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The effect of early puberty suppression on treatment options and outcomes in transgender patients


In the past 10–15 years, paediatric transgender care has emerged at the forefront of several general practice and subspecialty guidelines and is the topic of continuing medical education for various medical disciplines. Providers in specialties ranging from family medicine, paediatrics and adolescent medicine to endocrinology, gynaecology and urology are caring for transgender patients in increasing numbers. Current and evolving national and international best practice guidelines recommend offering a halt of endogenous puberty for patients with early gender dysphoria, in whom impending puberty is unacceptable for their psychosocial health and wellness. Pubertal blockade has implications for fertility preservation, transgender surgical care and psychosocial health, all of which must be considered and discussed with the patient and their family and/or legal guardian before initiation.

Key points

  • Puberty blockade is the earliest point of medical intervention indicated in paediatric patients expressing gender dysphoria and should be initiated as soon as signs of puberty are observed on physical examination.

  • Puberty blockade has been shown to positively affect mental health outcomes in adolescent patients with gender incongruence.

  • Blockade of puberty does affect future fertility options for transgender adults treated early in adolescence and patients should be counselled regarding the options available to them for future fertility.

  • Blockade of puberty prevents the development of secondary sexual characteristics and, therefore, reduces the number of gender-affirming therapies required to transition and also reduces the cost of surgical care.

  • A number of questions remain surrounding early intervention and pubertal blockade, including the future effects on surgical outcomes, cancer risk and economic outcomes.

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Fig. 1: Typical physical milestones of progression through male and female puberty according to Tanner stage.
Fig. 2: Theoretical examples of clinical and social progression of gender dysphoria when it is supported and unsupported, based on collective clinical experience.


  1. 1.

    Bonifacio, H. J. & Rosenthal, S. M. Gender variance and dysphoria in children and adolescents. Pediatr. Clin. North. Am. 62, 1001–1016 (2015).

    Google Scholar 

  2. 2.

    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. (American Psychiatric Association, 2013).

  3. 3.

    Lindmeier, C. WHO releases new International Classification of Diseases (ICD 11) (WHO, 2018).

  4. 4.

    Olson, K. R., Durwood, L., DeMeules, M. & McLaughlin, K. A. Mental health of transgender children who are supported in their identities. Pediatrics 137, e20153223 (2016).

    Google Scholar 

  5. 5.

    Rafferty, J. & Committee on psychosocial aspects of child and family health, Committee on adolescence & section on lesbian, gay, bisexual, and transgender health and wellness. Ensuring comprehensive care and support for transgender and gender-diverse children and adolescents. Pediatrics 142, e20182162 (2018).

    Google Scholar 

  6. 6.

    Malpas, J. Between pink and blue: a multi-dimensional family approach to gender nonconforming children and their families. Fam. Process 50, 453–470 (2011).

    Google Scholar 

  7. 7.

    Yeung, H., Luk, K. M., Chen, S. C., Ginsberg, B. A. & Katz, K. A. Dermatologic care for lesbian, gay, bisexual, and transgender persons: terminology, demographics, health disparities, and approaches to care. J. Am. Acad. Dermatol. 80, 581–589 (2019).

    Google Scholar 

  8. 8.

    Meerwijk, E. L. & Sevelius, J. M. Transgender population size in the United States: a meta-regression of population-based probability samples. Am. J. Public. Health 107, e1–e8 (2017).

    Google Scholar 

  9. 9.

    Herman, J. L., Flores, A. R., Brown, T. N. T., Wilson, B. D. M. & Conron, K. J. Age of Individuals Who Identify as Transgender in the United States (The Williams Institute, UCLA School of Law, 2017)

  10. 10.

    Johns, M. M. et al. Transgender identity and experiences of violence victimization, substance use, suicide risk, and sexual risk behaviors among high school students — 19 states and large urban school districts, 2017. MMWR Morb. Mortal. Wkly Rep. 68, 67–71 (2019).

    Google Scholar 

  11. 11.

    Spack, N. P. et al. Children and adolescents with gender identity disorder referred to a pediatric medical center. Pediatrics 129, 418–425 (2012).

    Google Scholar 

  12. 12.

