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February 2, 2005

Dementia and Testosterone Levels in Men—Reply

Author Affiliations

Letters Section Editor: Robert M. Golub, MD, Senior Editor.

JAMA. 2005;293(5):551-552. doi:10.1001/jama.293.5.552-a

In Reply: Dr Daniell raises possible confounders of the results of our study that demonstrated an inverse relationship between brain levels of testosterone and development of AD. Although we were unable to directly control for obesity, we believe that the contribution of an association with low testosterone to our observations is minimal. Obesity is also associated with elevated estradiol levels and we observed no significant relationship between brain levels of estradiol and neuropathological status. We also do not think that expectant care and opioid use as features of the agonal state explain our results. While it is likely that agonal state may significantly differ between individuals with and without AD, our design indirectly controlled for this possibility with the use of a third group, men with mild neuropathological changes who also showed low levels of testosterone. We reason that because death in this group was unrelated to neurological disease, agonal state in the control group and the mild neuropathological changes group should be similar. Moreover, our findings are consistent with the recent results of Moffat et al,1 who reported that serum levels of testosterone are negatively associated with clinical measures of AD. In their longitudinal study, agonal state was not a relevant factor, and the relationship between testosterone and AD was unaffected by variables such as obesity.

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