A new study identified the potential pathway responsible for linking high hemoglobin to polycystic ovary syndrome.
Some 5% to 18% of women worldwide suffer from a condition called polycystic ovary syndrome, a hormonal disorder that can cause irregular periods, cysts on the ovaries, difficulty with fertility, and has been linked to cardiovascular and metabolic issues.
Despite years of uncertainty about what causes polycystic ovary syndrome, a groundbreaking new study suggests that high hemoglobin levels may play a key role in its development. But the implications go beyond just polycystic ovary syndrome — elevated hemoglobin levels have also been linked to serious health conditions like diabetes and heart disease, as hemoglobin is responsible for transporting oxygen through the blood.
While previous small, limited studies have alluded to some connection between polycystic ovary syndrome and hemoglobin levels, this new finding brings us closer to understanding a potential cause.
“It seemed like there might be a connection, a missing piece of the puzzle, and we wanted to investigate if hemoglobin could play a role,” said Guiquan Wang, a researcher at Xiamen University in China in an email.
20,602 women with an average age of 31 and who were being treated for fertility issues were included in Wang’s study.
Of this population, 3,732 women (roughly 18%), were diagnosed with polycystic ovary syndrome. When the researchers analyzed their hemoglobin levels, they noted a distinct association, with women with higher levels being more likely to also have polycystic ovary syndrome. Even higher levels within the normal range for hemoglobin, which is between 110 to 150 g/L, were linked to worse odds. For every 10 g/L rise in hemoglobin, women had a 22% greater likelihood of experiencing polycystic ovary syndrome, while also showing high levels of male sex hormones, such as testosterone.
After establishing this correlation, Wang and his team wanted to explore the possibility of a causal link — a direct cause-and-effect relationship between two factors.
They used a statistical method called Mendelian randomization to determine if genetic variants that influence hemoglobin levels were also linked.
“Because these genetic variations are randomly assigned before birth, they help us figure out if the association we saw is truly causal and not just due to other factors,” said Wang. “This analysis confirmed that genetically higher hemoglobin levels increased PCOS risk.” Moreover, higher hemoglobin levels were also linked to higher testosterone levels.
By identifying specific gene variants linked to hemoglobin levels, the researchers were also able to discover particular biological pathways that appeared to be crucial for the link between hemoglobin levels and polycystic ovary syndrome.
One of the key pathways they identified is responsible for how cells react to oxygen levels. Building on this, the researchers found a few important genes that help explain the link between hemoglobin levels and polycystic ovary syndrome. These genes are also connected to the control of testosterone levels, which play a role in the condition.
Next, the researchers wanted to see if any of the implicated genes could make for therapeutic targets. “We used databases to check if these genes are already targeted by existing medications or if they are considered ‘druggable’ – meaning it’s biologically feasible to develop drugs that can affect them,” explained Wang. “This helps us prioritize which genes might be most promising for developing new treatments.”
Once the researchers identified these genes, they wanted to see if they actually influenced women with polycystic ovary syndrome. When they compared the activity of these genes in the blood and ovary cells of women with and without the condition, they found that the genes were more active in women with polycystic ovary syndrome. They also discovered that the levels of these genes in the blood were connected to higher testosterone levels.
While the researchers want to tease apart the specific biological mechanisms that are likely causing polycystic ovary syndrome, the link between hemoglobin levels and polycystic ovary syndrome could be more immediately useful for diagnoses.
“Hemoglobin levels, which are routinely measured in blood tests, could potentially be used as an early marker to identify women at higher risk of polycystic ovary syndrome,” said Wang. “This could allow for earlier interventions and preventative strategies.”
Understanding lifestyle factors and investigating therapeutic targets remain other goals for the team. “It’s still early days, but our research provides a strong rationale for exploring these therapeutic targets,” concluded Wang.
Reference: Guiquan Wang, et al., Multiomics and Systematic Analyses Reveal the Roles of Hemoglobin and the HIF-1 Pathway in Polycystic Ovary Syndrome, Advanced Science (2025). DOI:10.1002/advs.202411679
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