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    • Effect of Testosterone Injections on Estradiol and DHT in Young and Older Men

      The Effects of Injected Testosterone Dose and Age on the Conversion of Testosterone to Estradiol and Dihydrotestosterone in Young and Older Men




      "We found that during administration of graded doses of TE, the older men had higher total and free E2concentrations and higher total and free E2:T ratios than young men after adjusting for serum testosterone levels. In contrast to E2 levels, serum DHT levels and DHT:T ratios did not differ between young and older men. Regression modeling revealed that percentage fat mass independently and partly explained the difference in free E2 levels between young and older men, and jointly with SHBG explained most of the differences in free E2 levels as well as free E2:T ratios in the two groups. There also was an apparent effect of testosterone dose on metabolite to testosterone ratios; higher doses of testosterone were associated with seemingly lower metabolite to testosterone ratios in both young and older men. Mechanistic modeling indicated that the whole body conversion of testosterone to E2 and DHT was consistent with saturable Michaelis-Menten kinetics."


      Background: During testosterone (T) therapy, T is partly converted to 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT). Effects of age, testosterone dose, and body composition on total and free E2and DHT levels are unknown.

      Objective: We evaluated age and dose-related differences in E2 and DHT levels in response to graded doses of testosterone enanthate in young and older men.

      Methods: Fifty-one young (aged 1935 yr) and 52 older (aged 5975 yr) men completed treatment with monthly injections of a GnRH agonist plus randomly assigned weekly doses of testosterone enanthate (25, 50, 125, 300, or 600 mg) for 5 months.

      Results: During testosterone administration, total and free E2 levels increased dose-dependently (dose effect, P < 0.001) in both young and older men. Total and free E2 levels and E2:T ratios during T administration were higher in older than young men, but age-related differences in free E2 and free E2:T ratios were not significant after adjusting for testosterone levels, percentage fat mass, and SHBG. DHT levels and DHT:T ratios were dose-related but did not differ between young and older men. Mechanistic modeling of free hormone data revealed that the conversions of T to E2 and DHT were both consistent with saturable Michaelis-Menten kinetics. The in vivo Km values were estimated to be 1.83 nm for aromatase and 3.35 nm for 5α-reductase, independent of age. The Vmax parameter for E2 was 40% higher in older men than younger men, but Vmax for DHT was not significantly different between age groups.

      Conclusions: During im testosterone administration, E2 and DHT levels exhibit saturable increases with dose. The rate of whole body aromatization is higher in older men, partly related to their higher percentage fat mass, SHBG, and testosterone levels.

      FULL PAPER HERE





      This article was originally published in forum thread: Effect of Testosterone Injections on Estradiol and DHT in Young and Older Men
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