'Woefully little safety data'

Harvard professor says puberty blockers should be confined to rigorous research studies

Photo by Bernard Hermant on Unsplash

There is “woefully little safety data” for the use of hormone suppression drugs to block the natural puberty of children, according to Harvard University professor of medicine Marc B. Garnick.

Professor Garnick, who was involved in studies leading to regulatory approval of the hormone suppression drug Lupron for treatment of prostate cancer, was commenting on New York Times coverage of “growing concerns” about the use of this class of drugs by youth gender clinics.

“Puberty blockers” have been promoted as a safe, reversible way for transgender-identifying children to pause unwanted development while they ponder the next step in medicalised gender change. The side-effects, rationale and ethics of trans puberty blockade are under increasing scrutiny.

In a letter to the editor of The Times, Professor Garnick cites a range of safety issues with adult cancer patients on the same hormone suppression drugs, and warns that “woefully little safety data are available for the likely more vulnerable younger population [given these drugs as puberty blockers].

“The prudent and ethical use of such [hormone suppression] agents in the younger population should demand that every pubertal or pre-pubertal child be part of rigorous clinical research studies.

“[These studies should] evaluate both the short-term and longer-term effects of these agents to better define the true risks and benefits rather than relying on anecdotal information.”

Having researched these hormone suppression drugs for more than four decades, Professor Garnick says “physicians are still learning and continue to be concerned about the safety of these agents in adults.

He highlights “significant” bone loss in adults, and safety concerns about “cognitive, metabolic and cardiovascular effects.”

A Canada-based website, Life on ADT, tracks reports of side-effects when these drugs are used for “androgen deprivation therapy” with adult males suffering from prostate cancer.

Barriers to blockers

In Sweden and Finland, puberty blockers are no longer routine treatment for the distressing condition of gender dysphoria, while draft healthcare plans for England after the closure of the Tavistock gender clinic would confine these drugs to formal research.

In the United States and other developed countries, hormone suppression drugs are approved for use with children who enter “precocious puberty” before age 8-9.

Gender clinicians have sought to reassure trans-identified patients and their parents by suggesting that the unlicensed or “off-label” use of these drugs to block normally timed puberty will involve the same low risk as suppression of precocious puberty.

However, trans-identifying children are held back in development as their peers go into puberty, and it is unclear whether or not they miss a critical cognitive window that requires natural sex hormones.

It is also unclear the extent to which these gender patients can recover lost bone growth so as to avoid fractures in later life.

In Sweden, the shift to a more cautious treatment approach was influenced by reports of harm to adolescents on blockers — including a 15-year-old with osteopenia, a brittle-bone condition usually observed in the elderly.

Parents and patients of Australia’s most influential gender clinic at the Royal Children’s Hospital Melbourne have been told that the effects of puberty blocker drugs on the still maturing adolescent brain are unknown.

Reluctant pharma

In October, the news agency Reuters reported that American physicians had repeatedly asked the pharmaceutical companies that make hormone suppression drugs to seek approval for their use in gender medicine from the U.S. Food and Drug Administration.

The agency quoted a paediatric endocrinologist, Dr Brad Miller, as saying the companies had refused to do this.

“They would say it would cost a lot of money to get approval,” Miller said. “And they were not interested in going there because [trans treatment] was a political hot potato.”

Earlier this year, the state of Texas launched an investigation into two of these companies — Endo Pharmaceuticals and AbbVie Inc — over allegedly deceptive promotion of hormone suppression drugs for off-label use as puberty blockers.

In her interim report on youth gender care for England’s National Health Service, paediatrician Dr Hilary Cass says it is common for drugs to be used off-label with children because clinical trials to establish safety have been limited to adults or because a drug is targeting a different condition.

This does not make the off-label use “inherently unsafe”, she says, but where the drug use is “innovative [as it is with trans puberty blockers], patients receiving the drug should ideally do so under trial conditions.”

Dr Cass says it should not be “assumed that outcomes for, and side effects in, children treated for precocious puberty will necessarily be the same in children or young people with gender dysphoria.”

A 2021 study by Australian researchers linked with the gender service of The Children’s Hospital at Westmead, Sydney, pinpoints the effect on clinicians of prescribing off-label drugs.

“[Drugs] for puberty suppression were neither governmentally approved nor publicly reimbursed; their use and paid supply within the gender service was therefore ‘off-label’ and outside of an established legal or government-endorsed medical framework,” the researchers say.

“These factors undermined clinicians’ felt sense of safety.”