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'''Puberty blockers''' (also called '''puberty inhibitors''' or '''hormone blockers''') are medicines used to postpone [[puberty]] in children. The most commonly used puberty blockers are [[gonadotropin-releasing hormone agonist|gonadotropin-releasing hormone (GnRH) agonist]]s, which suppress the [[biosynthesis|production]] of [[sex hormone]]s, including [[testosterone]] and [[estrogen]].<ref name="Hemat2003">{{cite book | vauthors = Hemat RA |title=Andropathy|url=https://books.google.com/books?id=hfwlDwAAQBAJ&pg=PA120|date=2 March 2003|publisher=Urotext|isbn=978-1-903737-08-8|pages=120–}}</ref><ref name="Becker2001">{{cite book | first = Kenneth L. | last = Becker | name-list-style = vanc | title = Principles and Practice of Endocrinology and Metabolism|url=https://books.google.com/books?id=FVfzRvaucq8C&pg=PA973|year=2001|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-1750-2|pages=973–}}</ref><ref name="mayo">{{cite web |title=Pubertal blockers for transgender and gender diverse youth |url=https://www.mayoclinic.org/diseases-conditions/gender-dysphoria/in-depth/pubertal-blockers/art-20459075 |publisher=Mayo Clinic |access-date=15 December 2020 |language=en |date=16 August 2019}}</ref> In addition to their use in treating [[precocious puberty]], which involves puberty occurring at an unusually early age (and sometimes [[idiopathic short stature]]) in children, puberty blockers are also used for [[transgender]] children to delay the development of unwanted sex characteristics,<ref name="Stevens_2015">{{cite journal |vauthors=Stevens J, Gomez-Lobo V, Pine-Twaddell E |title=Insurance Coverage of Puberty Blocker Therapies for Transgender Youth |journal=[[Pediatrics (journal)|Pediatrics]] |volume=136 |issue=6 |pages=1029–31 |date=December 2015 |pmid=26527547 |doi=10.1542/peds.2015-2849 |doi-access=free }}</ref> so as to allow transgender youth more time to explore their [[gender identity]].<ref name="Alegría_2016">{{cite journal |vauthors=Alegría CA |title=Gender nonconforming and transgender children/youth: Family, community, and implications for practice |journal=[[Journal of the American Association of Nurse Practitioners]] |volume=28 |issue=10 |pages=521–527 |date=October 2016 |pmid=27031444 |doi=10.1002/2327-6924.12363 |s2cid=22374099 }}</ref>
'''Puberty blockers''' (also called '''puberty inhibitors''' or '''hormone blockers''') are medicines used to postpone [[puberty]] in children. The most commonly used puberty blockers are [[gonadotropin-releasing hormone agonist|gonadotropin-releasing hormone (GnRH) agonist]]s, which suppress the [[biosynthesis|production]] of [[sex hormone]]s, including [[testosterone]] and [[estrogen]].<ref name="Hemat2003">{{cite book | vauthors = Hemat RA |title=Andropathy|url=https://books.google.com/books?id=hfwlDwAAQBAJ&pg=PA120|date=2 March 2003|publisher=Urotext|isbn=978-1-903737-08-8|pages=120–}}</ref><ref name="Becker2001">{{cite book | first = Kenneth L. | last = Becker | name-list-style = vanc | title = Principles and Practice of Endocrinology and Metabolism|url=https://books.google.com/books?id=FVfzRvaucq8C&pg=PA973|year=2001|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-1750-2|pages=973–}}</ref><ref name="mayo">{{cite web |title=Pubertal blockers for transgender and gender diverse youth |url=https://www.mayoclinic.org/diseases-conditions/gender-dysphoria/in-depth/pubertal-blockers/art-20459075 |publisher=Mayo Clinic |access-date=15 December 2020 |language=en |date=16 August 2019}}</ref> In addition to their use in treating [[precocious puberty]], which involves puberty occurring at an unusually early age (and sometimes [[idiopathic short stature]]) in children, puberty blockers are also used for [[transgender]] children to delay the development of unwanted sex characteristics,<ref name="Stevens_2015">{{cite journal |vauthors=Stevens J, Gomez-Lobo V, Pine-Twaddell E |title=Insurance Coverage of Puberty Blocker Therapies for Transgender Youth |journal=[[Pediatrics (journal)|Pediatrics]] |volume=136 |issue=6 |pages=1029–31 |date=December 2015 |pmid=26527547 |doi=10.1542/peds.2015-2849 |doi-access=free }}</ref> so as to allow transgender youth more time to explore their [[gender identity]].<ref name="Alegría_2016">{{cite journal |vauthors=Alegría CA |title=Gender nonconforming and transgender children/youth: Family, community, and implications for practice |journal=[[Journal of the American Association of Nurse Practitioners]] |volume=28 |issue=10 |pages=521–527 |date=October 2016 |pmid=27031444 |doi=10.1002/2327-6924.12363 |s2cid=22374099 }}</ref>

Revision as of 19:26, 14 March 2024

"Hormone blocker" redirects here. For testosterone blockers, see Antiandrogen. For estrogen blockers, see Aromatase inhibitor.

