SAGE IVD recommended conditionally listing the total testosterone test in EDL 5:
• as a disease-specific IVD for use in health care facilities with clinical laboratories (Section II.b. Endocrine disorders);
• using immunoassay as assay format;
• using serum and plasma as specimen type;
• to diagnose testosterone deficiency in men with clinical hypogonadism

The applications proposed an immunoassay (chemiluminescence) for the quantitative determination of total testosterone in human serum or plasma as an aid in the diagnosis and management of conditions involving excess or deficiency of testosterone. This immunoassay can be used for diagnosing male hypogonadism and evaluating testosterone levels in clinical conditions. It was pointed out that this test is less relevant for diagnosing polycystic ovarian syndrome, as biochemical evidence alone is not the main criterion for diagnosing this syndrome. It was noted that testosterone is in the essential medicines list for hypogonadism and such a test has been a priority since 2021/2022. Certain limitations/concerns were discussed. • Immunoassays are less reliable at low testosterone concentrations compared with mass spectrometry. However, mass spectrometry is less widely available, although it is now available in many reference centres, even in LMICs. • Four products were mentioned in the application. The equipment and assays are expensive, potentially limiting accessibility in LMICs. • Limited or no data were given on the diagnostic accuracy, clinical utility, cost–effectiveness and prevalence of hypogonadism. Is was noted that the submission may have overestimated the disease burden of male hypogonadism. Although one member pointed out that this was a growing issue in Africa. Another member made the point that testosterone treatment is often overused and misused. Thus listing this test for testosterone treatment in males with clinical hypogonadism may help reduce this problem. After the discussion, 79% of the SAGE members supported conditional listing for the test, but only for diagnosing testosterone deficiency in men with clinical hypogonadism. The application for polycystic ovarian syndrome was excluded from the recommendation due to insufficient evidence and guideline support. SAGE IVD members recommended that applicants should be requested to provide further information on evidence for monitoring testosterone treatment, clinical utility, cost–effectiveness and prevalence of hypogonadism.

Tests and assays for total (bound and unbound) testosterone are usually performed in people suspected of disorders associated with a deficiency or excess of testosterone, which include diseases of the primary testosterone-producing organs and impairments of the pituitary gland and the hypothalamus. These tests can also be used to monitor anti-androgen and testosterone replacement therapy. The tests are usually performed on serum or plasma samples. No evidence has been supplied to support the clinical utility (benefit) or the clinical performance of tests for measuring total testosterone, for any target condition. Only data on technical (analytical) performance of four assays are available. It is unclear how these measures of technical performance will correlate with clinical utility. Further investigation is warranted to assess the clinical performance of these tests in detecting relevant target conditions in an intended use population. In its clinical practice guideline on testosterone therapy in men with androgen deficiency syndromes, the Endocrine Society (2010) suggests ‘…clinicians measure serum testosterone level…’ in people with specific symptoms and signs suggestive of androgen deficiency (very low certainty evidence) and suggests ‘…measurement of morning total testosterone level by a reliable assay as the initial diagnostic test.’ (very low certainty evidence) (doi: 10.1210/jc.2009-2354).

The selection and use of essential in vitro diagnostics: report of the fifth meeting of the WHO Strategic Advisory Group of Experts on In Vitro Diagnostics, 2024. World Health Organization. (To be published)