    Marshall, W. A. & Tanner, J. M. Variations in pattern of pubertal changes in girls. Arch. Dis. Child. 44, 291–303 (1969).

    CAS  Google Scholar 

  13. 13.

    Marshall, W. A. & Tanner, J. M. Variations in the pattern of pubertal changes in boys. Arch. Dis. Child. 45, 13–23 (1970).

    CAS  Google Scholar 

  14. 14.

    Ellis, B. J., Shirtcliff, E. A., Boyce, W. T., Deardorff, J. & Essex, M. J. Quality of early family relationships and the timing and tempo of puberty: effects depend on biological sensitivity to context. Dev. Psychopathol. 23, 85–99 (2011).

    Google Scholar 

  15. 15.

    Özen, S. & Darcan, Ş. Effects of environmental endocrine disruptors on pubertal development. J. Clin. Res. Pediatr. Endocrinol. 3, 1–6 (2011).

    Google Scholar 

  16. 16.

    Howard, S. R. Genes underlying delayed puberty. Mol. Cell. Endocrinol. 476, 119–128 (2018).

    CAS  Google Scholar 

  17. 17.

    Panagiotakopoulos, L. Transgender medicine — puberty suppression. Rev. Endocr. Metab. Disord. 19, 221–225 (2018).

    Google Scholar 

  18. 18.

    Roger, M. et al. Treatment of precocious puberty with LH-RH agonists. Multicenter study using D-Trp-6-LH-RH in a programmed-release form [French]. Rev. Fr. Gynecol. Obstet. 81, 297–305 (1986).

    CAS  Google Scholar 

  19. 19.

    Kreukels, B. P. C. & Cohen-Kettenis, P. T. Puberty suppression in gender identity disorder: the Amsterdam experience. Nat. Rev. Endocrinol. 7, 466–472 (2011).

    CAS  Google Scholar 

  20. 20.

    de Vries, A. L. C. et al. Young adult psychological outcome after puberty suppression and gender reassignment. Pediatrics 134, 696–704 (2014).

    Google Scholar 

  21. 21.

    Turban, J. L., King, D., Carswell, J. M. & Keuroghlian, A. S. Pubertal suppression for transgender youth and risk of suicidal ideation. Pediatrics 145, e20191725 (2020).

    Google Scholar 

  22. 22.

    Edwards-Leeper, L. & Spack, N. P. Psychological evaluation and medical treatment of transgender youth in an interdisciplinary ‘Gender Management Service’ (GeMS) in a major pediatric center. J. Homosex. 59, 321–336 (2012).

    Google Scholar 

  23. 23.

    Martinerie, L., Le Heuzey, M.-F., Delorme, R., Carel, J.-C. & Bargiacchi, A. Assessment and management of gender dysphoria in children and adolescents [French]. Arch. Pediatr. 23, 668–673 (2016).

    CAS  Google Scholar 

  24. 24.

    Ladjouze, A. & Donaldson, M. Primary gonadal failure. Best. Pract. Res. Clin. Endocrinol. Metab. 33, 101295 (2019).

    CAS  Google Scholar 

  25. 25.

    Chen, D., Simons, L., Johnson, E. K., Lockart, B. A. & Finlayson, C. Fertility preservation for transgender adolescents. J. Adolesc. Health 61, 120–123 (2017).

    Google Scholar 

  26. 26.

    Nahata, L., Tishelman, A. C., Caltabellotta, N. M. & Quinn, G. P. Low fertility preservation utilization among transgender youth. J. Adolesc. Health 61, 40–44 (2017).

    Google Scholar 

  27. 27.

    Chiniara, L. N., Viner, C., Palmert, M. & Bonifacio, H. Perspectives on fertility preservation and parenthood among transgender youth and their parents. Arch. Dis. Child. 104, 739–744 (2019).

    Google Scholar 

  28. 28.

    Joshi, S. et al. Clinical guide to fertility preservation in hematopoietic cell transplant recipients. Bone Marrow Transpl. 49, 477–484 (2014).

    CAS  Google Scholar 

  29. 29.