Puberty blockers (also called puberty inhibitors or hormone blockers) are medicines 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 use in treating precocious puberty, which involves puberty occurring at an unusually early age (and sometimes idiopathic short stature) in children, puberty blockers are also used for transgender children to delay the development of unwanted sex characteristics,[4] so as to allow transgender youth more time to explore their gender identity.[5]

While few studies have examined the effects of puberty blockers for gender non-conforming and transgender adolescents, the studies that have been conducted generally indicate that these treatments are reasonably safe, are reversible, and can improve psychological well-being in these individuals, including reducing suicidality.[6][7][8][9][10]

At least 18 US states have banned elements of gender affirming care for transgender youth including puberty blockers. Some of these state laws include criminal penalties for doctors that provide puberty blockers to their patients.[11][12]

Medical uses

See also:
GnRH agonist § Medical uses

Delaying or temporarily suspending puberty is a medical treatment for children whose puberty started abnormally early (precocious puberty).[13] Puberty blockers have been used on-label since the 1980s to treat precocious puberty in children,[14] and were approved for use in treating precocious puberty in children by the U.S. Food and Drug Administration (FDA) in 1993.[15] Puberty blockers are also commonly used for children with idiopathic short stature, for whom these medications can be used to promote development of long bones and increase adult height.[13] In adults, the same drugs have a range of different medical uses, including the treatment of endometriosis, breast and prostate cancer, and polycystic ovary syndrome.[16]

Puberty blockers prevent the development of biological

secondary sex characteristics.[17]

Gender-affirming care

Puberty blockers are sometimes prescribed 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 factors like bone mineral density, brain development and fertility in transgender patients.[18][10][19][20]

Puberty blockers have not received FDA approval for use on children who are transgender.

off-label prescription is common in children's medicine, and does not indicate an improper, illegal, or experimental use of medicine.[22] According to pediatric endocrinology expert Brad Miller, pharmaceutical companies that make puberty blocker drugs for children with gender dysphoria have refused to submit them for FDA approval because doing so would cost too much money and "because (transgender treatment) was a political hot potato."[21]

While few studies have examined the effects of puberty blockers for gender non-conforming and transgender adolescents, the studies that have been conducted generally indicate that these treatments are reasonably safe, are reversible, and can improve psychological well-being in these individuals.[6][7][8]

A 2020 review published in Child and Adolescent Mental Health found that puberty blockers are associated with such positive outcomes as decreased suicidality in adulthood, improved affect and psychological functioning, and improved social life.[18] A 2020 survey published in Pediatrics found that puberty blockers are associated with better mental health outcomes and lower odds of lifetime suicidal ideation.[23] 2022 study published in the Journal of the American Medical Association found a 60% reduction in moderate and severe depression and a 73% reduction in suicidality among transgender youth aged 13–20 who took puberty blockers and gender-affirming hormones over a 12-month follow-up.[24] A 2022 study published in The Lancet involving 720 transgender adolescents who took puberty blockers and hormones found that 98 percent continued to use hormones at a follow-up appointment.[25]

A 2020 commissioned review published by the

GRADE scale, however this review has attracted criticism from some in the field, due to this rating being due to a lack of randomized controlled trials, which have been described as neither feasible nor ethical in the context of puberty suppression for this purpose.[26][27] A 2024 systematic review re-affirmed the conclusions of the NICE report, concluding that the currently available studies have "significant conceptual and methodological flaws".[28][29] The Finnish government commissioned a review of the research evidence for treatment of transgender minors and the Finnish Ministry of Health concluded that there are no research-based health care methods for minors with gender dysphoria.[30] Nevertheless, they recommend the use of puberty blockers for minors on a case-by-case basis.[31][failed verification
]

The World Professional Association for Transgender Health's Standards of Care 8, published in 2022, declare puberty blocking medication as "medically necessary", and recommends them for usage in transgender adolescents once the patient has reached Tanner stage 2 of development, and state that longitudinal data shows improved outcomes for transgender patients who receive them.[32]

