Increases in bone mineral density in response to oral dehydroepiandrosterone replacement in older adults appear to be mediated by serum estrogens.
BACKGROUND
The mechanisms by which dehydroepiandrosterone (DHEA) replacement increases bone mineral density (BMD) in older adults are not known.


OBJECTIVE
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.


METHODS
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.


METHODS
The intervention was oral DHEA 50 mg/d or placebo for 12 months.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Jankowski
Catherine M
CM
Division of Geriatric Medicine, University of Colorado Denver, mail stop B179, Room 8111, 12631 East 17th Avenue, Aurora, Colorado 80045, USA.
Gozansky
Wendolyn S
WS
Kittelson
John M
JM
Van Pelt
Rachael E
RE
Schwartz
Robert S
RS
Kohrt
Wendy M
WM
D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D015519:Bone Density / Q000187:drug effects*; D019314:Dehydroepiandrosterone Sulfate / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D004311:Double-Blind Method; D004967:Estrogens / Q000097:blood* / Q000502:physiology*; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood
D015415:Biomarkers; D004967:Estrogens; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate; D007334:Insulin-Like Growth Factor I