Puberty blocker

Puberty blockers, also called puberty inhibitors, are drugs used to postpone puberty in children. These drugs are called gonadotropin-releasing hormone (GnRH) agonists, and they inhibit the action of testosterone. Delaying or temporarily suspending puberty is a medical treatment for children whose puberty started abnormally early (precocious puberty). They are also commonly used for children with idiopathic short stature and for whom these drugs can be used to promote development of long bones and increase adult height.[1] Additionally, they are used for transgender children, to stop the development of features that they considered their wrong sex,[2][3][4] with the intent to provide transgender youth more time to explore their identity.[5]

In adults, the same drugs are used to treat endometriosis,[6] prostate cancer, and other conditions.[7][8]

Medical uses

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 for children and adolescents and the halting of female features of breast development and menstruation.

Transgender youth are a specific target population of puberty blockers to halt the development of natal secondary sex characteristics.[2]. 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 effects of puberty blockers can be reversed by stopping the medication.[10] Puberty blockers give the future transgender individual a smoother transition into their desired gender identity as an adult.[5]

While there are few studies that 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.[11][12][13] In 2019, a study in the journal Pediatrics found that access to pubertal suppression during adolescence was associated with a lower odds of lifetime suicidality among transgender people.[14]

The potential risks of pubertal suppression in gender dysphoric youth treated with GnRH agonists may include adverse effects on bone mineralization.[15][16]

Research on the long term effects on brain development is limited, but a 2015 study published in Psychoneuroendocrinology observed the executive functioning in 20 transgender youth treated with puberty blockers compared to untreated youth with gender dysphoria and found that there was no difference in performance.[16][17][18][5]

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 each 3, 4 or 6 months (Lupron Depot-3 month, Lupron Depot-PED-3 month, Lupron Depot-4 month, Lupron Depot-6 Month). Lupron Depot can cost from $700 to $1,500 a month depending on the country where it is practiced.

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 during 12 months and it has to be replaced by another one later to continue the treatment. The total cost of histrelin treatment with the surgery 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]

References
  1. 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.
  2. Stevens, Jaime; Gomez-Lobo, Veronica; Pine-Twaddell, Elyse (2015-12-01). "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. "Looking at suppressing puberty for transgender kids". Associated Press. March 12, 2016.
  4. "Transgender Youth Using Puberty Blockers". KQED. August 19, 2016.
  5. Alegría, Christine Aramburu (2016-10-01). "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.
  6. Current treatments for endometriosis, Mayo Clininc, https://www.mayoclinic.org/diseases-conditions/endometriosis/diagnosis-treatment/drc-20354661
  7. Smith, M. R. (2006). Treatment-related osteoporosis in men with prostate cancer. Clinical Cancer Research, 12(20 pt 2), 6315-6319.
  8. Panday, K., Gona, A., Humphrey, M. B., (2014). Medication-induced osteoporosis: Screening and treatment strategies. Therapeutic Advances in Musculoskeletal Disease, 6, 185-202.
  9. Bayar, R. M. (2003-11-28). "Control of the Onset of Puberty". Annual Review of Medicine. 29: 509–520. doi:10.1146/annurev.me.29.020178.002453. PMID 206190.
  10. 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.
  11. 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."CS1 maint: ref=harv (link)
  12. 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.
  13. 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
  14. 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. Retrieved 11 February 2020.
  15. 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.
  16. 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.
  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.
  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.
  19. Kreher NC, Pescovitz OH, Delameter P, Tiulpakov A, Hochberg Z (Sep 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 (Oct 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.
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