Children with gender dysphoria will no longer receive puberty-suppressing hormones, also known as puberty blockers, as routine practice after an NHS England review concluded there was insufficient evidence for their safety and effectiveness.
Under the new policy, the hormones will be only available for children with gender dysphoria through clinical trials intended to fill gaps in medical knowledge, though provision is expected to be made in exceptional circumstances on a case-by-case basis. Treatment for young people already receiving the hormones will not be affected.
Therapies to suppress puberty arose from work in the 1960s and 70s, when researchers discovered what has been called “the conductor of the reproductive system”. In work that involved the dissection of hundreds of thousands of pig and lamb brains, Andrew Schally and Roger Guillemin extracted and determined the structure of gonadotropin-releasing hormone (GnRH) work that earned them the 1977 Nobel prize for medicine.
GnRH is produced in the brain’s hypothalamus. When released, it triggers the pituitary gland to secrete further substances, namely follicle-stimulating hormone and luteinizing hormone, which drive puberty and sexual development. In men, the hormones tell the testicles to make testosterone. In women, they make the ovaries produce oestrogen and progesterone.
What researchers found remarkable as they came to understand GnRH was that while pulses of the hormone stimulate the pituitary to churn out other puberty-driving hormones, a continuous dose effectively shuts down production of follicle-stimulating hormone and luteinizing hormone, putting puberty on ice.
Today, synthetic analogues of GnRH such as triptorelin are given for prostate cancer and endometriosis, and they are also approved for children with precocious puberty, a condition that affects more girls than boys. Affected girls can start puberty as toddlers, but hormone therapy applies the brakes. When children come off the drugs, they go through puberty as normal. “It’s been very beneficial in these children,” says Ashley Grossman, a professor of endocrinology at the University of Oxford.
Studies of children who received puberty-suppressing hormones for precocious puberty suggest the therapy is generally safe, but questions remain. Some researchers note that scant data on important outcomes such as cognitive development, fertility, and the risk of cancer and metabolic disease make it hard to draw firm conclusions about its long-term impact.
Less is known about the use of puberty-suppressing hormones in children with gender dysphoria. The drugs have been used off label – when a drug is prescribed for a use other than the one stated on the label – for the condition since the mid-1990s, to buy time for patients to explore their gender identity and to hold off potentially distressing sexual maturation.
But few large, robust studies have investigated the consequences. “It is a different situation if a child is about to go into puberty and you turn the whole thing off, and that is really what we don’t know about long term,” says Grossman.
Some studies find puberty suppression can improve mental health and wellbeing in young people suffering extreme distress with gender dysphoria, but many findings are based on small numbers of patients. Research in the field is often contested. Headline-making work from Massachusetts general hospital in 2020 found suicidal thoughts were less common in transgender adults who had received puberty-suppressing hormones in adolescence, compared with those who wanted them but went without. But critics said the survey used was unreliable. One claimed the study “contributed nothing”.
Puberty is a crucial time for bone and brain development. Several studies suggest puberty blockers affect bone density and potentially make bones weaker, but again the picture is not wholly clear. Jennifer Osipoff, a paediatric endocrinologist at Stony Brook University in New York, prescribes puberty blockers for gender dysphoria. To mitigate any risk to bone health, she supplements patients with calcium and vitamin D.
The possible impact of puberty suppression on the maturing brain has received little attention from researchers. One study flagged declines in IQ during hormone treatment for precocious puberty, but no one has systematically delved into the potential cognitive effects of halting puberty in adolescence and whether any changes are reversible.
For some researchers, these longer-term outcomes must be properly understood before prescribing the therapy. “No area of medicine can operate ethically in such a vacuum of knowledge,” says Sallie Baxendale, a professor of clinical neuropsychology at University College London. She also has “grave concerns” about adolescents’ capacity to give truly informed consent to medications that “interrupt the construction of the neural architecture that underpins complex decision making”.
Osipoff agrees there is “not a lot of scientific research”, but based on her patients and reports from other clinics she strongly believes the benefits outweigh the risks. The hormones can not only alleviate distress in gender dysphoria, she says, but may reduce the need for operations later on, for example, if a trans man wants to have breast tissue removed. “Seeing how severe the mental health problems have been in so many of my patients, to say there’s something I can do to help eliminate some of that distress and not offer it, that just seems inhumane,” she says.
