Dehydroepiandrosterone substitution in female adrenal failure: no impact on endothelial function and cardiovascular parameters despite normalization of androgen status.
BACKGROUND
Female adrenal insufficiency implicates reduced production of the adrenal androgen precursor dehydroepiandrosterone (DHEA) and low androgen levels. Oral DHEA restores androgen deficit but the clinical implications and safety of substitution therapy is uncertain. A putative DHEA receptor in vascular endothelium has been described and in vitro studies have shown involvement of DHEA in NO dependent pathways.


OBJECTIVE
To evaluate effects of DHEA substitution on cardiovascular parameters.


METHODS
Six months randomized, double-blind, placebo-controlled crossover study. Treatment consisted of DHEA 50-mg or placebo. Each treatment period was followed by a 2-month washout period.


METHODS
Ten females with documented adrenal failure were included. Androgen levels were measured. Cardiovascular evaluation was performed before and after every treatment period. Two patients left the study because of skin side effects and anxiety, respectively. All patients had low circulating androgens baseline and normal range androgens during DHEA treatment. We examined patients with noninvasive endothelial cell function, magnetic resonance imaging (MRI)-based cardiac output, echocardiography, ambulatory 24-h blood pressure and maximal oxygen consumption.


RESULTS
DHEA treatment normalized androgen status to levels seen in healthy women. DHEA and placebo treatment had no effect on echocardiographic parameters of myocardial dimensions or systolic and diastolic function, noninvasive endothelial cell function at the level of the brachial artery, 24-h blood pressure and heart rate, cardiac output and maximal oxygen consumption during exercise cycle testing. Remarkably, all participants had evidence of concentric left ventricular remodelling by echocardiography.


CONCLUSIONS
Restoration of physiological androgen levels using 6 months of DHEA replacement in this pilot study did not affect cardiovascular parameters and endothelial function in female adrenal insufficiency.
Christiansen
Jens Juel
JJ
Medical Department M, Aarhus Sygehus, Aarhus University Hospital, Denmark.
Andersen
Niels Holmark
NH
Sørensen
Keld E
KE
Pedersen
Erik Morre
EM
Bennett
Paul
P
Andersen
Marianne
M
Christiansen
Jens Sandahl
JS
Jørgensen
Jens Otto Lunde
JO
Gravholt
Claus Højbjerg
CH
D000309:Adrenal Insufficiency / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000328:Adult; D000728:Androgens / Q000097:blood*; D002302:Cardiac Output; D018592:Cross-Over Studies; D003687:Dehydroepiandrosterone / Q000627:therapeutic use*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D013196:Dihydrotestosterone / Q000097:blood; D004311:Double-Blind Method; D004452:Echocardiography; D004958:Estradiol / Q000097:blood; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000097:blood
D000728:Androgens; D013196:Dihydrotestosterone; D013739:Testosterone; D003687:Dehydroepiandrosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate