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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 (GnRH) agonists, which suppress the production of sex hormones, including testosterone and estrogen. 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, so as to allow transgender youth more time to explore their gender identity.

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.

The use of puberty blockers in transgender youth is supported by the Endocrine Society and the World Professional Association for Transgender Health (WPATH)

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.

Medical uses

Delaying or temporarily suspending puberty is a medical treatment for children whose puberty started abnormally early (precocious puberty). Puberty blockers have been used on-label since the 1980s to treat precocious puberty in children, and were approved for use in treating precocious puberty in children by the U.S. Food and Drug Administration (FDA) in 1993. 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. 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.

Puberty blockers prevent the development of biological secondary sex characteristics.

Gender-affirming care

Puberty blockers are sometimes prescribed to young transgender people, to temporarily halt the development of secondary sex characteristics. Puberty blockers allow patients more time to solidify their gender identity, without developing secondary sex characteristics, and give transgender youth a smoother transition into their desired gender identity as an adult. 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 factors like bone mineral density, brain development and fertility in transgender patients.

Puberty blockers have not received FDA approval for use on children who are transgender. The practice of off-label prescription is common in children's medicine, and does not indicate an improper, illegal, or experimental use of medicine. 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."

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. 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. A 2022 review published in the Annual Review of Medicine found clearly beneficial, lifesaving impacts of puberty blockers on a scale of up to six years, but found research lacking beyond that time frame. The World Professional Association for Transgender Health's Standards of Care 8, published in 2022, found puberty-blocking medication to be "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.

A 2020 commissioned review published by the UK's National Institute for Health and Care Excellence concluded that the quality of evidence for puberty blocker outcomes (for mental health, quality of life and impact on gender dysphoria) was of very low certainty based on a modified GRADE approach, but that "it is plausible, however, that a lack of difference in scores from baseline to follow-up is the effect of GnRH analogues in children and adolescents with gender dysphoria, in whom the development of secondary sexual characteristics might be expected to be associated with an increased impact on gender dysphoria, depression, anxiety, anger and distress over time without treatment." A 2024 systematic review using the same approach re-affirmed the conclusions of the NICE report, concluding that the currently available studies have "significant conceptual and methodological flaws".

The NICE review has been criticized by WPATH and EPATH for excluding studies combining puberty blockers and hormone replacement therapy and by parents of transgender youth for excluding evidence of its safety when used by cisgender youth undergoing precocious puberty. The review has also been criticized for prioritization of "high quality" evidence according to the GRADE approach, which designates randomized control trials (RCTs) as "high quality", since RCTs are widely considered unfeasible and unethical for transgender youth due to the fact those in the control group would have to be denied treatment. The review also deviated from GRADE guidance which states that "low or very low quality evidence can lead to a strong recommendation" by not taking the low-quality studies into account when forming evidence review recommendations.

The longest follow-up study followed a transgender man who began taking puberty blockers at age 13 in 1998, 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.

Criticism

The use of puberty blockers for gender affirming care has attracted some criticism, due primarily to the lack of randomized controlled trials within the research base. However, randomized controlled trials are not regarded as feasible or ethical in the case of research for gender-affirming care.

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. The Finnish Ministry supports the use of puberty blockers for minors on a case-by-case basis.

Adverse effects

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

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

Research on the long-term effects on brain development, cognitive function, fertility, and sexual function is limited. 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." 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)."

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.

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.

In 2022, the FDA reported that there have been six cases of idiopathic intracranial hypertension in 5 to 12-year-old children assigned female at birth taking puberty blockers. Five who experienced the side effect were receiving treatment for precocious puberty and one who experienced the side effect was transgender and was receiving treatment for gender dysphoria. Morissa Ladinsky, a pediatrician with University of Alabama-Birmingham who works with transgender youth, said that " 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".

A 2024 University College London review of the impact of suppressing puberty on psychological function found some evidence of a detrimental effect on IQ, and no evidence that cognitive effects were fully reversible.

