Dutch Protocol (Hormone Replacement Therapy)
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Puberty blockers (also called puberty inhibitors or hormone blockers) are medicines used to postpone
puberty Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a female, the testicles i ...
in children. The most commonly used puberty blockers are gonadotropin-releasing hormone (GnRH) agonists, which suppress the natural production of
sex hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects a ...
s, such as
androgen An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...
s (e.g.
testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...
) and
estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
s (e.g.
estradiol Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...
). Puberty blockers are used to delay puberty in children with
precocious puberty In medicine, precocious puberty is puberty occurring at an unusually early age. In most cases, the process is normal in every aspect except the unusually early age and simply represents a variation of normal development. There is early developm ...
. Since at least the 1980s, they are also used to delay the development of unwanted
secondary sex characteristic A secondary sex characteristic is a physical characteristic of an organism that is related to or derived from its sex, but not directly part of its reproductive system. In humans, these characteristics typically start to appear during pubert ...
s in
transgender A transgender (often shortened to trans) person has a gender identity different from that typically associated with the sex they were sex assignment, assigned at birth. The opposite of ''transgender'' is ''cisgender'', which describes perso ...
children, so as to allow transgender youth more time to explore their
gender identity Gender identity is the personal sense of one's own gender. Gender identity can correlate with a person's assigned sex or can differ from it. In most individuals, the various biological determinants of sex are congruent and consistent with the in ...
under what became known as the "Dutch Protocol". They have been shown to reduce depression and suicidality in transgender and nonbinary youth. The same drugs are also used in
fertility medicine Reproductive endocrinology and infertility (REI) is a surgical subspecialty of obstetrics and gynecology that trains physicians in reproductive medicine addressing hormonal functioning as it pertains to reproduction as well as the issue of infert ...
and to treat some
hormone-sensitive cancer A hormone-sensitive cancer, or hormone-dependent cancer, is a type of cancer that is dependent on a hormone for growth and/or survival. Examples include breast cancer, which is dependent on estrogens like estradiol, and prostate cancer, which is ...
s in adults. The use of puberty blockers is supported by the
Endocrine Society The Endocrine Society is a professional, international medical organization in the field of endocrinology and metabolism, founded in 1916 as The Association for the Study of Internal Secretions. The official name of the organization was changed t ...
and the
World Professional Association for Transgender Health The World Professional Association for Transgender Health (WPATH), formerly the Harry Benjamin International Gender Dysphoria Association (HBIGDA), is a professional organization devoted to the understanding and treatment of gender identity and ...
(WPATH). In the United States, twelve major American medical associations, including the
American Medical Association The American Medical Association (AMA) is an American professional association and lobbying group of physicians and medical students. This medical association was founded in 1847 and is headquartered in Chicago, Illinois. Membership was 271,660 ...
, the
American Psychological Association The American Psychological Association (APA) is the main professional organization of psychologists in the United States, and the largest psychological association in the world. It has over 170,000 members, including scientists, educators, clin ...
, and the
American Academy of Pediatrics The American Academy of Pediatrics (AAP) is the largest professional association of pediatricians in the United States. It is headquartered in Itasca, Illinois, and maintains an office in Washington, D.C. The AAP has published hundreds of poli ...
support the use of puberty blockers. In Australia, four medical organizations support them. The
United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Northwestern Europe, off the coast of European mainland, the continental mainland. It comprises England, Scotlan ...
has implemented a ban on prescribing puberty blockers to new patients under 18 for the treatment of
gender dysphoria Gender dysphoria (GD) is the distress a person experiences due to inconsistency between their gender identitytheir personal sense of their own genderand their sex assigned at birth. The term replaced the previous diagnostic label of gender i ...
except for use in clinical research trials, as of May 2024. In the 2020s, the provision of puberty blockers for gender dysphoria in children has become the subject of public controversy, with the United Kingdom stopping the routine prescription of puberty blockers and some states of the United States making their use a criminal offense.


Medical uses

Puberty blockers prevent the development of biological
secondary sex characteristics A secondary sex characteristic is a physical characteristic of an organism that is related to or derived from its sex, but not directly part of its reproductive system. In humans, these characteristics typically start to appear during puberty ...
.


Precocious puberty

Puberty blockers are commonly used to delay puberty in children with
precocious puberty In medicine, precocious puberty is puberty occurring at an unusually early age. In most cases, the process is normal in every aspect except the unusually early age and simply represents a variation of normal development. There is early developm ...
, a condition that activates the hypothalamic-pituitary-gonadal axis prematurely and initiates puberty at an inappropriate age. The main goal of treatment is to preserve children's adult height potential. Puberty blockers work by stabilizing puberty symptoms, decreasing growth velocity, and slowing skeletal maturation. The outcomes of treatment are assessed in terms of height, reproduction, metabolic, and psychosocial measures. The most pronounced effects on height have been seen in children experiencing the onset of puberty before 6 years of age; however there is variability in height outcomes across studies which can be attributed to varying study designs, time of symptom presentation, and time of treatment termination. A study investigating the effects of puberty blockers on reproductive health showed no significant difference in the number of irregular menstrual cycles, pregnancies, or pregnancy outcomes between women who received treatment for precocious puberty and those who opted out of treatment. In terms of psychosocial markers, preadolescents and adolescents diagnosed with precocious puberty have shown body image concerns and demonstrated poor emotional regulation and high anxiety. Individuals with precocious puberty, early adrenarche, and early normal puberty show less stress after treatment compared to individuals without preexisting developmental conditions. Moreover, they are utilized in the treatment of central precocious puberty resulting from conditions like
hypothalamic hamartomas Tuber cinereum hamartoma is a benign tumor in which a disorganized collection of neurons and glia accumulate at the tuber cinereum of the hypothalamus on the floor of the third ventricle. It is a congenital malformation, included on the spectrum ...
or
congenital adrenal hyperplasia Congenital adrenal hyperplasia (CAH) is a group of Genetic disorder#Autosomal recessive, autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the Biosy ...
, where early onset of puberty is a symptom. Additionally, puberty blockers can be prescribed for children with severe forms of idiopathic short stature, allowing for more time for growth before the closure of growth plates. These applications illustrate the versatility of puberty blockers in addressing various endocrine and growth-related disorders. Overall, puberty blockers have demonstrated an excellent safety and efficacy profile in the treatment of precocious puberty. The most common side effects reported include nonspecific headaches, hot flashes, and implant-related skin reactions.


