Puberty blocker

Puberty blockers, also called puberty inhibitors, are drugs used to postpone puberty in children. The most commonly used puberty blockers are gonadotropin-releasing hormone (GnRH) agonists, which inhibit the release of sex hormones, including testosterone and estrogen.[1] In addition to their various other medical uses, puberty blockers are used for transgender children to delay the development of unwanted sex characteristics,[2] with the intent to provide transgender youth more time to explore their identity.[3] The use of puberty blockers in transgender youth has been challenged on ethical and medical grounds, causing controversy over the morality and legality of their use.

Medical uses

Delaying or temporarily suspending puberty is a medical treatment for children whose puberty started abnormally early (precocious puberty). Puberty blockers are also commonly used for children with idiopathic short stature, for whom these drugs can be used to promote development of long bones and increase adult height.[4] In adults, the same drugs are used to treat endometriosis,[5] prostate cancer, and other conditions.[6][7] Puberty blockers prevent the development of biological secondary sex characteristics.[8] They slow the growth of sexual organs and production of hormones. Other effects include the suppression of male features of facial hair, deep voices, and Adam's apples, and the halting of female features of breast development and menstruation.

Puberty blockers are sometimes prescribed to young transgender people, to temporarily halt the development of secondary sex characteristics.[2] Puberty blockers allow patients more time to solidify their gender identity, without developing secondary sex characteristics.[3] If a child later decides not to transition to another gender the fully reversible medication can be stopped, allowing puberty to proceed.[9] Puberty blockers give transgender youth a smoother transition into their desired gender identity as an adult.[3]

While few studies have examined the effects of puberty blockers for gender non-conforming or transgender adolescents, the studies that have been conducted indicate that these treatments are reasonably safe, and can improve psychological well-being in these individuals.[10][11][12] In 2019, a study in the journal Pediatrics found that access to pubertal suppression during adolescence was associated with lower odds of lifetime suicidality among transgender people.[13]

The potential risks of pubertal suppression in gender dysphoric youth treated with GnRH agonists may include adverse effects on bone mineralization.[14][15] Additionally, genital tissue in transgender women may not be optimal for potential vaginoplasty later in life due to underdevelopment of the penis.[16]

Research on the long term effects on brain development is limited; however, a small 2015 study published in Psychoneuroendocrinology observed the planning and problem-solving abilities of 20 transgender youth treated with puberty blockers compared to untreated youth with gender dysphoria by using the Tower of London test and found that there were no significant differences in their reaction times and accuracy.[15][17][18][3]

Administration

The medication that is used in order to stop puberty comes in two forms: injections or an implant.

The injections are leuprorelin made intramuscularly by a health professional. The patient may need it monthly (Lupron Depot, Lupron Depot-PED) or every 3, 4 or 6 months (Lupron Depot-3 month, Lupron Depot-PED-3 month, Lupron Depot-4 month, Lupron Depot-6 month).

The implant is a small tube containing histrelin. The implant needs to be replaced every year and is implanted subcutaneously in the upper arm. The doctor makes a small cut in the anesthetized skin of the patient and then inserts the implant. The patient must be careful after the operation to keep the cut clean, dry, and to not move the bandage and the surgical strips or stitches used to close the incision on the skin. The drug is then gradually released in the body over 12 months and the implant has to be replaced to continue the treatment. The total cost of histrelin treatment with the surgery in the USA is $15,000.

The combination of bicalutamide (an antiandrogen) and anastrozole (an aromatase inhibitor) can be used to suppress male puberty as an alternative to GnRH analogues, or in the case of gonadotropin-independent precocious puberty, such as in familial male-limited precocious puberty (also known as testotoxicosis) in boys, where GnRH analogues are ineffective.[19][20]

Legal proceedings in the United Kingdom have sought to prohibit the use of puberty blockers for transgender children.[21] Legislation proposed in South Dakota sought to restrict access to puberty blockers, and other treatments, for transgender children under sixteen.[22] Significant data suggests that the use of puberty blockers increases the quality of life for transgender children, but criticism of the treatment persists regarding issues of informed consent and a perceived lack of research.[23][24][25][26]

Opponents of the use of puberty blockers argue that minors are not able to give proper consent.[25] Some advocates for the use of puberty blockers consider the psychological and developmental benefits of puberty blockers compelling enough to overlook the issue of informed consent in many cases.[27] Consent is often achieved after extensive analysis and counseling.[28]

Bioethicist Maura Priest contends that, even in the absence of parental permission, the use of puberty blockers could mitigate any adverse effects on familial relationships within the home of a transgender child. She posits that there are benefits to having access to puberty blockers, while psychological costs are often associated with untreated gender dysphoria in children.[27] Bioethicist Ashley Florence adds that counseling and educating the parents of transgender youth could also be beneficial to familial relationships.[29]

