Bhasin, S., Woodhouse, L., Dzekov, C., Dzekov, J., Sinha-Hikim, I, Shen, R., Singh, A. B., Drew, C. R., Casaburi, R., Bhasin, D., Berman, N., Bross, R., Phillips, J., Chen, X., Yaarasheski, K. E., Magliano, L, & Storer, T. W. (2001). Testosterone dose-response relationships in healthy young men. American Journal of Physiology: Endocrinology and Metabolism, 281, E1172-E1181.

This study determined the effects of graded doses of testosterone on body composition, muscle size, strength, power, sexual and cognitive functions, prostate-specific antigen, plasma lipids, hemoglobin, and insulin-like growth factor I (IGF-I) levels. Eugonadal men were assigned to one of five groups to receive monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist, to suppress endogenous testosterone secretion, and weekly injections of 25, 50, 125, 300, or 600 mg of testosterone enanthate for 20 weeks. Energy and protein intakes were standardized. Of the 61 men enrolled, 54 completed the study: 12 in group 1, 8 in group 2, 11 in group 3, 10 in group 4, and 13 in group 5.

The administration of the GnRH agonist plus graded doses of testosterone resulted in mean nadir testosterone concentrations of 253, 306, 542, 1,345, and 2,370 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Fat-free mass increased dose dependently in men receiving 125, 300, or 600 mg of testosterone weekly. Changes in fat-free mass were highly dependent on testosterone dose and correlated with log testosterone concentrations. Changes in leg press strength, leg power, thigh and quadriceps muscle volumes, hemoglobin, and IGF-I were positively correlated with testosterone concentrations, whereas changes in fat mass and plasma high-density lipoprotein (HDL) cholesterol were negatively correlated. Sexual function, visual-spatial cognition and mood, and PSA levels did not change significantly at any dose.

• The thigh muscle volume and quadriceps muscle volume did not significantly change in men receiving the low 25- or 50-mg doses but increased dose-dependently at higher doses of testosterone.
• Leg press strength did not change significantly in the 25- and 125-mg-dose groups but increased significantly in those receiving the 50-, 300-, and 600-mg doses. Leg power did not change significantly in men receiving the 25-, 50-, and 125-mg doses of testosterone weekly, but it increased significantly in those receiving the 300- and 600-mg doses.

Implication. The above two bulleted findings show that for exogenous testosterone to have any performance-enhancing effect, it must be taken in relatively large doses. Low doses will have no effect. This result is not surprising for with most drugs, a certain dose strength has to be administered to initiate an effective response.

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