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Routine determination of T is also recommended in case of isolated low sexual desire [24,168], although the prevalence of hypogonadism is low in the
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Hormones, Metabolism, Aging, and Men s Health with a complete anamnesis and physical examination, aging men with one or more of these complaints or conditions should be investigated when biochemical hypoandrogenism is suspected Some screening questionnaires were developed to facilitate the clinical diagnosis of LOH [157,162,163] Although not extensively used, they can be useful as an initial screening that could lead to a biochemical assessment The ADAM questionnaire is a simple and sensitive questionnaire, but performs marginally on speci city, particularly in the elderly [162] The AMS questionnaire from Heineman has also been validated in most languages [163], but has also a rather low speci city On their introduction, these instruments promised to offer a versatile tool to identify men with LOH in large-scale communities However, Beutel et al recently demonstrated that the ADAM score is unrelated to T levels and only moderately associated with age The AMS is unrelated both to T level and age They conclude that, based on their high correlations with depression, both seem to measure symptoms associated with depression rather than symptoms of LOH [164] In conclusion neither of these questionnaires replaces a proper history and clinical examination, and better instruments need to be developed
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Biochemical diagnosis
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What hormone should be measured The laboratory reference values of T and FT show a wider range than those for most other hormones (for instance, thyroid hormones), which makes it dif cult to establish whether measured values of T in patients are normal or abnormal Is a patient whose plasma levels of T fall from the upper to the lower range of normal T levels (a drop of as much as 50%), T de cient T levels may well remain within the reference range but may be inappropriately low for that particular individual or his particular age In thyroid pathophysiology, plasma thyroid-stimulating hormone (TSH) proves to be a better criterion of thyroid hyper/hypofunction than plasma T4 or T3, but it is uncertain whether plasma LH is a reliable indicator of male hypogonadism in the elderly man With aging there are reductions in LH pulse frequency and amplitude Several studies have found that LH levels are elevated in response to the decline of T levels
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with aging, but less so than is observed in younger men with similarly reductions in T levels [75] This may be due to a shift in the setpoint of the negative feedback of T on the hypothalamic pituitary unit, resulting in an enhanced negative feedback action, which consequently leads to a relatively lower LH output in response to lowered circulating levels of T Another factor is the fact that a number of aging men have chronic illnesses that may cause secondary hypogonadism Another variable that might be signi cant to assess the androgen status in old age is plasma levels of SHBG Its levels increase even with healthy aging, possibly due to a decrease in growth hormone (GH) production and an increase of the ratio of free estradiol over FT [75] Vermeulen and co-workers could demonstrate that the FT value calculated by TT/SHBG (according to a second-degree equation following the mass action law) as determined by immunoassay appears to be a rapid, simple, and reliable indicator of BT and FT, comparable to FT values obtained by equilibrium dialysis [165] An easy-to-use free calculator of calculated FT and BT can be found on wwwissamch So, determination of values of T and SHBG might provide a reasonable index of the androgen status in an aging person BT is also a rather reliable index, but it should be mentioned that direct FT assays using a T analog do not yield a reliable estimate of FT [165] What is a low T level The above has outlined the many unresolved questions as to the veri cation of de ciencies in the biologic action of androgens in old age, and has shown that there is no generally accepted lower limit of normal Consequently, a pragmatic approach to this issue must be taken in order to let aging androgende cient men bene t from replacement therapy, while the above theoretical but important questions are resolved by clinical investigations Vermeulen argues that, in the absence of convincing evidence for an altered androgen requirement in elderly men, he considers the normal range of T levels in young males also valid for elderly men [81,165] There is now general agreement (of cial recommendations of ISSAM, ISA, and EAU) that TT levels above 12 nmol/L (346 ng/mL), or FT above 250 pmol/L (72 pg/mL) do not require substitution [2] Similarly, based on the data
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