title: Salivary testosterone in female-to-male transgender adolescents during treatment with intra-muscular injectable testosterone esters.
abstract: BACKGROUND
  In 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.
  
  
  METHODS
  FtM 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.
  
  
  RESULTS
  An 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Hong N
authors.initials: HN
authors.lastname: Bui
authors.forename: Sebastian E E
authors.initials: SE
authors.lastname: Schagen
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Klink
authors.forename: Henriette A
authors.initials: HA
authors.lastname: Delemarre-van de Waal
authors.forename: Marinus A
authors.initials: MA
authors.lastname: Blankenstein
authors.forename: Annemieke C
authors.initials: AC
authors.lastname: Heijboer
mesh_terms: D000293:Adolescent; D000728:Androgens / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004952:Esters; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D012016:Reference Values; D012463:Saliva / Q000378:metabolism*; D012680:Sensitivity and Specificity; D057829:Gender-Affirming Procedures; D013739:Testosterone / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000728:Androgens; D004952:Esters; D013739:Testosterone