    Sonnenburg, D. W., Brames, M. J., Case-Eads, S. & Einhorn, L. H. Utilization of sperm banking and barriers to its use in testicular cancer patients. Support. Care Cancer 23, 2763–2768 (2015).

    CAS  Google Scholar 

  30. 30.

    Baram, S., Myers, S. A., Yee, S. & Librach, C. L. Fertility preservation for transgender adolescents and young adults: a systematic review. Hum. Reprod. Update 25, 694–716 (2019).

    Google Scholar 

  31. 31.

    Stukenborg, J.-B. et al. Spermatogonial quantity in human prepubertal testicular tissue collected for fertility preservation prior to potentially sterilizing therapy. Hum. Reprod. 33, 1677–1683 (2018).

    CAS  Google Scholar 

  32. 32.

    Onofre, J., Baert, Y., Faes, K. & Goossens, E. Cryopreservation of testicular tissue or testicular cell suspensions: a pivotal step in fertility preservation. Hum. Reprod. Update 22, 744–761 (2016).

    CAS  Google Scholar 

  33. 33.

    Fayomi, A. P. et al. Autologous grafting of cryopreserved prepubertal rhesus testis produces sperm and offspring. Science 363, 1314–1319 (2019).

    CAS  Google Scholar 

  34. 34.

    Schaefer, F., Marr, J., Seidel, C., Tilgen, W. & Schärer, K. Assessment of gonadal maturation by evaluation of spermaturia. Arch. Dis. Child. 65, 1205–1207 (1990).

    CAS  Google Scholar 

  35. 35.

    Cheng, P. J., Pastuszak, A. W., Myers, J. B., Goodwin, I. A. & Hotaling, J. M. Fertility concerns of the transgender patient. Transl. Androl. Urol. 8, 209–218 (2019).

    Google Scholar 

  36. 36.

    Martinez, F. & International Society for Fertility Preservation–ESHRE–ASRM Expert Working Group. Update on fertility preservation from the Barcelona International Society for Fertility Preservation-ESHRE-ASRM 2015 expert meeting: indications, results and future perspectives. Fertil. Steril. 108, 407–415.e11 (2017).

    Google Scholar 

  37. 37.

    Dinikina, Y. et al. Ovarian tissue cryopreservation in prepubertal patients with oncological diseases: multidisciplinary approach and outcomes. J. Matern. Fetal Neonatal Med. (2019).

    Article  Google Scholar 

  38. 38.

    Algarroba, G. N., Sanfilippo, J. S. & Valli-Pulaski, H. Female fertility preservation in the pediatric and adolescent cancer patient population. Best. Pract. Res. Clin. Obstet. Gynaecol. 48, 147–157 (2018).

    Google Scholar 

  39. 39.

    Light, A. D., Obedin-Maliver, J., Sevelius, J. M. & Kerns, J. L. Transgender men who experienced pregnancy after female-to-male gender transitioning. Obstet. Gynecol. 124, 1120–1127 (2014).

    CAS  Google Scholar 

  40. 40.

    Lee, P. A. et al. Efficacy and safety of leuprolide acetate 3-month depot 11.25 milligrams or 30 milligrams for the treatment of central precocious puberty. J. Clin. Endocrinol. Metab. 97, 1572–1580 (2012).

    CAS  Google Scholar 

  41. 41.

    Fuld, K., Chi, C. & Neely, E. K. A randomized trial of 1- and 3-month depot leuprolide doses in the treatment of central precocious puberty. J. Pediatr. 159, 982–987.e1 (2011).

    CAS  Google Scholar 

  42. 42.

    Carel, J.-C. et al. Three-month sustained-release triptorelin (11.25 mg) in the treatment of central precocious puberty. Eur. J. Endocrinol. 154, 119–124 (2006).

    CAS  Google Scholar 

  43. 43.

    Hewitt, J. K. et al. Hormone treatment of gender identity disorder in a cohort of children and adolescents. Med. J. Aust. 196, 578–581 (2012).

    Google Scholar 

  44. 44.

    Evans, M. B. et al. Evaluation of the cost-effectiveness of ovulation suppression with progestins compared with GnRH analogs in assisted reproduction cycles. Reprod. Biomed. Online 38, 691–698 (2019).

