Short-term dehydroepiandrosterone treatment increases platelet cGMP production in elderly male subjects.
OBJECTIVE
Several clinical and population-based studies suggest that dehydroepiandrosterone (DHEA) and its sulphate (DHEA-S) play a protective role against atherosclerosis and coronary artery disease in human. However, the mechanisms underlying this action are still unknown. It has recently been suggested that DHEA-S could delay atheroma formation through an increase in nitric oxide (NO) production.


METHODS
Twenty-four aged male subjects [age (mean +/- SEM): 65.4 +/- 0.7 year; range: 58.2-67.6 years] underwent a blinded placebo controlled study receiving DHEA (50 mg p.o. daily at bedtime) or placebo for 2 months. Platelet cyclic guanosine-monophosphate (cGMP) concentration (as marker of NO production) and serum levels of DHEA-S, DHEA, IGF-I, insulin, glucose, oestradiol (E(2)), testosterone, plasminogen activator inhibitor (PAI)-1 antigen (PAI-1 Ag), homocysteine and lipid profile were evaluated before and after the 2-month treatment with DHEA or placebo.


RESULTS
At the baseline, all variables in the two groups were overlapping. All parameters were unchanged after treatment with placebo. Conversely, treatment with DHEA (a) increased (P < 0.001 vs. baseline) platelet cGMP (111.9 +/- 7.1 vs. 50.1 +/- 4.1 fmol/10(6) plts), DHEA-S (13.6 +/- 0.8 vs. 3.0 +/- 0.3 micromol/l), DHEA (23.6 +/- 1.7 vs. 15.3 +/- 1.4 nmol/l), testosterone (23.6 +/- 1.0 vs. 17.7 +/- 1.0 nmol/l) and E(2) (72.0 +/- 5.0 vs. 60.0 +/- 4.0 pmol/l); and (b) decreased (P < 0.05 vs. baseline) PAI-1 Ag (27.4 +/- 3.8 vs. 21.5 +/- 2.5 ng/ml) and low-density lipoprotein (LDL) cholesterol (3.4 +/- 0.2 vs. 3.0 +/- 0.2 mmol/l). IGF-I, insulin, glucose, triglycerides, total cholesterol, HDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and homocysteine levels were not modified by DHEA treatment.


CONCLUSIONS
This study shows that short-term treatment with DHEA increased platelet cGMP production, a marker of NO production, in healthy elderly subjects. This effect is coupled with a decrease in PAI-1 and LDL cholesterol levels as well as an increase in testosterone and E(2) levels. These findings, therefore, suggest that chronic DHEA supplementation would exert antiatherogenic effects, particularly in elderly subjects who display low circulating levels of this hormone.
Martina
Valentino
V
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Italy. valentino.martina@unito.it
Benso
Andrea
A
Gigliardi
Valentina Ramella
VR
Masha
Andi
A
Origlia
Carla
C
Granata
Riccarda
R
Ghigo
Ezio
E
D000368:Aged; D050197:Atherosclerosis / Q000517:prevention & control; D015415:Biomarkers / Q000032:analysis; D001774:Blood Chemical Analysis / Q000379:methods; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D006152:Cyclic GMP / Q000097:blood*; D003687:Dehydroepiandrosterone / Q000008:administration & dosage* / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis; D014665:Vasodilator Agents / Q000008:administration & dosage*
D015415:Biomarkers; D014665:Vasodilator Agents; D009569:Nitric Oxide; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D006152:Cyclic GMP