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Abstract
BackgroundMost of the androgen replacement therapies were based on serum testosterone and without measurements of total androgen activities. Whether those with low testosterone also have low levels of androgen activity is largely unknown. We hence examined the association between testosterone and androstanediol glucuronide (AG), a reliable measure of androgen activity, in a nationally representative sample of US men.MethodsCross-sectional analysis was based on 1493 men from the Third National Health and Nutrition examination Survey (NHANES III) conducted from 1988 to 1991. Serum testosterone and AG were measured by immunoassay. Kernel density was used to estimate the average density of serum AG concentrations by quartiles of testosterone.ResultsTestosterone was weakly and positively correlated with AG (correlation coefficient = 0.18). The kernel density estimates show that the distributions are quite similar between the quartiles of testosterone. After adjustment for age, the distributions of AG in quartiles of testosterone did not change. The correlation between testosterone and AG was stronger in men with younger age, lower body mass index, non-smoking and good self-rated health and health status.ConclusionsSerum testosterone is weakly correlated with total androgen activities, and the correlation is even weaker for those with poor self-rated health. Our results suggest that measurement of total androgen activity in addition to testosterone is necessary in clinical practice, especially before administration of androgen replacement therapy.
Highlights
Most of the androgen replacement therapies were based on serum testosterone and without measurements of total androgen activities
An observational study showed that serum testosterone concentrations declined by 97% following castration in elderly men [3], but the total androgen metabolites has only reduced by 59% [3], which suggests that 41% of androgens remained in the prostate and free to stimulate prostate cancer after castration
Study variables Of the 2205 males aged at least 12 years who participated in NHANES III phase 1 (1988–1991) and attended a morning examination session, 1637 without taking androgen replacement therapy had surplus sera, previously stored at − 70 °C, assayed for sex steroids using competitive electrochemiluminescence immunoassays on the 2010 Elecsys autoanalyzer (Roche Diagnostics, Indianapolis, IN, USA) for serum testosterone and an enzyme immunoassay (Diagnostic Systems Laboratories, Webster, TX, USA) for a glucuronidated androgen metabolite, androstanediol glucuronide (AG) in 2005 at Children’s Hospital, Boston, Massachusetts [8, 9]
Summary
Most of the androgen replacement therapies were based on serum testosterone and without measurements of total androgen activities. Evidence from large randomized controlled trials (RCTs) or meta-analysis of RCTs shows that treatment with testosterone in elderly men is not beneficial and even harmful [2]. Such discrepancies may be due to the common causes of low testosterone and cardiovascular disease, such as underlying illness or aging, or may be because the measurement of serum testosterone does not fully reflect the total circulating androgen exposure. An observational study showed that serum testosterone concentrations declined by 97% following castration in elderly men [3], but the total androgen metabolites has only reduced by 59% [3], which suggests that 41% of androgens remained in the prostate and free to stimulate prostate cancer after castration. Glucuronidated androgen metabolites, mainly including androsterone glucuronide (ADT-G) and androstanediol glucuronide
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