    CAS  Google Scholar 

  45. 45.

    Grimstad, F. W. et al. Uterine pathology in transmasculine persons on testosterone: a retrospective multicenter case series. Am. J. Obstet. Gynecol. 220, 257.e1–257.e7 (2019).

    CAS  Google Scholar 

  46. 46.

    Carswell, J. M. & Roberts, S. A. Induction and maintenance of amenorrhea in transmasculine and nonbinary adolescents. Transgend. Health 2, 195–201 (2017).

    Google Scholar 

  47. 47.

    Spinder, T. et al. The effects of long term testosterone administration on pulsatile luteinizing hormone secretion and on ovarian histology in eugonadal female to male transsexual subjects. J. Clin. Endocrinol. Metab. 69, 151–157 (1989).

    CAS  Google Scholar 

  48. 48.

    Nakamura, A. et al. Dose-response analysis of testosterone replacement therapy in patients with female to male gender identity disorder. Endocr. J. 60, 275–281 (2013).

    CAS  Google Scholar 

  49. 49.

    Pelusi, C. et al. Effects of three different testosterone formulations in female-to-male transsexual persons. J. Sex. Med. 11, 3002–3011 (2014).

    Google Scholar 

  50. 50.

    Taub, R. L. et al. The effect of testosterone on ovulatory function in transmasculine individuals. Am. J. Obstet. Gynecol. 223, 229.e1–229.e8 (2020).

    CAS  Google Scholar 

  51. 51.

    Hakim, C., Padmanabhan, V. & Vyas, A. K. Gestational hyperandrogenism in developmental programming. Endocrinology 158, 199–212 (2017).

    CAS  Google Scholar 

  52. 52.

    Kim, H. J., Lee, D.-Y., Yoon, B.-K. & Choi, D. Uterine development after estrogen replacement therapy in women with different etiologies of primary hypogonadism. J. Pediatr. Adolesc. Gynecol. 29, 344–347 (2016).

    Google Scholar 

  53. 53.

    Gomez, A., Walters, P. C. & Dao, L. T. “Testosterone in a way is birth control”: contraceptive attitudes and experiences among transmasculine and genderqueer young adults. Contraception 94, 422–423 (2016).

    Google Scholar 

  54. 54.

    Committee on Adolescent Health Care. Committee Opinion No. 685: care for transgender adolescents. Obstet. Gynecol. 129, e11–e16 (2017).

    Google Scholar 

  55. 55.

    Uysal, G. et al. The efficacy of dienogest in the treatment of simple endometrial hyperplasia without atypia. Gynecol. Obstet. Invest. 83, 151–155 (2018).

    CAS  Google Scholar 

  56. 56.

    Trussell, J. Contraceptive failure in the United States. Contraception 83, 397–404 (2011).

    Google Scholar 

  57. 57.

    Sundaram, A. et al. Contraceptive failure in the United States: estimates from the 2006–2010 National Survey of Family Growth. Perspect. Sex. Reprod. Health 49, 7–16 (2017).

    Google Scholar 

  58. 58.

    Cohen-Kettenis, P. T. & Klink, D. Adolescents with gender dysphoria. Best Pract. Res. Clin. Endocrinol. Metab. 29, 485–495 (2015).

    Google Scholar 

  59. 59.

    Deshmukh, P., Antell, K. & Brown, E. J. Contraception update: progestin-only implants and injections. FP Essent. 462, 25–29 (2017).

    Google Scholar 

  60. 60.

    Belsey, E. M. Vaginal bleeding patterns among women using one natural and eight hormonal methods of contraception. Contraception 38, 181–206 (1988).

    CAS  Google Scholar 

  61. 61.

    Berenson, A. B., Odom, S. D., Breitkopf, C. R. & Rahman, M. Physiologic and psychologic symptoms associated with use of injectable contraception and 20 microg oral contraceptive pills. Am. J. Obstet. Gynecol. 199, 351.e1–12 (2008).

    Google Scholar 

  62. 62.

