As the numbers swell of adolescents worldwide who identify as transgender, puberty-blocking drugs have become the first line of intervention for even the youngest ones seeking medical treatment. However, they come with a cost, reveals research.
In the US, there are some 300 000 of these children, aged 13 to 17, and an untold number who are younger, and concerns are rising about the consequences of the drugs, a New York Times examination found.
The questions are fuelling government reviews in Europe, prompting a push for more research and leading prominent specialists to reconsider at what age to prescribe them and for how long.
Emma Basques (11) had identified as a girl since toddlerhood. Now, as she worried about male puberty starting, a Phoenix paediatrician advised: take a drug to stop it.
At 13, Jacy Chavira felt uncomfortable with her maturing body and was beginning to believe she was a boy. Use the drug, her Californian endocrinologist recommended: puberty would be suspended.
An 11-year-old in New York with depression said she no longer wanted to be a girl. A therapist said the drug was the best option.
“‘Puberty blockers really help kids like this,’” the child’s mother recalled the therapist saying.
Their use is portrayed as a safe, reversible, way to buy time to weigh a medical transition and avoid growing into a body that feels wrong. Transgender adolescents suffer from high rates of depression and other mental health issues. Studies show the drugs have eased patients’ gender dysphoria, a distress over the mismatch of their birth sex and gender identity.
“Anxiety drains away,” said Dr Norman Spack, who pioneered the use of puberty blockers for trans youth in the US and believes the drugs can be lifesaving.
Dutch doctors first offered puberty blockers to transgender adolescents three decades ago, followed with hormone treatment to help patients transition. Since then, the practice has spread worldwide, with varying protocols, little documentation of outcomes and no government approval of the drugs, including by the US Food and Drug Administration (FDA).
But there is emerging evidence of potential harm from using blockers, show reviews of scientific papers and interviews with more than 50 doctors and academic experts.
The drugs suppress oestrogen and testosterone, which help develop the reproductive system but also affect the bones, brain and other parts of the body.
During puberty, bone mass typically surges, determining a lifetime of bone health. When adolescents use blockers, bone density growth flatlines, on average, shows an analysis commissioned by The Times of observational studies examining the effects.
Many doctors treating trans patients believe they recover that loss when they go off blockers. But two studies from the analysis that tracked trans patients’ bone strength while using blockers and through the first years of sex hormone treatment found many do not fully rebound and lag behind their peers.
That could lead to heightened risk of debilitating fractures earlier than expected from normal ageing – in their 50s instead of 60s – and more immediate harm for those who start treatment with already weak bones.
“There’s a price,” said Dr Sundeep Khosla, who leads a bone research lab at the Mayo Clinic. “And that will probably be some deficit in skeletal mass.”
“The most difficult question is whether puberty blockers actually provide valuable time for children to consider their options, or whether they effectively ‘lock in’ children to a treatment pathway,” wrote Dr Hilary Cass, a paediatrician leading an independent review in England of medical treatments of adolescents presenting as transgender.
On her recommendation, England’s National Health Service last month proposed restricting use of the drugs for trans youths to research settings. Sweden and Finland have also placed limits on the treatment, concerned not just with the blockers’ risks, but the rise in young patients and the psychiatric issues many exhibit.
In the US, though, there is no universal policy.
Long-awaited research funded by the National Institutes of Health could provide more guidance. In 2015, four American gender clinics were awarded $7m to examine the effects of blockers and hormone treatment. They said the US had produced no data on the impact or safety of blockers, particularly among transgender patients under 12, leaving a “gap in evidence”.
Seven years in, they have yet to report key outcomes of their work, but say the findings are coming soon.
Many young patients and their families say the benefits of easing the despair of gender dysphoria outweigh the risks of taking blockers.
For others, the limited studies of trans medicine can make it difficult to fully evaluate the decision.
Three years after starting the drugs, Emma Basques believes she’s on the right path.
Jacy Chavira, now 22, decided that the medical treatment was not appropriate for her and resumed her female identity.
And the New York adolescent had such a significant loss in bone density after more than two years on blockers that the parents stopped the drugs.
Puberty blockers can be given as an injection or an implant. They were being used in the US and elsewhere, with approval by the FDA and its counterparts overseas, to treat prostate cancer; endometriosis, a painful disease causing uterine tissue to grow elsewhere in the body; and the unusually early onset of puberty, typically age six or seven.
By the time Emma Basques began taking blockers in 2019, multiple medical groups had endorsed their use, including the American Academy of Paediatrics and the international Endocrine Society, which in 2017 had described the limited research on the effects of the drugs on trans youth as “low-quality.” Still, they were encouraged by the “promising treatment”.
Doctors say it’s not unusual for research to lag behind the launch of new treatments or drugs to be used off-label on patients without FDA approval,.
An FDA spokeswoman said doctors have the discretion to do so, but added that just because a drug has been approved for one class of patients doesn’t mean it’s safe for another.
Emma Basques was on blockers for two years. After she turned 13 last year, a doctor prescribed oestrogen, starting her transition. She felt confident she was ready.
