Screening for endometriosis with genetic testing – a novel approach to early treatment

Approximately 6–10% of women of reproductive age suffer from endometriosis. Unfortunately, there is up to a 10-year delay in diagnosis, leading to a lack of treatment, progression of the condition and decrease in quality of life. Common symptoms include pelvic pain, heavy menstrual flow, dysmenorrhea, fatigue, and infertility. For women trying to conceive, delay in treatment can delay time to conception and may lead to the need for assisted reproductive techniques (ART). Early diagnosis and treatment are therefore key for this population. Currently, the gold standard for diagnosis is laparoscopic surgery, which can be both diagnostic and a treatment. This procedure is invasive and may not be the best approach for early diagnosis. Genetic testing provides an option for identifying candidates early.

Endometriosis is a complex condition caused by the interaction between genetic and environmental factors, including exposure to environmental toxins. Environmental contaminants, such as dioxins, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons, interfere with the estrogen signaling pathway and exert immunosuppressive effects. Therefore, an inability to clear these toxins effectively could lead to an increase in total body burden and development of endometriosis.

Glutathione-S-transferase (GST) is a family of enzymes that are responsible for the detoxification of xenobiotics such as carcinogens, environmental toxins and drugs. Due to its genetic sequence, the GSTT1 and GSTM1 genes are susceptible to deletions during DNA replication, leading to null genotypes. In laymen’s terms, the gene is missing, and the body is unable to produce the enzyme reducing detoxication capacity. GST null genotypes are associated with a risk factor for PCOS, low fetal birth weight in smokers during pregnancy, male infertility, myocardial infarction, various types of cancer and endometriosis.

In a meta-analysis, both GSTM1- and GSTT1-null genotypes are associated with an increased risk of endometriosis (OR=1.54, 95% CI: 1.30–1.83, P=0.001; OR=1.41, 95% CI: 1.10–1.82, P=0.007; respectively). In addition, there was a significant positive association between the combined GSTM1-GSTT1 null genotype and susceptibility to endometriosis (OR = 1.33, 95% CI: 1.03–1.72, P = 0.027).

While our understanding of GST enzymes in the pathophysiology of endometriosis is still novel, screening women with signs and symptoms of endometriosis using genetic testing could offer an opportunity for early intervention, including lifestyle, nutritional and pharmaceutical interventions.  The impact of the genetic variation depends on gene-environment interactions, such as environmental toxin exposure; dietary intake of fruits and vegetables and saturated fats; presence of nutrient deficiencies such as vitamin D that impact immune function and other risk factors linked to the development of endometriosis. Identifying genetic predispositions before the disease progresses could offer an opportunity to address these environmental factors early enough to make an impact on the development of endometriosis.


  1. Alves, M. M. C., Almeida, M., Oliani, A. H., Breitenfeld, L. & Ramalhinho, A. C. Women with polycystic ovary syndrome and other causes of infertility have a higher prevalence of GSTT1 deletion. Reproductive BioMedicine Online 41, 892–901 (2020).
  2. Chung, Y. K. et al. Association Between Polycystic Ovary Syndrome and the Polymorphisms of Aryl Hydrocarbon Receptor Repressor, Glutathione-S-transferase T1, and Glutathione-S-transferase M1 Genes. Gynecol Endocrinol 37, 558–561 (2021).
  3. Mehdizadehkashi, A. et al. The effect of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis. Gynecological Endocrinology 37, 640–645 (2021).
  4. Zhang, H. et al. Effect of glutathione S-transferase gene polymorphisms on semen quality in patients with idiopathic male infertility. J Int Med Res 49, 3000605211061045 (2021).
  5. Zhu, H., Bao, J., Liu, S., Chen, Q. & Shen, H. Null Genotypes of GSTM1 and GSTT1 and Endometriosis Risk: A Meta-Analysis of 25 Case-Control Studies. PLoS One 9, (2014).


Dr. Robyn Murphy, ND
Scientific Advisory Board Member