Testosterone dose-response relationships in healthy young men.
Testosterone increases muscle mass and strength and regulates other physiological processes, but we do not know whether testosterone effects are dose dependent and whether dose requirements for maintaining various androgen-dependent processes are similar. To determine the effects of graded doses of testosterone on body composition, muscle size, strength, power, sexual and cognitive functions, prostate-specific antigen (PSA), plasma lipids, hemoglobin, and insulin-like growth factor I (IGF-I) levels, 61 eugonadal men, 18-35 yr, were randomized 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 wk. Energy and protein intakes were standardized. 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 (change +3.4, 5.2, and 7.9 kg, respectively). The changes in fat-free mass were highly dependent on testosterone dose (P = 0.0001) and correlated with log testosterone concentrations (r = 0.73, P = 0.0001). 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. We conclude that changes in circulating testosterone concentrations, induced by GnRH agonist and testosterone administration, are associated with testosterone dose- and concentration-dependent changes in fat-free mass, muscle size, strength and power, fat mass, hemoglobin, HDL cholesterol, and IGF-I levels, in conformity with a single linear dose-response relationship. However, different androgen-dependent processes have different testosterone dose-response relationships.
Bhasin
S
S
Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA. SBHASIN@UCLA.EDU
Woodhouse
L
L
Casaburi
R
R
Singh
A B
AB
Bhasin
D
D
Berman
N
N
Chen
X
X
Yarasheski
K E
KE
Magliano
L
L
Dzekov
C
C
Dzekov
J
J
Bross
R
R
Phillips
J
J
Sinha-Hikim
I
I
Shen
R
R
Storer
T W
TW
D000328:Adult; D000726:Androgen Antagonists / Q000494:pharmacology; D001823:Body Composition / Q000187:drug effects*; D001834:Body Water / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D009747:Nutritional Physiological Phenomena; D012725:Sexual Behavior / Q000187:drug effects; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*
D000726:Androgen Antagonists; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone