The role of aromatization in testosterone supplementation: effects on cognition in older men.
OBJECTIVE
To determine the contribution of conversion of testosterone (T) to estradiol on cognitive processing in a population of healthy older men who received T supplementation.


METHODS
Sixty healthy, community-dwelling volunteers aged 50 to 90 years completed a randomized, double-blind, placebo-controlled study. Participants were randomized to receive weekly IM injections of 100 mg T enanthate plus daily oral placebo pill (T group, n = 20), 100 mg testosterone enanthate plus 1 mg daily of anastrozole, an aromatase inhibitor (oral pill), to block the conversion of T to estradiol (AT group, n = 19), or saline injection and placebo pill (placebo group, n = 21) for 6 weeks. Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline, week 3 and week 6 of treatment, and after 6 weeks of washout.


RESULTS
Circulating total T was increased from baseline an average of 238% in the T and AT treatment groups. Estradiol increased an average of 81% in the T group and decreased 50% in the AT group during treatment. Significant improvements in spatial memory were evident in the AT and T treatment groups. However, only the group with elevated estradiol levels (T group) demonstrated significant verbal memory improvement.


CONCLUSIONS
In healthy older men, improvement in verbal memory induced by testosterone administration depends on aromatization of testosterone to estradiol, whereas improvement in spatial memory occurs in the absence of increases in estradiol.
Cherrier
M M
MM
Department of Psychiatry and Behavioral Sciences, University of Washington Medical School, Seattle, WA, USA. cherrier@u.washington.edu.
Matsumoto
A M
AM
Amory
J K
JK
Ahmed
S
S
Bremner
W
W
Peskind
E R
ER
Raskind
M A
MA
Johnson
M
M
Craft
S
S
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000523:psychology; D000077384:Anastrozole; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004311:Double-Blind Method; D004958:Estradiol / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000188:drug therapy / Q000517:prevention & control*; D008875:Middle Aged; D009483:Neuropsychological Tests; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology; D017430:Prostate-Specific Antigen / Q000097:blood; D013037:Spatial Behavior / Q000187:drug effects* / Q000502:physiology; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000502:physiology* / Q000627:therapeutic use; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology; D014706:Verbal Learning / Q000187:drug effects* / Q000502:physiology
D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D013739:Testosterone; D004958:Estradiol; C004648:testosterone enanthate; D001141:Aromatase; D017430:Prostate-Specific Antigen