Contamination of collected blood samples by application of testosterone gel near the venipuncture site can cause spuriously elevated serum testosterone concentrations. Often this will be detected only in case of extreme discrepancies between lab result and clinical effects. Because in vitro testosterone cannot be metabolized as the testosterone in vivo we hypothesized that measuring estradiol, as a metabolite of testosterone after aromatizing, could give a biochemical clue for contamination.
To assess the prevalence of high serum testosterone-to-estradiol ratio in users of testosterone gel compared to users of long-acting testosterone injections (testosterone undecanoate, TU).
Design and Methods
In this study of the retrospective Amsterdam Cohort of Gender Dysphoria (ACOG) study, 474 trans men with testosterone (in nmol/l) and estradiol (in pmol/l) concentrations measured at least one year after oophorectomy, were included between 2004 and 2018. The proportion of trans men with a testosterone-to-estradiol ratio above the 97.5% percentile of the median of the TU injection users was measured in both groups. Both testosterone and estradiol were measured by or recalculated to LC-MS/MS. Logistic regression was used for statistical analysis.
168 trans men (42 ± 13 years) using testosterone gel and 306 trans men (35 ± 12 years) using TU injections were included. The groups had a similar average BMI of 26 kg/m2. The mean testosterone-to-estradiol ratio of the TU injection users was 0.29 nmol/l per pmol/l, the limit of the 97th percentile was 0.59. Of the testosterone gel users, 8.3% (95% CI 4.613.6%) had a testosterone-to-estradiol ratio above 0.59, vs 2.7% (95% CI 0.67.6%) in the TU injection users. The odds ratio (OR) for this difference was 3.3 (95% CI 0.911.8). Using a cut-off point of 0.60 (99th percentile) we found 13 samples (7.7%, 95% CI 4.212.9%) with a higher testosterone-to-estradiol ratio in the testosterone gel group and one (0.9% 95% CI 0.04.9%) in the TU group (OR 9.3, 95% CI 1.272.2).
Trans men using testosterone gel sometimes show a considerably increased testosterone-to-estradiol ratio compared to those using TU injections, probably caused by contamination at the phlebotomy site. However, the prevalence of such a high ratio is still quite low. We conclude that the testosterone-to-estradiol ratio can be used in clinical practice as a biochemical clue for contamination. Further studies might reveal whether measurements of other testosterone metabolites might improve the detection of spurious elevations.
22 May 2021 - 26 May 2021