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King DS, Sharp RL, Vukovich MD, et al. Effect of Oral Androstenedione on Serum Testosterone and Adaptations to Resistance Training in Young Men: A Randomized Controlled Trial. JAMA. 1999;281(21):2020–2028. doi:10.1001/jama.281.21.2020
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).
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
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  pmol/L), 5 (300 
pmol/L), and 8 (280  pmol/L) weeks compared with
presupplementation values (220  pmol/L). The serum estrone
concentration was significantly higher (P<.05) after 2 (153
 pmol/L) and 5 (142  pmol/L) weeks of androstenedione
supplementation compared with baseline (106  pmol/L). Knee
extension strength increased significantly (P<.05) and
similarly in the placebo (770  N vs 1095  N) and
androstenedione (717  N vs 1024  N) groups. The increase of
the mean cross-sectional area of type 2 muscle fibers was also similar
in androstenedione (4703  vs 5307  mm2;
P<.05) and placebo (5271  vs 5728 
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
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.
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