Dehydroepiandrosterone replacement therapy in hypoadrenal women: protein anabolism and skeletal muscle function

Abstract

Objective: To determine whether dehydroepiandrosterone (DHEA) replacement therapy in hypoadrenal women improves performance, muscle protein accretion, and mitochondrial functions.

Participants and methods: Thirty-three hypoadrenal women were enrolled in the study from May 1, 2002, through May 31, 2003. Twenty-eight completed a 12-week, prospective, randomized, placebo-controlled, crossover study with either daily placebo or 50 mg of DHEA with a 2-week washout period and then crossed over to the other treatment. Body composition, physical performance, whole-body and muscle protein metabolism, and mitochondrial functions were determined.

Results: Administration of DHEA significantly increased plasma levels of DHEA sulfate, testosterone, and androstenedione but did not change body composition, muscle strength, peak aerobic capacity, and whole-body protein turnover or synthesis rates of mitochondrial, sarcoplasmic, or mixed muscle proteins. Muscle mitochondrial oxidative enzymes and messenger RNA (mRNA) levels of genes encoding mitochondrial proteins and nuclear transcription factors did not change after DHEA administration. However, mRNA levels of muscle myosin heavy chain 1 (P=.004), which determines muscle fiber type, and those of insulinlike growth factor binding proteins 4 and 5 significantly decreased (P=.02 and P=.03, respectively).

Conclusion: Three months of DHEA administration increased DHEA sulfate and androgen levels but had no effect on physical performance, body composition, protein metabolism, or muscle mitochondrial biogenesis in hypoadrenal women. However, lowering of mRNA levels of binding proteins of insulinlike growth factor 1 and myosin heavy chain 1 suggests potential effects of longterm treatment with DHEA on muscle fiber type.

Trial registration: ClinicalTrials.gov NCT00279929.

Conflict of interest statement

Financial disclosure: The authors declare they have no financial conflicts of interest in the subject matter discussed in the manuscript

Figures

Figure 1

Skeletal muscle mRNA levels showing that DHEA administration significantly decreased IGFBP4, IGFBP5 and MHC1 mRNA levels with no significant effects on those of IGF-1, MHCIIa and IIx. * = indicates statistical significance DHEA = Dehydroepiandrosterone, IGF = Insulin Like Growth Factor, IGFBP = Insulin Like Growth Factor Binding Protein, MHC = Myosin Heavy Chain, mRNA = Messenger Ribonucleic Acid