The risks of puberty blockers

Written By Bel H

In recent years, as more evidence has come to light, several countries have effectively banned the prescription of puberty blockers to minors (often restricting them to clinical trials), due the risks and uncertainties.

On this page you’ll find information about:

  • As more evidence has come to light, medical bodies in many countries have retracted or amended statements that puberty blockers are fully reversible.

    However, false or evasive claims about the reversibility of puberty blockers (GnRH agonists) persist. For example, Australian guidelines refer to hormonal treatments, paradoxically, as "partially irreversible".

    Any claim that puberty blockers are reversible is misleading on several counts:

    1. The duration of use, and the age of initiation are key factors that amplify the risks of puberty blockers and cross-hormones.

      Children who receive puberty blockers at a very early age can experience a permanent loss of sexual function. Other side-effects, like the lack of accrual of bone mineral density, or effects on cognition are also highly time-dependent.

    2. Because every child is different, it may be impossible to be certain of how long any given patient will be able to suppress their puberty before they experience visible or invisible irreversible effects.

    3. Children only get one puberty. When a child's puberty is interrupted with puberty blockers - even if only for a short amount of time - the interruption to their natural course of their development can’t be reversed. When puberty is suppressed, other types of development continue to take place in the absence of the sex steroids usually produced during puberty. For example, children may continue to grow taller. The impact of hormone-deprived development isn’t fully understood.

    4. Most gender affirming treatment guidelines, like Australia’s, don't set strict limits on the age at which a patient can receive puberty blockers, or on the duration of treatment. Consequently, the application of puberty blockers varies significantly among patients. Given this variability of use, making sweeping claims about their irreversibility is inappropriate.

    5. Because children experience puberty only once, it's impossible to determine how they might have developed without the use of puberty blockers. This makes it difficult to draw comparisons or ascertain which effects are reversible and which are not.

    6. The risks and side effects of puberty blockers are still poorly studied (particularly, their effects on cognitive development) and it is premature to make definitive claims about their effects.

    7. The interactions and side-effects of different hormonal regimes (the specific drugs used, different combinations of drugs, and the route of administration) also remain very poorly understood.

  • Puberty blockers (also called GnRHa agonists) have been used to treat several conditions, such as precocious puberty. However, as the Clinical Advisory Network on Sex and Gender explain, treatment that is effective and safe in one context isn’t necessarily so in another:

    “Due to extensive testing in controlled clinical trials over many years, GnRHa [puberty blockers] have been approved for use in the treatment of adults with some forms of cancer. They are also approved for children who experience puberty at an abnormally early age (‘precocious puberty’) but will be stopped so that normal puberty can unfold and take place at the typical age of onset (Bangalore Krishna et al., 2019).

    Any particular drug will have a different risk:benefit profile depending on the indication (reason) it is given for a particular disease. It is wrong (if not pharmacologically unintelligible) to think that a drug being safe in precocious puberty means it will be safe when used for gender dysphoria to block pubertal development and plan to start lifelong exogenous opposite sex hormones. (For example, insulin can be life saving in diabetic ketoacidosis, and fatal in a healthy euglycaemic person.)”

DO WE KNOW ABOUT ALL THE RISKS?

In Australia, the use of hormonal treatments like GnRH agonsitst (puberty blockers) and cross-sex hormones (testosterone and estrogen) in gender affirming care, is 'off-label'.

Off-label prescribing refers to the use of medications for purposes, patient groups, or in ways that fall outside the TGA's approved indications.

This means these medications have not received specific approval from the Therapeutic Goods Administration (TGA) for use in gender affirming care.

While off-label prescribing is legal and common in various medical fields, it requires that healthcare providers to be well-informed about the treatment and base its use on scientific evidence.

  • Puberty blockers haven't been comprehensively tested for their use in gender affirming protocols, in which a range of drugs are used for variable amounts of time, on young people who are usually otherwise healthy. 
  • Due to the innate biological differences between the sexes, the guidelines also recommend different hormonal regimes for males and females.
  • The prescribed regime for patients who identify as ‘non-binary’ remains unclear, but it appears to be ‘tailored’. 
  • Consequently, the complete side effects of puberty blockers remains unclear, and it’s inappropriate to make generalised statements about their safety.

MOST GUIDANCE ON GENDER AFFIRMING CARE DOESN’T ADEQUATELY ADDRESS THIS COMPLEXITY

Treatment guidelines and medication labels don’t adequately address the complexity of the individualised and untested treatments provided in gender affirming care.

A two-part episode of the Australian podcast, The Good GP provides a glimpse into just how individualised and patient-driven these treatments have become.

Guidance on puberty blockers also often provides incomplete or inconsistent advice about potential risks and side-effects that are already known, leaving patients (and doctors) with incomplete information.

In cases where GnRH agonsists have only been well-tested on adults, or to treat certain illnesses (such as cancer), it may not be certain if the known risks are precisely the same for younger people seeking treatment for gender-related distress.