Available forms

A number of different puberty blockers are used. These include the GnRH agonists buserelin, histrelin, leuprorelin, nafarelin, and triptorelin. 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. GnRH antagonists are also expected to be effective as puberty blockers but have not yet been widely studied or used for this purpose. 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. They are not as effective as GnRH agonists and have more side effects. The antiandrogen bicalutamide has been used as an alternative puberty blocker in transgender girls for whom GnRH agonists were denied by insurance.

Centrally acting puberty blockers such as GnRH agonists are ineffective in peripheral precocious puberty, which is gonadotropin-independent. In this situation, direct inhibitors of sex hormone action and/or synthesis must be employed instead. 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. 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.

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

Legal and political challenges

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The prescription of puberty blockers to transgender children has been subject to misinformation and anti-transgender legislation.

Some opponents of the use of puberty blockers argue that minors are not able to give proper consent. Some advocates for the use of puberty blockers argue that there are psychological and developmental benefits of puberty blockers which are compelling enough to overlook the issue of informed consent in many cases. According to a 2019 study, a "multidisciplinary staged approach" is necessary "to ensure meaningful consent". According to the 2021 editorial, "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". 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. Bioethicist Florence Ashley contends that counseling and educating the parents of transgender youth could also be beneficial to familial relationships.

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

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. 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." 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. Similarly, most reviews noting psychological benefits refer to the classic Dutch study, which had very stringent requirements for medical treatment.

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. 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. The Alabama law was partially blocked by a federal judge a few days after the law took effect. In August 2022, Florida banned Medicaid from covering gender affirming care, including puberty blockers.

Puberty blockers have also been banned in Utah, Idaho, Montana, North Dakota, South Dakota, Iowa, Indiana, Kentucky, Mississippi, Florida, West Virginia, Tennessee, and Oklahoma.

Some state bans on gender affirming care including puberty blockers have been declared unconstitutional. 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. 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.

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), 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.

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.

Finland

In 2020, Finland revised its guidelines to prioritise psychotherapy over medical transition, but the Council for Choices in Health Care allows the use of puberty blockers in transgender children after a case-by-case assessment if there are no medical contraindications.

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, risk of infertility".

Norway

In 2020, the Norwegian Directorate for Health, the governmental body that develops health guidelines, released one for gender incongruence recommending puberty blockers between Tanner stage 2 and the age of 16 following an interdisciplinary assessment, stating they were reversible and there is no reliable evidence of adverse long-term effects. In 2023, the Norwegian Healthcare Investigation Board, an independent non-governmental organization, issued a non-binding report finding "there is insufficient evidence for the use of puberty blockers and cross sex hormone treatments in young people" and recommending restrictions on such care. The Directorate stated the guidelines acknowledged the limited evidence base and their recommendations were "limited to the organisation and content of services on different treatment levels necessary to fulfil patient rights, as required by Norwegian health regulation," further stating that they planned to begin talks with clinicians and patient representatives to determine whether revisions are necessary. Misinformation that Norway had banned gender affirming care proliferated on social media.

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. 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".

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.

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."

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. 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.

In March 2024, NHS England announced that it would no longer prescribe puberty blockers to minors outside of use in clinical research trials, citing insufficient evidence of safety or clinical effectiveness. Children already receiving puberty blockers via NHS England will be able to continue their treatment. 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. Children in England can still be prescribed puberty blockers through some private clinics that are not associated with NHS England.

United States

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

• The American Medical Association
• The American Psychological Association
• The American Academy of Pediatrics and the Endocrine Society
• The American Academy of Child and Adolescent Psychiatry (AACAP)
• The American Psychiatric Association
• The Pediatric Endocrine Society
• The American Association of Clinical Endocrinologists

Public opinion

The examples and perspective in this section deal primarily with the United States and do not represent a worldwide view of the subject. You may improve this section, discuss the issue on the talk page, or create a new section, as appropriate. (March 2024) (Learn how and when to remove this message)

An April 2021 PBS Newshour/NPR/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.

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.

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.

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.

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.

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External links

• Puberty Inhibitors, by Norman P. Spack, TransYouth Family Allies at the Wayback Machine (archived 2012-04-23)

• Gender transitioning and medicine
• Puberty
• Puberty blockers