A prospective comparison study of subcutaneous and intramuscular testosterone injections in transgender male adolescents
-
Hayley K. Baines
and
Kara J. Connelly
Abstract
Objectives
This prospective study compares testosterone injection type and effects on biochemical changes, clinical effects, and quality of life amongst transgender and gender diverse (TGD) adolescents assigned female at birth (AFAB) over the first 6 months of subcutaneous (SQ) vs. intramuscular (IM) testosterone injections as part of their gender affirming care.
Methods
Subjects were testosterone-naïve transgender adolescents, AFAB, ages 14–18 years old. Subjects were either randomized to injection type or selected a preferred injection type. At enrollment, subjects completed baseline labs and PedsQL™ quality of life questionnaire. At 3 month and 6 month follow up, subjects completed peak and trough testosterone levels, PedsQL™, masculinizing effects, and medication experience questionnaires.
Results
Twenty-six subjects participated with a median age 15.5 years. By 6-month follow up, trough testosterone levels were comparable between the two groups. Peak testosterone levels were higher in the IM group at 3-month follow up. Mild adverse effects were rare (12 %, all in SQ subjects) and limited to skin reaction only. Self-reported masculinization effects and quality of life were not statistically different between injection groups. A total of 92 % of participants was self-injecting by 3-month follow up.
Conclusions
In this prospective study, clinical and biochemical effects are similar between SQ and IM testosterone injections for transgender adolescents. Subjects expressed preference for both injection types. Both SQ and IM injection modalities are safe and effective for TGD youth initiating testosterone and both options should be offered to patients.
Funding source: Pediatric Endocrine Society
Award Identifier / Grant number: Rising Star Award
Funding source: Oregon Health and Science University
Award Identifier / Grant number: OHSU Tartar Trust Fellowship
Acknowledgments
Special thanks to Sheila Markwardt, MPH for biostatistics support and Michael Harris, PhD for assistance with questionnaire design. Thank you to all study participants for their contribution to this study.
-
Research ethics: The research related to human use has complied with all the relevant national regulations, institutional policies, and in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors' Institutional Review Board or equivalent committee. The study was approved by the OHSU Institutional Review Board (IRB) number 17454.
-
Informed consent: Informed consent was obtained from all individuals included in this study.
-
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. HB and KC heavily collaborated in study conception and design. HB was primary data collector, which KC reviewed. HB made primary data analysis, collaborated with biostatistician, and KC assisted with interpretation. HB drafted manuscript which was reviewed and revised by KC with additional content and references. HB and KC approved manuscript ready for publication.
-
Competing interests: Dr. Baines and Dr. Connelly state no conflict of interest.
-
Research funding: Dr. Baines was supported by NIH T32 Training Grant 4T32HD007497-15. The study was supported by the Pediatric Endocrine Society Rising Star Award, the OHSU Tartar Trust Fellowship and the OHSU Department of Pediatrics for biostatistics support. OHSU Oregon Clinical & Translation Research Institute REDCap grant support UL1TR002369. The PedsQL™ used with permission.
-
Data availability: All data generated or analysed during this study are included in this published article (and its supplementary files).
-
Clinical trial registry: ClinicalTrials.gov number NCT03864913 (registered March 6, 2019).
