Testosterone is a naturally occurring steroid hormone with anabolic and androgenic effects that increase muscle and promote male sexual characteristics. While testosterone provides benefits, its use in sports is controversial and banned. Athletes attempted to use supplements like androstenedione to boost testosterone levels, but these were found to have unintended effects like increased estrogen levels and potential health issues. Test labs and drug tests must work to prevent athletes from gaining unfair advantages through new designer steroids that try to circumvent regulations.

1. To or not to “ Juice” “ Juice” ? Supplemental Testosterone in Sports Javier Amigon Daniel Ho Alex Lukatskiy Gwenael Gatto By:

2. Testosterone is a naturally occurring steroid. Background Testosterone Androgenic effects -Male secondary sex characteristics Anabolic Effects Medical Use 2 3 4 5 1 0 1 6 7 8 9 1 4 1 3 1 2 1 1 1 5 1 6 1 7 O 1 9 H 1 8 O H 2 2 H H H 2 5 A B C D

3. Schematic Representation of Intermolecular Interactions between Testosterone and Amino Acids in the Ligand Binding Domain of the Androgen Receptor Testosterone in the Androgen Receptor Hydrogen Bonding

4. Schematic Representation of Intermolecular Interactions between Testosterone and Amino Acids in the Ligand Binding Domain of the Androgen Receptor Testosterone in the Androgen Receptor Van der Waals Forces

5. Cell Membrane Nucleus Cytoplasm Muscle Growth DNA Biological Mechanism of Testosterone T T A

7. Testosterone banned (1991, Controlled Substances Act) Testosterone is Banned in Sports Dietary supplements Emergence of testosterone precursors. Ex. Androstenedione (“Andro”) -1998

8. Testosterone in Sports Athlete’s desire to improve athletic performance. Supplemental testosterone via injections, pills or topical creams. Floyd Landis- Tour de France Mark McGwire –Major League Baseball Notable Athletes:

9. Synthesis of Androstenedione Corticosterone Keto-Enol Tautomerization 1. Na + - OCH 3 o o 2. O H O H O O H O H H O

10. Synthesis of Androstenedione (cont.) Androstenedione + + . . . . . . . . . . -

11. Proton NMR Spectroscopy H H H H H H Androstenedione O O (s, 6H)

12. Testosterone Proton NMR Spectroscopy H H H H H H H Electron donating effects of oxygen. Neighboring protons more shielded. (S,1H) (t,1H) (s,3H) (s,3H)

13. Androstenedione IR Spectroscopy

14. Testosterone IR Spectroscopy

15. Does Androstenedione Make You Stronger? Increases estrone and estradiol levels in men Androstenedione Aromatase Testosterone Estradiol Aromatase Estrone The Result?

16. Man Boobs! (aka Gynecomastia)

17. Conclusions Desired results not achieved. Other methods to bypass laws. Designer Steroids - BALCO, Olympics How to stay ahead of designer steroid manufacturers?

18. References Floyd Landis: http://www.roadcycling.com/artman/uploads/5_landis_podium_002.jpg Mark McGwire: http://www.misunderestimation.com/wp-content/uploads/2007/01/GotJuice.jpg Homer Simpson: http://users. bigpond .net.au/ simpsons /mirror. jpg Health Effects of Androstenedione. FDA White Paper. U.S. Food and Drug Administration. Retrieved on 4/13/09. http://www.fda.gov/oc/whitepapers/andro.html. FDA Warning on Androstenedione (Andro). National Center for Complementary and Alternative Medicine. Retrieved on 4/24/09. http://nccam.nih.gov/news/alerts/androstenedione/consumeradvisory.htm. Koert , Willem and Aede de Groot. The Anabolics Book. Retrieved on 4/10/09. http://www.ergogenics.org/anabolenboek/index21en.html. Yesalis, Charles E. (1999). Medical, Legal, and Societal Implications of Androstenedione Use. JAMA . 1999;281(21):2043-2044. Leder et al. (2002). Effects of Oral Androstenedione Administration on Serum Testosterone and Estradiol Levels in Postmenopausal Women. The Journal of Clinical Endocrinology & Metabolism 87(12):5449–5454. Cawley et al. The detection of androstenedione abuse in sport: a mass spectrometry strategy to identify the 4-hydroxyandrostenedione metabolite. Rapid Commun. Mass Spectrom. 2008; 22: 4147–4157. Le Pera et al (2003). A straightforward chemical synthesis of 17-ketosteroids by cleavage of the C-17-dihydroxyacetone Side chain in corticosteroids. Steroids 68 (2003) 139–142.