Michael Biggs has said that studies on the effects of puberty blockers on transgender children lack transparency or validity.[30][25] Physician Carl Heneghan has called the use of puberty blockers to treat transgender children an "unregulated live experiment on children." While some studies suggesting the benefits of using puberty blockers to treat transgender youth have been critiqued for systematic errors or a lack of transparency, the vast majority of research has not been subject to such criticism. Opponents express concern over validation of a child's gender dysphoria; however, research has shown that treatment with puberty blockers prevents harmful behavior and does not increase gender dysphoria.[31] Research has suggested that the use of puberty blockers decreases the risk of depression and contributes to the mitigation of behavioral issues.[31] Opponents to the use of puberty blockers have argued that puberty blockers encourage children to go through with cross-sex hormones and gender reassignment surgery. A study regarding the long term effects of puberty blockers found that, upon later assessment, subjects did not regret transitioning and were less likely to experience depression in early adulthood.[31]

References
  1. "Pubertal blockers for transgender and gender diverse youth". Mayo Clinic. 16 August 2019. Retrieved 15 December 2020.
  2. Stevens, Jaime; Gomez-Lobo, Veronica; Pine-Twaddell, Elyse (1 December 2015). "Insurance Coverage of Puberty Blocker Therapies for Transgender Youth". Pediatrics. 136 (6): 1029–1031. doi:10.1542/peds.2015-2849. ISSN 0031-4005. PMID 26527547.
  3. Alegría, Christine Aramburu (1 October 2016). "Gender nonconforming and transgender children/youth: Family, community, and implications for practice". Journal of the American Association of Nurse Practitioners. 28 (10): 521–527. doi:10.1002/2327-6924.12363. ISSN 2327-6924. PMID 27031444. S2CID 22374099.
  4. Sara E. Watson, Ariana Greene, Katherine Lewis, and Erica A. Eugster (2015). Bird's-eye view of GnRH analog use in a pediatric endocrinology referral center. Endocrine Practice: June 2015, Vol. 21, No. 6, pp. 586-589.
  5. Current treatments for endometriosis, Mayo Clinic, https://www.mayoclinic.org/diseases-conditions/endometriosis/diagnosis-treatment/drc-20354661
  6. Smith, M. R. (2006). Treatment-related osteoporosis in men with prostate cancer. Clinical Cancer Research, 12(20 pt 2), 6315-6319.
  7. Panday, K., Gona, A., Humphrey, M. B., (2014). Medication-induced osteoporosis: Screening and treatment strategies. Therapeutic Advances in Musculoskeletal Disease, 6, 185-202.
  8. Bayar, R. M. (28 November 2003). "Control of the Onset of Puberty". Annual Review of Medicine. 29: 509–520. doi:10.1146/annurev.me.29.020178.002453. PMID 206190.
  9. Supporting and Caring for Transgender Children (PDF) (Report). American Academy of Pediatrics. September 2016. p. 11. To prevent the consequences of going through a puberty that doesn’t match a transgender child’s identity, healthcare providers may use fully reversible medications that put puberty on hold.
  10. Mahfouda, Simone; Moore, Julia K; Siafarikas, Aris; Zepf, Florian D; Lin, Ashleigh (2017). "Puberty suppression in transgender children and adolescents". The Lancet Diabetes & Endocrinology. Elsevier BV. 5 (10): 816–826. doi:10.1016/s2213-8587(17)30099-2. ISSN 2213-8587. PMID 28546095. The few studies that have examined the psychological effects of suppressing puberty, as the first stage before possible future commencement of CSH therapy, have shown benefits."
  11. Rafferty, Jason (October 2018). "Ensuring Comprehensive Care and Support for Transgender and Gender-Diverse Children and Adolescents". Pediatrics. 142 (4): e20182162. doi:10.1542/peds.2018-2162. PMID 30224363. Retrieved 23 July 2019. Often, pubertal suppression...reduces the need for later surgery because physical changes that are otherwise irreversible (protrusion of the Adam’s apple, male pattern baldness, voice change, breast growth, etc) are prevented. The available data reveal that pubertal suppression in children who identify as TGD generally leads to improved psychological functioning in adolescence and young adulthood.