References
1. de Vries, AL, McGuire, JK, Steensma, TD, Wagenaar, EC, Doreleijers, TA, Cohen-Kettenis, PT. Young adult psychological outcome after puberty suppression and gender reassignment. Pediatrics 2014;134:696–704. https://doi.org/10.1542/peds.2013-2958.Search in Google Scholar PubMed
2. Rosenthal, SM. Approach to the patient: transgender youth: endocrine considerations. J Clin Endocrinol Metab 2014;99:4379–89. https://doi.org/10.1210/jc.2014-1919.Search in Google Scholar PubMed
3. Coleman, E, Radix, AE, Bouman, WP, Brown, GR, de Vries, ALC, Deutsch, MB, et al.. Standards of care for the health of transsexual, transgender, and gender nonconforming people, Vol 8. Int J Transgend Health 2022;23(Suppl):S1–259.Search in Google Scholar
4. Hembree, WC, Cohen-Kettenis, PT, Gooren, L, Hannema, S, Meyer, WJ, Murad, MH, et al.. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2017;102:3869–903. https://doi.org/10.1210/jc.2017-01658.Search in Google Scholar PubMed
5. Laurenzano, SE, Newfield, RS, Marinkovic, M. Subcutaneous testosterone is effective and safe as gender-affirming hormone therapy in transmasculine and gender-diverse adolescents and young adults: a single center’s 8-year experience. Transgender Health 2021;6:343–52. https://doi.org/10.1089/trgh.2020.0103.Search in Google Scholar PubMed PubMed Central
6. Olson, J, Schrager, SM, Clark, LF, Dunlap, SL, Belzer, M. Subcutaneous testosterone: an effective delivery mechanism for masculinizing young transgender men. LGBT Health 2014;1:165–7. https://doi.org/10.1089/lgbt.2014.0018.Search in Google Scholar PubMed
7. Spratt, DI, Stewart, II, Savage, C, Craig, W, Spack, N, Chandler, DW, et al.. Subcutaneous injection of testosterone is an effective and preferred alternative to intramuscular injection: demonstration in female-to-male transgender patients. J Clin Endocrinol Metab 2017;102:2349–55. https://doi.org/10.1210/jc.2017-00359.Search in Google Scholar PubMed
8. Kaminetsky, J, Jaffe, JS, Swerdloff, RS. Pharmacokinetic profile of subcutaneous testosterone enanthate delivered via a novel, prefilled single-use autoinjector: a phase II study. Sex Med 2015;3:269–79. https://doi.org/10.1002/sm2.80.Search in Google Scholar PubMed PubMed Central
9. Turner, L, Ly, LP, Desai, R, Singh, GKS, Handelsman, TD, Savkovic, S, et al.. Pharmacokinetics and acceptability of subcutaneous injection of testosterone undecanoate. J Endocr Soc 2019;3:1531–40. https://doi.org/10.1210/js.2019-00134.Search in Google Scholar PubMed PubMed Central
10. Wilson, DM, Kiang, TKL, Ensom, MHH. Pharmacokinetics, safety, and patient acceptability of subcutaneous versus intramuscular testosterone injection for gender-affirming therapy: a pilot study. Am J Health Syst Pharm 2018;75:351–8. https://doi.org/10.2146/ajhp170160.Search in Google Scholar PubMed
11. Varni, JW, Seid, M, Kurtin, PS. PedsQL 4.0: reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic core scales in healthy and patient populations. Med Care 2001;39:800–12. https://doi.org/10.1097/00005650-200108000-00006.Search in Google Scholar PubMed
12. Pleil, AM, Kimel, M, McCormack, J, Rajicic, N, Hey-Hadavi, J. Psychometric assessment of the Injection Pen Assessment Questionnaire (IPAQ): measuring ease of use and preference with injection pens for human growth hormone. Health Qual Life Outcome 2012;10:126. https://doi.org/10.1186/1477-7525-10-126.Search in Google Scholar PubMed PubMed Central
13. Olson-Kennedy, J, Okonta, V, Clark, LF, Belzer, M. Physiologic response to gender-affirming hormones among transgender youth. J Adolesc Health 2018;62:397–401. https://doi.org/10.1016/j.jadohealth.2017.08.005.Search in Google Scholar PubMed PubMed Central
14. Becerra-Culqui, TA, Liu, Y, Nash, R, Cromwell, L, Flanders, WD, Getahun, D, et al.. Mental health of transgender and gender nonconforming youth compared with their peers. Pediatrics 2018;141:e20173845. https://doi.org/10.1542/peds.2017-3845.Search in Google Scholar PubMed PubMed Central
15. Herman, JL, Brown, TNT, Haas, AP. Suicide thoughts and attempts among transgender adults. Los Angeles, CA: The Williams Institute; 2019.Search in Google Scholar
16. Price-Feeney, M, Green, AE, Dorison, S. Understanding the mental health of transgender and nonbinary youth. J Adolesc Health 2020;66:684–90. https://doi.org/10.1016/j.jadohealth.2019.11.314.Search in Google Scholar PubMed
17. Reisner, SL, Vetters, R, Leclerc, M, Zaslow, S, Wolfrum, S, Shumer, D, et al.. Mental health of transgender youth in care at an adolescent urban community health center: a matched retrospective cohort study. J Adolesc Health 2015;56:274–9. https://doi.org/10.1016/j.jadohealth.2014.10.264.Search in Google Scholar PubMed PubMed Central
