Thesis (MPhil (Physiological Sciences))--University of Stellenbosch, 2006. / Background. Creatine monohydrate is widely used for its purported ergogenic and anabolic properties. The mechanism by which creatine supplementation enhances muscle growth is not understood. This study was undertaken to determine whether creatine monohydrate supplementation increases the conversion rate of testosterone to dihydrotestosterone. An increase in dihydrotestosterone could partly explain the beneficial effect of creatine monohydrate on muscle hypertrophy. Methods. Subcommittee C of the research committee of the University of Stellenbosch approved the study. Project number 2001/ C045. The study was designed as a double blind crossover with subjects (n = 20) in each leg of the study. Group 1 (n = 10) taking creatine monohydrate and group 2 (n = 10) glucose during the first leg of the study. In accordance with crossover study design the groups were reversed in the second leg of the study. Gelatin capsules were filled with 5g of either creatine monohydrate or 5g of glucose. Subjects taking creatine monohydrate also took 25g of glucose to improve absorption of creatine. Subjects took creatine monohydrate 25g plus 25g of glucose (ten capsules in all) or glucose ten capsules per day for seven days in the loading phase. In the maintenance phase they took 5g of creatine monohydrate plus 25g of glucose (six capsules in all) per day or six capsules of glucose, for 14 days. The groups were reversed after a six-week washout period and the dosages repeated as per crossover study design. Blood samples were taken on day zero of the study as baseline measurements, repeated on day 7, (after the loading phase), and again on day 21, (after the maintenance phase). These were again repeated in the second leg of the study as per crossover design. Serum was separated within one hour of collection and stored at minus 70 oC. Testosterone and dihydrotestosterone concentrations were determined using a radio-immunoassay kit by an accredited university laboratory. The percentage conversion of testosterone to dihydrotestosterone was calculated. The results were statistically analyzed: A paired t - tests at the beginning of each leg of the study and repeated measure analysis of variance, for the pooled data for each condition over the whole study. Results. The difference in blood levels of testosterone and dihydrotestosterone on both days 0, were not statistically significant. This made the pooling of the data possible. The difference in the percentage conversion of testosterone to dihydrotestosterone over the study period between the creatine monohydrate condition and the glucose condition, was however significant (p < 0.0001). In this small study highly significant statistical results were obtained. The answer to how creatine taken as a supplement exerts its effect may lie in the increased rate of conversion of testosterone to dihydrotestosterone. Conclusion. With the known greater androgenic effect of dihydrotestosterone as opposed to testosterone, the increase in testosterone conversion to dihydrotestosterone could explain how creatine supplementation exerts its anabolic effect in susceptible individuals. A larger study should be done to confirm these results and answer the questions arising from the findings.