The onset of late life hypogonadism

Those of us interested in the field of male hypogonadism welcome the opinion paper by John Morley (The diagnosis of late life hypogonadism. Aging Male 2007;10:217–20) [1]. Not only is the author a well respected expert in the discipline but the article contains challenges worth heeding.

There is wide acceptance that a diagnosis of hypogonadism should include both clinical and biochemical parameters. These parameters, however, have been very controversial.

A number of questionnaires have been proposed but, as the manuscript indicates, their clinical accuracy remains to be defined [2]. It is my view that these questionnaires are useful as part of the initial clinical assessment, excellent for standardization of clinical studies but not yet proven to be reliable outcome measures of intervention. In the absence of better instruments, they have to do for the time being.

Let us go now to the core and really interesting and intriguing part of the paper: the need for a positive response to treatment to be part and parcel of the clinical picture and diagnosis of a testosterone deficiency syndrome (TDS). This notion represents an evolutionary refinement of a concept that we initially proposed four years ago [3]. It was our view, then that in the presence of a convincing clinical picture but unsupportive biochemical determinations, a three-month trial of testosterone supplementation was warranted. This to be followed by quarterly assessment to determine the advisability of continuing therapy. Dr Morley's view goes beyond that. It proposes that to rule in or out the diagnosis of a TDS in late life the response to T administration be included. The proposal has a lot of merit. It allows the treatment, in responding cases, to continue and would demand additional investigation for initially overlooked co-morbidities. It would also question the reliability of the initial diagnosis in men who failed adequate treatment. Unfortunately, the proposal, at this early juncture, is not free of pitfalls. Firstly, latitude needs to be given to the clinical assessment (with or without questionnaires) over the biochemical assessment which is still marred by controversy related to biological variations and assays of unequal accuracy. If we had a universally acceptable standard for T assays the situation would be greatly simplified. Secondly, there is a problem in real life situations with available commercial preparations of T and the prescribing attitudes of physicians; the educational needs in this regard are indeed substantial. Thirdly, we would need a clear definition of what constitutes a ‘positive response to treatment’. If one has a man responding positively to all questions of the ADAM questionnaire, confirmed biochemical hypogonadism and resolution only of his sexual desire difficulties following adequate T treatment, how should the response be rated? Fourthly, the duration of treatment necessary to complete the diagnosis will need to be defined unambiguously; three months might be sufficient for some manifestations but not for others. Finally, would the three ‘diagnostic’ components carry the same diagnostic weight? In other words, would a positive response overrule any other consideration?

Allow me to reiterate that, in my opinion, Dr Morley's proposal is commendable, well thought out and unquestionably deserving of fine tuning and additional research. At this point, the hypothesis could be tested with retrospective studies. In the future, perhaps a consortium of interested parties could develop a well planned study to test and confirm it.