    Zheng, S. R., Zheng, H. M., Qian, S. Z., Sang, G. W. & Kaper, R. F. A randomized multicenter study comparing the efficacy and bleeding pattern of a single-rod (Implanon) and a six-capsule (Norplant) hormonal contraceptive implant. Contraception 60, 1–8 (1999).

    CAS  Google Scholar 

  63. 63.

    Mansour, D., Korver, T., Marintcheva-Petrova, M. & Fraser, I. S. The effects of Implanon on menstrual bleeding patterns. Eur. J. Contracept. Reprod. Health Care 13, 13–28 (2008).

    CAS  Google Scholar 

  64. 64.

    Darney, P., Patel, A., Rosen, K., Shapiro, L. S. & Kaunitz, A. M. Safety and efficacy of a single-rod etonogestrel implant (Implanon): results from 11 international clinical trials. Fertil. Steril. 91, 1646–1653 (2009).

    Google Scholar 

  65. 65.

    Freeman, S. & Shulman, L. P. Considerations for the use of progestin-only contraceptives. J. Am. Acad. Nurse Pract. 22, 81–91 (2010).

    Google Scholar 

  66. 66.

    Schwartz, A. R., Russell, K. & Gray, B. A. Approaches to vaginal bleeding and contraceptive counseling in transgender and gender nonbinary patients. Obstet. Gynecol. 134, 81–90 (2019).

    Google Scholar 

  67. 67.

    Zigler, R. E. & McNicholas, C. Unscheduled vaginal bleeding with progestin-only contraceptive use. Am. J. Obstet. Gynecol. 216, 443–450 (2017).

    CAS  Google Scholar 

  68. 68.

    Guss, C. E. Intrauterine devices in gender minority youth: an option to decrease dysphoria and unintended pregnancies. J. Adolesc. Health 65, 3–4 (2019).

    Google Scholar 

  69. 69.

    Nolan, I. T., Dy, G. W. & Levitt, N. Considerations in gender-affirming surgery: demographic trends. Urol. Clin. North. Am. 46, 459–465 (2019).

    Google Scholar 

  70. 70.

    James, S. E. et al. The report of the 2015 U.S. Transgender Survey. National Center for Transgender Equality (2016).

  71. 71.

    Zurada, A. et al. The evolution of transgender surgery. Clin. Anat. 31, 878–886 (2018).

    Google Scholar 

  72. 72.

    Morrison, S. D. et al. Facial feminization: systematic review of the literature. Plast. Reconstr. Surg. 137, 1759–1770 (2016).

    CAS  Google Scholar 

  73. 73.

    Horbach, S. E. R. et al. Outcome of vaginoplasty in male-to-female transgenders: a systematic review of surgical techniques. J. Sex. Med. 12, 1499–1512 (2015).

    Google Scholar 

  74. 74.

    Safa, B., Lin, W. C., Salim, A. M., Deschamps-Braly, J. C. & Poh, M. M. Current concepts in feminizing gender surgery. Plast. Reconstr. Surg. 143, 1081e–1091e (2019).

    CAS  Google Scholar 

  75. 75.

    Berli, J. U. et al. What surgeons need to know about gender confirmation surgery when providing care for transgender individuals: a review. JAMA Surg. 152, 394–400 (2017).

    Google Scholar 

  76. 76.

    van der Sluis, W. B., Tuynman, J. B., Meijerink, W. J. H. J. & Bouman, M.-B. Laparoscopic intestinal vaginoplasty in transgender women: an update on surgical indications, operative technique, perioperative care, and short- and long-term postoperative issues. Urol. Clin. North. Am. 46, 527–539 (2019).

    Google Scholar 

  77. 77.

    Cristofari, S. et al. Postoperative complications of male to female sex reassignment surgery: a 10-year French retrospective study. Ann. Chir. Plast. Esthet. 64, 24–32 (2019).

    CAS  Google Scholar 

  78. 78.

    van der Sluis, W. B., Bouman, M., Meijerink, W., Neefjes-Borst, E. A. & van Bodegraven, A. A. Refractory diversion neovaginitis in a sigmoid-colon-derived neovagina: clinical and histopathological considerations. Frontline Gastroenterol. 7, 227–230 (2016).

