Differences in the apparent metabolic clearance rate of testosterone in young and older men with gonadotropin suppression receiving graded doses of testosterone.
BACKGROUND
Recently we found that testosterone levels are higher in older men than young men receiving exogenous testosterone. We hypothesized that older men have lower apparent testosterone metabolic clearance rates (aMCR-T) that contribute to higher testosterone levels.


OBJECTIVE
The objective of the study was to compare aMCR-T in older and young men and identify predictors of aMCR-T.


METHODS
Sixty-one younger (19-35 yr) and 60 older (59-75 yr) men were given a monthly GnRH agonist and weekly testosterone enanthate (TE) (25, 50, 125, 300, or 600 mg) for 5 months. Estimated aMCR-T was calculated from the amount of TE delivered weekly and trough serum testosterone concentrations, corrected for real-time absorption kinetics from the im testosterone depot.


RESULTS
Older men had lower total (316 +/- 13 vs. 585 +/- 26 ng/dl, P < 0.00001) and free testosterone (4 +/- 0.1 vs. 6 +/- 0.3 ng/dl, P < 0.00001) and higher SHBG (52 +/- 3 vs. 33 +/- 2 nmol/liter, P < 0.00001) than younger men at baseline. Total and free testosterones increased with TE dose and were higher in older men than young men in the 125-, 300-, and 600-mg dose groups. aMCR-T was lower in older men than young men (1390 +/- 69 vs. 1821 +/- 102 liter/d, P = 0.006). aMCR-T correlated negatively with age (P = 0.0007), SHBG (P = 0.046), and total testosterone during treatment (P = 0.02) and percent body fat at baseline (P = 0.01) and during treatment (P = 0.004). aMCR-T correlated positively with lean body mass at baseline (P = 0.03) and during treatment (P = 0.01). In multiple regression models, significant predictors of aMCR-T included lean body mass (P = 0.008), percent fat mass (P = 0.009), and SHBG (P = 0.001).


CONCLUSIONS
Higher testosterone levels in older men receiving TE were associated with an age-related decrease in apparent testosterone metabolic clearance rates. Body composition and SHBG were significant predictors of aMCR-T.
Coviello
Andrea D
AD
Department of Medicine, Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, Massachusetts 02118, USA. coviello@bu.edu
Lakshman
Kishore
K
Mazer
Norman A
NA
Bhasin
Shalender
S
D000328:Adult; D000367:Age Factors; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006062:Gonadotropins / Q000819:agonists*; D020249:Hormone Replacement Therapy; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010349:Patient Compliance / Q000706:statistics & numerical data; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
D006062:Gonadotropins; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; C004648:testosterone enanthate