  12. Hembree, Wylie C; Cohen-Kettenis, Peggy T; Gooren, Louis; Hannema, Sabine E; Meyer, Walter J; Murad, M Hassan; Rosenthal, Stephen M; Safer, Joshua D; Tangpricha, Vin; T'Sjoen, Guy G (November 2017). "Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology & Metabolism. 102 (11): 3881. doi:10.1210/jc.2017-01658. PMID 28945902. Treating GD/gender-incongruent adolescents entering puberty with GnRH analogs has been shown to improve psychological functioning in several domains
  13. Turban, Jack (February 2020). "Pubertal Suppression for Transgender Youth and Risk of Suicidal Ideation". Pediatrics. 145 (2): e2019172. doi:10.1542/peds.2019-1725. PMC 7073269. PMID 31974216.
  14. Rafferty, Jason (October 2018). "Ensuring Comprehensive Care and Support for Transgender and Gender-Diverse Children and Adolescents". Pediatrics. 142 (4): e20182162. doi:10.1542/peds.2018-2162. PMID 30224363. Retrieved 23 July 2019.
  15. Rosenthal SM (2016). "Transgender youth: current concepts". Ann Pediatr Endocrinol Metab. 21 (4): 185–192. doi:10.6065/apem.2016.21.4.185. PMC 5290172. PMID 28164070.
  16. "Buying time or arresting development? The dilemma of administering hormone blockers in trans children and adolescents". Porto Biomedical Journal. 2 (5): 153–156. 1 September 2017. doi:10.1016/j.pbj.2017.06.001. ISSN 2444-8664.
  17. de Vries, Annelou L. C.; Cohen-Kettenis, Peggy T. (2012). "Clinical management of gender dysphoria in children and adolescents: the Dutch approach". Journal of Homosexuality. 59 (3): 301–320. doi:10.1080/00918369.2012.653300. ISSN 1540-3602. PMID 22455322. S2CID 11731779.
  18. Staphorsius, Annemieke S.; Kreukels, Baudewijntje P.C.; Cohen-Kettenis, Peggy T.; Veltman, Dick J.; Burke, Sarah M.; Schagen, Sebastian E.E.; Wouters, Femke M.; Delemarre-van de Waal, Henriëtte A.; Bakker, Julie (June 2015). "Puberty suppression and executive functioning: An fMRI-study in adolescents with gender dysphoria". Psychoneuroendocrinology. 56: 190–199. doi:10.1016/j.psyneuen.2015.03.007. PMID 25837854. S2CID 16826643.
  19. Kreher NC, Pescovitz OH, Delameter P, Tiulpakov A, Hochberg Z (September 2006). "Treatment of familial male-limited precocious puberty with bicalutamide and anastrozole". The Journal of Pediatrics. 149 (3): 416–20. doi:10.1016/j.jpeds.2006.04.027. PMID 16939760.
  20. Reiter EO, Mauras N, McCormick K, Kulshreshtha B, Amrhein J, De Luca F, O'Brien S, Armstrong J, Melezinkova H (October 2010). "Bicalutamide plus anastrozole for the treatment of gonadotropin-independent precocious puberty in boys with testotoxicosis: a phase II, open-label pilot study (BATT)". Journal of Pediatric Endocrinology & Metabolism. 23 (10): 999–1009. doi:10.1515/jpem.2010.161. PMID 21158211. S2CID 110630.
  21. "Children not able to give proper consent to puberty blockers, court told". BBC News. 7 October 2020.
  22. "Ban on treatments for transgender kids fails in South Dakota". Associated Press. 10 February 2020. Retrieved 14 December 2020.
  23. Richards, Christopher. "Use of Puberty Blockers for Gender Dysphoria: A Momentous Step in the Dark". Archives of Disease in Childhood.
  24. Bannerman, Lucy. "Trans Puberty Blockers Investigated". The Times.
  25. Cohen, Deborah, Barnes, Hannah. "Gender Dysphoria in Children: Puberty Blockers Study Draws further Criticism". British Medical Journal.CS1 maint: multiple names: authors list (link)
  26. "Children not able to give 'proper' consent to puberty blockers, court told". BBC News. 7 October 2020. Retrieved 14 December 2020.
  27. Priest, Maura (1 February 2019). "Transgender Children and the Right to Transition: Medical Ethics When Parents Mean Well but Cause Harm". The American Journal of Bioethics. 19 (2): 45–59. doi:10.1080/15265161.2018.1557276. ISSN 1526-5161. PMID 30784385.
  28. Butler, Gary, Wren, Carmichael, Polly. "Puberty Blocking in Gender Dysphoria: Suitable for all?". Archives of Disease in Childhood.CS1 maint: multiple names: authors list (link)
  29. Florence, Ashley. "Puberty Blockers Are Necessary, but They Don't Prevent Homelessness: Caring for Transgender Youth by Supporting Unsupportive Parents". American Journal of Bioethics.
  30. Biggs, Michael. "Puberty Blockers and Suicidality in Adolescents Suffering from Gender Dysphoria". Archives of Sexual Behavior.
  31. "Buying time or arresting development? The dilemma of administering hormone blockers in trans children and adolescents". Porto Biomedical Journal. 2 (5): 153–156. 1 September 2017. doi:10.1016/j.pbj.2017.06.001. ISSN 2444-8664.

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