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Puberty blocker

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Puberty blockers, also called puberty inhibitors or hormone blockers, are drugs used to postpone puberty in children. The most commonly used puberty blockers are gonadotropin-releasing hormone (GnRH) agonists, which suppress the production 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]

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. Little is known about the long-term side effects of hormone or puberty blockers in children with gender dysphoria. Although puberty blockers are known to be safe and physically reversible treatment if stopped in the short term, it is also not known whether hormone blockers affect the development of the factors like bone mineral density, brain development and fertility in transgender patients.[10][11][12][13] 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,[14][15][16] 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.[17]

A review published in Child and Adolescent Mental Health found that puberty blockers are fully reversible, and that they are associated with such positive outcomes as decreased suicidality in adulthood, improved affect and psychological functioning, and improved social life.[18]

Adverse effects on bone mineralization and compromised fertility are potential risks of pubertal suppression in gender dysphoric youth treated with GnRH agonists.[15][19] Additionally, genital tissue in transgender women may not be optimal for potential vaginoplasty later in life due to underdevelopment of the penis.[20]

Research on the long-term effects on brain development is limited.[21][22]

Available forms

A number of different puberty blockers are used.[23][24] These include the GnRH agonists buserelin, histrelin, leuprorelin, nafarelin, and triptorelin.[23][24] GnRH agonists are available and used as daily subcutaneous injections, depot subcutaneous or intramuscular injections lasting 1 to 6 months, implants lasting 12 months, and nasal sprays used multiple times per day.[23][24] GnRH antagonists are also expected to be effective as puberty blockers but have not yet been widely studied or used for this purpose.[23][25] Progestogens used at high doses such as medroxyprogesterone acetate and cyproterone acetate have been used as puberty blockers in the past or when GnRH agonists are not possible.[23] They are not as effective as GnRH agonists and have more side effects.[23] The antiandrogen bicalutamide has been used as an alternative puberty blocker in transgender girls for whom GnRH agonists were denied by insurance.[26][27]

Centrally acting puberty blockers such as GnRH agonists are ineffective in peripheral precocious puberty, which is gonadotropin-independent.[28] In this situation, direct inhibitors of sex hormone action and/or synthesis must be employed instead.[28] Treatment options for peripheral precocious puberty in girls, such as in McCune–Albright syndrome, include ketoconazole, the aromatase inhibitors testolactone, fadrozole, anastrozole, and letrozole, and the antiestrogens tamoxifen and fulvestrant.[28] Treatment possibilities for peripheral precocious puberty in boys, such as in familial male-limited precocious puberty, include the antiandrogens bicalutamide, spironolactone, and cyproterone acetate, ketoconazole, and the aromatase inhibitors testolactone, anastrozole, and letrozole.[28]

Legal and political challenges

There is criticism regarding issues of informed consent and limited research support for the use of puberty blockers on transgender children.[29][30][31][32][excessive citations] The Endocrine Society 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)."[16]

Some opponents of the use of puberty blockers argue that minors are not able to give proper consent.[33] 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.[34] Consent is often achieved after extensive analysis and counseling.[35] 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".[36]

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.[34] Bioethicist Florence Ashley adds that counseling and educating the parents of transgender youth could also be beneficial to familial relationships.[37]

Michael Biggs has said that studies on the effects of puberty blockers on transgender children lack transparency or validity.[33][38] Opponents express concern over validation of a child's gender dysphoria; however, research has shown that treatment with puberty blockers prevents harmful behavior[vague] and does not increase gender dysphoria.[20] Research has suggested that the use of puberty blockers decreases the risk of depression and contributes to the mitigation of behavioral issues.[20] Opponents to the use of puberty blockers have argued that puberty blockers encourage children to go through with hormone replacement therapy 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.[20]

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.[20]  Almost all (98%) children who took puberty blockers in a significant recent study by the main UK child/adolescent gender clinic continued on to hormone replacement therapy.[39] Similarly, most reviews[16][20] noting psychological benefits refer to the classic Dutch study[22] which had very stringent requirements for medical treatment.[40]

In April 2021, Arkansas passed a ban on treatment of minors under 18 with puberty blockers, but it was temporarily blocked by a federal judge a week before the law was set to take effect.[41][42] In April 2022, Alabama passed a ban from minors under 19 from obtaining puberty blockers and made it a felony for a doctor to prescribe puberty blockers to a minor, the law was partially blocked by a federal judge a few days after the law took effect.[43][44]

Efforts to ban puberty blockers are opposed by the American Medical Association,[45] the American Academy of Child and Adolescent Psychiatry (AACAP),[46] the American Academy of Pediatrics,[47] the American Psychiatric Association,[48] the Endocrine Society,[49] the American College of Obstetricians and Gynecologists,[50] the American Psychological Association,[51] and the World Professional Association for Transgender Health.[52]

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.[53] 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."[53]

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.[54]


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