Gender dysphoria

Puberty blockers are sometimes prescribed to young transgender people with
gender dysphoria Gender dysphoria (GD) is the distress a person experiences due to inconsistency between their gender identitytheir personal sense of their own genderand their sex assigned at birth. The term replaced the previous diagnostic label of gender i ...
to temporarily halt the development of secondary sex characteristics. While there is evidence to suggest transgender youth may benefit from
gender-affirming hormone therapy Gender-affirming hormone therapy (GAHT), also called hormone replacement therapy (HRT) or transgender hormone therapy, is a form of hormone therapy in which sex hormones and other sex-hormonal agent, hormonal medications are administered to transg ...
(HRT) even at early puberty, there may be restrictions on prescribing HRT at younger ages. Puberty blockers are intended to allow patients more time to solidify their gender identity and give them a smoother transition into their desired gender identity as an adult. If a child later decides not to transition, the medication can be stopped and puberty will proceed. The "Dutch Protocol" is the first known example of the use puberty blockers to treat gender dysphoria in children. It was developed by
Peggy Cohen-Kettenis Peggy may refer to: People * Peggy (given name), people with the given name or nickname Arts and entertainment * ''Peggy'' (musical), a 1911 musical comedy by Stuart and Bovill * ''Peggy'' (album), a 1977 Peggy Lee album * ''Peggy'' (1916 ...
in the 1990s. The initial article describing the Dutch Protocol stated that the treatment was reversible and that a study of 54 children showed evidence that it had an overall positive outcome for those treated. A number of subsequent studies supported the treatment as safe and effective at delaying development of secondary sexual characteristics, and it became the standard treatment in the field. Studies examining the effects of puberty blockers for
gender non-conforming Gender nonconformity or gender variance is gender expression by an individual whose behavior, mannerisms, and/or appearance does not match masculine or feminine gender norms. A person can be gender-nonconforming regardless of their gender identi ...
and transgender adolescents have generally indicated that these treatments are reasonably safe, are reversible, and can improve psychological well-being in these individuals. The
World Professional Association for Transgender Health The World Professional Association for Transgender Health (WPATH), formerly the Harry Benjamin International Gender Dysphoria Association (HBIGDA), is a professional organization devoted to the understanding and treatment of gender identity and ...
's Standards of Care 8, published in 2022, declared puberty-blocking medication to be
medically necessary Medicine is the science and practice of caring for patients, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care practic ...
and recommends them for usage in transgender adolescents once the patient has reached
Tanner stage The Tanner scale (also known as the Tanner stages or sexual maturity rating (SMR)) is a scale of physical development as pre-pubescent children transition into adolescence, and then adulthood. The scale defines physical measurements of developme ...
2 of development, because longitudinal data shows improved outcomes for transgender patients who receive them. Puberty blockers are associated with such positive outcomes as decreased suicidality, improved affect and psychological functioning, and improved social life.


