Puberty blockers: what the evidence says, and why scientists are still studying them

Puberty blockers are not new medicines

One of the biggest misconceptions surrounding puberty blockers is that they are new or experimental drugs.

In fact, the medicines most commonly referred to as puberty blockers, known as gonadotrophin-releasing hormone (GnRH) agonists, have been used in medicine for more than 40 years.

They were first developed to treat conditions where hormones need to be temporarily suppressed.

For these conditions, doctors have extensive experience of prescribing these medicines, and their short-term safety profile is well understood.

The debate surrounding puberty blockers is, therefore, not about whether the medicines themselves are established. Instead, it centres on whether they improve outcomes when used for children and young people experiencing gender dysphoria, and which patients are most likely to benefit.

How do puberty blockers work?

Puberty blockers act on the pituitary gland, reducing the release of hormones that trigger puberty.

This pauses the development of secondary sexual characteristics such as breast development, voice deepening, and menstruation while treatment continues.

Their effects are generally considered reversible once treatment stops, although some questions remain about longer-term effects on bone density, fertility, and other aspects of development, particularly when treatment is followed by gender-affirming hormones. Understanding these longer-term outcomes is one reason why researchers continue to study their use.

Why has their use become controversial?

For most medical treatments, years of research gradually establish who benefits, who does not, what the risks are, and how treatment compares with alternatives.

Gender dysphoria in children and young people has proved more difficult to study.

Over the past 15 years, referrals to specialist gender identity services increased rapidly in several countries. At the same time, clinicians recognised that many young people presenting with gender-related distress also had other healthcare needs, including anxiety, depression, autism spectrum conditions, or neurodevelopmental differences.

What did the Cass Review conclude?

The independent review of NHS gender identity services for children and young people, led by paediatrician Dr Hilary Cass, examined the available evidence and the organisation of NHS services.

One of its central conclusions was that the evidence supporting puberty blockers for gender dysphoria was limited and uncertain, particularly regarding long-term benefits and risks.

Importantly, the review did not conclude that puberty blockers had been proven to be ineffective or harmful. Rather, it concluded that the existing evidence was not strong enough to answer important clinical questions with confidence.

One recommendation was that puberty blockers should only be prescribed within a formal research setting while stronger evidence is gathered.

Why isn't there stronger evidence around puberty blockers already?

This is a question many people ask.

If puberty blockers have been used for decades, why do researchers still say the evidence is limited?

The answer lies in an important principle of evidence-based medicine.

A medicine can have decades of evidence supporting one use without automatically having equally strong evidence for every other use.

For example, aspirin has been prescribed safely for pain relief for generations. Later, researchers discovered it could reduce the risk of heart attacks in some people, but also increase bleeding risk in others. Those questions required entirely different studies.

Similarly, puberty blockers are well established for treating early puberty, where the goal is to delay unusually early physical development until a more typical age.

Using the same medicines for gender dysphoria asks different questions. Treatment may continue for longer, aims are different, and researchers are interested in psychological wellbeing, quality of life, physical development, and long-term outcomes extending into adulthood.

Those questions require their own evidence.

How medical evidence is built

Medical research rarely provides all the answers immediately.

Instead, evidence usually develops over time.

Doctors often begin by reporting individual cases or small groups of patients. Researchers then carry out observational studies, following larger numbers of people to look for patterns.

Where appropriate and practical, larger clinical trials compare different approaches under carefully controlled conditions.

Finally, systematic reviews combine results from many high-quality studies to provide the clearest picture possible.

Each stage strengthens confidence in the evidence, but each also has limitations.

Observational studies can show associations but cannot always demonstrate cause and effect because the people receiving different treatments may differ in important ways.

Randomised controlled trials are generally considered the strongest way of comparing treatments because participants are assigned to different groups using methods designed to reduce bias. However, these studies are often expensive, take years to complete, and are not always possible or ethical for every research question.

Evidence-based medicine therefore relies on considering the whole body of evidence rather than any single study.

What evidence exists for puberty blockers?

Most of the published research into puberty blockers for gender dysphoria has consisted of observational studies, many involving relatively small numbers of participants.

Several studies have reported improvements in psychological wellbeing for some young people during treatment.

However, many studies have also had limitations, including small sample sizes, lack of comparison groups, and relatively short follow-up.

The Cass Review concluded that these limitations meant it was difficult to determine with confidence which improvements were caused by treatment, which young people were most likely to benefit, and what the longer-term outcomes would be.

Why is a new clinical trial being launched?

Following the recommendations of the Cass Review, researchers developed the PATHWAYS study to help answer some of these unanswered questions.

The trial will recruit children and young people who meet strict eligibility criteria following comprehensive specialist assessment. Researchers will collect detailed information about physical health, mental health, and longer-term outcomes.

This is intended to produce stronger evidence than has previously been available.

At the end of July 2026, the High Court dismissed a legal challenge that sought to prevent the study from going ahead, meaning recruitment can now begin. The court found that the trial had undergone appropriate scientific and ethical review and could proceed.

Why do experts sometimes disagree?

Disagreement in medicine does not necessarily mean that one side is ignoring the evidence.

Often, experts agree about the quality of the available evidence but differ in how they believe decisions should be made when that evidence is incomplete.

Some clinicians argue that uncertainty means treatments should be restricted until stronger evidence becomes available.

Others argue that carefully selected patients may still benefit and that clinicians should retain greater flexibility while research continues.

This distinction is important because scientific evidence and healthcare policy are related, but they are not the same thing.

What this means for patients and families

Puberty blockers are well-established medicines that have been used safely for decades to treat several medical conditions.

Their use for children and young people with gender dysphoria is different because the clinical questions being asked are different, and the evidence to answer those questions remains incomplete.

The Cass Review concluded that more high-quality research is needed, not because the medicines themselves are new, but because clinicians need better evidence about who is most likely to benefit, what the long-term outcomes are, and how treatment compares with other approaches.

The new UK clinical trial is designed to help answer those questions. Whatever its findings, it should provide stronger evidence to support future decisions by young people, families and healthcare professionals.

In medicine, uncertainty is not unusual. New treatments, new uses for existing medicines, and changing patterns of illness all create questions that research aims to answer. As evidence grows, guidance evolves, allowing care to become increasingly informed by the best available science rather than opinion alone.