Salivary testosterone in female-to-male transgender adolescents during treatment with intra-muscular injectable testosterone esters

IntroductionIn our hospital, female-to-male (FtM) transgender adolescents from the age of 16 are treated with two- or four-weekly intra-muscular injections of testosterone-esters. Some patients treated with four-weekly injections have complaints of fatigue and experience mood swings towards the end of the inter-injection period, which calls for an evaluation of the time-course of testosterone levels between injections. Evaluation of salivary testosterone is a practical approach for sequential measurements. Since only ∼2% of total serum testosterone is present in saliva, a sensitive assay is necessary. The objective was to develop an isotope dilution-liquid chromatography–tandem mass spectrometry method (ID-LC–MS/MS) for salivary testosterone measurements and to evaluate the testosterone profiles after testosterone-ester mixture injections in FtM-adolescents.ExperimentalFtM treated with 125 mg/2 weeks or with 250 mg/4 weeks depots of testosterone-ester mixture collected saliva at different time intervals. Salivary testosterone was measured by a thoroughly validated ID-LC–MS/MS assay.ResultsAn ID-LC–MS/MS method for measuring salivary testosterone was developed with adequate accuracy and specificity. The reference range was established at 135–400 pmol/L. Testosterone levels peaked supra-physiologically immediately post-injection, and decreased to levels within the male reference range after nine days in all patients. 250 mg/4 weeks depots resulted in values below the reference range at the end of the 4 weeks.DiscussionThe development of an adequate ID-LC–MS/MS method for measuring salivary testosterone allowed us to investigate the testosterone profile in FtM-adolescents after testosterone-esters mixture injections. These injections lead to extreme concentrations which may affect the wellbeing of the patients.

► An ID-LC–MS/MS method for measuring salivary testosterone (T) was developed.
► The ID-LC–MS/MS method has adequate accuracy and specificity.
► The reference range for salivary T by ID-LC–MS/MS was 135–400 pmol/L.
► Female to male-adolescents are treated with T-esters mixture injections.
► T profile after these injections was investigated by salivary T measurements.