Types

Puberty blocker medications are used to delay the physical changes associated with puberty, offering individuals more time to explore their gender identity. The most common type of puberty blockers are GnRH (gonadotropin-releasing hormone) analogues, such as leuprolide acetate and histrelin acetate, which suppress the release of sex hormones like testosterone and estrogen. These medications are typically administered via injections or implants. Another type of puberty blocker includes progestins, such as medroxyprogesterone acetate, which can be taken orally or by injection and work by reducing the body's production of sex hormones. In some cases, aromatase inhibitors are used off-label to block the conversion of androgens into estrogens, although they are less commonly prescribed. Each type of medication has specific benefits and potential side effects, and the choice of which to use depends on the individual's medical needs and the advice of their healthcare provider. A number of different drugs are used as puberty blockers. * Gonadotropin-releasing hormone (GnRH) agonists: Specific examples include:
buserelin Buserelin, sold under the brand name Suprefact among others, is a medication which is used primarily in the treatment of prostate cancer and endometriosis. It is also used for other indications such as the treatment of premenopausal breast canc ...
,
histrelin Histrelin acetate, sold under the brand name Supprelin among others, is a nonapeptide analogue of gonadotropin-releasing hormone (GnRH) with added potency. When present in the bloodstream, it acts on particular cells of the pituitary gland cal ...
,
leuprorelin Leuprorelin, also known as leuprolide, is a manufactured version of a hormone used to treat prostate cancer, breast cancer, endometriosis, uterine fibroids, for early puberty, as part of transgender hormone therapy, or to perform chemical ca ...
,
nafarelin Nafarelin, sold under the brand name Synarel among others, is a gonadotropin-releasing hormone agonist (GnRH agonist) medication which is used in the treatment of endometriosis and early puberty. It is also used to treat uterine fibroids, to c ...
, and
triptorelin Triptorelin, sold under the brand name Decapeptyl among others, is a medication that acts as an agonist analog of gonadotropin-releasing hormone, repressing expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). It is a ...
. GnRH agonists are available and used as daily
subcutaneous injection Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion. A subcutaneous injection is administered as a bolus (medicine), bolus into the subcutis, the layer of skin directly below the dermis and ...
s,
depot Depot may refer to: Places * Depot, Poland, a village * Depot Glacier (disambiguation) * Depot Island (disambiguation) * Depot Nunatak * Depot Peak Brands and enterprises * Maxwell Street Depot, a restaurant in Chicago, United States * Of ...
subcutaneous or
intramuscular injection Intramuscular injection, often abbreviated IM, is the medical injection, injection of a substance into a muscle. In medicine, it is one of several methods for parenteral, parenteral administration of medications. Intramuscular injection may be ...
s lasting 1 to 6 months,
implant Implant can refer to: Medicine *Implant (medicine), or specifically: **Brain implant **Breast implant **Buttock augmentation, Buttock implant **Cochlear implant **Contraceptive implant **Dental implant **Fetal tissue implant **Implantable cardiov ...
s lasting 12 months, and
nasal spray Nasal sprays are used to deliver medications Route of administration#Local, locally in the nasal cavities or systemic administration, systemically. They are used locally for conditions such as nasal congestion and allergic rhinitis. In some sit ...
s used multiple times per day. *
GnRH antagonist Gonadotropin-releasing hormone antagonists (GnRH antagonists) are a class of medications that receptor antagonist, antagonize the gonadotropin-releasing hormone receptor (GnRH receptor) and thus the action of gonadotropin-releasing hormone (GnRH ...
s are also expected to be effective at delaying puberty but have not yet been widely studied or used for this purpose. Examples of
GnRh antagonists Gonadotropin-releasing hormone antagonists (GnRH antagonists) are a class of medications that antagonize the gonadotropin-releasing hormone receptor (GnRH receptor) and thus the action of gonadotropin-releasing hormone (GnRH). They are used in ...
include ganirelix and
cetrorelix Cetrorelix (, ), or cetrorelix acetate (, ), sold under the brand name Cetrotide, is an injectable gonadotropin-releasing hormone (GnRH) gonadotropin-releasing hormone antagonist, antagonist. A synthetic compound, synthetic decapeptide, it is us ...
, drugs that are typically used to treat infertility. *
Progestogen Progestogens, also sometimes written progestins, progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestoge ...
s used at high doses such as
medroxyprogesterone acetate Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of ...
and
cyproterone acetate Cyproterone acetate (CPA), sold alone under the brand name Androcur or Ethinylestradiol/cyproterone acetate, with ethinylestradiol under the brand names Diane or Diane-35 among others, is an antiandrogen and progestin medication used in the tre ...
have been used as puberty blockers in the past or when GnRH agonists are not possible. For precocious puberty, they are not as effective as GnRH agonists (especially in avoiding a hit to adult height) and have more
side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...
s. They are cheaper than GnRH agonists and potentially have fewer side effects for individuals with gender dysphoria (very small sample size). *
Antiandrogens Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking th ...
:
Bicalutamide Bicalutamide, sold under the brand name Casodex among others, is an antiandrogen medication that is primarily used to treat prostate cancer. It is typically used together with a gonadotropin-releasing hormone (GnRH) analogue or surgical remo ...
has been used as a cheaper alternative puberty blocker in transgender girls for whom GnRH agonists were denied by insurance. The antiandrogens
spironolactone Spironolactone, sold under the brand name Aldactone among others, is classed as a diuretic medication. It can be used to treat edema, fluid build-up due to hepatic cirrhosis, liver disease or kidney disease. It is also used to reduce risk o ...
and
cyproterone acetate Cyproterone acetate (CPA), sold alone under the brand name Androcur or Ethinylestradiol/cyproterone acetate, with ethinylestradiol under the brand names Diane or Diane-35 among others, is an antiandrogen and progestin medication used in the tre ...
are not as strong. In the United States, the main providers of puberty blockers are
Endo International Endo International plc is an American Irish-domiciled generics and specialty branded pharmaceutical company that generated over 93% of its 2017 sales from the U.S. healthcare system. While Endo's management, operations, and customers are almost e ...
and
AbbVie AbbVie Inc. is an American pharmaceutical company headquartered in North Chicago, Illinois. It is ranked sixth on the list of largest biomedical companies by revenue. In 2023, the company's seat in Forbes Global 2000 was 74, and rank 89 on the ...
.
Endo International Endo International plc is an American Irish-domiciled generics and specialty branded pharmaceutical company that generated over 93% of its 2017 sales from the U.S. healthcare system. While Endo's management, operations, and customers are almost e ...
creates histerelin acetate (Vantas) while
AbbVie AbbVie Inc. is an American pharmaceutical company headquartered in North Chicago, Illinois. It is ranked sixth on the list of largest biomedical companies by revenue. In 2023, the company's seat in Forbes Global 2000 was 74, and rank 89 on the ...
manufactures
leuprolide acetate Leuprorelin, also known as leuprolide, is a manufactured version of a hormone used to treat prostate cancer, breast cancer, endometriosis, uterine fibroids, for early puberty, as part of transgender hormone therapy, or to perform chemical cast ...
(Lupron Depot). Other companies within the United States are also in the mix such as
Pfizer Pfizer Inc. ( ) is an American Multinational corporation, multinational Pharmaceutical industry, pharmaceutical and biotechnology corporation headquartered at The Spiral (New York City), The Spiral in Manhattan, New York City. Founded in 184 ...
who distributes histerelin acetate (Supprelin LA) and Tolmar Pharmaceuticals who create their own
leuprolide acetate Leuprorelin, also known as leuprolide, is a manufactured version of a hormone used to treat prostate cancer, breast cancer, endometriosis, uterine fibroids, for early puberty, as part of transgender hormone therapy, or to perform chemical cast ...
(Fensolvi). Outside of the United States, companies such as
Ferring Pharmaceuticals Ferring Pharmaceuticals is a Swiss multinational biopharmaceutical company specialising in areas such as reproductive health, maternal health, gastroenterology and urology. Ferring has been developing treatments for mothers and babies for over 50 ...
,
Ipsen Ipsen is a French biopharmaceutical company headquartered in Paris, France, with a focus on drug development and commercialization in three therapeutic areas: oncology, rare diseases and neuroscience. Ipsen is one of the world's top 15 biopha ...
,
Takeda Pharmaceutical Company The is a Japanese multinational pharmaceutical company. It is the third largest pharmaceutical company in Asia, behind Sinopharm and Shanghai Pharmaceuticals, and one of the top 20 largest pharmaceutical companies in the world by revenue (t ...
,
Astellas Pharma is a Japanese multinational pharmaceutical company, formed on 1 April 2005 from the merger of and . Astellas is a member of the Mitsubishi UFJ Financial Group (MUFJ) keiretsu. History Early foundations Fujisawa Shoten was started in 1894 ...
,
Sandoz Sandoz Group AG is a Swiss company that focuses on generic pharmaceuticals and biosimilars. Prior to October 2023, it was part of a division of Novartis that was established in 2003, when Novartis united all of its generics businesses under the ...
, and Sun Pharmaceutical Industries supply much of the rest of the world with the various puberty blockers.
Ferring Pharmaceuticals Ferring Pharmaceuticals is a Swiss multinational biopharmaceutical company specialising in areas such as reproductive health, maternal health, gastroenterology and urology. Ferring has been developing treatments for mothers and babies for over 50 ...
, based out of Switzerland, generate two separate products of
triptorelin Triptorelin, sold under the brand name Decapeptyl among others, is a medication that acts as an agonist analog of gonadotropin-releasing hormone, repressing expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). It is a ...
(Decapeptyl and Gonapeptyl). Originating in France,
Ipsen Ipsen is a French biopharmaceutical company headquartered in Paris, France, with a focus on drug development and commercialization in three therapeutic areas: oncology, rare diseases and neuroscience. Ipsen is one of the world's top 15 biopha ...
also produces
triptorelin Triptorelin, sold under the brand name Decapeptyl among others, is a medication that acts as an agonist analog of gonadotropin-releasing hormone, repressing expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). It is a ...
(Decapeptyl). German/Swiss company
Sandoz Sandoz Group AG is a Swiss company that focuses on generic pharmaceuticals and biosimilars. Prior to October 2023, it was part of a division of Novartis that was established in 2003, when Novartis united all of its generics businesses under the ...
makes
leuprorelin Leuprorelin, also known as leuprolide, is a manufactured version of a hormone used to treat prostate cancer, breast cancer, endometriosis, uterine fibroids, for early puberty, as part of transgender hormone therapy, or to perform chemical ca ...
(Leuprorelin Acetate, Lucrin, Eligard). In Japan,
Takeda Pharmaceutical Company The is a Japanese multinational pharmaceutical company. It is the third largest pharmaceutical company in Asia, behind Sinopharm and Shanghai Pharmaceuticals, and one of the top 20 largest pharmaceutical companies in the world by revenue (t ...
and
Astellas Pharma is a Japanese multinational pharmaceutical company, formed on 1 April 2005 from the merger of and . Astellas is a member of the Mitsubishi UFJ Financial Group (MUFJ) keiretsu. History Early foundations Fujisawa Shoten was started in 1894 ...
create
leuprorelin Leuprorelin, also known as leuprolide, is a manufactured version of a hormone used to treat prostate cancer, breast cancer, endometriosis, uterine fibroids, for early puberty, as part of transgender hormone therapy, or to perform chemical ca ...
(Lupron Depot) and
goserelin Goserelin, sold under the brand name Zoladex among others, is a medication which is used to suppress production of the sex hormones (testosterone and estrogen), particularly in the treatment of breast cancer and prostate cancer. It is an injectab ...
(Zoladex). Indian company Sun Pharmaceutical Industries mainly produces
leuprolide acetate Leuprorelin, also known as leuprolide, is a manufactured version of a hormone used to treat prostate cancer, breast cancer, endometriosis, uterine fibroids, for early puberty, as part of transgender hormone therapy, or to perform chemical cast ...
generic injectables.
AbbVie AbbVie Inc. is an American pharmaceutical company headquartered in North Chicago, Illinois. It is ranked sixth on the list of largest biomedical companies by revenue. In 2023, the company's seat in Forbes Global 2000 was 74, and rank 89 on the ...
is also a player internationally.