    Google Scholar 

  79. 79.

    van der Sluis, W. B. et al. Diversion neovaginitis after sigmoid vaginoplasty: endoscopic and clinical characteristics. Fertil. Steril. 105, 834–839.e1 (2016).

    Google Scholar 

  80. 80.

    Bouman, M.-B. et al. Patient-reported esthetic and functional outcomes of primary total laparoscopic intestinal vaginoplasty in transgender women with penoscrotal hypoplasia. J. Sex. Med. 13, 1438–1444 (2016).

    Google Scholar 

  81. 81.

    Manrique, O. J. et al. Complications and patient-reported outcomes in male-to-female vaginoplasty-where we are today: a systematic review and meta-analysis. Ann. Plast. Surg. 80, 684–691 (2018).

    CAS  Google Scholar 

  82. 82.

    Garcia, M. M. Sexual function after shallow and full-depth vaginoplasty: challenges, clinical findings, and treatment strategies — urologic perspectives. Clin. Plast. Surg. 45, 437–446 (2018).

    Google Scholar 

  83. 83.

    Hadj-Moussa, M., Ohl, D. A. & Kuzon, W. M. Feminizing genital gender-confirmation surgery. Sex. Med. Rev. 6, 457–468.e2 (2018).

    Google Scholar 

  84. 84.

    LeBreton, M. et al. Genital sensory detection thresholds and patient satisfaction with vaginoplasty in male-to-female transgender women. J. Sex. Med. 14, 274–281 (2017).

    Google Scholar 

  85. 85.

    Buvat, J. & Bou Jaoudé, G. Significance of hypogonadism in erectile dysfunction. World J. Urol. 24, 657–667 (2006).

    Google Scholar 

  86. 86.

    Cornelisse, V. J., Jones, R. A., Fairley, C. K. & Grover, S. R. The medical care of the neovagina of transgender women: a review. Sex. Health 14, 442–450 (2017).

    Google Scholar 

  87. 87.

    Oelschlager, A.-M. A., Debiec, K. & Appelbaum, H. Primary vaginal dilation for vaginal agenesis: strategies to anticipate challenges and optimize outcomes. Curr. Opin. Obstet. Gynecol. 28, 345–349 (2016).

    Google Scholar 

  88. 88.

    Coleman, E. et al. Standards of care for the health of transsexual, transgender, and gender-nonconforming people, version 7. Int. J. Transgend. 13, 165–232 (2012).

    Google Scholar 

  89. 89.

    Massie, J. P., Morrison, S. D., Van Maasdam, J. & Satterwhite, T. Predictors of patient satisfaction and postoperative complications in penile inversion vaginoplasty. Plast. Reconstr. Surg. 141, 911e–921e (2018).

    CAS  Google Scholar 

  90. 90.

    Wierckx, K. et al. Sexual desire in trans persons: associations with sex reassignment treatment. J. Sex. Med. 11, 107–118 (2014).

    Google Scholar 

  91. 91.

    Lawrence, A. A. Factors associated with satisfaction or regret following male-to-female sex reassignment surgery. Arch. Sex. Behav. 32, 299–315 (2003).

    Google Scholar 

  92. 92.

    Holmberg, M., Arver, S. & Dhejne, C. Supporting sexuality and improving sexual function in transgender persons. Nat. Rev. Urol. 16, 121–139 (2019).

    CAS  Google Scholar 

  93. 93.

    Coleman, E. et al. Standards of care for the health of transsexual, transgender, and gender-nonconforming people. WPATH (2012).

  94. 94.

    Deutsch, M. Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People (UCSF Transgender Care, 2016).

  95. 95.

    Chandhoke, G., Shayegan, B. & Hotte, S. J. Exogenous estrogen therapy, testicular cancer, and the male to female transgender population: a case report. J. Med. Case Rep. 12, 373 (2018).

    Google Scholar 

  96. 96.

    Ingham, M. D., Lee, R. J., MacDermed, D. & Olumi, A. F. Prostate cancer in transgender women. Urol. Oncol. 36, 518–525 (2018).

    Google Scholar 

  97. 97.

    Deebel, N. A. et al. Prostate cancer in transgender women: incidence, etiopathogenesis, and management challenges. Urology 110, 166–171 (2017).

