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][2][3] In addition to their various other medical uses, puberty blockers are used for transgender children to delay the development of unwanted sex characteristics,[4] so as to allow transgender youth more time to explore their identity.[5]

The use of puberty blockers in transgender youth has also been challenged on ethical and medical grounds, causing controversy over the legality of their use in certain jurisdictions.

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.[6] In adults, the same drugs are used to treat endometriosis[7] and prostate cancer.[8] Puberty blockers prevent the development of biological secondary sex characteristics.[9] 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.[4] Puberty blockers allow patients more time to solidify their gender identity, without developing secondary sex characteristics.[5] If a child later decides not to transition to another gender the medication can be stopped, allowing puberty to proceed, as the effects are fully reversible.[10][11] Puberty blockers give transgender youth a smoother transition into their desired gender identity as an adult.[5]

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,[12][13][14] and an association has been found between puberty blockers and decreased lifetime suicidality.[10] A 2020 UK Department of Health and Social Care commissioned review found that the quality of evidence was of very low certainty for puberty blocker outcomes regarding mental health, quality of life and impact on gender dysphoria.[15]

Adverse effects on bone mineralization and compromised fertility are potential risks of pubertal suppression in gender dysphoric youth treated with GnRH agonists.[13][16] Additionally, genital tissue in transgender women may not be optimal for potential vaginoplasty later in life due to underdevelopment of the penis.[17]

Research on the long term effects on brain development is limited.[18][19]

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 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.[20][21]

In April 2021, the U.S. state of Arkansas passed a ban on treatment of minors under 18 with puberty blockers, though it was temporarily blocked by a federal judge. (See Transgender rights in the United States § Treatment for children.)

There is criticism regarding issues of informed consent and limited research support for the use of puberty blockers on transgender children.[22][23][24][25] The Endocrine Association Guidelines call for more rigorous safety and effectiveness evaluations and careful assessment of "the effects of prolonged delay of puberty in adolescents on bone health, gonadal function, and the brain (including effects on cognitive, emotional, social, and sexual development)."[14]

Some opponents of the use of puberty blockers argue that minors are not able to give proper consent.[26] 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] A 2021 editorial in The Lancet Child & Adolescent Health stated "Disproportionate emphasis is given to young people’s inability to provide medical consent, a moot point given that—like any medical care—parental consent is required. ... what matters ethically is whether an individual has a good enough reason for wanting treatment", and that "Social conservatives in the USA, UK, and Australia frame gender-affirming care as child abuse and medical experimentation. This stance wilfully ignores decades of use of and research about puberty blockers and hormone therapy".[29]

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 Florence Ashley adds that counseling and educating the parents of transgender youth could also be beneficial to familial relationships.[30]

Michael Biggs has said that studies on the effects of puberty blockers on transgender children lack transparency or validity.[26][31] 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.[17] Research has suggested that the use of puberty blockers decreases the risk of depression and contributes to the mitigation of behavioral issues.[17] 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.[17]

Opponents of the use of puberty blockers in adolescents argue that gender identity is still fluctuating at this age and that blockers might interfere with gender identity formation and development of a free sexuality, as well as pointing to what they consider to be high rates of desistance after puberty.[17]  Almost all (98%) children who took puberty blockers in a significant recent study by the main UK child/adolescent gender clinic continued on to hormones.[32] Similarly, most reviews[14][17] noting psychological benefits refer to the classic Dutch study[19] which had very stringent requirements for medical treatment,[33] a later study found that despite positive overall experience with GaNRH, there did not appear to be improved psychological function.[32]

Medical organization policy changes

On June 30, 2020, the British National Health Service changed the information it displayed on its website regarding the reversibility of the effects of puberty blockers and their use in the treatment of minors with gender dysphoria, according to a report by BBC's Woman's Hour.[34] Specifically, the NHS removed "the effects of treatment with GnRH analogues are considered to be fully reversible, so treatment can usually be stopped at any time after a discussion between you, your child and your MDT (multi-disciplinary team)," and added "little is known about the long-term side effects of hormone or puberty blockers in children with gender dysphoria. Although the Gender Identity Development Service (GIDS) advises this is a physically reversible treatment if stopped, it is not known what the psychological effects may be. It’s also not known whether hormone blockers affect the development of the teenage brain or children’s bones. Side effects may also include hot flushes, fatigue and mood alterations."[34]

Following the Bell v Tavistock decision by the High Court of Justice for England and Wales, in which the High Court ruled children under 16 were not competent to give informed consent to puberty blockers — overturned by the Court of Appeal in September 2021 — Sweden's Karolinska Institute, administrator of the second-largest hospital system in the country, announced in March 2021 that it would discontinue providing puberty blockers or cross-sex hormones to children under 16. Additionally, the Karolinska Institute changed its policy to cease providing puberty blockers or cross-sex hormones to teenagers 16–18, outside of approved clinical trials.[35]