Adverse effects


Short-term side effects

In the short term, they are generally considered safe and well-tolerated by most individuals. One of the primary effects is the suppression of secondary sexual characteristics, such as breast development in assigned females at birth or deepening of the voice in assigned males at birth. This can significantly alleviate the distress associated with gender dysphoria in transgender youth. Additionally, by halting the rapid growth spurts of puberty, these medications provide more time for growth in stature, particularly beneficial for children diagnosed with idiopathic short stature or central precocious puberty. Common short-term side effects may include injection site reactions, headaches, mood swings, changes in weight or appetite, fatigue, insomnia, muscle aches and changes in breast tissue, but these are usually manageable. Despite their benefits, there are some considerations regarding the short-term use of puberty blockers. One concern is the potential impact on bone density. Since puberty is a critical period for bone development, delaying it may temporarily reduce bone mineral density, which could be monitored through regular bone density scans. To protect against lower bone density, doctors recommend exercise,
calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...
, and
Vitamin D Vitamin D is a group of structurally related, fat-soluble compounds responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, along with numerous other biological functions. In humans, the most important compo ...
. Another consideration is the potential impact on psychological well-being. While many individuals experience relief from gender dysphoria, the delay in physical development might also cause anxiety or social difficulties in some cases, particularly in environments where peers are progressing through puberty. It is crucial for healthcare providers to closely monitor the physical and emotional well-being of individuals on puberty blockers, ensuring that the benefits outweigh any short-term risks or discomforts. In 2016, the FDA ordered drugmakers to add warning labels to puberty blocker drugs that states: "Psychiatric events have been reported in patients", including symptoms "such as crying, irritability, impatience, anger and aggression." In 2022, the FDA reported that there have been six cases of
idiopathic intracranial hypertension Idiopathic intracranial hypertension (IIH), previously known as pseudotumor cerebri and benign intracranial hypertension, is a condition characterized by increased intracranial pressure (pressure around the brain) without a detectable cause. The m ...
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 The University of Alabama at Birmingham (UAB) is a Public university#United States, public List of research universities in the United States, research university in Birmingham, Alabama, United States. Founded in 1969 and part of the University ...
who works with transgender youth, said that " diopathic intracranial hypertensionis 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".


Long-term uncertainty

Little is known about the long-term side effects of puberty blockers in children with gender dysphoria. Although puberty blockers are known to be safe and are a fully reversible treatment if stopped in the short term, it is not known whether puberty blockers affect the development of factors like bone mineral density, brain development and fertility in transgender patients. There is limited high-quality research on puberty suppression among adolescents experiencing gender dysphoria or incongruence. No conclusions on impact on gender dysphoria, mental health and cognitive development could be drawn. The
Endocrine Society The Endocrine Society is a professional, international medical organization in the field of endocrinology and metabolism, founded in 1916 as The Association for the Study of Internal Secretions. The official name of the organization was changed t ...
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)." 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 getting 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.


Neurological effects

Research on the long-term effects on brain development and cognitive function is limited. According to a 2024
systematic review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on ...
, no conclusions can be drawn about the effects of puberty blockers on cognitive development. Another 2024 systematic review, using both human and animal studies found some evidence of sex-specific impact on cognitive function in mammals, and no evidence that cognitive effects were fully reversible.


Fertility and sexual function

Research on the long-term effects on fertility and sexual function is limited. The long-term use of puberty blockers presents several uncertainties, particularly concerning fertility and sexual function. Since these medications suppress the production of sex hormones during a critical period of sexual maturation, their extended use may impact the development of reproductive organs and future fertility. For instance, individuals assigned male at birth who take puberty blockers might experience underdeveloped testes, potentially affecting sperm production later in life. Similarly, individuals assigned female at birth might have impaired ovarian function, impacting their ability to conceive. Additionally, there is concern that prolonged suppression of puberty may influence sexual function, including libido and the ability to achieve sexual arousal and satisfaction. These potential effects underscore the importance of careful, individualized medical counseling and consideration of fertility preservation options, such as sperm or egg banking, before initiating long-term puberty blocker treatment. Ongoing research is crucial to better understand these long-term impacts and to provide clearer guidance to patients and their families. Additionally, genital tissue in transgender women may not be optimal for potential
vaginoplasty Vaginoplasty is any surgical procedure that results in the construction or reconstruction of the vagina. It is a type of genitoplasty. Pelvic organ prolapse is often treated with one or more surgeries to repair the vagina. Sometimes a vaginoplas ...
later in life due to underdevelopment of the penis when using penile inversion vaginoplasty. Several other methods such as bowel vaginoplasty, which uses part of the sigmoid colon to form the canal instead, or a
peritoneal pull-through vaginoplasty Feminizing gender-affirming surgery for transgender women and transfeminine non-binary people describes a variety of surgical procedures that alter the body to provide physical traits more comfortable and affirming to an individual's gender ident ...
which harvests a skin graft from the peritoneum are not affected by this as they do not require the penile tissue to form the vaginal canal.


Bone health

A systematic review of studies investigating the long-term effects of treating precocious puberty with GnRH agonists found that
bone mineral density Bone density, or bone mineral density, is the amount of bone mineral in bone tissue. The concept is of mass of mineral per volume of bone (relating to density in the physics sense), although clinically it is measured by proxy according to opti ...
decreases during treatment but normalizes afterward, with no lasting effects on
peak bone mass Peak bone mass is the maximum amount of bone a person has during their life. It typically occurs in the early 20s in females and late 20s in males. Peak bone mass is typically lower in females than males, and is also lower in White people and Asians ...
. A review focused on the treatment of adolescents experiencing gender dysphoria found that bone health may be compromised during treatment, although the long-term outcomes of puberty suppression alone were not possible to determine.


Research status

A study published in the
Journal of the American Medical Association ''JAMA'' (''The Journal of the American Medical Association'') is a peer-reviewed medical journal published 48 times a year by the American Medical Association. It publishes original research, reviews, and editorials covering all aspects of ...
in 2022 found a 60% reduction in moderate to severe depression and a 73% reduction in suicidality in trans and nonbinary youth prescribed puberty blockers. A multi-year study published in September 2024 found that restrictions to transgender care, including restriction on access to gender-affirming puberty blockers, showed a direct link to negative mental health outcomes for transgender youth. The study followed the enactment of several laws in US states on restricting such access, which led to an increase of
suicide attempts A suicide attempt is an act in which an individual tries to kill themselves but survives. Mental health professionals discourage describing suicide attempts as "failed" or "unsuccessful", as doing so may imply that a suicide resulting in death is ...
of 7-72% in transgender youth within one to two years following the enactment of laws restricting access. In September 2024, the
New South Wales government The Government of New South Wales, also known as the NSW Government, is the executive state government of New South Wales, Australia. The government comprises 11 portfolios, led by a ministerial department and supported by several agencies. Th ...
in
Australia Australia, officially the Commonwealth of Australia, is a country comprising mainland Australia, the mainland of the Australia (continent), Australian continent, the island of Tasmania and list of islands of Australia, numerous smaller isl ...
released an independent review into puberty blockers that they commissioned which found that the benefits of puberty blockers outweigh any possible risks. The review concluded that puberty blockers are "safe, effective and reversible". In January 2025, a
systematic review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on ...
led by
Gordon Guyatt Gordon Henry Guyatt (born November 11, 1953) is a Canadian physician. He is also a Distinguished University Professor in the Departments of Health Research Methods, Evidence and Impact (formerly Clinical Epidemiology & Biostatistics) and Medicine ...
, found the evidence surrounding puberty blockers to be of low certainty in relation to global function, depression, gender dysphoria, bone mineral density, and progression to cross-sex hormones. Some studies showed improvements while others showed little to no change. Guyatt said that he was worried the results would be misused to justify denying blockers to trans youth seeking them, that banning care based on the evidence being low certainty was "a clear violation of the principles of evidence-based shared decision-making and is unconscionable", and that patient autonomy should be supported.