The longest follow-up study followed a transgender man who began taking puberty blockers at age 13 in 1988, before later taking hormone treatments, and later got gender confirmation surgery as an adult. His health was monitored for 22 years and at age 35 in 2010 was well-functioning, in good physical health with normal metabolic, endocrine, and bone mineral density levels. There were no clinical signs of a negative impact on brain development from taking puberty blockers.[33]

A 2023 Boston Children's Hospital study published in the Journal of Adolescent Health compared groups of transgender and gender diverse youth who had taken puberty blockers and transgender and gender diverse youth who had not taken puberty blockers, finding the group that had taken puberty blockers had reduced levels of anxiety, depression, and suicidal thoughts.[34]

Adverse effects

Short-term side effects of puberty blockers include headaches, fatigue, insomnia, muscle aches and changes in breast tissue, mood, and weight.[35]

Adverse effects on bone mineralization and compromised fertility are potential risks of pubertal suppression in gender dysphoric youth treated with GnRH agonists.[7][36] To protect against lower bone density, doctors recommend exercise, calcium, and Vitamin D.[37] Additionally, genital tissue in transgender women may not be optimal for potential vaginoplasty later in life due to underdevelopment of the penis.[38]

Research on the long-term effects on brain development, cognitive function, fertility, and sexual function is limited.[21][39][40] A 2020 study conducted by John Strang and other researchers suggested that "pubertal suppression may prevent key aspects of development during a sensitive period of brain organization", adding that "we need high-quality research to understand the impacts of this treatment – impacts which may be positive in some ways and potentially negative in others."[21] The Endocrine Society Guidelines, while endorsing the use of puberty blockers for treatment of gender dysphoria, underscores the need 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)."[8]

In 2016, the FDA ordered drugmakers to add warning labels to puberty blocker drugs being used to treat children with precocious puberty stating: "Psychiatric events have been reported in patients", including symptoms "such as crying, irritability, impatience, anger and aggression." The warning labels were added after the FDA received reports of 10 children who had

suicidal thoughts, including one attempt at suicide. One of these children, a 14-year-old, was taking a puberty blocker drug for gender dysphoria.[21]

In 2017, it was reported that the FDA had received more than 10,000 reports of adverse events from women who took

Lupron in order to grow taller.[41]

In 2022, the FDA reported that there have been six cases of

University of Alabama-Birmingham who works with transgender youth, said that "[Idiopathic intracranial hypertension] is an inordinately well-known side effect that can happen for many, many different medications, most commonly, oral birth control pills." Referring to the six reported side effects, Ladinsky said that "It doesn't even approach any semblance of what we call in medicine, statistical significance".[44]

Available forms

A number of different puberty blockers are used.

GnRH antagonists are also expected to be effective as puberty blockers but have not yet been widely studied or used for this purpose.[45][47] 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.[45] They are not as effective as GnRH agonists and have more side effects.[45] The antiandrogen bicalutamide has been used as an alternative puberty blocker in transgender girls for whom GnRH agonists were denied by insurance.[48][49]

Centrally acting puberty blockers such as GnRH agonists are ineffective in

peripheral precocious puberty, which is gonadotropin-independent.[50] In this situation, direct inhibitors of sex hormone action and/or synthesis must be employed instead.[50] 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.[50] 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.[50]

In the United States, the main providers of puberty blockers are Endo International and AbbVie.[21]

Legal and political challenges

The prescription of puberty blockers to transgender children has been subject to misinformation and anti-transgender legislation.[51][52][53][54]

Some opponents of the use of puberty blockers argue that minors are not able to give proper consent.

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.[56] Bioethicist Florence Ashley contends that counseling and educating the parents of transgender youth could also be beneficial to familial relationships.[59]

One study found that the use of puberty blockers decreases the risk of depression and reduces behavioral issues.[38] Opponents have argued that potentially negative "effects may be too subtle to observe during the follow-up sessions by clinical assessment alone".[38]

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.[38] Opponents also argue that puberty blockers "may alter the course of gender identity development, essentially 'locking in' a gender identity that may have reconciled with biological sex during the natural course of puberty."[60] 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.[61] Similarly, most reviews[8][38] noting psychological benefits refer to the classic Dutch study,[40] which had very stringent requirements for medical treatment.[62]

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.[63][64] 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 with a punishment of up to ten years in prison.[65] The Alabama law was partially blocked by a federal judge a few days after the law took effect.[66][67] In August 2022, Florida banned Medicaid from covering gender affirming care, including puberty blockers.[68]

