The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women.
OBJECTIVE
The biological role of the adrenal sex steroid precursors--DHEA and DHEA sulphate (DS) and their decline with ageing remains undefined. We observed previously that administration of a 50 daily dose of DHEA for 3 months to age-advanced men and women resulted in an elevation (10%) of serum levels of insulin-like growth factor-I (IGF-I) accompanied by improvement of self-reported physical and psychological well-being. These findings led us to assess the effect of a larger dose (100 mg) of DHEA for a longer duration (6 months) on circulating sex steroids, body composition (DEXA) and muscle strength (MedX).


METHODS
Healthy non-obese age-advanced (50-65 yrs of age) men (n = 9) and women (n = 10) were randomized into a double-blind placebo-controlled cross-over trial. Sixteen subjects completed the one-year study of six months of placebo and six months of 100 mg oral DHEA daily.


METHODS
Fasting early morning blood samples were obtained. Serum DHEA, DS, sex steroids, IGF-I, IGFBP-1, IGFBP-3, growth hormone binding protein (GHBP) levels and lipid profiles as well as body composition (by DEXA) and muscle strength (by MedX testing) were measured at baseline and after each treatment.


RESULTS
Basal serum levels of DHEA, DS, androsternedione (A), testosterone (T) and dihydrotestosterone (DHT) were at or below the lower range of young adult levels. In both sexes, a 100 mg daily dose of DHEA restored serum DHEA levels to those of young adults and serum DS to levels at or slightly above the young adult range. Serum cortisol levels were unaltered, consequently the DS/cortisol ratio was increased to pubertal (10:1) levels. In women, but not in men, serum A, T and DHT were increased to levels above gender-specific young adult ranges. Basal SHBG levels were in the normal range for men and elevated in women, of whom 7 of 8 were on oestrogen replacement therapy. While on DHEA, serum SHBG levels declined with a greater (P < 0.02) response in women (-40 +/- 8%; P = 0.002) than in men (-5 +/- 4%; P = 0.02). Relative to baseline, DHEA administration resulted in an elevation of serum IGF-I levels in men (16 +/- 6%, P = 0.04) and in women (31 +/- 12%, P = 0.02). Serum levels of IGFBP-1 and IGFBP-3 were unaltered but GHBP levels declined in women (28 +/- 6%; P = 0.02) not in men. In men, but not in women, fat body mass decreased 1.0 +/- 0.4 kg (6.1 +/- 2.6%, P = 0.02) and knee muscle strength 15.0 +/- 3.3% (P = 0.02) as well as lumbar back strength 13.9 +/- 5.4% (P = 0.01) increased. In women, but not in men, an increase in total body mass of 1.4 +/- 0.4 kg (2.1 +/- 0.7%; P = 0.02) was noted. Neither gender had changes in basal metabolic rate, bone mineral density, urinary pyridinoline cross-links, fasting insulin, glucose, cortisol levels or lipid profiles. No significant adverse effects were observed.


CONCLUSIONS
A daily oral 100 mg dose of DHEA for 6 months resulted in elevation of circulating DHEA and DS concentrations and the DS/cortisol ratio. Biotransformation to potent androgens near and slightly above the range of their younger counterparts occurred in women with no detectable change in men. Given this hormonal milieu, an increase in serum IGF-I levels was observed in both genders but dimorphic responses were evident in fat body mass and muscle strength in favour of men. These differences in response to DHEA administration may reflect a gender specific response to DHEA and/or the presence of confounding factor(s) in women such as oestrogen replacement therapy.
Morales
A J
AJ
Department of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, USA.
Haubrich
R H
RH
Hwang
J Y
JY
Asakura
H
H
Yen
S S
SS
D000368:Aged; D000375:Aging / Q000097:blood / Q000187:drug effects*; D000735:Androstenedione / Q000097:blood; D001823:Body Composition / Q000187:drug effects*; D003687:Dehydroepiandrosterone / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D013196:Dihydrotestosterone / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D015914:Estrogen Replacement Therapy; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects*; D012737:Sex Factors; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood
D012739:Gonadal Steroid Hormones; D012738:Sex Hormone-Binding Globulin; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D007334:Insulin-Like Growth Factor I; D006854:Hydrocortisone