    Google Scholar 

  98. 98.

    Tollinche, L. E. et al. The perioperative care of the transgender patient. Anesth. Analg. 127, 359–366 (2018).

    Google Scholar 

  99. 99.

    Mahfouda, S. et al. Gender-affirming hormones and surgery in transgender children and adolescents. Lancet Diabetes Endocrinol. 7, 484–498 (2019).

    CAS  Google Scholar 

  100. 100.

    Safa, B., Lin, W. C., Salim, A. M., Deschamps-Braly, J. C. & Poh, M. M. Current concepts in masculinizing gender surgery. Plast. Reconstr. Surg. 143, 857e–871e (2019).

    CAS  Google Scholar 

  101. 101.

    Cuccolo, N. G. et al. Masculinizing chest reconstruction in transgender and nonbinary individuals: an analysis of epidemiology, surgical technique, and postoperative outcomes. Aesthetic Plast. Surg. 7 (Suppl 8), 38 (2019).

    Google Scholar 

  102. 102.

    Kühn, S. et al. Mastectomy in female-to-male transgender patients: a single-center 24-year retrospective analysis. Arch. Plast. Surg. 46, 433–440 (2019).

    Google Scholar 

  103. 103.

    Top, H. & Balta, S. Transsexual mastectomy: selection of appropriate technique according to breast characteristics. Balk. Med. J. 34, 147–155 (2017).

    Google Scholar 

  104. 104.

    Cuccolo, N. G. et al. Mastectomy in transgender and cisgender patients: a comparative analysis of epidemiology and postoperative outcomes. Plast. Reconstr. Surg. Glob. Open 7, e2316 (2019).

    Google Scholar 

  105. 105.

    Taniguchi, F. et al. Gonadotropin-releasing hormone analogues reduce the proliferation of endometrial stromal cells but not endometriotic cells. Gynecol. Obstet. Invest. 75, 9–15 (2013).

    CAS  Google Scholar 

  106. 106.

    Stone, J. P., Hartley, R. L. & Temple-Oberle, C. Breast cancer in transgender patients: a systematic review. Part 2: female to male. Eur. J. Surg. Oncol. 44, 1463–1468 (2018).

    Google Scholar 

  107. 107.

    Joint, R., Chen, Z. E. & Cameron, S. Breast and reproductive cancers in the transgender population: a systematic review. BJOG 125, 1505–1512 (2018).

    CAS  Google Scholar 

  108. 108.

    Kiran, T. et al. Cancer screening rates among transgender adults: cross-sectional analysis of primary care data. Can. Fam. Physician 65, e30–e37 (2019).

    Google Scholar 

  109. 109.

    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2013).

  110. 110.

    Hembree, W. C. et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an Endocrine Society clinical practice guideline. Endocr. Pract. 23, 1437 (2017).

    Google Scholar 

  111. 111.

    Olson-Kennedy, J. et al. Impact of early medical treatment for transgender youth: protocol for the longitudinal, observational trans youth care study. JMIR Res. Protoc. 8, e14434 (2019).

    Google Scholar 

  112. 112.

    Chen, D. et al. Multidisciplinary care for gender-diverse youth: a narrative review and unique model of gender-affirming care. Transgend. Health 1, 117–123 (2016).

    Google Scholar 

  113. 113.

    Winter, S. et al. Transgender people: health at the margins of society. Lancet 388, 390–400 (2016).

    Google Scholar 

  114. 114.

    Hatzenbuehler, M. L. & Pachankis, J. E. Stigma and minority stress as social determinants of health among lesbian, gay, bisexual, and transgender youth: research evidence and clinical implications. Pediatr. Clin. North. Am. 63, 985–997 (2016).

    Google Scholar 

  115. 115.

    Drescher, J., Haller, E. & Yarbrough, E. Position Statement on Discrimination Against Transgender and Gender Diverse Individuals (APA, 2018).

  116. 116.

    Kosciw, J. G. et al. The 2017 National School Climate Survey: The Experiences of Lesbian, Gay, Bisexual, Transgender, and Queer Youth in Our Nation’s Schools (Gay, Lesbian and Straight Education Network (GLSEN), 2018).