Puberty blockers have also been banned in Utah,[69] Idaho,[70] Montana,[71] North Dakota,[72] South Dakota,[73] Iowa,[74] Indiana,[75] Kentucky,[76] Mississippi,[77] Florida,[78] West Virginia,[79] Tennessee,[80] and Oklahoma.[81]

Some state bans on gender affirming care including puberty blockers have been declared unconstitutional.[82] Furthermore, bans on puberty blockers have been criticized as governments interfering with the patient-doctor relationship and taking away healthcare decisions from parents and families for their children.[83][84] State level bans on gender affirming care, including puberty blockers, in the United States have led some families with transgender children to move out of their states.[85][86][87]

Stances of medical organizations

More than a dozen major American and Australian medical associations, as well as the World Professional Association for Transgender Health (WPATH),[88] generally support puberty blockers for transgender youth and have come out against efforts to restrict their use. In Europe, however, some medical groups and countries have taken a more precautionary stance following systematic reviews of the evidence base, discouraging or limiting the use of puberty blockers.[89][21]

Australia

The Royal Australasian College of Physicians, the Royal Australian College of General Practitioners, the Australian Endocrine Society, and AusPATH all support access to puberty blockers for transgender youth.[90]

Finland

The Council for Choices for Healthcare in Finland supports the use of puberty blockers in transgender children after a case-by-case assessment if there are no medical contraindications.[91] However, In 2021, Finnish national health authorities issued guidelines that favour other interventions such as psychotherapy, with hormonal treatments being limited to specific circumstances.[92][93]

France

In 2022, France's Académie Nationale de Médecine recommended the "greatest reserve" when considering puberty blockers due to potential side effects, including "impact on growth, bone weakening, [and] risk of infertility".[94]

Norway

In 2023, the Norwegian Healthcare Investigation Board issued a report finding "there is insufficient evidence for the use of puberty blockers and cross sex hormone treatments in young people".[95]

Sweden

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.[96] On 22 February 2022, Sweden's National Board of Health and Welfare said that puberty blockers should only be used in "exceptional cases" and said that their use is backed by "uncertain science".[97][98]

However, other providers in Sweden continue to provide puberty blockers, and a clinician's professional judgment determines what treatments are recommended or not recommended. Youth are able to access gender-affirming care when doctors deem it medically necessary. The treatment is not banned in Sweden and is offered as part of its national healthcare service.[98][99][100]

United Kingdom

On 30 June 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. Specifically, the NHS removed language stating that puberty blockers were "fully reversible" and that "treatment can usually be stopped at any time". In its place, the NHS stated that "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."[101]

The Bell v Tavistock decision by the High Court of Justice for England and Wales ruled children under 16 were not competent to give informed consent to puberty blockers, but this was overturned by the Court of Appeal in September 2021.

Efforts to ban puberty blockers for transgender youth are opposed by the British Medical Association.[102] The National Health Service currently supports the use of puberty blockers for children under 16 years of age only in the context of centrally administered clinical research, and strongly discourages seeking treatment from unregulated sources.[103][104]

On 12 March 2024, NHS England announced that the National Health Service would no longer prescribe puberty blockers to children outside of use in clinical research trials, citing concerns that there was not enough evidence about either how safe they were to take or whether they were clinically effective to justify prescribing them to children and young people.[105][106] NHS England hopes to have a study into the use of puberty blockers in place by December 2024, with eligibility criteria yet to be decided.[105]

United States

The use of puberty blockers in transgender youth is supported by:

Public opinion

An April 2021

Marist poll with the question "Do you support or oppose legislation that would prohibit gender transition-related medical care for minors" found 66% of Americans would oppose a ban, including 69% of Democrats, 70% of Republicans, and 64% of Independents.[117]

A February 2022 poll by LGBT support service The Trevor Project and Morning Consult found that 52 percent of American adults expressed some level of support for transgender minors having access to puberty blockers if it is recommended by their doctor and supported by their parents.[118][119]

A Washington Post-KFF poll conducted in November 2022 found that 68 percent of adults oppose access to puberty-blocking medication for transgender children ages 10 to 14, and 58 percent oppose access to hormonal treatments for transgender children ages 15 to 17.[120]

In a January 2023 Deseret News/HarrisX poll, 55 percent of Americans supported banning gender hormone therapy for transgender minors with parental or guardian approval, while 45 percent opposed such a ban.[121]

A September 2023 poll by 19th News/SurveyMonkey found that 39 percent of American adults supported transgender minors having access to any kind of gender-affirming care, including puberty blockers, hormones, therapy, and surgery.[122]

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External links

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