Endometriosis

Endometriosis is common with substantial impacts on the health and well-being for many of those suffering with the disease. To understand the impacts in Australia, I work with Professor Gita Mishra and Dr Sally Mortlock from the Australian Longitudinal Study on Women’s Health. Our recent results show the disease effects one in nine (11%) of women of reproductive age in Australia (Rowlands et al., 2021, 32757329). The direct and indirect costs for endometriosis in Australia are over $7 billion each year with most of the substantial cost burden falling on individuals through increased healthcare costs, impacts on employment and reduced lifetime income.

Women with endometriosis report higher rates of menstrual disorders, pain symptoms, bowel and urinary symptoms, and non-specific symptoms such as severe tiredness and difficulty sleeping (Gete et al., 2023, 37499990). They have higher rates of health service use and this persists, even a decade after diagnosis (Mishra et al., 2025, 39986328). The chronic and recurrent nature of the disease affects quality of life and women with surgically confirmed endometriosis were more likely to leave full time employment following diagnosis (Rowlands et al., 2022, 34757012).

Genetic factors account for about half of the risk of developing endometriosis. In a series of studies with colleagues around the world, we set out to find the specific genetic risk factors responsible (Nyholt et al., 2012, 23104006; Painter et al., 2011, 21151130; Sapkota et al., 2017, 28537267) to provide a window into causes of the disease. This work has accelerated in the last 5 years and the most recent genetic map reports 42 regions in the genome with genetic markers influencing disease (Rahmioglu et al., 2023, 36914876). 

A hallmark of the disease is the variation between individuals in how the disease presents and the poor correlation between symptoms and clinical observations. This suggests that there may be distinct subtypes of endometriosis. Higher genetic risk is associated with more severe forms of disease (Lee et al., 2013, 23193196; Painter et al., 2011, 21151130) and we are participating in the next generation of genetic studies that will have a greater emphasis on looking more closely at different disease presentations. 

Related diseases and conditions are often diagnosed along with endometriosis. These include other gynaecological conditions, multiple pain traits, gastrointestinal conditions, and immune/inflammatory conditions (McGrath et al., 2023a, 37159502; McGrath et al., 2023b, 37410157). These comorbidities can often complicate diagnosis due to overlapping symptoms. The co-occurrence may result from shared biological pathways or confounding factors such as the need for more frequent healthcare visits. Genetic evidence supports causal links for the overlap between endometriosis and shorter menstrual cycles, uterine fibroids, lower testosterone, and gastrointestinal disorders (Adewuyi et al., 2021, 32959083; Yang et al., 2023, 37909040). 

A major objective of genetic mapping studies is to understand how genetic risk factors modify disease risk because it tells us about the causes of endometriosis. Genetic variants can act through genetic effects on gene expression (Fung et al., 2018, 30061686; Mortlock et al., 2020, 32103259) and epigenetic signals on the DNA (Mortlock et al., 2023, 37587191), but discovery is not always easy because individual effects are small and may act during development or in specific cell types. Progress is being made identifying hormonal regulation and cell proliferation and cell adhesion as important pathways in disease development (Fung et al., 2018, 30061686; Mortlock et al., 2023, 37587191; Mortlock et al., 2020, 32103259). 

Diagnosis and treatment are a major clinical challenge because patients present with variable symptoms including severe pelvic pain and the symptoms overlap with other related conditions. There is significant diagnostic delay and variable response to treatments. We are analysing patient reported symptoms, related conditions, and genetic risk factors to help with disease prediction and earlier diagnosis. Studies in ALSWH data show promise for defining a set of symptom questions to reduce diagnostic delay and genetic risk prediction may help. Genetic risk scores a not diagnostic for individuals but show but there is a nine-fold difference in risk between those with the highest and lowest scores.  

Lack of good disease models to study in the laboratory has made functional studies difficult and slowed progress. With Dr Brett McKinnon, we have recently developed cell culture methods to study different cell types from diverse individuals. We can analyse responses of specific cell types to genetic and hormonal conditions and culture the cells together to mimic relevant tissues. This gives us the ability to observe differences in cell development between individuals and identified a specific subset of cells that is far more common in endometriosis patients (McKinnon et al., 2022, 35725766). We are developing these cell-based systems for drug screening to provide personalised treatments and develop novel drug targets.