Boris Johnson has backed a ban on trans women competing in some elite swimming races - but insisted people should be "as understanding as possible".
Fina, swimming's world governing body, voted last week to stop transgender athletes from competing in women's elite races if they have gone through any part of the process of male puberty.
Mr Johnson told reporters on a trip to Rwanda: “I haven’t studied it in detail but I see no reason to dissent."
Asked by a reporter “can a woman be born with a penis", he replied: “Not without being a man. That’s about as far as I’ve got on the subject”.
Asked if there was a “difference between a woman and a trans woman”, he left a long pause before saying “Yeah.”
Pushed on his views, he said: “Look, it’s very very important that as a society we should be as understanding of everybody else as possible. I’ve always stood for that.
“When you start to move from issues of sexuality to issues of gender you start to raise particular problems.
“I think I’ve spoken of three concerns I’ve had in the past.
“They are to do with the age at which you can be ‘Gillick competent’ to transition, the question of safe spaces for women, and the difficulties you have in sporting competitions.
“These are all very difficult problems and you have to be very sensitive. But those are some of the areas.”
The International Olympic Committee (IOC) said it is up to each international sports body to set their own rules for transgender athletes' inclusion, despite criticism from tennis great Martina Navratilova.
Navratilova, a gay rights trailblazer, had slammed the IOC last week for what she said was a lack of leadership on the issue.
"The IOC has completely punted," Navratilva, who has won a total of 59 Grand Slam titles, told The Australian newspaper.
"That 'Oh, we will leave it up to the individual federations'. How can these individual federations within their country make their different rules?" she said.
"They have to do the research and the implementation ... and it costs money to then figure it out, and it's impossible."
LGBT rights group Athlete Ally earlier said FINA's new eligibility criteria was "discriminatory" and "harmful", while transgender cyclist Veronica Ivy described the policy as "unscientific".
IOC spokesperson Mark Adams said on Friday: “This is a very divisive, a very difficult situation, a very difficult topic where we have to try to balance fairness with inclusivity.”
Sasha Misra, Associate Director of Communications and Campaigns, questioned why journalists were asking questions about a "tiny, vulnerable minority" at a time of multiple national crises.
She said: "We know that the majority of the public feel supportive and compassionate towards trans people, who are their family, friends and neighbours.
"All that is achieved by this kind of media coverage is that trans people feel less safe in their day to day lives, and the public has less opportunity to hear from the government on the pressing political matters of the day.
"The Prime Minister might welcome the distraction, but he should not be fooled into thinking that anti-trans talking points will win votes."