NW Spine - Library

© 2001

During recent correspondence with the editor of this fine publication, we agreed that we continue to be astonished at the number of questions we receive regarding prohormone dietary supplements. In the latter half of the past decade, prohormones have been in the media spotlight and have been the subject of much debate, even at the legislative level.

Because users of prohormones generally wish to mimic the effects of anabolic-androgenic steroids (AAS) with prohormones, some insight into AAS action may be helpful. In a recent publication, a colleague and I summarized the current thinking on the actions of anabolic-androgenic steroids (Frounfelter & Bradley-Popovich, 2000):

The exact physiological mechanism of AAS is not well understood. It is thought that there are three physiologic pathways for AAS to act. First, these drugs cause increased protein synthesis in cells that are sensitive to AAS. Second, AAS provide an anti-catabolic effect by decreasing the effects of catabolic hormones released secondary to intense exercise. Finally, AAS are thought to help increase nitrogen retention, an indicator of protein synthesis, by shifting to a positive nitrogen balance, thus making better utilization of ingested protein in the cellular environment.

 

Recent evidence suggests that one myotrophic [muscle growth promoting] action of AAS in vivo is to increase the number of myonuclei, which occurs in skeletal muscle fibers through the enlistment of nearby satellite cells that are developmentally residual muscle precursors. Previous research has shown regulatory effects of anabolic steroids on satellite cells in in vitro. Greater satellite cell activity leads to greater fusion of nuclei with muscle cells, the end result of which being more nuclei to direct protein synthesis and to maintain a more favorable nucleus-to-volume ratio. Normally, muscle growth potential has a ceiling described as the nucleus-to-volume ratio (aka DNA unit or nuclear domain), which recognizes that a nucleus can reliably sustain a limited volume of cell. Because myonuclei [muscle cell nuclei] persist until near the point of cell death, once incorporated, the additional nuclei may be a permanent cellular fixture in healthy myocytes [muscle cells].

The end result of these possible AAS actions is enhancement of body composition, and, in some cases, athletic performance. The key question is, can prohormones exert any of these effects?

Prohormones are relatively inactive substances that, once introduced into the body, are thought to be converted into active hormones, such as testosterone. Although usually consumed orally, some crafty marketers have introduced inhalable delivery systems for prohormones. Less kind terms for prohormones include steroid-like compounds, nonprescription steroids, and prodrugs.

Much of the published research on the effects of prohormone supplementation is very recent. The prohormones currently en vogue are androstenedione ("andro"), and androstenediol. The underlying premise is that these hormones are converted to testosterone in the body (Schnirring, 1998).

Increases in free (unbound, active) testosterone concentration following supplementation have been nonsignificant in some studies using androstenedione (King et al., 1999; Quindry et al., 2000) or androstenediol (Earnest, Olson, Beckham, Broeder, & Bruel, 1999; Quindry et al.). In contrast, some studies report significant increases in free testosterone following androstenedione ingestion (Antonio & Sanders, 1999; Earnest et al.). As Dr. Stan Reents explains, "Lack of an increase in testosterone levels after ingesting androstenedione should not be surprising, really, since the conversion of androstenedione to testosterone in males is very slight" (2000). Unfortunately, it appears that an individual’s own testosterone secretion may be decreased within one month of regularly using androstenedione (Quindry et al.).

Limited data exist to show augmented strength and lean body mass with androstenedione supplementation (Van Gammeren et al., 2000). Much more research exists that has found no performance-enhancing benefits to supplementation with androstenedione (King et al., 1999; Thomson et al., 2000; Wallace, Lim, Cutler, & Bucci, 1999; Ziegenfuss, Berardi, & Lowery, 2000) or androstenediol (Thomson et al.). Likewise, most studies have found no positive effect of prohormones on lean body mass (Antonio & Sanders, 1999; Dominick et al., 2000; King et al., Wallace et al). One study indicates that androstenedione does not enhance muscle growth and may even promote muscle breakdown (Rasmussen, Volpi, Gore, & Wolfe, 2000). Indeed, prohormone research has been remarkably consistent in one regard: occurrence of side effects.

Some studies have even reported an increase in body fat following supplementation with androstenedione (Antonio & Sanders; Dominick et.al.) or assorted prohormones (Van Gammeren et al.) despite resistance exercise. An increase in body fat is perhaps due to the fact that most studies have demonstrated an increase in female hormone levels with supplementation of these prohormones (Brown, Kohut, Franke, Jackson, Vukovich, & King, 2000; King et al.; Leder, Longcope, Catlin, Ahrens, Schoenfeld, & Finkelstein, 2000; Quindry et al.; Rasmussen et al.), with one exception (Ziegenfuss et al.). This conversion to female hormones is also supported by anecdotal evidence from two personal male acquaintances who are exercise physiologists that experienced tender breasts during androstenedione supplementation. Additionally, a decrease in good cholesterol (HDL) has been observed in some longer studies using androstenedione (Brown et al.; King et al.) and androstenediol (Brown et al.), while a case report using androstenedione (Antonio & Sanders) did not document a decrease in HDL.

