Characterization of verbal and spatial memory changes from moderate to supraphysiological increases in serum testosterone in healthy older men

Abstract

Background: It has been suggested that cognitive changes in response to T supplementation may occur within an ideal range. The objective of this study was to compare the cognitive responses of older, eugonadal men in whom moderate or large increases in serum testosterone levels was induced by exogenous testosterone supplementation.

Design: Randomized, double-blind, placebo-controlled study with subsequent grouping of participants according to average increase in circulating T from baseline.

Setting: Community dwelling participants.

Participants: Fifty-seven healthy, eugonadal, community dwelling male volunteers, mean age 67 years (+/-11 years).

Interventions: Participants were randomized to receive weekly intramuscular (i.m.) injections of either 50, 100 or 300 mg T enanthate or placebo (saline) injection for 6 weeks. Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline, weeks 3 and 6 of treatment and after 6 weeks of wash-out.

Main outcome measures: Performance on cognitive tests of verbal and spatial memory.

Results: Men with moderate increases in serum T and/or its metabolites demonstrated significant improvements in verbal and spatial memory. In contrast, men with large or low increases in circulating T levels, failed to demonstrate significant changes in memory.

Conclusion: These results suggest that in healthy older men, beneficial changes in cognitive function induced by T supplementation are most evident with moderate changes in cognition from moderate to high T supplementation increases in T levels. Large or no to low increases in T levels do not appear to appreciably effect cognition.

Figure 1a

Mean total points correct on the Route Test, a measure of spatial and navigational memory. Figure 1b. Mean total points correct on Word List recall, a measure of verbal memory. Diamond represents men who demonstrated no change in serum T (0-10 nmol/L) during treatment. Square represents men who demonstrated a moderate increase in serum T (11-50 nmol/L) during treatment. Triangle represents men who demonstrated a large increase in serum T (> 50 nmol/L) during treatment. Error bars represent standard error of measurement. Men with a moderate increase in serum T levels evidenced a significant improvement on the Route test during treatment and at washout compared to baseline (*p<.05) and compared to men who had no increase or a large increase in serum T levels (*p<.05) (1a). Men with a moderate increase in serum T levels during treatment also demonstrated a significant improvement on the Word List test compared to baseline (*p<.05) (1b). There was no significant change from baseline for Route Test or Word list in the no or large increase groups.

Figure 2

(a-d). Scatter- plots and best fit regression lines depicting the relationship between the change in testosterone from baseline (log transformed) for the top two figures and change from baseline performance on (a) Route test (top left) and (b) Word list (top right). For the bottom two figures, change in estradiol from baseline (log transformed) and change from baseline performance on (c) Route test (bottom left) and (d) Word list (bottom right). Asterisk indicates significant linear regression line F(1,36) = 6.7, p<.01, multiple R = .397.