Endometriosis affects roughly 10% of reproductive age women and girls globally (1). It gets its name from the word ‘endometrium’ which is the tissue that lines the uterus. Endometriosis happens when tissue similar to the endometrium grows outside of the uterus on ovaries, fallopian tubes, tissues that hold the uterus in place or outer surfaces of the uterus. This is problematic because endometriosis growths may swell and bleed during the menstrual period, and this can cause swelling and pain. The growths can also continue to expand and cause further problems which can lead to infertility. Symptoms of endometriosis include pain, bleeding or spotting, digestive problems, and not being able to get pregnant or infertility (2). 

Endometriosis being a complex disease, it is currently difficult to pinpoint a specific cause. It may result from a complex interaction between genetic and environmental factors (3). Possible causes include problems with menstrual period flow, genetic factors, immune system problems, hormones and surgery (2). One of the current priorities of the World Health Organisation is to continue research on endometriosis and to better understand genetic and environmental factors in order to have more personalised treatments (4).

Oestrogen is thought to have a role in endometriosis because it helps to thicken the lining of the uterus during the menstrual cycle (2), and it promotes the endometriosis tissue to grow and shed (5). This facilitates the inflammation and pain associated with the disease. Medical treatments for endometriosis focus on lowering oestrogen levels or increasing progesterone. For this reason, functional polymorphisms on genes encoding enzymes involved in sex steroid metabolism may contribute to an increased risk of endometriosis and symptoms. 

Endometriosis and Genetics

The CYP17A1 gene hydroxylates pregnenolone to androstenedione, and progesterone to testosterone - and a SNP (rs743572) present on this gene can increase its activity, leading to a more rapid conversion to cortisol, androgens and oestrogens. This pathway can be further upregulated by stress, alcohol, blood sugar dysregulation and excess insulin. 

Oestrone (E1) and oestradiol (E2) - key factors for endometrial tissue proliferation (6) - are derived from testosterone via the CYP19A1 enzyme. SNPs on CYP19A1 can also increase its activity and lead to a higher conversion of androgens to oestrogens, which may worsen symptoms of endometriosis (4). Maintaining a healthy weight, balancing blood sugar, reducing inflammation and stress will help balance CYP19A1 activity. DIM, green tea, zinc, vitamin E, resveratrol, flavonoids and aromatase inhibitors can reduce its activity.

By a mechanism that is still unclear, CYP1A1 also seems to be related to endometriosis - possibly through the metabolism of environmental pollutants or its role in catechol oestrogen metabolism (6). The rs4646903 polymorphism has been associated with infertility and severe endometriosis (7). Phase II detoxification pathways (methylation, sulphation, glucuronidation and glutathione conjugation) can help eliminate the excess of oestrogen. Clearly, aromatase (coded by the CYP19A1 gene) play a role in endometriosis, and aromatase inhibitors have been shown to suppress the growth of endometriosis, reducing pelvic inflammation and pain (8).

Oestrogens exert their action via their receptors, one of them being ESR1 (9). Research has shown that SNPs (known as XbaI and PvuII) on the ESR1 gene may be associated with susceptibility to endometriosis. These two SNPs have been reported to be related to numerous oestrogen-related diseases. Although their mechanism is not totally clear, they could be a biomarker to predict the future susceptibility of these diseases and to allow early therapeutic intervention in women at high risk for endometriosis (10).

Another family of genes that has been researched in the role of endometriosis is the GSTs. A large number of studies have found that the GSTM1 null genotype almost doubles the risk of developing endometriosis. Additionally, a significant positive association has been observed between the dual null genotype GSTM1-GSTT1 and endometriosis susceptibility (11, 12). Individuals with these genotypes are considered to be at risk because the implantation of ectopic endometrial tissues occurs as a result of the enzymatic alteration in the detoxification process (13).

Methylation could also play a role in endometriosis, possibly via COMT and MTHFD1 genes. As described above, oestrogens are an important factor in endometriosis and COMT constitutes a crucial element in oestrogen metabolism (14). Another study suggests that COMT could have a role in the pain associated with endometriosis as they observed that patients with severe pain tend to have a higher frequency of the met/met (slow) genotype than those with minimal pain (15). 

A SNP on MTHFD1 which confers lower activity may reduce the supply of methyl-folate to recycle homocysteine to methionine. This could increase dependency on betaine (cofactor for BHMT) and its substrate choline (found in eggs) to support conversion of homocysteine to methionine. Depletion of choline may increase risk of endometriosis, and related infertility (16).

In addition to being a hormonal disease, endometriosis is also a chronic inflammation disorder. The levels of interleukin (IL-1, IL-6, IL-8), nerve growth factor (NGF), other immune cells and inflammatory factors are increased in peritoneal fluid and endometriosis lesions. These factors contribute to serious symptoms of pain such as chronic pelvic pain, dysmenorrhea and painful intercourse (17). A study suggests that variant allele carriers of the -174CG SNP on IL-6 may be at slightly higher risk of developing endometriosis (18).

Lifecode Gx Reports

Based on this analysis, we believe that our Hormones report is the most appropriate for clients suffering from endometriosis. This report describes the genes, nutrients, lifestyle and environmental factors that can impact steroid hormones and endometriosis progression and/or symptoms.