Some proponents of prohormones may speculate that persons with lower testosterone levels than the relatively young, male subjects used in most of the studies above would benefit more so from testosterone precursors. Persons with lower testosterone include older individuals, women, and patients with certain hormonal deficiencies. However, data are even more lacking in these groups. While there are other forms of prohormones with slight molecular differences, there simply are no data to recommend their use at this time. In addition, even if small, sustained elevations in testosterone production could be achieved with prohormones, we can’t be certain that it will have a meaningful impact on body composition or performance. Finally, effective doses of prohormones would likely carry a similar risk of side effects as that associated with anabolic steroids (Schnirring, 1998).

This brief review has shown that the preponderance of evidence does not support the use of prohormones to improve performance or body composition. In contrast, reports of side effects during clinical trials are quite common. Buying a supplement that simply doesn’t work is frustrating and wasteful. Furthermore, squandering financial resources on a supplement that results in only negative side effects is humiliating and potentially harmful.

Antonio, J. & Sanders, M. (1999). Effects of self-administered androstenedione on a young male body builder: A single-subject study. Current Therapeutic Research, 60, 486-491.

Brown, G., Kohut, M., Franke, W., Jackson, D., Vukovich, M, & King, D. (2000). Serum hormonal and lipid responses to androgenic supplementation in 30-59 year old men. [Abstract]. Medicine and Science in Sports and Exercise, 32 (Suppl.), S122.

Dominick, G., Quindry, J., Brittingham, K., Panton, J., Breuel, J., Earnest, C., Olson, M., & Broeder, C. (2000). The andro project: Androstenediol or androstenedione use on body composition in men [Abstract]. Medicine and Science in Sports and Exercise, 32 (Suppl.), S177.

Earnest, C., Olson, M., Beckham, S., Broeder, C., & Bruel, K. (1999). Oral 4-androstene-3,17-dione and 4-androstene-3,17-diol supplementation in young males [Abstract]. Journal of Parenteral and Enteral Nutrition, 23, S16.

Frounfelter, G. G & Bradley-Popovich, G. E. (2000). Ethical considerations regarding anabolic-androgenic steroid use: Emphasis on the exercise professional. Professionalization of Exercise Physiology Online, 3. Available at: http://www.css.edu/users/tboone2/asep/Greg.doc.

King, D., Sharp, R., Vukovich, M., Brown, G., Reifenrath, T., Uhl, N., & Parsons, K. (1999). Effect of oral androstenedione on serum testosterone and adaptations to resistance training in young men: A randomized controlled trial. Journal of the American Medical Association, 281, 2020-2028.

Leder, B., Longcope, C., Catlin, D., Ahrens, B., Schoenfeld, D., & Finkelstein, J. (2000). Oral androstenedione administration and serum testosterone concentrations in young men. Journal of the American Medical Association, 283, 779-782.

Quindry, J., Brittingham, K., Panton, L., Breuel, J., Earnest, C., Olson, M., & Broeder, C. (2000). The andro project: Androstenediol or androstenedione use on sex-hormone profiles in men [Abstract]. Medicine and Science in Sports and Exercise, 32 (Suppl.), S122.

Rasmussen, B., Volpi, E., Gore, D., & Wolfe, R. (2000). Androstenedione does not stimulate muscle protein anabolism in young healthy men. Journal of Clinical Endocrinology and Metabolism, 85, 55-59.

Reents, S. (2000). Sport and exercise pharmacology. Champaign, IL: Human Kinetics.

Schnirring, L. Androstenedione et al: Nonprescription steroids. The Physician and Sports Medicine, 26 (11), 15-18.

Thomson, J., Quindry, J., Brittingham, K., Panton, L., Breuel, J., Earnest, C., Olson, M., & Broeder, C. (2000). The andro project: Effects of androstenediol or androstenedione use on strength in men [Abstract]. Medicine and Science in Sports and Exercise, 32 (Suppl.), S177.

Van Gammeren, D., Uelmen, J., Ehler, L., Raether, J., Sanders, M., Ziegenfuss, T., & Antonio, J. (2000). Effects of legal androgens on strength and body composition in bodybuilders [Abstract]. Medicine and Science in Sports and Exercise, 32 (Suppl.), S177.

Wallace, M., Lim, J., Cutler, A., & Bucci, L. (1999). Effects of dehydroepiandrosterone vs androstenedione supplementation in men. Medicine and Science in Sports and Exercise, 31 , 1788-1792.

Ziegenfuss, T., Berardi, J., & Lowery, L. (2000). Effects of an androgen mixture on testosterone, estradiol, and anaerobic performance [Abstract]. Medicine and Science in Sports and Exercise, 32 (Suppl.), S122.

Dr. Greg Bradley-Popovich holds dual master's degrees in Exercise Physiology and Human Nutrition from West Virginia University as well as a doctorate in Physical Therapy from Creighton University. He is the Director of Clinical Research at Northwest Spine Management, Rehabilitation, and Sports Conditioning in Portland, Oregon.

Back to Library Main Page