However, this uncertainty doesn't absolve gender affirming care providers from their duty of full disclosure. In Australia, healthcare providers have a duty to warn patients about material risks of a treatment or intervention (risks that a reasonable person would attach significance to), as part of obtaining their informed consent. [2]

Are patient’s being warned of all the risks?

Just some of the known, likely or possible side-effects of puberty blockers include:

Cardiovascular problems [7] including heart attack [9], stroke [9] and abnormal heath rhythms/increased risks of long QT syndrome [5][10][13]

Seizures [10][12][13][14]

Liver dysfunction [7][10][13][14][5]

Mood changes, including depression [6][7][9][10][12][13][14]

Hypertension [4][10], intracranial hypertension [5][15]

Tumour: pituitary [7] tumour flare [9] meningioma [3][5]

Embolism [7][8][10]

High blood sugar [7][9][13]

Ovarian and fallopian tube disorders [10] ovarian cycts [8]

Oedema [8][10]

Painful, obstructed or frequent urination [6][7][9][10][14]

Spinal cord pressure/compression [7][9]

Hypercalcemia [8][9]

Sexual Dysfunction (see below)

Cognitive Impairment (see below)

Puberty blockers can lead to temporary or permanent sexual dysfunction, including;

  • Vaginal or testicular atrophy [1][3][10]
  • Anorgasmia (inability to organism ) [5][6]
  • Painful sexual intercourse (dyspareunia) [3][11] 
  • Erectile dysfunction [1][2] 
  • Decreased libido [1][2][10]

The age at which patients receive puberty blockers, and the duration of treatment can amplify the risks of sexual dysfunction. [7]

Patients who received puberty blockers at the early stages of their puberty have reported that they have never experienced an orgasm, a condition known as anaorgasmia:

“When you block puberty, the problem is that a lot of the kids are orgasmically naive. So in other words, if you've never had an orgasm pre-surgery and then your puberty's blocked, it's very difficult to achieve that afterwards...” - Dr. Marci Bowers, Gender Surgeon [5]

Current Australian guidelines don’t stipulate a minimum age limit for treatments.

Infertility

When used in conjunction with cross-sex hormones, puberty blockers can lead to infertility. The use of puberty blockers increases the likelihood that a patients will go on to take cross-sex hormones.

The risk of infertility is so high that Australian treatment guidelines recommend that fertility preservation and counseling must take place before hormonal interventions begin.

“Fertility preservation information and counselling should be provided to all adolescents prior to commencement of puberty suppression or gender affirming hormones” RCH guidelines, p14 [10]

Many former patients have spoken about the devastating impact of gender affirming care on their fertility and sexual function. [8]

Evidence is emerging that puberty blockers can have negative effects on adolescent neurodevelopment and IQ.

A 2024 review of the known effects of puberty blockers [1] found that that there is only a small amount of research available, but that what is available indicates that puberty blockers may irreversibly interrupt critical windows of neurodevelopment and diminish the cognitive capacity of patients.

The review found a total of 16 studies had examined the impact of puberty blockers on cognitive function. Only five of the 16 studies studies looked at the impact of puberty blockers on cognitive development in young people, three of which found lower IQs in patients treated with puberty blockers.

Most of the remaining studies were conducted in animals. These investigations revealed that puberty suppression drugs may impair cognitive development in various species. For instance, one study observed that sheep treated with puberty blockers exhibited decreased long-term spatial memory performance.[2] Furthermore, these animal studies uncovered sex-specific variations in responses to puberty suppression treatments, suggesting that males and females may be affected differently by these interventions.

The impact of puberty blockers upon cognitive functioning may be time dependent. According to the Cass review:

“[A study] found no difference between adolescents who were treated with puberty blockers for less than one year compared to those not treated, but found worse executive functioning in those treated for more than one year compared to those not treated.”  - [3][4]

Referencing a 2017 paper by Sisk [5], Dr Cass has also written:

"...adolescent sex hormone surges may trigger the opening of a critical period for experience-dependent rewiring of neural circuits underlying executive function (i.e. maturation of the part of the brain concerned with planning, decision making and judgement). If this is the case, brain maturation may be temporarily or permanently disrupted by puberty blockers, which could have significant impact on the ability to make complex risk-laden decisions, as well as possible longer-term neuropsychological consequences."

Puberty is a time of extraordinary physical, cognitive, and psychosocial maturation. A Baxendale explains, it’s considered to be a key window of development or neuronal plasticity:

“Windows of plasticity for neurodevelopment are staggered throughout development (from birth to the third decade of life) and follow a set pattern with sensory pathways (vision, hearing) prioritised in infancy, followed by motor and language functions in early childhood. Adolescence is a critical window of development for executive functions (behavioural and cognitive) and social cognition.” - Baxendale, S. [1]

Because pubertal development is ongoing, once it has been interrupted - even for a very brief period of time - it’s impossible to go back in time and undo that interruption, or to know how someone given puberty blockers might have developed without them.

