Endometriosis is a chronic, multifaceted, and often difficult to treat disease that affects roughly 10% of reproductive aged females globally.¹ At this time, a single consistent cause of endometriosis has not been clearly identified. Endometriosis results in the growth of hormone responsive and behaviorally altered endometrial-like cells outside the endometrium or uterus. These lesions adhere to and affect multiple tissue and organ sites, which can result in many (often debilitating) symptoms such as painful periods, pelvic pain and infertility among others.

Despite not having a singular identified cause, there are multiple theories behind the pathogenesis of endometriosis. The original theory proposes retrograde or backward menstruation where endometrial tissue is pushed into the pelvic cavity. However, most women have some degree of retrograde menstruation and do not develop endometriosis. There is emerging evidence that genetics and the pelvic terrain, which includes inflammatory processes, immune dysfunction, toxic exposures, and microbiome dysregulation may play strong roles in the development of endometriosis. Due to the variety of potential origins, the goal of treatment is often to manage pain and improve fertility (when desired). Using DUTCH to evaluate hormones, hormone metabolism, and inflammatory markers can be a useful tool for managing driving factors for endometriosis in addition to common symptoms such as pain. 

While it is possible that you may not find anything abnormal on the DUTCH test of a patient with endometriosis, there are patterns that may help guide your thought process in patient and disease management. DUTCH Providers can access the DUTCH Mini Guide for Endometriosis in the Provider Portal for a quick reference to have on hand when interpreting the DUTCH test. To get access to this Mini Guide and more, become a DUTCH Provider today!

The following is a list of DUTCH patterns to keep in mind for your patient with endometriosis.

Estrogen Levels 

It is well established that estrogen feeds endometriosis lesion growth. Estrogen levels may be higher for these patients at baseline due to high aromatase activity in endometriosis cells that increase estradiol production. Lowering estrogen can reduce oxidative stress and pain by limiting lesion growth each cycle. When estrogen and estrogen metabolites appear elevated on the DUTCH test, it may be beneficial to evaluate further underlying causes of these elevated levels in addition to evaluating the efficiency of phase I and II detoxification pathways to keep estrogen levels in check.

Estrogen Detoxification

Supporting optimal phase 1 metabolism to 2-OH-E1 metabolites is important to create more anti-proliferative metabolites. Optimal phase 1 metabolism helps to mitigate risks associated with having excess oxidative 4-OH-E1 and excess proliferative 16-OH-E1 metabolites.

Sluggish Phase 2 methylation can back up physiologically active estrogen metabolites and contribute to a higher estrogen load, which may exacerbate a condition like endometriosis. Phase 2 estrogen methylation is done by the COMT enzyme. If COMT function appears low, COMT support may improve estrogen levels.

Progesterone Levels

Progesterone serves as an inhibitory hormone in endometrial cell growth. Low levels of progesterone relative to estrogen can contribute to estrogen dominance, which may worsen endometriosis activity and symptoms.  

While normalizing progesterone levels may be beneficial, it is important to mention that endometriosis cells may have “progesterone resistance”. Even if a patient with endometriosis has normal levels of progesterone, their lesions may not respond to progesterone in normal and expected ways.² For more information regarding this topic, please register for our upcoming webinar, Progesterone Resistance and Endometriosis with Lindsey Szczepanski, MSN, APRN, WHNP-BC. 

Androgen Levels

Research continues to unfold regarding the inverse relationship between androgen levels and symptoms of painful periods and pelvic pain in women with endometriosis.³  In other words, low androgens may be associated with worse pain. Assessing testosterone and DHEA levels on the DUTCH test may be useful to determine whether they need to be normalized to help manage those common painful symptoms. 

Conversely, if both androgens and estrogens are elevated, investigating the cause for elevated androgens and reducing them may be beneficial as they may be contributing to elevated estrogens through aromatization. 

Inflammatory Markers and Patterns

Inflammation is a known driver in the etiology of endometriosis and pain.⁴ Evaluating clues for inflammatory patterns on the DUTCH test may provide insight into underlying inflammatory processes that are driving endometriosis in your patient. The following markers and patterns may be helpful to evaluate when assessing inflammation:

• Elevated quinolinate, kynurenate, 8OHdg, cortisol and DHEA, 5a-reductase activity, and 16-OH-E1 and 4-OH-E1 metabolites
• Additionally, quinolinate may be elevated with increased exposure to phthalates, which are known endocrine disrupting chemicals (EDCs). EDCs have a strong link to the etiology of endometriosis and may be worth addressing as part of your patient’s care plan.⁵
• High cortisol metabolites relative to free cortisol, which indicates an elevated Cortisol Clearance Rate (CCR)
• High or low pyroglutamate

Indican

Gastrointestinal symptoms are common in patients with endometriosis. Research linking the gut microbiome and endometriosis continues to emerge.⁶  Endometriosis may impact gastrointestinal motility by adhering to the small and large intestine. This adherence can thereby disrupt the rhythm of migrating motor complexes, which can consequently contribute to many GI symptoms and microbiome changes.⁷  Elevated Indican on the DUTCH test may indicate dysbiosis in the gut, in addition to constipation, hypochlorhydria, and pancreatic insufficiency. If the Indican is elevated, it may be helpful to assess their microbiome with further testing and support healthy digestion and bowel movements. Supporting healthy and regular bowel movements is beneficial for Phase 3 detoxification of estrogen through the gut, which is important for modulating estrogen levels in these patients. 

