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This version published online on August 22, 2006
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-0867
A more recent version of this article appeared on November 1, 2006
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*ESTRADIOL
*TESTOSTERONE

Submitted on April 21, 2006
Accepted on August 15, 2006

Dehydroepiandrosterone (DHEA) Secretion in Healthy Older Men and Women: Effects of Testosterone and Growth Hormone Administration in Older Men

Ranganath Muniyappa MD, PhD, Kelli A. Wong BA, Howard L. Baldwin MA, John D. Sorkin MD, PhD, Michael L. Johnson PhD, Shalender Bhasin MD, S. Mitchell Harman MD, PhD, and Marc R. Blackman MD*

Endocrine Section (RM, KAW, HLB, MRB), Laboratory of Clinical Investigation, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, MD 20892; Department of Veterans Affairs and Veterans Affairs Medical Center, Baltimore Geriatric Research, Education and Clinical Center (GRECC), and the University of Maryland School of Medicine, Division of Gerontology (JDS), Baltimore, MD 21201; Departments of Pharmacology and Internal Medicine (MLJ), University of Virginia Health System, Charlottesville, Virginia 22908; Endocrine Section (SB), Dept. of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118; and Kronos Longevity Research Institute (SMH), Phoenix, Arizona 85016

* To whom correspondence should be addressed. E-mail: blackmam{at}mail.nih.gov.

Context; Aging is associated with diminished gonadal steroid and GH/IGF-I axis activity; whether these changes contribute to the parallel declines of DHEA and DHEAS production is unknown, as are the effects of sex steroid and/or GH administration on DHEA and DHEAS production.

Objective: To evaluate AM DHEAS concentrations and nocturnal DHEA secretory dynamics in healthy older men and women, before and after chronic administration of sex steroid(s) alone, GH alone, sex steroid(s) combined with GH, or placebo alone.

Design: We compared nocturnal DHEA secretory dynamics (8 PM-8 AM, q20 min sampling, analyzed by multiparameter deconvolution and Approximate Entropy (ApEn) algorithms) in healthy older (65-88 yr) men (n = 68) and women (n = 36), both before and after 26 weeks of administration of sex steroid(s) alone [Testosterone(T) in men or Estrogen/Progesterone (E/P) in women], GH alone, sex steroid(s) combined with GH, or placebo alone.

Results: AM concentrations of DHEAS were lower; nocturnal DHEA pulsatile production rate, burst frequency and amplitude were higher; and half life was shorter; in women (P < 0.05). Nocturnal integrated DHEA concentrations, total production rate and ApEn did not differ significantly by sex. Because of small treatment group sizes in women, only hormone intervention results in men are presented. In men, T and T+GH administration significantly decreased nocturnal integrated DHEA, but not AM DHEAS concentrations. GH alone exerted no significant effects on nocturnal DHEA secretion or AM DHEAS.

Conclusions; Spontaneous nocturnal DHEA secretion is sexually dimorphic in healthy older individuals, and T administration decreases nocturnal DHEA secretion in older men. The clinical significance of sex steroid modulation of DHEA secretion in older persons remains to be elucidated.
Key words: DHEA • Pulsatility • Hormone Replacement • Aging






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