For the millions of women living with Polycystic Ovary Syndrome (PCOS), struggles with fertility, miscarriages, and long-term health risks are common challenges. New research published in Nature Medicine offers insights into why these issues occur and points toward more targeted treatments that could help.
Scientists from Karolinska Institutet in Sweden have created a “cell atlas” of the uterine lining (endometrium) in women with PCOS, showing differences at the cellular level compared to women without the condition.
“These results show that the growth of the cells is affected, which may explain why it can take longer for affected women to become pregnant and why they are more likely to miscarry, as well as contributing to the increased risk of endometrial cancer,” explains Professor Elisabet Stener-Victorin, who led the research.
The research team analyzed almost 250,000 cell nuclei from the uterine linings of 17 women – 12 with PCOS and 5 without. All women were of similar age, weight, and BMI, and samples were taken during the same phase of the menstrual cycle to ensure accurate comparisons.
The research showed that women with PCOS had more epithelial cells (which line the uterus) and fewer stromal cells (which provide structural support). The researchers also found altered gene expression, with many genes related to cell attachment, communication, and immune functions showing different activity levels. The study identified that certain cell types in the endometrium showed PCOS-specific patterns of disrupted interaction.
“Our analyses show that certain cell types in the endometrium have disrupted communication and interaction specific to PCOS,” says Gustaw Eriksson, one of the study’s first authors and a doctoral student in Professor Stener-Victorin’s research group.
These cellular differences help explain some of the most distressing aspects of PCOS. The altered cell composition and gene expression can make it harder for embryos to implant in the uterus, leading to fertility challenges. Additionally, the disrupted cellular environment may not provide adequate support for early pregnancy, potentially explaining the higher miscarriage rates. Changes in cell growth patterns likely contribute to the higher rates of endometrial cancer seen in PCOS patients as well.
The researchers didn’t stop at identifying problems – they also looked at potential solutions. After women with PCOS took the diabetes drug metformin (with or without lifestyle changes) for 16 weeks, many of the problematic gene expressions normalized.
“We can show that metformin seems to have many more functions in women with PCOS than lowering blood sugar,” says Professor Stener-Victorin. “In the study, all the women were overweight, but it is likely that metformin has similar effects in affected women who are not overweight but insulin resistant if they have problems getting pregnant or have repeated miscarriages.”
The study also found that lifestyle modifications like diet and exercise helped improve some cellular patterns, though not as dramatically as medication.
This research may help in developing more targeted PCOS treatments. By identifying which cell types and cellular processes are affected, scientists can work on medications that address the specific dysfunctions.
“As we identified changes in gene expression in specific cell types, this study provides crucial guidance for developing more targeted treatments for PCOS-related endometrial dysfunction,” explains Professor Stener-Victorin.
PCOS affects 11-13% of women of reproductive age, making it the most common hormonal disorder in this population. Beyond reproductive issues, the condition is often associated with irregular or absent periods, elevated male hormones (leading to symptoms like excess body hair), insulin resistance, higher risk for type 2 diabetes, and increased cardiovascular disease risk.
While there’s currently no cure for PCOS, this new research brings hope that more effective treatments targeting its reproductive consequences may be on the horizon.