Cortisol

HPA axis dysfunction can be common in patients with endometriosis due to the chronic pain, stress, and impacted quality of life that endometriosis can cause.⁸ Evaluating the DUTCH test for signs of HPA axis dysfunction via high or low cortisol patterns may be beneficial to modulate stress, maintain resilience, and indirectly improve other physiological processes intricately tied to the HPA axis. These processes include but are not limited to immune function, inflammatory responses, and hypothalamic-pituitary-gonadal (HPG) axis function, which are all key players in endometriosis.⁹

Endometriosis and the DUTCH Test

Addressing these pertinent findings on the DUTCH test may be helpful to improve symptoms and quality of life while managing this disease. Standard management of endometriosis includes an array of hormone and immune modulating pharmaceuticals, in addition to anti-inflammatories, emerging therapies such as Low Dose Naltrexone (LDN)¹⁰, and of course surgical management in severe cases. Lifestyle, dietary, and nutraceutical approaches are useful adjuncts in the whole person care of patients with endometriosis. Promising nutraceutical interventions emerging in the management of endometriosis in terms of pain reduction and/or lesion activity include palmitoylethanolamide (PEA)^{11, 12}, N-Acetyl Cysteine (NAC)¹³, specialized pro-resolving mediators¹⁴, and curcumin¹⁵, among many others.

While endometriosis is often thought of as a reproductive or pre-menopausal condition, due to its systemic effects, symptoms may endure in post-menopause for some women even though estrogen levels are low at this time. Caution should be taken with menopausal hormone therapy (MHT) in post-menopausal women with a history of endometriosis as estrogen therapy may potentially reactivate the condition in some women.^{16, 17} As always, individual assessment and monitoring should be used in those cases. 

References:

1.  World Health Organization. Endometriosis. World Health Organization; 2023. Accessed February 5, 2025. .

2.  Zhang P, Wang G. Progesterone Resistance in Endometriosis: Current Evidence and Putative Mechanisms. Int J Mol Sci. 2023;24(8):6992. Published 2023 Apr 10. doi:10.3390/ijms24086992

3.  Evans SF, Hull ML, Hutchinson MR, Rolan PE. Androgens, Endometriosis and Pain. Frontiers in Reproductive Health. 2021;3. doi:10.3389/frph.2021.792920

4.  Leonardi M, Hicks C, El-Assaad F, El-Omar E, Condous G. Endometriosis and the microbiome: a systematic review. BJOG 2020; 127: 239–249.

5.  Dutta S, Banu SK, Arosh JA. Endocrine disruptors and endometriosis. Reprod Toxicol. 2023;115:56-73. doi:10.1016/j.reprotox.2022.11.007

6.  Tang F, Deng M, Xu C, et al. Unraveling the microbial puzzle: exploring the intricate role of gut microbiota in endometriosis pathogenesis. Front Cell Infect Microbiol. 2024;14:1328419. Published 2024 Feb 16. doi:10.3389/fcimb.2024.1328419

7.  Mathias JR, Franklin R, Quast DC, et al. Relation of Endometriosis and Neuromuscular Disease of the Gastrointestinal Tract: New Insights.

8.  Hannibal KE, Bishop MD. Chronic stress, cortisol dysfunction, and pain: a psychoneuroendocrine rationale for stress management in pain rehabilitation. Phys Ther. 2014;94(12):1816-1825. doi:10.2522/ptj.20130597

9.  Appleyard CB, Flores I, Torres-Reverón A. The Link Between Stress and Endometriosis: from Animal Models to the Clinical Scenario. Reprod Sci. 2020;27(9):1675-1686. doi:10.1007/s43032-020-00205-7

10.  Maksym RB, Hoffmann-Młodzianowska M, Skibińska M, Rabijewski M, Mackiewicz A, Kieda C. Immunology and Immunotherapy of Endometriosis. J Clin Med. 2021;10(24):5879. Published 2021 Dec 15. doi:10.3390/jcm10245879

11.  Stochino Loi E, Pontis A, Cofelice V, et al. Effect of ultramicronized-palmitoylethanolamide and co-micronized palmitoylethanolamide/polydatin on chronic pelvic pain and quality of life in endometriosis patients: An open-label pilot study. Int J Womens Health. 2019;11:443-449. Published 2019 Aug 12. doi:10.2147/IJWH.S204275

12.  Caruso S, Iraci Sareri M, Casella E, Ventura B, Fava V, Cianci A. Chronic pelvic pain, quality of life and sexual health of women treated with palmitoylethanolamide and α-lipoic acid. Minerva Ginecol. 2015;67(5):413-419.

13.  Porpora MG, Brunelli R, Costa G, et al. A promise in the treatment of endometriosis: an observational cohort study on ovarian endometrioma reduction by N-acetylcysteine. Evid Based Complement Alternat Med. 2013;2013:240702. doi:10.1155/2013/240702

14.  de Fáveri C, Fermino PMP, Piovezan AP, Volpato LK. The Inflammatory Role of Pro-Resolving Mediators in Endometriosis: An Integrative Review. Int J Mol Sci. 2021;22(9):4370. Published 2021 Apr 22. doi:10.3390/ijms22094370

15.  Vallée A, Lecarpentier Y. Curcumin and Endometriosis. Int J Mol Sci. 2020;21(7):2440. Published 2020 Mar 31. doi:10.3390/ijms21072440

16.  Gemmell LC, Webster KE, Kirtley S, Vincent K, Zondervan KT, Becker CM. The management of menopause in women with a history of endometriosis: A systematic review. Human Reproduction Update. 2017;23(4):481-500. doi:10.1093/humupd/dmx011

17.  Secosan C, Balulescu L, Brasoveanu S, Balint O, Pirtea P, Dorin G, Pirtea L. Endometriosis in Menopause—Renewed Attention on a Controversial Disease. Diagnostics. 2020; 10(3):134.