Summary
A medRxiv preprint reports that abnormal uterine bleeding linked to fibroids and bleeding arising from a primary endometrial disorder show different molecular and cellular features. The findings support investigating cause-specific treatment strategies, but the study did not test personalised therapies.
A study of endometrial tissue has found distinct molecular and cellular patterns in two forms of abnormal uterine bleeding (AUB), challenging the use of a single biological model for a symptom with several causes.
The medRxiv preprint, posted on September 17, 2026, compared women whose bleeding was associated with uterine fibroids (AUB-L) with women classified as having a primary endometrial disorder (AUB-E). The researchers found 81 genes with different expression levels between the two groups and identified differences in where sex-steroid receptors were located within the endometrium.
The authors argue that treatment could eventually be better matched to the biological cause of bleeding rather than guided mainly by the shared symptom. The work is a preprint and reports molecular findings, not results from a trial of cause-specific treatment.
How the study compared the two forms of AUB
The researchers examined endometrial tissue collected at different stages of the menstrual cycle from 73 women: 32 in the AUB-L group and 41 in the AUB-E group. All participants had regular menstrual cycles, allowing the investigators to account for the substantial changes that naturally occur in the endometrium across the cycle.
Three types of analysis were used. Quantitative reverse-transcription polymerase chain reaction, or quantitative RT-PCR, measured selected gene transcripts in tissue from all 73 participants. Bulk RNA sequencing, which measures the activity of many genes across a tissue sample, was performed for 35 participants. Quantitative immunohistochemistry examined the location and amount of selected proteins in tissue from 18 participants.
The study found that menstrual-cycle stage remained the main influence on overall gene expression in the endometrium of women with AUB and regular cycles. After accounting for cycle stage, however, the clinical cause of AUB was associated with a distinct global gene-expression pattern. The comparison between AUB-L and AUB-E identified 81 differentially expressed genes, using a false-discovery-rate threshold of less than 0.05.
A difference involving progesterone receptors
The researchers also found that the cause of AUB was associated with the spatial distribution of sex-steroid receptors. In particular, epithelial cells in the endometrial glands retained progesterone receptor B expression during the mid-secretory phase in the AUB-L group, whereas this pattern was not seen in the AUB-E group.
The mid-secretory phase follows ovulation and is a period when progesterone normally influences the endometrium. A receptor is a cellular protein that receives and transmits a hormone’s signal; the location of that receptor can affect which cells respond to the hormone. The finding therefore points to a difference in how endometrial tissue may respond to hormonal signals in the two clinical settings.
Why the finding matters for treatment research
AUB is a symptom rather than a single disease. Fibroids and disorders originating in the endometrium can both produce abnormal bleeding, while the tissue-level mechanisms behind those conditions may differ. The study’s results provide molecular evidence for separating these causes when investigating treatment response.
The authors propose moving towards precision therapeutics guided by distinct endometrial phenotypes—measurable biological patterns in tissue—instead of assuming that one medical approach should work equally across all causes of AUB. That proposal remains a direction for future clinical research: this study characterised tissue and gene activity, but did not compare treatments or measure whether a molecularly matched therapy improves bleeding, quality of life or the need for surgery.
The report received ethical approval from NHS Health Research Authority research ethics committees, with references 19/SS/0102 and 20/ES/0119. It is available as a medRxiv preprint, so its findings are preliminary and have not yet been presented in a peer-reviewed journal article.