Effect (or Noneffect) of Oral Androstenedione on Serum Testosterone and Muscle Performance

Abstract & Commentary

Synopsis: Androstenedione supplementation does not increase serum testosterone concentrations or enhance skeletal muscle adaptation to training.

Source: King DS, et al. JAMA 1999;281:2020-2028.

Androstenedione, a precursor to testosterone, is normally produced by the adrenal glands and testes and is converted to testosterone. Androstenedione is also produced by some plants and has been marketed as a product to increase blood testosterone levels and to be used as a "natural" alternative to anabolic steroid use. However, whether androstenedione actually increases blood testosterone or produces anabolic androgenenic effects or has toxicity is not known. It is also known that androstenedione may be converted to estrogen directly. King and associates from the Exercise Biochemistry Laboratory at the University of Iowa conducted an eight-week randomized, controlled study of 20 healthy, normotestosterogenic men 19-29 years of age who performed eight weeks of whole-body resistance training. The subjects were randomized to receive either 300 mg/day of androstenedione or placebo. Levels of serum-free testosterone and total testosterone were not increased by androstenedione administration. Serum estrone increased significantly in the treatment group. No significant differences in skeletal muscle adaptation were seen between the two groups. However, there were no changes in the liver function tests of control or treatment groups. King et al conclude that eight weeks of androstenedione supplementation does not increase serum testosterone concentrations or enhance skeletal muscle adaptation to training.

Comment by Myron Genel, MD, FAAP

Clinicians should welcome this study, since it provides some counterbalance to the "hoopla" that accompanied the use of androstenedione as a "nutritional supplement" to increase athletic performance. While promotional materials for androstenedione have been popular for some time within the fitness and muscle-building communities, much of the current hype stems from the disclosure by Mark McGwire during his record-setting home run output during the 1998 baseball season that he had been using androstenedione as a supplement to a rigorous strengthening program. Billed as a "natural" precursor of testosterone, androstenedione sales have boomed, especially among athletes who believe this is a safe alternative to anabolic steroids. The JAMA study, designed and performed by a group highly skilled in both medicine and athletics, demonstrates quite nicely not only that androstenedione administration does not increase serum testosterone levels but also that it is a precursor to naturally circulating estrogens. This may be particularly significant for male athletes during adolescence, when they are especially prone to develop gynecomastia. It has been common for me to see fairly accomplished adolescent male athletes who did not shower with their teammates because of embarrassment over presumably natural gynecomastia. Since the JAMA study failed to detect any difference in muscular response to resistance training, albeit over a relatively short eight-week period, perhaps clinicians can use this finding to dissuade adolescents from taking androstenedione as well as other putative enhancers of athletic performance. However, whether this advice will be accepted is dubious, for I am convinced that many dedicated athletes from junior high school on will consider doing or taking almost anything they believe may enhance their performance—even marginally. (Dr. Genel is Professor of Pediatrics [Endocrinology], Yale University School of Medicine.)