Concerns about insufficient evidence for gender dysphoria

The use of puberty blockers for gender-affirming care has attracted some criticism, due primarily to the lack of
randomized controlled trials A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical ...
within the research base. A 2020 commissioned review published by the UK's
National Institute for Health and Care Excellence The National Institute for Health and Care Excellence (NICE) is an executive non-departmental public body of the Department of Health and Social Care (United Kingdom), Department of Health and Social Care. As the national health technolog ...
(NICE) 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 The GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) is a method of assessing the certainty in evidence (also known as quality of evidence or confidence in effect estimates) and the strength of recommendations in ...
, but that it was plausible that the outcomes would have been worse without treatment. A subsequent systematic review re-affirmed the conclusions of the NICE report, concluding that the currently available studies have "significant conceptual and methodological flaws". A 2024 review of evidence on behalf of the
Cass Review The Independent Review of Gender Identity Services for Children and Young People (commonly, the Cass Review) was commissioned in 2020 by NHS England and NHS Improvement and led by Hilary Cass, a retired consultant paediatrician and the former p ...
came to a similar conclusion. The NICE review has been criticized by organizations that support the use of puberty blockers such as
WPATH The World Professional Association for Transgender Health (WPATH), formerly the Harry Benjamin International Gender Dysphoria Association (HBIGDA), is a professional organization devoted to the understanding and treatment of gender identity and ...
and
EPATH The World Professional Association for Transgender Health (WPATH), formerly the Harry Benjamin International Gender Dysphoria Association (HBIGDA), is a professional organization devoted to the understanding and treatment of gender identity and ...
, and in an WPATH's ''
International Journal of Transgender Health The ''International Journal of Transgender Health'' is a quarterly peer-reviewed academic journal covering research on gender dysphoria and gender incongruence, the medical treatment of transgender individuals, social and legal acceptance of gend ...
'' article by Cal Horton for excluding studies combining puberty blockers and hormone therapy, and also by parents of transgender youth for excluding evidence of its safety when used, albeit at a much younger age, by cisgender youth being treated for
precocious puberty In medicine, precocious puberty is puberty occurring at an unusually early age. In most cases, the process is normal in every aspect except the unusually early age and simply represents a variation of normal development. There is early developm ...
. Horton criticised the review for prioritizing high-quality evidence according to the
GRADE approach The GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) is a method of assessing the certainty in evidence (also known as quality of evidence or confidence in effect estimates) and the strength of recommendations in ...
, which designates
randomized control trials In common usage, randomness is the apparent or actual lack of definite pattern or predictability in information. A random sequence of events, symbols or steps often has no order and does not follow an intelligible pattern or combination. I ...
(RCTs) as "high quality", since RCTs are widely considered infeasible and unethical for transgender youth if those in the control group are denied medical treatment. Horton also argued that it had not followed 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 Finnish Ministry of Health also concluded that there are no research-based health care methods for minors with gender dysphoria. Their guidelines permit the use of puberty blockers for minors on a case-by-case basis.


Legal status

Puberty blockers have not received FDA approval for use on children who are transgender, and are instead issued "off-label". The practice of
off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication (medicine), indication or in an unapproved age group, dose (biochemistry), dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) ca ...
prescription is common in children's medicine because many drugs lack pediatric-specific information in their marketing authorisation or approval. Doctors use their professional judgment to decide how to use these drugs, and the term 'off-label' itself does not indicate an improper, illegal, or experimental use of medicine. According to
pediatric endocrinology Pediatric endocrinology (British: Paediatric) is a medical subspecialty dealing with disorders of the endocrine glands, such as variations of physical growth and sexual development in childhood, diabetes and many more. By age, pediatric endocrino ...
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."


Political challenges

The prescription of puberty blockers has been a polarizing issue on an international scale. On the one hand, opponents for the use of puberty blockers argue that minors are unable to provide informed consent, treatment interferes with typical gender identity development, and there are high rates of detransitioning after puberty, rendering treatment ineffective. On the other hand, proponents argue that there are psychological and developmental benefits of puberty blockers which may outweigh the risks associated with treatment, such as a lower risk of depression and reduced behavioral issues. In the United States, the growing disarray between opponents and proponents has led to the dissemination of misinformation and consequently the establishment of anti-transgender ("anti-trans") legislation.


Informed consent

Groups continue building on the discussion on informed consent. A 2019 study found that a "multidisciplinary approach" is necessary "to ensure meaningful consent" is acquired and treatment is initiated with a strong ethical foundation. A 2021 editorial adds a pragmatic perspective, claiming that "disproportionate emphasis is given to young people's inability to provide medical consent" and that "what matters ethically is whether an individual has a good enough reason for wanting treatment".
Bioethicist Bioethics is both a field of study and professional practice, interested in ethics, ethical issues related to health (primarily focused on the human, but also increasingly includes animal ethics), including those emerging from advances in biolo ...
Maura Priest shares this perspective. She claims 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 and that the psychological costs associated with untreated gender dysphoria in children are avoidable. Another bioethicist,
Florence Ashley Florence Ashley is a Canadian academic, activist and law professor at the University of Alberta. They specialize in trans law and bioethics. They have numerous academic publications, including a book on the law and policy of banning transgender ...
, adds that counseling and educating the parents of transgender youth could also be beneficial to familial relationships.


Puberty blockers in the US

In April 2021,
Arkansas Arkansas ( ) is a landlocked state in the West South Central region of the Southern United States. It borders Missouri to the north, Tennessee and Mississippi to the east, Louisiana to the south, Texas to the southwest, and Oklahoma ...
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 Alabama ( ) is a U.S. state, state in the Southeastern United States, Southeastern and Deep South, Deep Southern regions of the United States. It borders Tennessee to the north, Georgia (U.S. state), Georgia to the east, Florida and the Gu ...
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 Florida ( ; ) is a U.S. state, state in the Southeastern United States, Southeastern region of the United States. It borders the Gulf of Mexico to the west, Alabama to the northwest, Georgia (U.S. state), Georgia to the north, the Atlantic ...
banned
Medicaid Medicaid is a government program in the United States that provides health insurance for adults and children with limited income and resources. The program is partially funded and primarily managed by U.S. state, state governments, which also h ...
from covering gender affirming care, including puberty blockers. As of July 2024, 26 states have enacted some form of ban on gender-affirming care for minors, but not all of these ban puberty blockers. Currently, only 18 of the 26 states have complete bans which are fully in effect. Six states have only partial bans and two are currently blocked from taking effect. While some states have banned all forms of medical transition, others have banned only specific types such as surgery. Six states have exceptions which allow minors who were already receiving gender affirming care prior to the ban to continue their treatments. Currently, all 26 states make exceptions for puberty blockers, hormones and surgery for cisgender and intersex children. Only one state, West Virginia, makes exceptions in cases of "severe dysphoria". There is also currently only one state, Missouri, that has a ban which is set to expire after a certain period of time. Nearly all states with restrictions include specific provisions with penalties for providers and 4 states include provisions directed at parents or guardians. An additional 4 states include laws/policies that impact school officials such as teachers and counselors, among others. In response to these bans, many Democrat-controlled states have gone in the opposite direction and enacted laws protecting access to gender affirming care for minors and adults. These laws, often called "shield" laws, often explicitly combine protections for gender-affirming care and abortion and cover a variety of protections including protecting both providers and patients from being punished, mandating insurance providers to cover the procedures and acting as "sanctuary states" that protect patients traveling to the state from other states that have banned such treatments among other things. As of June 2024, 16 states and the District of Columbia have enacted "shield" laws. The UK's
Cass Review The Independent Review of Gender Identity Services for Children and Young People (commonly, the Cass Review) was commissioned in 2020 by NHS England and NHS Improvement and led by Hilary Cass, a retired consultant paediatrician and the former p ...
was cited in the Indiana legislation to ban puberty blockers. Some US 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.


