Researchers from the University of Edinburgh in the UK identified a key protein called HIF-1 that could explain why heavy bleeding occurs.
They studied the womb lining, known as the endometrium. This is shed during menstruation, leaving behind a wound-like surface that must heal to limit blood loss.
The team discovered that lowered levels of oxygen - known as hypoxia - stimulates production of HIF-1, which drives repair of the womb lining.
Women with heavy periods had reduced levels of HIF-1 compared with those with normal blood loss, researchers said.
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"Our findings reveal for the first time that HIF-1 and reduced levels of oxygen in the womb are required during a period to optimise repair of the womb lining," said Jackie Maybin from the MRC Centre for Reproductive Health at the University of Edinburgh.
"Excitingly, increasing levels of the HIF-1 protein in mice shows real promise as a novel, non-hormonal medical treatment," said Maybin, lead author of the study published in the journal Nature Communications.
Diagnosing heavy menstrual bleeding can be subjective, but the medical community defines it as blood loss of more than 80 millilitres per menstrual cycle.
The condition can lead to severe anaemia - where there are not enough red blood cells to carry oxygen around the body.
It can lead to severe abdominal pain and disrupt daily life, as well as giving rise to other symptoms, such as bloating, unscheduled bleeding, and fatigue.
The researchers say there is a "clear, unmet" need for treatment that does not tamper with hormones and fertility.
"This research lays the much needed groundwork to developing new treatment options for women grappling with this condition," said Neha Issar-Brown, Head of Population and Systems Medicine at the MRC.
"The fact that preliminary results suggest no interference with fertility makes it even more promising," she said.