Dehydroepiandrosterone supplementation in women with adrenal failure: impact on twenty-four hour GH secretion and IGF-related parameters.
OBJECTIVE
In women, GH secretion is strongly influenced by oestrogen status, whereas the role of androgens is unclear. We, therefore, examined GH secretory dynamics during low vs. normalized androgen levels in women with adrenal failure.


METHODS
Ten females with adrenal failure (AF), mean age of 42 years (range 22-54 years).


METHODS
The effects of 8 days of oral dehydroepiandrosterone (DHEA; 50 mg/day) were studied in a double-blind placebo-controlled, cross-over design. A control group of healthy women was studied once without any treatment.


METHODS
Before and after each treatment period, blood was sampled for measurement of androgens, IGF-I, IGFBP-3 and GHBP. A 24-h GH profile with measurements every 20 min was performed at the end of each period.


RESULTS
DHEA supplementation normalized the mean circulating levels of testosterone and androgen precursors. The secretory pattern of GH was unaltered during DHEA [placebo vs. DHEA; half-life 22.83 +/- 1.24 vs. 21.45 +/- 1.19 (min), P = 0.429; pulse frequency 9.9 +/- 0.7 vs. 10.5 +/- 0.5 (/24 h), P = 0.502; total production rate 62.27 +/- 13.44 vs. 52.61 +/- 7.06 (microg/l/day), P = 0.317]. Subgroup analysis, however, indicated that DHEA treatment increased GH secretion in patients not receiving oestrogen (n = 5), whereas the opposite was observed among patients receiving exogenous oestrogen derivatives (n = 5). Compared to the control group (CON), GH half-life was longer in AF (half-life CON: 16.48 +/- 0.91, P = 0.001). The additional features of GH secretion were similar. Unexpectedly, the levels of IGF-I, IGFBP-3 and GHBP were elevated in the patients as compared to controls, without significant effects of DHEA [AF vs. CON. IGF-I: 186 +/- 20 vs. 144 +/- 7 (microg/l), P = 0.04; IGFBP-3: 5196 +/- 224 vs. 3687 +/- 212 (microg/l), P = 0.001; GHBP: 2.27 +/- 0.25 vs. 1.41 +/- 0.13 (nmol/l), P = 0.002].


CONCLUSIONS
(1) Short-term DHEA administration in women with adrenal failure normalizes the circulating levels of androgens without uniformly affecting the GH-IGF axis; (2) The observation that exogenous oestradiol may mask a stimulatory effect of DHEA on GH secretion merits future investigation.
Christiansen
Jens Juel
JJ
Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital and Institute of Experimental Clinical Research, Aarhus University, Aarhus, Denmark. juel@dadlnet.dk
Gravholt
Claus Højbjerg
CH
Fisker
Sanne
S
Svenstrup
Birgit
B
Bennett
Paul
P
Veldhuis
Johannes
J
Andersen
Marianne
M
Christiansen
Jens S
JS
Jørgensen
Jens O L
JO
D000309:Adrenal Insufficiency / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D000328:Adult; D016022:Case-Control Studies; D018592:Cross-Over Studies; D003687:Dehydroepiandrosterone / Q000627:therapeutic use*; D004311:Double-Blind Method; D004967:Estrogens / Q000008:administration & dosage; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008875:Middle Aged; D011986:Receptors, Somatotropin / Q000097:blood; D012636:Secretory Rate; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000097:blood
D004967:Estrogens; D018972:Insulin-Like Growth Factor Binding Protein 3; D011986:Receptors, Somatotropin; D013739:Testosterone; D003687:Dehydroepiandrosterone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone