Introduction: The Australian ‘Evidence-based guideline for the assessment and management of polycystic ovary syndrome’ (PCOS) recommends calculated bioavailable testosterone, calculated free testosterone or free androgen index (FAI) as first-line tests for hyperandrogenism in PCOS. Androstenedione is recommended as a second-line test.
The availability of liquid chromatography-tandem mass spectrometry (LC-MS/MS) sex steroid assays in some clinical laboratories allows more accurate measurement, particularly at low concentrations, than is possible with immunoassay. LC-MS/MS can also measure multiple hormones simultaneously for little more than the cost of measuring a single hormone. However, doing this may generate results that are clinically useful but have not been requested by the clinician.
In our experience of using LC/MS-MS for routine sex steroid measurement the FAI is usually requested for the investigation of PCOS but may be normal while the (unrequested) androstenedione is elevated. Recent publications using LC-MS/MS sex steroid assays suggest that hyperandrogenism may be missed if only testosterone or FAI is measured.
Methods: Androstenedione and FAI of 425 women (16–45 years) with clinical notes indicating menstrual irregularlity, subfertility, ?PCOS or hirsutism were compared. Androstenedione, testosterone and 17-hydroxyprogesterone were measured by LC-MS/MS on a Shimadzu HPLC and ABSciex-QTRAP-5500 and sex hormone-binding globulin (SHBG) on the Immulite 2000.
Hyperandrogenism was defined as elevated androstenedione or FAI using the laboratory’s upper reference limits for premenopausal women. Normal 17-hydroxyprogesterone excluded congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
Results: 38 (9%) women had normal FAI but elevated androstenedione, 30 (7%) had elevated FAI with normal androstenedione and 47 (11%) had both elevated.
Conclusion: The use of LC/MS-MS to measure sex steroid hormones has shown that hyperandrogenism may be missed without androstenedione measurement. Simultaneous 17-hydroxyprogesterone measurement can exclude 21-hydroxylase deficiency in follicular phase specimens. LC-MS/MS sex steroid measurement, including androstenedione, testosterone and 17-hydroxyprogesterone, should be routinely used in the assessment of hyperandrogenism in women.