Puberty blocker

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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 off-label 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[edit]

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] and prostate cancer.[6] Puberty blockers prevent the development of biological secondary sex characteristics.[7] 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 off label[8] (with the FDA) 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 medication can be stopped, allowing puberty to proceed, as the effects are fully reversible.[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] A 2020 UK Department of Health 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.[13]

Adverse effects on bone mineralization and compromised fertility are potential risks of pubertal suppression in gender dysphoric youth treated with GnRH agonists.[11][14] Additionally, genital tissue in transgender women may not be optimal for potential vaginoplasty later in life due to underdevelopment of the penis.[15]

Research on the long term effects on brain development is limited.[14][16][3]

Administration[edit]

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 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.[citation needed]

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.[17][18]

Legal and political challenges[edit]

Legal proceedings in the United Kingdom have sought to prohibit the use of puberty blockers for transgender children.[19] Legislation proposed in South Dakota sought to restrict access to puberty blockers, and other treatments, for transgender children under sixteen.[20] There is criticism regarding issues of informed consent and limited research support for the use of puberty blockers on transgender children.[21][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)."[12]

Some opponents of the use of puberty blockers argue that minors are not able to give proper consent.[23] 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.[26] Consent is often achieved after extensive analysis and counseling.[27]

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.[26] Bioethicist Ashley Florence adds that counseling and educating the parents of transgender youth could also be beneficial to familial relationships.[28]

Michael Biggs has said that studies on the effects of puberty blockers on transgender children lack transparency or validity.[29][23] Physician Carl Heneghan has called the use of puberty blockers to treat transgender children an "unregulated live experiment on children." 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.[15] Research has suggested that the use of puberty blockers decreases the risk of depression and contributes to the mitigation of behavioral issues.[15] 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.[15]

Opponents of the use of puberty blockers in adolescents argue that gender identity is still fluctuating at this age and blockers might interfere with gender identity formation and development of a free sexuality.[15]  Also, in around 70–90% of children with GD, it does not persist after puberty.[15] 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.[30] Similarly, most reviews[12][15] noting psychological benefits refer to the classic Dutch study[16] which had very stringent requirements for medical treatment,[31]  later studies have had mixed results.[30]

References[edit]

  1. ^ Mayo Clinic Staff (16 August 2019). "Pubertal blockers for transgender and gender diverse youth". Mayo Clinic. Retrieved 15 December 2020.
  2. ^ a b 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.
  3. ^ a b c d 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.
  4. ^ 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.
  5. ^ Mayo Clinic Staff. "Current treatments for endometriosis". Mayo Clinic.
  6. ^ 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.
  7. ^ 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.
  8. ^ Office of the Commissioner (18 April 2019). "Understanding Unapproved Use of Approved Drugs "Off Label"". FDA. Retrieved 26 March 2021.
  9. ^ 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.
  10. ^ Mahfouda S, Moore JK, Siafarikas A, Zepf FD, Lin A (October 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. 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. ^ a b 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.
  12. ^ a b c 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);
  13. ^ "Evidence review: Gonadotrophin releasing hormone analogues for children and adolescents with gender dysphoria". 2020. Retrieved 1 April 2021. The critical outcomes for decision making arethe impact on gender dysphoria, mental healthand quality of life. The quality of evidence for these outcomes was assessed as very low certainty using modified GRADE.
  14. ^ a b 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.
  15. ^ a b c d e f g 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.
  16. ^ a b 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.
  17. ^ 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.
  18. ^ 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 & Metabolism. 23 (10): 999–1009. doi:10.1515/jpem.2010.161. PMID 21158211. S2CID 110630.
  19. ^ "Children not able to give proper consent to puberty blockers, court told". BBC News. 7 October 2020.
  20. ^ Groves S (10 February 2020). "Ban on treatments for transgender kids fails in South Dakota". Associated Press. Retrieved 14 December 2020.
  21. ^ 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.
  22. ^ Bannerman L (26 July 2019). "Use of puberty blockers on transgender children to be investigated". The Times.
  23. ^ a b c 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.
  24. ^ Holt A (7 October 2020). "Children not able to give 'proper' consent to puberty blockers, court told". BBC News. 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. ^ a b Priest M (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. PMID 30784385. S2CID 73456261.
  27. ^ 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.
  28. ^ Ashley F (February 2019). "Puberty Blockers Are Necessary, but They Don't Prevent Homelessness: Caring for Transgender Youth by Supporting Unsupportive Parents". The American Journal of Bioethics: AJOB. 19 (2): 87–89. doi:10.1080/15265161.2018.1557277. PMID 30784386. S2CID 73478358.
  29. ^ 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. PMID 32495241. S2CID 219314661.
  30. ^ a b 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. 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]. ”
  31. ^ 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. 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.

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