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This version published online on April 12, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-0553
A more recent version of this article appeared on July 1, 2005
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Submitted on March 11, 2005
Accepted on April 5, 2005

Independent and Combined Effects of Testosterone and Growth Hormone on Extracellular Water in Hypopituitary Men

Gudmundur Johannsson, James Gibney, Troels Wolthers, Kin-Chuen Leung, and Ken K Y Ho*

Pituitary Research Unit, Garvan Institute of Medical Research and Department of Endocrinology, St. Vincent's Hosptial, Sydney, Australia

* To whom correspondence should be addressed. E-mail: k.ho{at}garvan.org.au.

Context: Symptoms of fluid retention in GH-deficient patients during GH replacement are greater in men than in women, suggesting that testosterone may augment or estradiol attenuate the antinatriuretic actions of GH. The mechanisms underlying the sodium retaining effects of GH are poorly understood.

Aim: To investigate the effects of GH and testosterone, alone and in combination, on extracellular water (ECW) and the hormonal mechanisms involved.

Design: Two separate open label randomized two-period crossover studies, the first compared the effects of GH alone with GH and testosterone, and the second the effects of testosterone alone with GH and testosterone.

Participants: Twelve hypopituitary men with GH deficiency and hypogonadism.

Intervention: Weeks of GH (0.5 mg/d) and testosterone enanthate 250 mg by intramuscular injection

Outcome measures: Extracellular water (ECW), IGF-I, plasma renin activity (PRA), aldosterone, atrial natriuretic peptide (ANP).

Results: GH treatment significantly increased (P < 0.05) both IGF-I and ECW and these changes were enhanced by co-treatment with testosterone (P = 0.07 for both). PRA, aldosterone and ANP levels did not change. Testosterone treatment alone did not change the IGF-I concentration whereas co-treatment with GH induced a marked increase. Testosterone alone increased (P < 0.05) ECW and the effect was augmented (P < 0.01) by co-treatment with GH. While PRA and ANP did not change, plasma aldosterone fell with single and combined treatments.

Conclusion: GH and testosterone exerted independent and additive effects on ECW. The mechanisms of fluid retention for both hormones are likely to be exerted on the renal tubules. This is the first direct evidence that testosterone increases ECW.




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