J Clin Endocrinol Metab. 2008 Dec;93(12):4767-73. doi: 10.1210/jc.2007-2614. Epub 2008 Sep 23.
The mechanisms by which dehydroepiandrosterone (DHEA) replacement increases bone mineral density (BMD) in older adults are not known.
The aims were to determine the effects of DHEA therapy on changes in sex hormones and IGF-I and their associations with changes in BMD.
DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blinded, placebo-controlled trial was conducted at an academic research institution. Participants were 58 women and 61 men, aged 60-88 yr, with low serum DHEA sulfate (DHEAS) levels.
The intervention was oral DHEA 50 mg/d or placebo for 12 months.
BMD and serum DHEAS, testosterone, estradiol (E(2)), estrone (E(1)), SHBG, IGF-I, and IGF binding protein 3 were measured before and after intervention. Free testosterone and estrogen (FEI) indices were calculated.
The average changes in hip and spine BMD (DHEA vs. placebo) ranged from 1.1 to 1.6%. Compared with placebo, DHEA replacement increased serum DHEAS, testosterone, free testosterone index, E(1), E(2), FEI, and IGF-I (all P < 0.001) and decreased SHBG (P = 0.02) in women and, in men, increased DHEAS, E(1), FEI (all P < 0.001), and E(2) (P = 0.02) and decreased SHBG (P = 0.037). The changes in total and regional hip BMD were associated with 12-month E(2) (all P <or= 0.001) and FEI (all P <or= 0.013). The effects of DHEA treatment were eliminated by adjustment for 12-month E(2).
The significant increases in hip BMD in older adults undergoing DHEA replacement were mediated primarily by increases in serum E(2) rather than direct effects of DHEAS.
脱氢表雄酮（DHEA）替代治疗增加老年人骨矿物质密度（BMD）的机制尚不清楚。
旨在确定DHEA治疗对性激素和IGF-I变化的影响及其与BMD变化的关联。
设计、地点和参与者：在一所学术研究机构进行了一项随机、双盲、安慰剂对照试验。参与者为58名女性和61名男性，年龄在60 - 88岁之间，血清硫酸脱氢表雄酮（DHEAS）水平较低。
干预为口服DHEA 50 mg/d或安慰剂，为期12个月。
在干预前后测量BMD以及血清DHEAS、睾酮、雌二醇（E₂）、雌酮（E₁）、性激素结合球蛋白（SHBG）、IGF-I和IGF结合蛋白3。计算游离睾酮和雌激素（FEI）指数。
髋部和脊柱BMD的平均变化（DHEA组与安慰剂组相比）在1.1%至1.6%之间。与安慰剂相比，DHEA替代治疗使女性血清DHEAS、睾酮、游离睾酮指数、E₁、E₂、FEI和IGF-I升高（均P < 0.001），SHBG降低（P = 0.02）；在男性中，DHEAS、E₁、FEI升高（均P < 0.001），E₂升高（P = 0.02），SHBG降低（P = 0.037）。全髋和局部髋部BMD的变化与12个月时的E₂（均P ≤ 0.001）和FEI（均P ≤ 0.013）相关。对12个月时的E₂进行校正后，DHEA治疗的效果消失。
接受DHEA替代治疗的老年人髋部BMD显著增加主要是由血清E₂升高介导的，而非DHEAS的直接作用。
