Wes Streeting, the Health Secretary, has refused to intervene in an NHS puberty blocker trial despite concerns about children's safety.
The drugs were banned last year in the wake of the independent Cass Review, which found no evidence to support their use and warned they may also disrupt brain development.
However, an NHS trial to examine the evidence around their use in children is now awaiting the green light from the ethics regulator, which controversially approved a previous pilot into the drugs in 2011 but failed to ensure the results were shared.
Some 6,000 children are currently on the national gender clinic waiting list and could be eligible to receive the drugs if their clinical team and parents agree.
Kemi Badenoch, the Conservative Party leader and former equalities minister, has led criticism of the planned trial, with campaigners expressing concern it could act as a "loophole" to be "exploited" by activists despite the ban.
However, Mr Streeting insisted it must go ahead to build the evidence base around the use of the drugs, as had been recommended by the Cass Review.
A Department of Health spokesman said Mr Streeting had "been crystal clear about the need for children's healthcare to be evidence-led" and that extending the puberty blocker ban had been "one of his first acts in office".
However, Mrs Badenoch said it was "hard to believe there could ever be an ethical way of trialling these irreversible drugs for this purpose".
Parents of trans-identifying children have also raised concerns.
A spokesman for Bayswater Support Group, which advocates for evidence-based care on behalf of 600 families with trans-identifying children, said those responsible for the first trial had not been "held to account for their role in the initial Tavistock scandal" and "the whole process appears at risk of being replicated, with more children being knowingly harmed".
They said it was "inconceivable" that the NHS was "poised to re-open a back door to further vulnerable children taking medically unnecessary and potentially irreversible drugs".
Keith Jordan, a spokesman for Our Duty, a support group for parents with gender-questioning children, said the first trial "should have produced clear data on the harms of this treatment pathway" and that it was "telling" that the data had been suppressed.
He said the Health Research Authority (HRA) needed to "act to protect the vulnerable, not rubber-stamp another unethical experiment" and added: "We know that whenever a loophole is created activists will find ways to enlarge and exploit it."
Experts have pointed to the multiple failures of the initial puberty blocker trial run by the Tavistock gender clinic and University College London, which began in 2011, and said they feared the scandal would be repeated.
The "Early Intervention Study" was approved by the HRA almost 15 years ago, after initially being rejected on ethical grounds. It took nine years for the results to be published. The HRA has been criticised for failing to monitor the trial, which did not require parental consent.
Puberty blockers are currently banned in the UK after Mr Streeting made a temporary suspension indefinite on the advice of the Commission on Human Medicines.
However, last week it emerged that the new NHS trial into the drugs, run by researchers from King's College London, would be backed by £11 million in government funding.
The Cass Review, led by Baroness Cass, the former president of the Royal College of Paediatrics and Child Health, recommended a study to gather further evidence into the effectiveness of puberty blockers, and for existing data on children, who are now adults and had been through the Tavistock's gender clinic, to be collated and analysed.
Details of the new NHS trial have yet to be submitted to the regulator for ethical approval, it is understood.
If it is, a research ethics committee (REC) will be assigned to assess whether it meets the necessary standards. At least a third of the panel of up to 15 members will be "lay" people with no expertise in the relevant field of study.
Mrs Badenoch said: "Puberty blockers have never been certified as a safe or effective treatment for children with gender distress, and it is hard to believe there could ever be an ethical way of trialling these irreversible drugs for this purpose."
She said the Cass Review had made clear that "a holistic approach" was required.
Dr Michael Biggs, associate professor of sociology at the University of Oxford, said that during the last trial, the HRA "allowed the researchers to suppress the results".
He said it was crucial the HRA and the Medicines and Healthcare products Regulatory Agency (MHRA) "ensure that the proposed clinical trial of puberty blockers is clinically and ethically justified before approving it" and ensure "the results are published as soon as possible".
"Otherwise the Tavistock scandal will be repeated, this time with even more children being subjected to an unethical experiment," he added.
Dr Louise Irvine, co-chairman of the Clinical Advisory Network on Sex and Gender, said that during the previous trial "the supervision, regulation and accountability process by the HRA was totally inadequate" and said it had "failed to do its job".
She said the proposed application meant it would be held to the highest clinical standards but warned that "the world is watching".
In 2019, the HRA published an investigation into how it handled the Tavistock trial and concluded it had "acted within its standard operating procedures and its normal practice in relation to this study".
Under new legislation passed last month, clinical trials are legally required to publish a summary of results within 12 months of the end of the trial or face regulatory action by the MHRA, which also has the power to stop or halt a trial if it has concerns.
More than 1,000 children were prescribed puberty blockers while being cared for by the Tavistock clinic between 2011 and its closure in 2023.
One of those patients was Keira Bell, a biological woman who was given the drugs and had surgery to become a trans man. She later regretted the decision and has now "de-transitioned".
Ms Bell has threatened the NHS with a lawsuit if it ploughs ahead with the "unethical and unlawful" trial.
Dr Caroline Johnson, the shadow health minister and consultant paediatrician, said the trial would be "watched like a hawk" and that it was vital "everything is done absolutely by the book".
Helen Joyce, director of advocacy at human rights charity Sex Matters, said the HRA's approach to the first puberty blocker trial had contributed to the "normalisation of the practice in mainstream medicine".
A spokesman for the HRA said: "The HRA is the appointing authority for research ethic committees in England, but each committee gives an ethical opinion using an established ethical review framework that ensures a consistent approach to ethical matters in different applications.
"RECs review all of the information submitted by a study team in an application and offer an opinion on the ethics of the approach. RECs do not decide what research takes place and how it is carried out. They carry out their ethical review using an established framework for the review of health and social care research in the UK."
A Department of Health spokesman said: "The secretary of state has been crystal clear about the need for children's healthcare to be evidence-led. One of his first acts in office was to extend a ban on puberty-suppressing hormones following expert, independent advice from the Cass Review.
"This also recommended a clinical trial be set up [to] help us better understand the effects of these hormones, providing the robust evidence required.
"The number of participants on the trial will be restricted by carefully considered eligibility criteria, which will be scrutinised as part of the ethical approval process and published once finalised.
"This will provide a safe and controlled environment for young people and will be conducted to the highest scientific and ethical standards."
An NHS England spokesman said the study "has been subject to independent academic peer review and a review by the National Institute for Health Care and Research committee ahead of seeking the usual strict ethical and regulatory approvals which ensure stringent safeguards in scientific research".