  117. 117.

    Becerra-Culqui, T. A. et al. Mental health of transgender and gender nonconforming youth compared with their peers. Pediatrics 141, e20173845 (2018).

    Google Scholar 

  118. 118.

    Newcomb, M. E. et al. High burden of mental health problems, substance use, violence, and related psychosocial factors in transgender, non-binary, and gender diverse youth and young adults. Arch. Sex. Behav. 49, 645–659 (2019).

    Google Scholar 

  119. 119.

    Travers, R., Bauer, G. & Pyne, J. Impacts of Strong Parental Support for Trans Youth: a Report Prepared for Children’s Aid Society of Toronto and Delisle Youth Services (Trans PULSE, 2012).

  120. 120.

    GLSEN 2015 National School Climate Survey (NSCS) — Executive Summary.pdf.

  121. 121.

    Safer, J. D. & Tangpricha, V. Care transgender persons. N. Engl. J. Med. 381, 2451–2460 (2019).

    Google Scholar 

  122. 122.

    Kaltiala-Heino, R., Bergman, H., Työläjärvi, M. & Frisén, L. Gender dysphoria in adolescence: current perspectives. Adolesc. Health Med. Ther. 9, 31–41 (2018).

    Google Scholar 

  123. 123.

    Marks, D. H., Hagigeorges, D., Manatis-Lornell, A. J., Dommasch, E. & Senna, M. M. Excess hair, hair removal methods, and barriers to care in gender minority patients: a survey study. J. Cosmet. Dermatol. 19, 1494–1498 (2019).

    Google Scholar 

  124. 124.

    Hardy, T. L. D., Rieger, J. M., Wells, K. & Boliek, C. A. Acoustic predictors of gender attribution, masculinity-femininity, and vocal naturalness ratings amongst transgender and cisgender speakers. J. Voice 34, 300.e11–300.e26 (2018).

    Google Scholar 

  125. 125.

    Ngaage, L. M. et al. Gender surgery beyond chest and genitals: current insurance landscape. Aesthet. Surg. J. (2019).

    Article  Google Scholar 

  126. 126.

    Ngaage, L. M. et al. Health insurance coverage of gender-affirming top surgery in the United States. Plast. Reconstr. Surg. 144, 824–833 (2019).

    CAS  Google Scholar 

  127. 127.

    Ngaage, L. M. et al. A review of insurance coverage of gender affirming genital surgery. Plast. Reconstr. Surg. 145, 803–812 (2019).

    Google Scholar 

  128. 128.

    Canner, J. K. et al. Temporal trends in gender-affirming surgery among transgender patients in the United States. JAMA Surg. 153, 609–616 (2018).

    Google Scholar 

  129. 129.

    Defreyne, J., Motmans, J. & T’sjoen, G. Healthcare costs and quality of life outcomes following gender affirming surgery in trans men: a review. Expert. Rev. Pharmacoecon. Outcomes Res. 17, 543–556 (2017).

    Google Scholar 

  130. 130.

    Dowshen, N. L., Christensen, J. & Gruschow, S. M. Health insurance coverage of recommended gender-affirming health care services for transgender youth: shopping online for coverage information. Transgend. Health 4, 131–135 (2019).

    Google Scholar 

  131. 131.

    Littman, L. Parent reports of adolescents and young adults perceived to show signs of a rapid onset of gender dysphoria. PLoS ONE 13, e0202330 (2018).

    Google Scholar 

  132. 132.

    Kimberly, L. L. et al. Ethical issues in gender-affirming care for youth. Pediatrics 142, e20181537 (2018).

    Google Scholar 

  133. 133.

    Pediatric Endocrine Society. PES 2019 transgender statement. PES (2019).

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All authors researched data for the article and wrote the manuscript. L.P. made substantial contributions to discussion of content and reviewed and edited the manuscript before submission.

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Correspondence to Leonidas Panagiotakopoulos.

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Panagiotakopoulos, L., Chulani, V., Koyama, A. et al. The effect of early puberty suppression on treatment options and outcomes in transgender patients. Nat Rev Urol 17, 626–636 (2020).

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