RecruitingPhase IIIInterventional

PATHWAYS TRIAL, PATHWAYS HORIZON INTENSIVE, PATHWAYS CONNECT

The PATHWAYS Trial is a study for young people in the UK experiencing gender incongruence, meaning their gender identity differs from the sex they were assigned at birth. This can be distressing, especially during puberty. The study investigates medicines that temporarily pause puberty, called GnRHa. While these medicines are used in some places, we need more good quality evidence on their benefits and risks. The trial will compare starting this medication straight away versus waiting for one year, to see how it affects quality of life, mental health, physical development, and gender-related distress. It aims to provide clear, independent information for young people, families, and doctors making decisions about this treatment.

At a glance

Status

Recruiting

Phase

Phase III

Enrolment target

526

Start

05 Jan 2026

Estimated completion

30 Jun 2028

Gender incongruence

What is this study about?

The PATHWAYS Trial is an important study looking into puberty-stopping medicines for young people in the UK. These medicines are for those who feel their gender identity (who they feel they are on the inside) doesn't match the sex they were given at birth. This feeling, called gender incongruence, can be confusing and upsetting, especially when their body starts to change during puberty.

Currently, some places use medicines to temporarily pause puberty. These medicines are called GnRHa. They work by gently stopping the body from making the hormones that cause puberty changes. Although they're already used, we don't have enough clear, reliable information about how helpful they are and if there are any risks specifically for young people with gender incongruence. That's where the PATHWAYS Trial comes in.

The main goal of this study is to gather strong evidence. It wants to find out how these puberty-stopping medicines affect things like a young person's happiness, their mental health, how their body develops, their memory and thinking, and how much distress they feel about their gender. By comparing young people who start treatment right away with those who wait a year, the study hopes to give better answers and help future young people, their families, and doctors make informed choices.

Key takeaways

The study explores puberty-pausing medicines for young people with gender incongruence.
It compares starting treatment immediately versus waiting one year.
Aims to gather reliable evidence on benefits and risks for future decisions.
Involves regular clinic visits, health checks, questionnaires, and follow-ups.
Participants can choose to leave the study at any time.
Study starts in early 2026 and runs until June 2030.

Who may be eligible?

To take part in the PATHWAYS Trial, a young person must be receiving care from an NHS Gender Service and have a clear diagnosis of gender incongruence. This means their gender identity is different from the sex they were registered as when they were born, and this feeling has lasted for at least two years. They also need to want puberty-stopping treatment.

The young person must already be going through puberty, but not too far along, usually between early and later stages. A doctor will check this during an examination. They also need to be younger than 15 years and 11 months old when they join the study. They can't have taken puberty-stopping hormones or other gender-affirming hormones before.

Before joining, the young person will have some health checks like bone scans, blood and urine tests, and a physical exam to make sure the study is a safe and suitable option for them.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

I have been diagnosed with gender incongruence by an NHS Gender Service.
I want to explore puberty-stopping treatment for my gender incongruence.
I am currently going through puberty (not too early or too late).
I am under 15 years and 11 months old.
I have not previously taken puberty-pausing or other gender-affirming hormones.

Answer every question to see your result.

What does participation involve?

If you join the PATHWAYS Trial, there are a few things involved. You'll be put into one of two groups by chance: one group will start the puberty-stopping medicine right away, and the other group will wait for one year before starting. Both groups will be carefully looked at for two years to see how the timing of treatment affects your life.

You'll have regular visits to the clinic, fill out questionnaires about how you're feeling, and have health checks including blood tests and scans, like bone scans and sometimes X-rays. Some participants will also have brain scans and memory & thinking tests. These checks help the study team understand any changes.

After the initial two years, you'll be followed up for another 2.5 years, and potentially longer, to see the long-term effects. There's also a related study, PATHWAYS HORIZON-Intensive, for young people not taking the puberty-stopping medicine, to help compare different support pathways.

Potential risks and benefits

We don’t know yet if the treatment will definitely help participants, but by taking part, you'll help us learn more about what works and what doesn't with puberty-stopping hormones. This information can then help other young people, parents, and doctors make important decisions in the future. These medicines are generally safe and commonly used for other conditions, with most side effects like headaches, hot flushes, tiredness, or mood changes being mild and temporary. However, there are some less common but important risks, including potential effects on bone strength, and in very rare cases, a condition causing severe headaches and vision problems (IIH), or changes in heart rhythm. There's also a very small, theoretical chance of long-term effects on fertility, bone health, sexual development, or memory. You'll have extra scans to check your bone health, which involve a tiny amount of radiation, similar to what we naturally get each year. Taking blood samples is generally safe, but can cause a small pinch, bruising, or dizziness. You can always stop taking part in the study at any time.

Locations (2)

University College London Hospitals NHS Foundation Trust
City only
London, England
Bristol Royal Hospital for Children
Approximate
Bristol, England

Common questions

What is 'gender incongruence'?

It's when a person's inner feeling of being male, female, both, or neither (their gender identity) doesn't match the sex they were thought to be when they were born.

What are 'puberty-stopping medicines'?

These are medicines that temporarily pause the changes that happen during puberty, like breast development or voice deepening. They are not permanent and can be stopped.

Will I have to take part if I'm offered a place?

No, taking part is completely your choice. Even if you join, you can leave the study at any time without having to give a reason, and it won't affect your regular NHS care.

Who is paying for this study?

The study is funded by a partnership between NHS England and the National Institute for Health and Care Research (NIHR), which are both UK health organisations.

Where will the study take place?

Recruitment for the study will happen through NHS Gender Services for Children and Young People across England.

How to find out more

Emily Simonoff

pathwaysenquiries@kcl.ac.uk N/A Official trial record

Always speak to your GP or specialist before deciding to take part in a study.