Puberty blockers in Italy

The Italian National Bioethics Committee and the Italian Medicines Agency have demonstrated support for the use of puberty blockers in adolescents with gender dysphoria, expanding coverage by adding them to the list of medications covered by the National Health Service. Still, challenges with accessing puberty blocker medications persist. Specific clinical criteria must be satisfied for treatment including comprehensive medical evaluations, parental consent, and the exhaustion of all other clinical interventions.


Puberty blockers in Canada

The British Columbia Infants Act of 1996 grants minors legal decision-making authority if they can consent to a clinical intervention and their healthcare provider believes it is in their best interest. As a result, providers are required to evaluate if their patients have a robust and realistic understanding of hormone therapy, risks, benefits, and alternatives. Although some incorporate the gender-affirming care model into practice, others demonstrate reluctance to prescribe puberty blockers. A qualitative study investigating the experience of trans youth in seeking and receiving gender-affirming care at Canadian specialty clinics shows a mix of positive and negative outcomes. People reported improvements in their well-being, frustrations with treatment protocols and wait lists, and concerns with their transition journey.


Stances of medical organizations

More than a dozen major American and Australian medical associations, as well as the
World Professional Association for Transgender Health The World Professional Association for Transgender Health (WPATH), formerly the Harry Benjamin International Gender Dysphoria Association (HBIGDA), is a professional organization devoted to the understanding and treatment of gender identity and ...
(WPATH), and the
Endocrine Society The Endocrine Society is a professional, international medical organization in the field of endocrinology and metabolism, founded in 1916 as The Association for the Study of Internal Secretions. The official name of the organization was changed t ...
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 cautionary stance, discouraging or limiting the use of puberty blockers. However, these countries have not outright banned or criminalized the treatment unlike many US States.


Australia

Access to puberty blockers for transgender youth in Australia is supported by: * The
Royal Australasian College of Physicians The Royal Australasian College of Physicians (RACP) is a not-for-profit professional organisation responsible for training and educating physicians and paediatricians across Australia and New Zealand. The RACP is responsible for training both ...
, * The
Royal Australian College of General Practitioners Royal may refer to: People * Royal (name), a list of people with either the surname or given name * A member of a royal family or royalty Places United States * Royal, Arkansas, an unincorporated community * Royal, Illinois, a village * Ro ...
, * The Australian Endocrine Society, * AusPATH. An independent review into gender-affirming care for minors commissioned by the New South Wales government and released in September 2024 found that puberty blockers are "safe, effective and reversible", while acknowledging that the evidence for this and other interventions "remains weak due to poor study designs, low participant numbers and single-centre recruitment", calling for more long-term research.


Austria

In Austria puberty blockers may be recommended for adolescents who are at least in Tanner stage 2 of puberty and exhibit a stable/persistent gender incongruence (ICD-11 HA60). The use of puberty blockers in youth experiencing gender dysphoria has been endorsed by the following organizations: * Österreichische Gesellschaft für Kinder- und Jugendpsychiatrie (Austrian Society for Child and Adolescent Psychiatry) (ÖGKJP) * Österreichische Gesellschaft für Gynäkologie und Geburtshilfe (Austrian Society of Gynecology and Obstetrics) (OEGGG)


Canada

According to the Canadian Pediatric Society in 2024, "Current evidence shows puberty blockers to be safe when used appropriately, and they remain an option to be considered within a wider view of the patient's mental and psychosocial health."


Chile

The following medical organizations have expressed their support for puberty blockers for transgender children and adolescents: *The Chilean Pediatric Society *The Chilean Society of Psychiatry and Neurology of Childhood and Adolescence *The Chilean Society of Childhood and Adolescent Gynecology


Denmark

Danish guidelines published in 2023 recommend the use of puberty blockers on transgender patients at either Tanner stage two or three, as a means of buying time for patients to consider their gender more fully before making a decision.


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

Transgender children in France are eligible for puberty blockers with parental permission at any age, and usually receive them at age 15 or 16. In 2022,
France France, officially the French Republic, is a country located primarily in Western Europe. Overseas France, Its overseas regions and territories include French Guiana in South America, Saint Pierre and Miquelon in the Atlantic Ocean#North Atlan ...
's
Académie Nationale de Médecine Situated at 16 Rue Bonaparte in the 6th arrondissement of Paris, the Académie nationale de médecine (National Academy of Medicine) was created in 1820 by King Louis XVIII at the urging of baron Antoine Portal. At its inception, the institu ...
urged caution when considering puberty blockers due to potential side effects, including "impact on growth, bone weakening, ndrisk of infertility". This change to the guidelines has not changed actual practice. In late 2024, the French
Society of Pediatric Endocrinology and Diabetology A society () is a group of individuals involved in persistent social interaction or a large social group sharing the same spatial or social territory, typically subject to the same Politics, political authority and dominant cultural expecta ...
released the country's first ever guidelines for medical care of trans youth, in which they recommended patients who have hit at least Tanner stage 2 to receive puberty blockers along with calcium and vitamin D supplements.


Germany

Transgender healthcare guidelines published by the Association of the Scientific Medical Societies in Germany recommend that the use of puberty-suppressing medication be considered for young individuals who have attained at least Tanner stage 2 of pubertal development. A prerequisite is a diagnosis of persistent gender incongruence (as per ICD-11 HA60). The use of puberty blockers has been endorsed by numerous medical organizations: * (German Society for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy) (DGKJP) * (Academy for Ethics in Medicine) (AEM) * (German Medical Society for Behavioral Therapy) (DÄVT) * (German Society for Endocrinology) (DGE) * (German Society for Gynecology and Obstetrics) (DGGG) * (German Society for Pediatric and Adolescent Medicine) (DGKJ) * (German Society for Pediatric and Adolescent Endocrinology and Diabetology) (DGPAED) * (German Society for Medical Psychology) (DGMP) * (German Society for Psychiatry and Psychotherapy, Psychosomatics and Neurology) (DGPPN) * (German Society for Psychoanalysis, Psychotherapy, Psychosomatics and Depth Psychology) (DGPT) * (German Society for Sex Research) (DGfS) * (German College for Psychosomatic Medicine) (DKPM) * Bundesverband für Kinder- und Jugendlichenpsychotherapie e.V. (Federal Association for Child and Adolescent Psychotherapy) (bkj) * (Professional Association of German Psychologists) (BDP) * Berufsverband für Kinder und Jugendpsychiatrie, Psychosomatik und Psychotherapie (Professional Association for Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy) (BKJPP) * Bundesarbeitsgemeinschaft der Leitenden Klinikärzte für Kinder- und Jugendpsychiatrie, -psychosomatik und -psychotherapie (Federal Association of Senior Clinicians for Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy) (BAG) * (Federal Chamber of Psychotherapists) (BPtK) * (German Psychoanalytic Society) (DPG) * (German Society for Systemic Therapy, Counseling, and Family Therapy) (DGSF) * Gesellschaft für Sexualwissenschaft (Society for Sexology) (GSW) * (Child and Adolescent Psychotherapy and Behavioral Therapy) (KJPVT) * (Association for Lesbian, Gay, Bisexual, Trans*, Intersex, and Queer People in Psychology) (VLSP) * Vereinigung Analytischer Kinder- und Jugendlichenpsychotherapeuten in Deutschland (Association of Analytical Child and Adolescent Psychotherapists in Germany) (VAKJP)


