Diagnostic Accuracy of a Single Serum Testosterone Measurement: The False Negative Rate

Presentation Number: THR-122
Date of Presentation: March 5th, 2015

Xiao Ni1 and David Muram*2
1Eli Lilly and Company, Indianapolis, IN, 2Eli Lilly and Company

Abstract

To diagnose hypogonadism, evidence-based guidelines recommend, in addition to clinical signs and symptoms, a measurement of morning total testosterone (TT) level by a reliable assay followed by a repeated measurement of TT for confirmation. While at least two measurements are recommended for the diagnosis of hypogonadism, only one measurement of TT level is recommended 3 to 6 months after treatment initiation to determine if dose adjustment is needed.  The aim of this post-hoc analysis was to evaluate the diagnostic accuracy of a single serum TT measurement in men receiving testosterone replacement therapy who had serum average concentration (Cavg) below normal range (<300 ng/dL). Androgen-deficient men (N=155), enrolled in an open-label, multi-center, titration trial, were started on 60-mg daily morning dose of testosterone solution 2% (Axiron®) applied to axillae (30 mg/axilla). On Days 15, 60, and 120, TT levels were measured at 2, 4, 8, 12, 16 and 20 hours post-dose and serum testosterone Cavg was determined. If necessary, dose was adjusted on days 45 and 90 to maintain Cavg in the normal range (300-1050 ng/dL).  Cavg was determined to be below normal (<300 ng/dL) for 31 patients on day 15, 16 patients on Day 60, and 17 patients on Day 120; per protocol, these patients were titrated up at the next visit from the 60-mg dose to the 90-mg daily dose, or from the 90-mg dose to the 120-mg daily dose. In total, there were 64 instances when Cavg was determined to be below normal. However, 12 (40%) patients on Day 15, 10 (63%) patients on Day 60, and 6 (35%) patients on Day 120 with a Cavg below normal had a 2-hour serum TT determination within the normal range in.  The average percentage (across all days) of discordant results between Cavg and serum TT measurements, where TT was in the normal range, declined as the time from application increased, from 44% at 2 hours, to 38% at 4 hours, 22% at 8 hours to as low as 3% at 16 hours.  In conclusion, the diagnostic accuracy of a single TT measurement in men whose Cavg was below the normal range was as low as 56% at 2 hours, varying at different time points post-dose, which may reflect the pharmacokinetic profile and may be related to the rate of testosterone absorption and  clearance. In men receiving topical testosterone therapy, whose Cavg is below normal, relying on a single TT determination could result in less than optimal dosing which may lead to discontinuation of therapy due to perceived lack of treatment effect.

 

Disclosure: XN: Employee, Eli Lilly & Company. DM: Employee, Eli Lilly & Company.