Wes Streeting is under growing pressure to scrap the puberty blocker clinical trial after Northern Ireland refused to take part due to a legal challenge.
The devolved nation said it would halt participation until the outcome of a judicial review, which has been launched by gender-critical campaigners.
The UK-wide research will involve about 220 children under the age of 16 who are going through puberty and will examine the impact of the puberty blocker drugs on their physical and emotional well-being.
Legal letters have already been issued to the medical regulators responsible for the trial and copied to Health Secretary Mr. Streeting.
At the weekend, Stormont's health minister, Mike Nesbitt, said: 'Having taken account of the ongoing judicial review into the UK government's clinical trial of puberty blockers, I have decided to suspend Northern Ireland's agreement to participate in the UK-wide Pathways trial until the legal process has concluded.
'Should the trial ultimately be given the green light to proceed, I shall take the views of executive colleagues before any potential lifting of the pause.'
The recruitment of the trial's participants has already been delayed until the start of April.
However, the campaigners bringing the High Court challenge want to apply for an emergency injunction preventing the start of the trial until the case has concluded.
They question the trial's safety and transparency and whether it meets the expected 'ethical principles'.
Participants in the £10.7 million trial will be put on the drugs for up to two years and placed randomly in two groups, one starting treatment immediately and the other after 12 months.
More than 137,000 people signed an e-petition within 72 hours opposing the trial.
The drugs, which pause the development of secondary sex characteristics such as breasts and periods, were banned for under-18s in gender medicine last year.
Baroness Hilary Cass, who led the 2024 independent review into NHS gender care, told the BBC today she was in favour of the trial because it would create an evidence base and stop 'charlatans' handing out drugs inappropriately.
However, one of those involved in the legal challenge is Keira Bell, who took the now closed Tavistock gender clinic to court in 2020 after she was given puberty blockers and cross-sex hormones as a teenager.
She said on X yesterday: 'Our legal case against the puberty blocker trial has halted Northern Ireland's involvement until it has concluded. Confirmation that the UK will do the same [would be] very welcomed.'
Fellow campaigner psychotherapist James Esses added: 'Wes Streeting, for the sake of our children, do the right thing and pull the plug on this safeguarding monstrosity.'