But the 11-year-old in New York, who had begun puberty and started at a new school, was increasingly distressed – refusing to bath or go to school and, for the first time, expressing a desire to no longer have a girl’s body.
When the parents consented to blockers in 2018, they hoped the drug would bring emotional stability.
The first two years were promising, with the patient, by then a teen, taking Prozac as well as blockers. But a bone scan in the third year showed the teen’s bone density had plummeted – as much as 15% in some bones – from average levels to the range of osteoporosis more common in older adults.
The doctor recommended starting testosterone, saying it would help the teen regain bone strength. But the parents had lost faith in the medical counsel. “I worry we’ve done permanent damage,” said the mother.
A full accounting of blockers’ risk to bones is not possible. While the Endocrine Society recommends baseline bone scans and then repeat scans every one to two years for trans youths, WPATH and the American Academy of Paediatrics provide little guidance. Some doctors require regular scans and recommend calcium and exercise to help to protect bones; others don’t.
But it’s increasingly clear the drugs are associated with bone development deficit. During the teen years, bone density typically surges by about 8% to 12% annually.
The analysis commissioned by The Times examined seven studies from the Netherlands, Canada and England involving about 500 transgender teens from 1998 through to 2021.
Researchers observed that while on blockers, the teens gained no bone density, on average, and lost significant ground compared with their peers.
The findings match what practitioners of the treatment have seen, including Dr Catherine Gordon, a paediatric endocrinologist and bone researcher at Houston’s Baylor College of Medicine.
So far, only two small studies, by Dutch doctors, have tracked the bone development of trans patients from beginning blockers through to early hormone treatment. In both studies, dozens of patients started blockers at 14 or 15, on average, and began oestrogen or testosterone at 16. The participants, followed in one study up to 18, and in the other to 22, saw their bones strengthen, on average, once they were on hormones. Still, most patients continued to lag; trans men neared average levels, but trans women fell far below.
After more than a year on blockers, a 15-year-old in Texas, who had not had a baseline scan, showed spinal bone density so low it was below the first percentile for the teen’s age and weight, indicating osteoporosis, show medical records.
A Swedish transgender adolescent who took the drugs from 11 to 14 with no bone scans until the last year of treatment developed osteoporosis and sustained a compression fracture in his spine, showed an X-ray.
“The patient now suffers from continued back pain,” medical records note, describing a “permanent disability” from the blockers.
Some US and Australian practitioners won’t provide the drugs to patients who are well into puberty, concerned the treatment poses the greatest threat to bones in that period.
“You’re potentially taking on risks I feel should be avoided,” said Dr Stephen Rosenthal, medical director of the University of California, San Francisco, Child and Adolescent Gender Center.
Like many physicians, he believes the benefits of blockers to alleviate gender dysphoria are greater than any risks to bones.
Jacy Chavira, in California, had already cut her hair short and begun binding her chest when she was prescribed blockers at 13. A therapist and her parents agreed that gender dysphoria could explain the mounting anxiety she was experiencing during early puberty.
Once on blockers, she became fixated on moving ahead with a medical transition.
After turning 16, her paediatric endocrinologist prescribed testosterone. But soon she started having doubts. Her body was growing more masculine, but she was secretly wearing dresses. At 17, in a consultation for breast removal, she worried about the potential loss of feeling in the nipples. To her, this was a sign of not wanting to undergo the surgery.
She realised her anguish had stemmed from a larger inner conflict, and that continuing with a gender transition would be a mistake. “I believe it was an issue with my identity, accepting who I was, and not just the physical female portion of it,” she said.
Like her, most patients who take puberty blockers move on to hormones to transition, as many as 98% in British and Dutch studies. While many doctors see that as evidence that the right adolescents are getting the drugs, others worry some young people are being swept into medical interventions too soon.
Some doctors and researchers are concerned puberty blockers may disrupt a formative period of mental growth. With adolescence comes critical thinking, more sophisticated self-reflection and other significant leaps in brain development. Sex hormones affect social and problem-solving skills. It’s believed that brain growth is connected to gender identity, but research in these areas is still very new.
In a 2020 paper, 31 global psychologists, neuroscientists and hormone experts urged more study of the effects of blockers on the brain.
“If the brain is expecting to receive those hormones at a certain time and doesn’t, what happens?” said Dr Sheri Berenbaum, head of a gender research lab at Penn State, and one of the paper’s authors. “We don’t know.”
The physicians in the Amsterdam clinic, where the treatment began, have lowered their minimum ages for starting blockers and hormones. But they are very cautious in selecting patients.
Methodology
The analysis commissioned by The New York Times examined the findings of seven observational studies from the Netherlands, England and Canada, documenting the association between puberty blockers and bone density in about 500 adolescents.
In each study, bone density was measured at the spine and the hip using Dual-energy X-ray absorptiometry, or DEXA scan. The analysis looked at group means, because not every study released individual person data. Each study’s findings were weighted based on its number of participants.
The change in bone density while adolescents were on blockers was observed to be zero. The analysis also showed that the adolescents’ Z-scores, a measure of bone density that is benchmarked to peers, consistently fell during treatment with blockers.
The studies included are:
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