  1. Endometriosis-uk.org. 2022. Endometriosis Facts and Figures | Endometriosis UK. [online] Available at: <https://www.endometriosis-uk.org/endometriosis-facts-and-figures>
  2. Womenshealth.gov. 2022. Endometriosis | Office on Women's Health. [online] Available at: <https://www.womenshealth.gov/a-z-topics/endometriosis>
  3. Szczepańska, M., Wirstlein, P., Skrzypczak, J. and Jagodziński, P., 2013. Polymorphic variants of CYP17 and CYP19A and risk of infertility in endometriosis. Acta Obstetricia et Gynecologica Scandinavica. Available at: <https://obgyn.onlinelibrary.wiley.com/doi/10.1111/aogs.12210>
  4. Who.int. 2022. Endometriosis. [online] Available at: <https://www.who.int/news-room/fact-sheets/detail/endometriosis>
  5. nhs.uk. 2022. Endometriosis - Treatment. [online] Available at: <https://www.nhs.uk/conditions/endometriosis/treatment/>
  6. Trabert, B., Schwartz, S., Peters, U., De Roos, A., Chen, C., Scholes, D. and Holt, V., 2011. Genetic variation in the sex hormone metabolic pathway and endometriosis risk: an evaluation of candidate genes. Fertility and Sterility, 96(6), pp.1401-1406.e3. Available at: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228888/>
  7. Barbosa, A., de Souza, S., Frare, A., Costa e Silva, R., da Costa, I., Freitas e Silva, K., Ribeiro Júnior, C., Bordin, B. and Moura, K., 2016. Association of CYP1A1 (cytochrome P450) MspI polymorphism in women with endometriosis. Genetics and Molecular Research, 15(3). Available at: <https://pubmed.ncbi.nlm.nih.gov/27706624/>
  8. Advanced Women's Health Care | New England Center for Endometriosis. 2022. What Estrogen Does – and Doesn’t – Have To Do with endometriosis. [online] Available at: <https://www.advancedwomenshealthcare.us/blog/estrogen-and-endometriosis>
  9. Paskulin, D., Cunha-Filho, J., Paskulin, L., Souza, C. and Ashton-Prolla, P., 2013. ESR1rs9340799 Is Associated with Endometriosis-Related Infertility andIn VitroFertilization Failure. Disease Markers, 35, pp.907-913. Available at: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880708/>
  10. Hsieh, Y., Wang, Y., Chang, C. and Lin, C., 2006. Estrogen receptor α-351 XbaI*G and -397 PvuII*C-related genotypes and alleles are associated with higher susceptibilities of endometriosis and leiomyoma. MHR: Basic science of reproductive medicine, 13(2), pp.117-122. Available at: <https://pubmed.ncbi.nlm.nih.gov/17121748/>
  11. Zhu, H., Bao, J., Liu, S., Chen, Q. and Shen, H., 2014. Null Genotypes of GSTM1 and GSTT1 and Endometriosis Risk: A Meta-Analysis of 25 Case-Control Studies. PLoS ONE, 9(9), p.e106761. Available at: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160205/>
  12. XIN, X., JIN, Z., GU, H., LI, Y., WU, T., HUA, T. and WANG, H., 2016. Association between glutathione S-transferase M1/T1 gene polymorphisms and susceptibility to endometriosis: A systematic review and meta-analysis. Experimental and Therapeutic Medicine, 11(5), pp.1633-1646. Available at: <https://www.spandidos-publications.com/10.3892/etm.2016.3110>
  13. Kubiszeski EH, de Medeiros SF, da Silva Seidel JA, Barbosa JS, Galera MF, Galera BB. Glutathione S-transferase M1 and T1 gene polymorphisms in Brazilian women with endometriosis. J Assist Reprod Genet. 2015;32(10):1531-1535.Available at: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615927/>
  14. Christofolini DM, Teles JS, Vilarino FL, André GM, Bianco B, Barbosa CP. COMT polymorphism and the risk of endometriosis-related infertility. Gynecol Endocrinol. 2011 Dec;27(12):1099-102. Available at: <https://pubmed.ncbi.nlm.nih.gov/21495799/>
  15.  Xu, X., Ding, J., Rana, N. and Dmowski, W., 2007. Association between COMT gene polymorphism and endometriosis-associated pain: an interim analysis. Fertility and Sterility, 88, p.S213. Available at: <https://www.fertstert.org/article/S0015-0282(07)02382-5/fulltext#relatedArticles>
  16. Szczepańska M, Mostowska A, Wirstlein P, Lianeri M, Marianowski P, Skrzypczak J, Jagodziński PP. Polymorphic variants of folate and choline metabolism genes and the risk of endometriosis-associated infertility. Eur J Obstet Gynecol Reprod Biol. 2011 Jul;157(1):67-72. Available at: <https://pubmed.ncbi.nlm.nih.gov/21429654/>
  17. Wei, Y., Liang, Y., Lin, H. et al. Autonomic nervous system and inflammation interaction in endometriosis-associated pain. J Neuroinflammation 17, 80 (2020). Available at: <https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-020-01752-1>
  18. Wieser F, Fabjani G, Tempfer C, Schneeberger C, Sator M, Huber J, Wenzl R. Analysis of an interleukin-6 gene promoter polymorphism in women with endometriosis by pyrosequencing. J Soc Gynecol Investig. 2003 Jan;10(1):32-6. PMID: 12517591. Available at: <https://pubmed.ncbi.nlm.nih.gov/12517591/>

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