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A Randomized Controlled Trial

Douglas S. King, PhD; Rick L. Sharp, PhD; Matthew D. Vukovich, PhD; Gregory A. Brown, MS; Tracy A. Reifenrath, MS; Nathaniel L. Uhl; Kerry A. Parsons, MS

JAMA. 1999;281:2020-2028.

Context  Androstenedione, a precursor to testosterone, is marketed to increase blood testosterone concentrations as a natural alternative to anabolic steroid use. However, whether androstenedione actually increases blood testosterone levels or produces anabolic androgenic effects is not known.

Objectives  To determine if short- and long-term oral androstenedione supplementation in men increases serum testosterone levels and skeletal muscle fiber size and strength and to examine its effect on blood lipids and markers of liver function.

Design and Setting  Eight-week randomized controlled trial conducted between February and June 1998.

Participants  Thirty healthy, normotestosterogenic men (aged 19-29 years) not taking any nutritional supplements or androgenic-anabolic steroids or engaged in resistance training.

Interventions  Twenty subjects performed 8 weeks of whole-body resistance training. During weeks 1, 2, 4, 5, 7, and 8, the men were randomized to either androstenedione, 300 mg/d (n=10), or placebo (n=10). The effect of a single 100-mg androstenedione dose on serum testosterone and estrogen concentrations was determined in 10 men.

Main Outcome Measures  Changes in serum testosterone and estrogen concentrations, muscle strength, muscle fiber cross-sectional area, body composition, blood lipids, and liver transaminase activities based on assessments before and after short- and long-term androstenedione administration.

Results  Serum free and total testosterone concentrations were not affected by short- or long-term androstenedione administration. Serum estradiol concentration (mean [SEM]) was higher (P<.05) in the androstenedione group after 2 (310 [20] pmol/L), 5 (300 [30] pmol/L), and 8 (280 [20] pmol/L) weeks compared with presupplementation values (220 [20] pmol/L). The serum estrone concentration was significantly higher (P<.05) after 2 (153 [12] pmol/L) and 5 (142 [15] pmol/L) weeks of androstenedione supplementation compared with baseline (106 [11] pmol/L). Knee extension strength increased significantly (P<.05) and similarly in the placebo (770 [55] N vs 1095 [52] N) and androstenedione (717 [46] N vs 1024 [57] N) groups. The increase of the mean cross-sectional area of type 2 muscle fibers was also similar in androstenedione (4703 [471] vs 5307 [604] mm²; P<.05) and placebo (5271 [485] vs 5728 [451] mm²; P<.05) groups. The significant (P<.05) increases in lean body mass and decreases in fat mass were also not different in the androstenedione and placebo groups. In the androstenedione group, the serum high-density lipoprotein cholesterol concentration was reduced after 2 weeks (1.09 [0.08] mmol/L [42 (3) mg/dL] vs 0.96 [0.08] mmol/L [37 (3) mg/dL]; P<.05) and remained low after 5 and 8 weeks of training and supplementation.

Conclusions  Androstenedione supplementation does not increase serum testosterone concentrations or enhance skeletal muscle adaptations to resistance training in normotestosterogenic young men and may result in adverse health consequences.

Author Affiliations: Exercise Biochemistry Laboratory, Department of Health and Human Performance, Iowa State University, Ames (Drs King, Sharp, and Vukovich, Messrs Brown and Uhl, and Mss Reifenrath and Parsons); and Experimental and Applied Sciences, Golden, Colo (Dr Vukovich).

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