Italy

In 2018, the Italian National Bioethics Committee and the Italian Medicines Agency released an opinion that was supportive of the use of puberty blockers in adolescents with gender dysphoria on a case-by-case basis and with some safeguards. However, they also called for more research to better understand its effects. As of February 2019, puberty blockers and cross sex hormones are provided free of charge in Italy and are covered by the National Health Service. Still, challenges with accessing puberty blocker medications persist. Specific clinical criteria must be satisfied for treatment including comprehensive medical evaluations, parental consent, and the exhaustion of all other clinical interventions. Additionally, the use of puberty blockers in transgender youth is supported by: *The Italian Society of Endocrinology (SIE) *The Italian Society of Andrology and Sexual Medicine (SIAMS) *The Italian Society of Gender, Identity and Health (SIGIS)


Japan

The Japanese Society of Psychiatry and Neurology (JSPN) published its updated guidelines in August 2024 on the treatment of gender dysphoria. The guidelines continued to recommend puberty suppression in trans patients, noting it is "self-evident" that, unless puberty is suppressed, development of sex characteristics are irreversible in AMAB individuals. They made recommendations that doctors administering such treatment report more detailed information on outcomes going forward.


Mexico

In June 2020, the Mexican federal government released "The Protocol for Access without Discrimination to Health Care Services for Lesbian, Gay, Bisexual, Transsexual, Transvestite, Transgender, and Intersex Persons and Specific Care Guidelines." The guidelines are used in healthcare facilities administered by the government. The guidelines state that the process of identifying one's sexual orientation, gender identity and/or expression can occur at early ages. Thus, the guidelines recommend that medical facilities and doctors consider the use of puberty blockers and cross-sex hormones as a treatment for transgender minors when appropriate. In addition to the guidelines, multiple Mexican states have modified their civil codes to recognize gender-affirming healthcare as a right for transgender people under the age of eighteen.


The Netherlands

The Dutch
Ministry of Health, Welfare and Sport The Ministry of Health, Welfare and Sport (; VWS) is the Ministries of the Netherlands, Dutch Ministry responsible for public health, health care, quality of life, social work and sport. The Ministry was created in 1951 as the "Ministry of Socia ...
publishes guidelines recommending the use of puberty blockers in transgender adolescents of at least Tanner Stage II with informed consent and approval of an endocrinologist. This guideline, published in 2016, is endorsed by the following Dutch medical organizations: * Nederlands Internisten Vereniging (Dutch Internists Association) * Nederlands Huisartsen Genootschap (Dutch Society of General Practitioners) * Nederlands Instituut van Psychologen (Dutch Institute of Psychologists) * Nederlandse Vereniging voor Kindergeneeskunde (Dutch Association for Pediatrics) * Nederlandse Vereniging voor Obstetrie & Gynaecologie (Dutch Association for Obstetrics & Gynaecology) * Nederlandse Vereniging voor Plastische Chirurgie (Dutch Association for Plastic Surgery) * Nederlandse Vereniging voor Psychiatrie (Dutch Psychiatry Association) * Transvisie (Transvision, a patient organization for transgender patients)


New Zealand

The use of puberty blockers for transgender people is supported by: * The Professional Association for Transgender Health Aotearoa (PATHA) * The Royal Australian and New Zealand College of Psychiatrists (RANZCP) * The Society of Youth Health Professionals Aotearoa New Zealand (SYHPANZ) * The New Zealand Sexual Health Society * The New Zealand Society of Endocrinology * The College of Child and Youth Nurses * The New Zealand College of Clinical Psychologists * The New Zealand Pediatrics Society * The New Zealand Psychological Society * The Auckland Sexual Health Service In November 2024, the Ministry of Health released an evidence brief on puberty blockers. The brief found there to be a lack of evidence for both the efficacy and harms of puberty blockers and recommended "a more precautionary approach". The country did not ban puberty blockers and one doctor who provides the treatments in New Zealand said it "would not change the way in which he practiced". In April 2025, potential further restrictions on access to puberty blockers proposed by the ministry were met with backlash by a number of New Zealand medical bodies.


Norway

In 2020, the Norwegian Directorate for Health, the governmental body that develops health guidelines, released one for
gender incongruence Gender dysphoria (GD) is the distress a person experiences due to inconsistency between their gender identitytheir personal sense of their own genderand their sex assigned at birth. The term replaced the previous diagnostic label of gender ide ...
recommending puberty blockers between
Tanner stage 2 The Tanner scale (also known as the Tanner stages or sexual maturity rating (SMR)) is a scale of physical development as pre-pubescent children transition into adolescence, and then adulthood. The scale defines physical measurements of developmen ...
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 changing to a cautious approach. The Norwegian Healthcare Investigation Board is not responsible for setting healthcare policy, and the Directorate, which is, has not implemented the recommendations, though they have said they are considering them. Misinformation that Norway had banned gender affirming care proliferated on social media.


Sweden

Sweden's
Karolinska Institute The Karolinska Institute (KI; ; sometimes known as the (Royal) Caroline Institute in English) is a research-led medical university in Solna within the Stockholm urban area of Sweden and one of the foremost medical research institutes globally ...
, 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 The Swedish National Board of Health and Welfare () is a Swedish government agency. The agency was the result of a merger between the National Swedish Board of Health and the Swedish Royal Board of Social Affairs in 1968. , it is headed by di ...
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