18. Aldridge, Z, Patel, S, Guo, B, Nixon, E, Pierre Bouman, W, Witcomb, GL, et al.. Long-term effect of gender-affirming hormone treatment on depression and anxiety symptoms in transgender people: a prospective cohort study. Andrology 2020. https://doi.org/10.1111/andr.12884.Search in Google Scholar PubMed
19. Colizzi, M, Costa, R, Todarello, O. Transsexual patients’ psychiatric comorbidity and positive effect of cross-sex hormonal treatment on mental health: results from a longitudinal study. Psychoneuroendocrinology 2014;39:65–73. https://doi.org/10.1016/j.psyneuen.2013.09.029.Search in Google Scholar PubMed
20. Heylens, G, Verroken, C, De Cock, S, T’Sjoen, G, De Cuypere, G. Effects of different steps in gender reassignment therapy on psychopathology: a prospective study of persons with a gender identity disorder. J Sex Med 2014;11:119–26. https://doi.org/10.1111/jsm.12363.Search in Google Scholar PubMed
21. Johansson, A, Sundbom, E, Höjerback, T, Bodlund, O. A five-year follow-up study of Swedish adults with gender identity disorder. Arch Sex Behav 2010;39:1429–37. https://doi.org/10.1007/s10508-009-9551-1.Search in Google Scholar PubMed
22. Ruppin, U, Pfäfflin, F. Long-term follow-up of adults with gender identity disorder. Arch Sex Behav 2015;44:1321–9. https://doi.org/10.1007/s10508-014-0453-5.Search in Google Scholar PubMed
Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/jpem-2023-0237).
© 2023 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review
- Clinical heterogeneity and therapeutic options for idiopathic infantile hypercalcemia caused by CYP24A1 pathogenic variant
- Original Articles
- Growth hormone use in pediatric inflammatory bowel disease
- Extremely and very preterm children who were born appropriate for gestational age show no differences in cortisol concentrations or diurnal rhythms compared to full-term children
- A prospective comparison study of subcutaneous and intramuscular testosterone injections in transgender male adolescents
- Excess body weight and dyslipidemia at well-child visit
- Body mass index evolution and ovarian function in adolescent girls who received GnRH agonist treatment for central precocious puberty or early and fast puberty
- Assessment of pubertal onset and disorders of puberty in Indian children and youth with type-1 diabetes
- A different approach to the evaluation of the genotype-phenotype relationship in biotinidase deficiency: repeated measurement of biotinidase enzyme activity
- Expected vs. perceived effects of gender-affirming hormone therapy among transmasculine adolescents
- Developmental scores in offspring of women with subclinical hypothyroidism in pregnancy are affected by gender and thyrotropin cutoff
- Assessment of the diagnosis, treatment, and follow-up of a group of Turkish pediatric glycogen storage disease type 1b patients with varying clinical presentations and a novel mutation
- IGAm: A novel index predicting long-term survival in patients with early-diagnosed inherited metabolic disorders
- Case Report
- Persistent hypercalcemia mimicking hypophosphatasia after discontinuation of a ketogenic diet: a case report
Articles in the same Issue
- Frontmatter
- Review
- Clinical heterogeneity and therapeutic options for idiopathic infantile hypercalcemia caused by CYP24A1 pathogenic variant
- Original Articles
- Growth hormone use in pediatric inflammatory bowel disease
- Extremely and very preterm children who were born appropriate for gestational age show no differences in cortisol concentrations or diurnal rhythms compared to full-term children
- A prospective comparison study of subcutaneous and intramuscular testosterone injections in transgender male adolescents
- Excess body weight and dyslipidemia at well-child visit
- Body mass index evolution and ovarian function in adolescent girls who received GnRH agonist treatment for central precocious puberty or early and fast puberty
- Assessment of pubertal onset and disorders of puberty in Indian children and youth with type-1 diabetes
- A different approach to the evaluation of the genotype-phenotype relationship in biotinidase deficiency: repeated measurement of biotinidase enzyme activity
- Expected vs. perceived effects of gender-affirming hormone therapy among transmasculine adolescents
- Developmental scores in offspring of women with subclinical hypothyroidism in pregnancy are affected by gender and thyrotropin cutoff
- Assessment of the diagnosis, treatment, and follow-up of a group of Turkish pediatric glycogen storage disease type 1b patients with varying clinical presentations and a novel mutation
- IGAm: A novel index predicting long-term survival in patients with early-diagnosed inherited metabolic disorders
- Case Report
- Persistent hypercalcemia mimicking hypophosphatasia after discontinuation of a ketogenic diet: a case report
