"We initially set out to understand how the skin renews itself, and whether there is a hierarchy with stem cells at the top. We were surprised to discover strong differences in the way stem cells renew the skin in females and males," said Dr. Dan Engelman, the study's first author.

What do hormones actually do?

The team ran a series of hormone experiments:

• Castrated male mice lost their main source of testosterone — and their skin cells started behaving like female cells.
• Adding back dihydrotestosterone (DHT), an active form of testosterone, restored the typical male pattern.
• Removing the ovaries slowed stem cell multiplication and nearly erased the sister-cell synchrony.
• Estradiol, a form of estrogen, reversed the drop in stem cell proliferation.

The picture: testosterone speeds up how quickly skin cells mature and leave the stem cell layer, while estrogens boost stem cell proliferation and coordinate newly produced cells.

The researchers also applied testosterone to human skin reconstructed in the lab. The hormone accelerated stem cell differentiation there too, hinting that at least part of the mouse mechanism may work in people.

Why do wounds close faster in females?

When the team examined wounds on the animals' backs, female mice closed them substantially faster — especially in the first few days after injury. That early edge traces partly to stem cells switching on sooner and working in a coordinated way. As healing progressed, the gap between the sexes gradually narrowed.

Doctors have long noticed sex differences in wound healing, inflammatory conditions and skin cancer rates, but the underlying biology stayed incomplete. This work offers a mechanism: hormones tuning stem cell behavior.

What could this mean for medicine?

If the findings hold up in humans, they could steer treatments that account for a patient's sex — from recovery after burns and surgery to chronic wounds in people with diabetes, a problem affecting millions worldwide. The results may also inform new approaches to skin cancer, one of the most common cancer types.

The caveats are real, though. Faster healing and coordinated stem cell behavior were demonstrated in mice, and only one experiment — the testosterone test on lab-grown human skin — touched on human biology. More research will need to confirm how closely the mouse processes match our own.

"This study is a technological tour de force, and the discovery of differences between male and female skin stem cells is fascinating and entirely unexpected," Prof. Blanpain said. "Sex is a parameter too often overlooked in biology and medicine."

His team now plans to study sex differences in how skin cancers form and progress, and to identify the molecular mechanisms responsible.

Funding came from the FNRS, TELEVIE, the WEL Research Institute, the Fondation contre le Cancer, the European Research Council and several Belgian foundations.