The idea that pubertal development can simply resume as normal, regardless of the amount of time that puberty is suppressed, doesn’t comport with any established science on human development. [1][6] While puberty blockers have been used since the 1980s for various conditions, they’ve never before been prescribed to developmentally healthy children on as large a scale as they currently are. As such, their use in this context is experimental.

Proponents say that puberty blockers give children time to pause and consider their options. However, tracking of gender patients indicates that patients treated with puberty blockers go on to take cross-sex hormones at a much higher rate that those who don’t.

Dr Hilary Cass, author of systematic review commissioned by the UK’s National Health Service has written:

"The most difficult question is whether puberty blockers do indeed provide valuable time for children and young people to consider their options, or whether they effectively ‘lock in’ children and young people to a treatment pathway which culminates in progression to feminising/ masculinising hormones by impeding the usual process of sexual orientation and gender identity development. " [16]

Research suggests that without medicalisation, the majority of adolescents who present with gender related distress will desist over time. Desistence refers to the cessation of transgender identity or gender dysphoria.

Studies into natural rates of desistence put the number at 80% or more:

However, when children are given puberty blockers, around 90% of them will persist and progress to cross-sex hormones:

  • 2011: A study reported that of 70 patients, none "withdrew from puberty suppression, and all started cross‐sex hormone treatment,". [6]
  • 2018:  A study of medical files of people who attended a Dutch gender identity clinic from 1972 to 2015 reported that only 1.9% of adolescents who started puberty suppression treatment desisted. [7]
  • 2021: A study found that 98% (43 of 44) of patients who started on puberty suppression progressed to cross-sex hormones.[8]
  • A 2022 study showed that 7.4% (16 of 217) of children under 16 at referral discontinued puberty blockers. [9]
  • A 2022 a review of the literature concluded that, "Without medication, most will desist from the dysphoria in time. Yet over 90% of those treated with puberty blockers progress to cross-sex hormones and often surgery, with irreversible consequences." [10]
  • 2024: A review of seven studies found that discontinuation among patients who received puberty blockers ranged from 0% patients to 8%. [11]

The impact of puberty blockers on gender dysphoria, persistence and the increased likelihood that patients will undertake further medical interventions has raised significant concerns about potential iatrogenic harm - that is, harm resulting from medical treatment.

Because hormones influence our psychology and neurology [12][13][14], clinicians question whether the state of arrested development induced by puberty blockers could actually '‘lock-in’ a child’s perceived sense of self that would otherwise matured and changed. [15] [16]

In a letter to Australia’s Minister for Health, Professor of Paediatrics and Child Health, Dr John Whitehall wrote:

“How can [their] future be contemplated appropriately in a child whose sexualising influences have been neutered by drugs? How can a child be expected to develop a ‘world view’ including identity when its limbic system has been affected?”  
- Professor John Whitehall  [15]

Puberty suppressants are known to have an adverse effect on bone mineral density [1][2][3][4][5][6][7][8]. The duration of treatment seems to correlate with the degree of density reduction. In severe instances, this could increase the risk of developing conditions such as osteoporosis or osteopenia [2][4][3]: 

“I need to get checked for osteoporosis because I do have a pretty severe back pain just going up the spinal cord,” - ‘Kobe’, prescribed puberty blockers at 13 

In 2021, an analysis by Biggs found:

 “…after 2 years of GnRHa, up to a third of patients had abnormally low bone density, in the lowest 2.3% of the distribution for their sex and age.” [3]

Another study found that between the initiation of puberty blockers and age 22 years, the lumbar areal Bone Mineral Density z scores decreased significantly in transwomen and trended downwards in transmen. [4]

When a child’s puberty is suppressed, other types of development continue to take place in the absence of the sex steroids that their bodies would usually produce during puberty. For example, they may continue to grow taller, though not not necessarily in line with expected growth patterns. [5]

The impact of hormone-deprived development isn’t fully understood, but studies have found that bone mass doesn’t accrue at normal rates when puberty is halted. [3][4]

Cianca et al write:

“Puberty represents a window of opportunity to build a strong skeleton. In TGD youth, the particular hormonal milieu and the altered timing of puberty can have a negative impact on bone growth and mineralization.” [1]

Australian Standards of Care and Treatment Guidelines for trans and gender diverse children and adolescents Version 1.4

In Australia’s RCH treatment guidelines for gender affirming care, the risk of bone density loss is used to warn against the prolonged use of puberty blockers. [8] This seems to contradict the notion that puberty blockers are completely reversible, safe, and allow for an unhurried period of reflection.

The RCH guidelines also advise that "Improvement in bone mineral density is seen following commencement of oestrogen and testosterone." However, the guidelines fail to provide specific recommendations on the safe duration of puberty blocker use. This absence of clear time limits is notable, given the potential risks.

This lack of specificity could potentially lead to uncertainty in clinical decision-making regarding the long-term use of puberty blockers and the transition to cross-sex hormones.

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Bel H
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