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How best to test for testosterone

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Another article which shows that we can’t trust anything in our profit first system.  It is as Ben Goldacre says:  the devil is in the details.  In this case it is the lab tests for testosterone.  Each service does what is in their financial interest.   

 

https://academic.oup.com/biomedgerontology/article/57/2/M76/547924

Andropause: Clinical Implications of the Decline in Serum Testosterone Levels With Aging in Men

The Journals of Gerontology: Series A, Volume 57, Issue 2, 1 February 2002, Pages M76–M99, https://doi.org/10.1093/gerona/57.2.M76

 

Because SHBG levels increase with aging, many older men with low-normal total T levels have free or bioavailable T levels that are below the normal range for young men. Therefore, measurements of bioavailable or free T using ammonium sulfate precipitation or equilibrium dialysis, respectively, or calculated from measurements of total T and SHBG are recommended to diagnose androgen deficiency in older men. Unfortunately, these measurements of free and bioavailable T are not usually performed in local laboratories and are only available through commercial reference laboratories. Most local laboratories measure free T using a solid-phase direct analog immunoassay kit. Although free T measurements using this method correlate with those using equilibrium dialysis, values obtained differ substantially [e.g., by more than an order of magnitude in women (53)] from those obtained by equilibrium dialysis or calculated from SHBG, and vary directly with alterations in SHBG levels (52)(53)(54)(55)(56). Therefore, free T measurements using direct analog immunoassay kits may not provide useful clinical information beyond that of total T levels. They tend to under-diagnose older men with androgen deficiency and over-diagnose androgen deficiency in men with low SHBG levels (e.g., moderately obese men). Free T levels measured using a direct analog immunoassay should not be used in situations where SHBG levels may be altered (e.g., older men).

Age-Related Alterations in Androgen Action and Active Metabolism of T

Besides the limited studies of T negative feedback mentioned previously, a systematic evaluation of age-related changes in androgen action in androgen-responsive target organs has not been performed. Androgen receptor gene expression in the CA1 region of the hippocampus and the number of androgen receptor binding sites in genital skin are decreased in older compared with young men (112)(113)(114). Androgen receptor expression and nuclear androgen receptor levels in the prostate are unchanged in older men without benign prostatic hyperplasia (BPH) and are similar to those in young men (115)(116)(117). However, prostate androgen receptor expression is reduced, and nuclear androgen receptor levels are increased in older men with BPH compared with young men.

The length of trinucleotide CAG repeats in the androgen receptor gene is variable and is associated with differences in transcriptional activity, with a shorter CAG repeat length associated with greater androgen receptor activity and possibly overall greater androgen action (118). In the Massachusetts Male Aging Study (MMAS), serum total and free T levels were found to be associated with the CAG repeat length in the androgen receptor gene (40). Older men with lower serum T levels had an androgen receptor genotype characterized by a shorter CAG repeat length, suggesting overall greater androgen activity. It is hypothesized that, in older men with shorter CAG repeat length, increased androgen action at the level of the hypothalamic-pituitary axis may result in greater feedback suppression of gonadotropin and, in turn, endogenous T secretion. This may be an intrinsic mechanism that underlies the physiological decline in serum T levels with aging. A shorter CAG repeat length in the androgen receptor gene also has been associated with an increased risk and severity of BPH and prostate cancer (119)(120)(121)(122)(123)(124)(125) and an earlier age at diagnosis and aggressiveness of prostate carcinoma (126)(127)(128)(129).

Androgen action is not simply a function of androgen receptor expression in target tissues and CAG repeat length, but involves a complex interaction among androgen ligands such as T, the androgen receptor, and tissue-specific coactivators and corepressors with androgen-response elements in specific genes (130)(131). Age-related alterations of the latter and other transcription factors in androgen target tissues and their effects on androgen action have not been investigated. However, the preliminary findings reviewed suggest that, in addition to circulating T levels, age-associated changes in androgen action may play important roles in the alterations of physiological function that occur with normal aging and in the pathophysiology of age-related pathologies.

T is actively metabolized to the potent estrogen, estradiol (E2), by the enzyme aromatase, which is located primarily in adipose tissue, and to 5 alpha-dihydrotestosterone (DHT), a more potent androgen than T, by the enzymes 5 alpha-reductase type 1 and 2, which are located predominantly in skin and the prostate (132)(133)(134). Many of the actions of T are mediated, at least in part, by its active metabolites, E2 (e.g., bone, brain, and lipids) and DHT (e.g., prostate). Despite declining T levels, serum total E2 and DHT levels do not change or decrease only slightly with aging (24)(26)(34)(37)(38)(135)(136)(137)(138)(139). This suggests that, with aging, there is a relative increase in aromatization of T to E2 (perhaps due to increased adipose tissue mass) and 5 alpha-reduction of T to DHT and/or reductions in the metabolic clearance of E2 and DHT. Because serum SHBG levels increase with aging, serum bioavailable or free E2 and DHT levels would be expected to decrease with aging. The physiological significance of bioavailable E2 and DHT is not clear. However, recent studies suggest that bioavailable E2 levels decline with aging and correlate better than T with bone mineral density in men (26)(137)(139)(140).

Serum markers of peripheral androgen action such as 3 alpha-, 17 beta-androstanediol glucuronide (3 alpha-diol G) decrease markedly with aging, suggesting an overall decline in the total circulating androgen pool (24)(138)(141). Tissue concentrations of DHT decrease within the epithelial compartment and E2 increase within the stromal compartment of the normal and BPH prostate gland with aging, emphasizing the importance of active metabolism of T in androgen target organs and within specific regions of these organs (142)(143)(1

 https://academic.oup.com/biomedgerontology/article/57/2/M76/547924

 

 

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Prof. Marcia Angell, Harvard: “We certainly are in a health care crisis, ... If we had set out to design the worst system that we could imagine, we couldn't have imagined one as bad as we have.” Her excellent 77 minute lecture on pharma http://www.youtube.com/watch?v=ZqKY6Gr6D3Q