Lord Coe has issued a warning over the future of women's sport if sporting organisations get regulations for transgender athletes wrong.
At the weekend American swimmer Lia Thomas became the first known transgender athlete to win the highest US national college title with victory in the women's 500-yard freestyle.
"I think that the integrity of women's sport if we don't get this right, and actually the future of women's sport, is very fragile," World Athletics president Coe said.
American Thomas swam for the Pennsylvania men's team for three seasons before starting hormone replacement therapy in spring 2019.
She has since shattered records for her university swimming team.
USA Swimming updated its policy for elite swimmers in February to allow transgender athletes to swim in elite events, alongside criteria that aim to reduce any unfair advantage, including testosterone tests for 36 months before competitions.
"There is no question to me that testosterone is the key determinant in performance," Coe told the Times.
"Look at the nature of 12 or 13-year-old girls. I remember my daughters would regularly outrun male counterparts in their class but as soon as puberty kicks in that gap opens and it remains. Gender cannot trump biology.
"You can't be oblivious to public sentiment, of course not. But science is important. If I wasn't satisfied with the science that we have and the experts that we have used and the in-house teams that have been working on this for a long time, if I wasn't comfortable about that, this would be a very different landscape."
World Athletics rules state a transgender athlete must have low testosterone levels continuously for a period of at least 12 months to be allowed to compete.
Rival critical of rules allowing transgender athlete to compete
On Monday Hungary's Reka Gyorgy accused the National Collegiate Athletic Association of denying her a "spot in the final" of its swimming championships by allowing Thomas to compete.
Gyorgy missed out on a place in the consolation final by one spot.
"It hurts me," Gyorgy reportedly said in a letter sent to the NCAA.
"This is my last college meet ever and I feel frustrated.
"It feels like that final spot was taken away from me because of the NCAA's decision to let someone who is not a biological female compete."
Gyorgy, 25, competed at the Olympic Games for Hungary in 2016 and has been part of the Virginia Tech swimming team for five years.
She finished 17th in the preliminary races for the 500-yard freestyle, one place away from qualifying for the B final.
Gyorgy acknowledged that Thomas is "doing what she is passionate about and deserves that right" but said she "would like to critique the NCAA rules that allow her to compete against us".
"I'm writing this letter right now in hopes that the NCAA will open their eyes and change these rules in the future," Gyorgy said.
"It doesn't promote our sport in a good way and I think it is disrespectful against the biologically female swimmers who are competing in the NCAA."
Writing in Newsweek, US Olympic silver medallist Erica Sullivan - who competed against Thomas at last week's NCAA championships, said she was "proud to support" Thomas and backed her inclusion.
She wrote: "Like anyone else in this sport, Lia has trained diligently to get to where she is and has followed all of the rules and guidelines put before her. Like anyone else in this sport, Lia doesn't win every time. And when she does, she deserves, like anyone else in this sport, to be celebrated for her hard-won success, not labelled a cheater simply because of her identity.
"As a woman in sports, I can tell you that I know what the real threats to women's sports are: sexual abuse and harassment, unequal pay and resources and a lack of women in leadership."