As of May 2024, prescription of puberty blockers to new patients under 18 for the treatment of gender dysphoria is banned for both private medical practices (by a law in parliament in May) and the official state healthcare
National Health Service The National Health Service (NHS) is the term for the publicly funded health care, publicly funded healthcare systems of the United Kingdom: the National Health Service (England), NHS Scotland, NHS Wales, and Health and Social Care (Northern ...
(NHS) which stopped their use earlier, in the aftermath of the
Cass Review The Independent Review of Gender Identity Services for Children and Young People (commonly, the Cass Review) was commissioned in 2020 by NHS England and NHS Improvement and led by Hilary Cass, a retired consultant paediatrician and the former p ...
except for use in clinical research trials. Previously, on 30 June 2020, the NHS changed its website, replacing the statement that puberty blockers were "fully reversible" and that "treatment can usually be stopped at any time"; with "little is known about the long-term side effects of hormone or puberty blockers in children with gender dysphoria. The ''
Bell v Tavistock ''Bell v Tavistock'' was a case before the Court of Appeal (England and Wales) on the question of whether puberty blockers could be prescribed to under-16s with gender dysphoria. ≈ The Court of Appeal said that "it was for clinicians rather ...
'' decision by the
High Court of Justice The High Court of Justice in London, known properly as His Majesty's High Court of Justice in England, together with the Court of Appeal (England and Wales), Court of Appeal and the Crown Court, are the Courts of England and Wales, Senior Cour ...
for England and Wales ruled children under 16 were not competent to give
informed consent Informed consent is an applied ethics principle that a person must have sufficient information and understanding before making decisions about accepting risk. Pertinent information may include risks and benefits of treatments, alternative treatme ...
to puberty blockers, but this was overturned by the
Court of Appeal An appellate court, commonly called a court of appeal(s), appeal court, court of second instance or second instance court, is any court of law that is empowered to Hearing (law), hear a Legal case, case upon appeal from a trial court or other ...
in September 2021. In 2022, the
British Medical Association The British Medical Association (BMA) is a registered trade union and professional body for physician, doctors in the United Kingdom. It does not regulate or certify doctors, a responsibility which lies with the General Medical Council. The BMA ...
opposed restrictions on puberty blockers, and the NHS restricted their use for children under 16 years of age to centrally administered clinical research. The April 2024,
Cass Review The Independent Review of Gender Identity Services for Children and Young People (commonly, the Cass Review) was commissioned in 2020 by NHS England and NHS Improvement and led by Hilary Cass, a retired consultant paediatrician and the former p ...
stated that there was inadequate evidence to justify the widespread use of puberty blockers for gender dysphoria, and that more research was needed to provide evidence as to the effectiveness of this treatment, in terms of reducing distress and improving psychological functioning. This led to a ''de facto'' moratorium of the routine provision of puberty blockers for gender dysphoria within
NHS England NHS England, formally the NHS Commissioning Board for England, is an executive non-departmental public body of the Department of Health and Social Care. It oversees the budget, planning, delivery and day-to-day operation of the commissioning si ...
and NHS Scotland outside of clinical trials, and a subsequent ban on private prescription of puberty blockers in the United Kingdom. Children already receiving puberty blockers via NHS England will be able to continue their treatment. In England, a clinical trial into puberty blockers is planned for early 2025. In July 2024, the
Royal College of General Practitioners The Royal College of General Practitioners (RCGP) is the professional body for general (medical) practitioners (GPs/ Family Physicians/ Primary Care Physicians) in the United Kingdom. The RCGP represents and supports GPs on key issues including ...
stated that for patients under 18, no general practitioner should prescribe puberty blockers outside of a clinical trial, and the prescription of gender-affirming hormones should be left to specialists. They affirmed they will fully implement the Cass Review recommendations. In December 2024, the
Northern Ireland Executive The Northern Ireland Executive (Irish language, Irish: ''Feidhmeannas Thuaisceart Éireann'', Ulster Scots dialect, Ulster Scots: ''Norlin Airlan Executive'') is the devolution, devolved government of Northern Ireland, an administrative branc ...
announced a permanent ban on puberty blockers for under-18s, with the Executive's Deputy First Minister,
Emma Little-Pengelly Emma Little-Pengelly ( Little; born 31 December 1979) is a Northern Irish barrister and Democratic Unionist Party (DUP) politician serving as the First Minister and deputy First Minister of Northern Ireland, deputy First Minister of Northern ...
, saying it was "the right approach, informed by medical and scientific advice. The protection and safety of our young people must be paramount." The following day, the Health Secretary,
Wes Streeting Wesley Paul William Streeting (; born 21 January 1983) is a British politician who has served as Secretary of State for Health and Social Care since July 2024. A member of the Labour Party, he has been the Member of Parliament (MP) for Ilford ...
, announced in the
House of Commons The House of Commons is the name for the elected lower house of the Bicameralism, bicameral parliaments of the United Kingdom and Canada. In both of these countries, the Commons holds much more legislative power than the nominally upper house of ...
that the previously enacted ban on puberty blockers in England would be made indefinite and would be reviewed in 2027.


United States

Since 1993 the US Food and Drug Administration (FDA) has supported the use of puberty blockers to treat precocious puberty. Currently under FDA regulation the use of puberty blockers is considered on-label for the treatment of central precocious puberty. For years, the
FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
,
Endocrine Society The Endocrine Society is a professional, international medical organization in the field of endocrinology and metabolism, founded in 1916 as The Association for the Study of Internal Secretions. The official name of the organization was changed t ...
, American Academy of Pediatrics (AAP) and many other pediatric associations have supported the use of
Gonadotropin-releasing hormone analogs A GnRH modulator, or GnRH receptor modulator, also known as an LHRH modulator or LHRH receptor modulator, is a type of medication which modulates the GnRH receptor, the biological target of the hypothalamic hormone gonadotropin-releasing horm ...
(GnRHas) in central precocious puberty (CPP). Access to treatment depends on the classification of precocious puberty as well as other guidelines implemented by the Endocrine Society. To determine if you are experiencing precocious puberty and should receive treatment it is required your doctor take a medical history, physical exam, blood test, and x-rays. In 2009, the Lawson Wilkins Pediatric Endocrine Society and European Society for Pediatric Endocrinology published a consensus statement highlighting the effectiveness of
Gonadotropin-releasing hormone analogs A GnRH modulator, or GnRH receptor modulator, also known as an LHRH modulator or LHRH receptor modulator, is a type of medication which modulates the GnRH receptor, the biological target of the hypothalamic hormone gonadotropin-releasing horm ...
(GnRHas) in early onset central precocious puberty. They confirmed that the use of
Gonadotropin-releasing hormone analogs A GnRH modulator, or GnRH receptor modulator, also known as an LHRH modulator or LHRH receptor modulator, is a type of medication which modulates the GnRH receptor, the biological target of the hypothalamic hormone gonadotropin-releasing horm ...
(GnRHas) has had a positive effect on increasing adult height. However these Endocrine Societies believe additional research should be conducted before routinely suggesting GnRHAs for other conditions. There is still some uncertainty surrounding the effectiveness of GnRHas when utilized for other conditions. Currently under FDA regulation, the use of puberty blockers in pediatrics with gender dysphoria is considered off-label. The use of puberty blockers in youth experiencing gender dysphoria has been supported by the following organizations: * The
American Medical Association The American Medical Association (AMA) is an American professional association and lobbying group of physicians and medical students. This medical association was founded in 1847 and is headquartered in Chicago, Illinois. Membership was 271,660 ...
* The
American Psychological Association The American Psychological Association (APA) is the main professional organization of psychologists in the United States, and the largest psychological association in the world. It has over 170,000 members, including scientists, educators, clin ...
* The
American Academy of Pediatrics The American Academy of Pediatrics (AAP) is the largest professional association of pediatricians in the United States. It is headquartered in Itasca, Illinois, and maintains an office in Washington, D.C. The AAP has published hundreds of poli ...
* The
American Academy of Child and Adolescent Psychiatry The American Academy of Child and Adolescent Psychiatry (AACAP) is a 501(c)(3) non-profit professional association in the United States dedicated to facilitating psychiatric care for children and adolescents. The Academy is headquartered in Wash ...
(AACAP) * The
American Psychiatric Association The American Psychiatric Association (APA) is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the largest psychiatric organization in the world. It has more than 39,200 members who are in ...
* The
Endocrine Society The Endocrine Society is a professional, international medical organization in the field of endocrinology and metabolism, founded in 1916 as The Association for the Study of Internal Secretions. The official name of the organization was changed t ...
* The Pediatric Endocrine Society * The
American Association of Clinical Endocrinologists The American Association of Clinical Endocrinology (AACE) is a professional community of physicians specializing in endocrinology, diabetes, and metabolism. AACE's mission is elevating clinical endocrinology to improve global health. The associ ...
* The
American College of Obstetricians and Gynecologists The American College of Obstetricians and Gynecologists (ACOG) is a professional association of physicians specializing in obstetrics and gynecology in the United States. Several Latin American countries are also represented within Districts of ...
* The
American College of Physicians The American College of Physicians (ACP) is a Philadelphia-based national organization of internal medicine physicians, who specialize in the diagnosis, treatment, and care of adults. With 161,000 members, ACP is the largest medical-specialty or ...
There has been an increase in youth requesting treatment for gender affirming medical care. The increased medical coverage and societal awareness of transgender youth may be shifting accessibility to care.


References

* {{Authority control Gender transition and medicine Puberty Cultural politics