An audit of the measurement and reporting of male testosterone levels in UK clinical biochemistry laboratories

Abstract

Introduction: A number of guidance documents have been published in recent years for the diagnosis and management of hypogonadism (HG). Laboratory practice has a major role in supporting guidelines with accurate and precise serum total testosterone (TT) methods and standardised pre-and post-analytical protocols. Our study investigated whether laboratory practice currently supports the management guidelines for HG. Methods: An internet-based questionnaire survey of senior laboratory biochemists (UK/Republic of Ireland) was conducted (April-May 2018). Questions reflected sampling, laboratory practice, reference ranges and reporting of results. The results were analysed in conjunction with data obtained from the UK National External Quality Assurance Service (UK NEQAS) on testosterone assay performance. Results: Analyses of 96 laboratory surveys returned the following: 74 laboratories stated that the optimal sampling time was communicated to users; 81 laboratories used immunoassays; 76 laboratories included reference ranges for adult men (31 had dual/multiple age-related intervals). Wide variability in lower/upper limits was evident in the common immunoassays; the majority of reference ranges were from manufacturers (50.0%) or historical (18.8%). Action limits based on TT levels were used by 64 laboratories, but 63 did not report a borderline range as suggested by the guidelines. Protocols for cascading tests based on TT were evident in 58 laboratories, with 50 laboratories offering estimated free testosterone; interpretative comments were provided by 67 laboratories, but no references were made to the management guidelines. Data from UK NEQAS demonstrated considerable variation in testosterone assay performance. Conclusions: Our survey has highlighted inconsistencies that could lead to HG (and other conditions requiring measurement of TT) not being managed appropriately. The results from this survey and from UK NEQAS reinforce the requirement for action to be considered regarding the standardisation of testosterone assays and harmonisation of laboratory practice. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Lessons learnt from the variation across 6741 family/general practices in England in the use of treatments for hypogonadism

“…Nevertheless, we feel that the differences that we report between general practices and potential determinants of the differences in testosterone prescribing at a general practice level are important findings. Unless there is a strong clinical context (eg a pubertal male with small testes) or raised LH level indicating organic testicular failure, at least 2 fasted early morning samples for serum testosterone should be taken, 6‐8 with addition of SHBG if necessary—in order to estimate circulating free testosterone 29 —before a diagnosis of hypogonadism is made.…”

“…The precise cut points on the basis of morning testosterone levels vary across guidance documents both within and between areas of the world 4‐7 . Moreover, reference ranges quoted by UK laboratories are not commonly derived from fasting samples only or from samples taken in the morning (<11:00 AM) and are usually manufacturer derived (50%) or historical (18.8%) 8 …”

Clinical characteristics and comorbidities associated with testosterone prescribing in men

“…A recent survey of 96 UK clinical biochemistry laboratories reported discrepancies between laboratory TT reference ranges and treatment thresholds recommended by clinical guidelines. 32 We speculate this disconnect may also partly explain why men with TT < 8 nmol/L, despite hypogonadal symptoms, were not prescribed TRT. In addition, 59.4% of men in Group A did not have repeat TT measurements despite index TT < 8 nmol/L and clinical guidelines suggesting two morning TT measurements in men for the diagnosis of hypogonadism.…”

Association Between Low Serum Testosterone and the Development of Metabolic Syndrome in Elderly Taiwanese Men

“…Finally, in the United Kingdom, with a high percentage of immunoassays, considerable variation was noted in testosterone measurement and required further work to achieve standardization. 43 The current geriatrics practice in Taiwan has yet to include T during routine health examination. Therefore, the current study suggests incorporating T in the examination list for men, especially those over 65 years old.…”