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Effects of Dehydroepiandrosterone and Alprazolam on Hypothalamic-Pituitary Responses to Exercise

Departments of Military and Emergency Medicine (P.A.D.), Medical and Clinical Psychology (M.M.F.), and Pediatrics (M.A.P.), Uniformed Services University of the Health Sciences; Bethesda, Maryland 20814; and Pediatric and Reproductive Endocrinology Branch (G.P.C.), National Institute of Child Health and Human Development, Bethesda Maryland 20892

Address all correspondence and requests for reprints to: Patricia A. Deuster, Ph.D., MPH, Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814-4799. E-mail: pdeuster{at}usuhs.mil.

Context: The hypothalamic-pituitary-adrenal axis (HPA) is restrained by activation of -amino-butyric acid receptors. Alprazolam (APZ) and dehydroepiandrosterone (DHEA) are purported to be -amino-butyric acid agonists and antagonists, respectively.

Objective: Our objective was to examine the effects of APZ and DHEA alone and in combination on HPA axis activity.

Design: This was a double-blind, crossover, placebo-controlled study.

Setting: The study setting was the general community.

Participants: Subjects consisted of 15 men (age, 20–45 yr) with a body mass index of 20–25 kg/m².

Interventions: DHEA (100 mg/d) or placebo was given for 4 wk, followed by a 2-wk washout; participants ingested 0.5 mg APZ or placebo 10 and 2 h before high-intensity exercise.

Outcome Measures: We measured basal and exercise-induced ACTH, arginine vasopressin (AVP), cortisol, DHEA, and GH responses. It was hypothesized that DHEA would enhance and APZ would blunt exercise-induced ACTH and cortisol release.

Results: DHEA significantly increased the AVP response to exercise (P < 0.01). APZ treatment significantly increased basal GH and blunted plasma cortisol, ACTH, AVP, and DHEA responses to exercise (P < 0.05). DHEA and APZ in combination significantly increased the GH response to exercise (P < 0.01).

Conclusions: DHEA may alter a subset of receptors involved in AVP release. Together DHEA and APZ may up-regulate GH during exercise by blunting a suppressive (HPA axis) and potentiating an excitatory (glutamate receptor) system.

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