References

  1. ↑ Hemat RA (2 March 2003). Andropathy. Urotext. pp. 120–. ISBN 978-1-903737-08-8.
  2. ↑ Becker KL (2001). Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. pp. 973–. ISBN 978-0-7817-1750-2.
  3. ↑ "Pubertal blockers for transgender and gender diverse youth". Mayo Clinic. 16 August 2019. Retrieved 15 December 2020.
  4. 1 2 Stevens J, Gomez-Lobo V, Pine-Twaddell E (December 2015). "Insurance Coverage of Puberty Blocker Therapies for Transgender Youth". Pediatrics. 136 (6): 1029–31. doi:10.1542/peds.2015-2849. PMID 26527547.
  5. 1 2 3 Alegría CA (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. PMID 27031444. S2CID 22374099.
  6. ↑ Watson SE, Greene A, Lewis K, Eugster EA (June 2015). "Bird's-eye view of GnRH analog use in a pediatric endocrinology referral center". Endocrine Practice. 21 (6): 586–9. doi:10.4158/EP14412.OR. PMC 5344188. PMID 25667370.
  7. ↑ "Current treatments for endometriosis". Mayo Clinic.
  8. ↑ Panday K, Gona A, Humphrey MB (October 2014). "Medication-induced osteoporosis: screening and treatment strategies". Therapeutic Advances in Musculoskeletal Disease. 6 (5): 185–202. doi:10.1177/1759720X14546350. PMC 4206646. PMID 25342997.
  9. ↑ Boyar RM (November 2003). "Control of the onset of puberty". Annual Review of Medicine. 29: 509–20. doi:10.1146/annurev.me.29.020178.002453. PMID 206190.
  10. 1 2 Rew, Lynn; Young, Cara C.; Monge, Maria; Bogucka, Roxanne (February 2021). "Review: Puberty blockers for transgender and gender diverse youth-a critical review of the literature". Child and Adolescent Mental Health. 26 (1): 3–14. doi:10.1111/camh.12437. ISSN 1475-357X. PMID 33320999. S2CID 229282305.
  11. ↑ Murchison G, Adkins D, Conard LA, Elliott T, Hawkins LA, Newby H, et al. (September 2016). Supporting and Caring for Transgender Children (PDF) (Report). American Academy of Pediatrics. 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.
  12. ↑ Mahfouda S, Moore JK, Siafarikas A, Zepf FD, Lin A (October 2017). "Puberty suppression in transgender children and adolescents". The Lancet Diabetes & Endocrinology. 5 (10): 816–826. doi:10.1016/s2213-8587(17)30099-2. 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.
  13. 1 2 Rafferty J (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. 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.
  14. 1 2 3 Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH, et al. (November 2017). "Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology and Metabolism. 102 (11): 3869–3903. 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", "In the future, we need more rigorous evaluations of the effectiveness and safety of endocrine and surgical protocols. Specifically, endocrine treatment protocols for GD/gender incongruence should include the careful assessment of the following: (1) the effects of prolonged delay of puberty in adolescents on bone health, gonadal function, and the brain (including effects on cognitive, emotional, social, and sexual development);
  15. ↑ "Evidence review: Gonadotrophin releasing hormone analogues for children and adolescents with gender dysphoria". 2020. Retrieved 1 April 2021. The critical outcomes for decision making are the impact on gender dysphoria, mental health and quality of life. The quality of evidence for these outcomes was assessed as very low certainty using modified GRADE.{{cite web}}: CS1 maint: url-status (link)
  16. ↑ Bangalore Krishna, Kanthi; Fuqua, John S.; Rogol, Alan D.; Klein, Karen O.; Popovic, Jadranka; Houk, Christopher P.; Charmandari, Evangelia; Lee, Peter A.; Freire, A. V.; Ropelato, M. G.; Yazid Jalaludin, M. (2019). "Use of Gonadotropin-Releasing Hormone Analogs in Children: Update by an International Consortium". Hormone Research in Paediatrics. 91 (6): 357–372. doi:10.1159/000501336. ISSN 1663-2826. PMID 31319416. GnRHa therapy prevents maturation of primary oocytes and spermatogonia and may preclude gamete maturation, and currently there are no proven methods to preserve fertility in early pubertal transgender adolescents.
  17. 1 2 3 4 5 6 Giovanardi G (September 2017). "Buying time or arresting development? The dilemma of administering hormone blockers in trans children and adolescents". Porto Biomedical Journal. 2 (5): 153–156. doi:10.1016/j.pbj.2017.06.001. PMC 6806792. PMID 32258611.
  18. ↑ Rosenthal SM (December 2016). "Transgender youth: current concepts". Annals of Pediatric Endocrinology & Metabolism. 21 (4): 185–192. doi:10.6065/apem.2016.21.4.185. PMC 5290172. PMID 28164070. The primary risks of pubertal suppression in gender dysphoric youth treated with GnRH agonists include adverse effects on bone mineralization, compromised fertility, and unknown effects on brain development.
