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d) HRT Failure . The above study did not really address the issue that sometimes a man waits and waits for HRT to fix his issues and it simply never happens. This is not necessarily a disaster, because it often a) means that one has other more critical underlying issues such as hypothyroidism, or b) that the protocol needs tuning. In the case of the latter, high estradiol is a common culprit, since it essentially negates the beneifts of the increased testosterone levels. In both of these cases, it pays to have a knowledgeable and experienced physician overseeing your therapy.