  19. 1 2 de Vries AL, Cohen-Kettenis PT (2012). "Clinical management of gender dysphoria in children and adolescents: the Dutch approach". Journal of Homosexuality. 59 (3): 301–20. doi:10.1080/00918369.2012.653300. PMID 22455322. S2CID 11731779.
  20. ↑ 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.
  21. ↑ Reiter EO, Mauras N, McCormick K, Kulshreshtha B, Amrhein J, De Luca F, et al. (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 and Metabolism. 23 (10): 999–1009. doi:10.1515/jpem.2010.161. PMID 21158211. S2CID 110630.
  22. ↑ Richards C, Maxwell J, McCune N (June 2019). "Use of puberty blockers for gender dysphoria: a momentous step in the dark". Archives of Disease in Childhood. 104 (6): 611–612. doi:10.1136/archdischild-2018-315881. PMID 30655265. S2CID 58613069.
  23. ↑ Bannerman L (26 July 2019). "Use of puberty blockers on transgender children to be investigated". The Times.
  24. ↑ Holt A (7 October 2020). "Children not able to give 'proper' consent to puberty blockers, court told". BBC News Online. Retrieved 14 December 2020.
  25. ↑ "Little is known about the effects of puberty blockers". The Economist. 18 February 2021. ISSN 0013-0613. Retrieved 25 March 2021.
  26. 1 2 Cohen D, Barnes H (September 2019). "Gender dysphoria in children: puberty blockers study draws further criticism". BMJ (Clinical Research Ed.). 366: l5647. doi:10.1136/bmj.l5647. PMID 31540909. S2CID 202711942.
  27. 1 2 Priest M (February 2019). "Transgender Children and the Right to Transition: Medical Ethics When Parents Mean Well but Cause Harm". American Journal of Bioethics. 19 (2): 45–59. doi:10.1080/15265161.2018.1557276. PMID 30784385. S2CID 73456261.
  28. ↑ Butler G, Wren B, Carmichael P (June 2019). "Puberty blocking in gender dysphoria: suitable for all?". Archives of Disease in Childhood. 104 (6): 509–510. doi:10.1136/archdischild-2018-315984. PMID 30655266. S2CID 58539498.
  29. ↑ The Lancet Child & Adolescent Health (14 May 2021). "A flawed agenda for trans youth". The Lancet Child & Adolescent Health. 5 (6): 385. doi:10.1016/S2352-4642(21)00139-5. ISSN 2352-4642. PMID 34000232.
  30. ↑ Ashley F (February 2019). "Puberty Blockers Are Necessary, but They Don't Prevent Homelessness: Caring for Transgender Youth by Supporting Unsupportive Parents". American Journal of Bioethics. 19 (2): 87–89. doi:10.1080/15265161.2018.1557277. PMID 30784386. S2CID 73478358.
  31. ↑ Biggs M (October 2020). "Puberty Blockers and Suicidality in Adolescents Suffering from Gender Dysphoria". Archives of Sexual Behavior. 49 (7): 2227–2229. doi:10.1007/s10508-020-01743-6. PMC 8169497. PMID 32495241. S2CID 219314661.
  32. 1 2 Carmichael P, Butler G, Masic U, Cole TJ, De Stavola BL, Davidson S, et al. (February 2021). "Short-term outcomes of pubertal suppression in a selected cohort of 12 to 15 year old young people with persistent gender dysphoria in the UK". PLOS One. 16 (2): e0243894. Bibcode:2021PLoSO..1643894C. doi:10.1371/journal.pone.0243894. PMC 7853497. PMID 33529227. We found no evidence of change in psychological function with GnRHa treatment as indicated by parent report (CBCL) or self-report (YSR) of overall problems, internalising or externalising problems or self-harm. This is in contrast to the Dutch study which reported improved psychological function across total problems, externalising and internalising scores for both CBCL and YSR and small improvements in CGAS [24].
  33. ↑ Zucker KJ (October 2019). "Adolescents with Gender Dysphoria: Reflections on Some Contemporary Clinical and Research Issues". Archives of Sexual Behavior. 48 (7): 1983–1992. doi:10.1007/s10508-019-01518-8. PMID 31321594. S2CID 197663705. According to Cohen-Kettenis, Delemarre-van de Waal, and Gooren (2008), these included the following: (1) the presence of gender dysphoria from early childhood on; (2) an exacerbation of the gender dysphoria after the first signs of puberty; (3) the absence of psychiatric comorbidity that would interfere with a diagnostic evaluation or treatment; (4) adequate psychological and social support during treatment; and (5) a demonstration of knowledge of the sex/gender reassignment process.
  34. 1 2 "Women and Gaming; ICU nurse Dawn Bilbrough; Poulomi Basu; Puberty blockers". Woman's Hour. 30 June 2020. Retrieved 1 November 2021.
  35. ↑ "Doubts are growing about therapy for gender-dysphoric children". The Economist. 13 May 2021. Retrieved 2 November 2021.
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