Endometriosis: Symptoms, Treatment, and the Future of Non-Invasive Diagnosis

Science
Verfasst von Dr Amy Whitbread

Endometriosis is a chronic, estrogen-dependent inflammatory disease characterized by the presence of endometrial-like tissue outside the uterus [1]. Affecting approximately 1 in 10 women worldwide, it is a leading cause of pelvic pain and infertility [2, 3]. However, despite its prevalence, endometriosis remains underdiagnosed, with a staggering average delay of 7-10 years before definitive diagnosis [4]. This delay highlights the urgent need for non-invasive diagnostic tools that could provide earlier detection and better access to care.

Pathophysiology of Endometriosis

The exact cause of endometriosis remains unclear, but several theories are commonly explored:

  • Retrograde Menstruation: Menstrual blood containing endometrial cells flows backward into the peritoneal cavity, where these cells implant and proliferate [5].

  • Coelomic Metaplasia: Peritoneal cells transform into endometrial-like cells under hormonal or environmental influences [6].

  • Immune Dysregulation and Inflammation: Endometriosis is linked to chronic systemic inflammation, altered immune responses [7], dysbiosis of the gut microbiota [8], and increased levels of pro-inflammatory cytokines (e.g., IL-6, TNF-α) [9, 10].

Lesions can develop on the ovaries (endometriomas), peritoneum, bladder, bowel, and even extra-abdominal sites such as the diaphragm and lungs. These lesions respond to hormonal fluctuations, leading to cyclic bleeding, fibrosis, and adhesion formation that contribute to pain, organ dysfunction, and infertility.

Clinical Presentation and Symptoms

Endometriosis presents with a wide spectrum of symptoms, which can vary greatly between individuals [11, 12].

Here are some of the more common symptoms:

  • Chronic Pelvic Pain: This is one of the most prevalent symptoms, often described as a persistent, dull, or sharp pain in the pelvic region. It can be cyclical, worsening during menstruation, or constant, affecting daily activities and quality of life.

  • Dysmenorrhea (Secondary): Painful menstruation (menstrual cramps), often severe enough to interfere with daily activities.

  • Dyspareunia: Pain during sexual intercourse, which can affect intimate relationships and emotional well-being.

  • Dyschezia and Dysuria: Painful bowel movements or urination, particularly during menstruation. This can be due to endometrial tissue affecting the bladder or bowel.

  • Gastrointestinal Symptoms: Bloating, nausea, and alternating constipation or diarrhea, often misdiagnosed as IBS.

  • Fatigue and Heavy Menstrual Bleeding: Many women report chronic fatigue and heavy periods, which can exacerbate the impact on quality of life and mental health.

  • Infertility: Endometriosis is associated with infertility, affecting 30%–50% of women diagnosed with the condition. The exact mechanism is not fully understood but may involve anatomical changes and inflammation.

The Need for Non-Invasive Diagnosis

Currently, the gold standard for diagnosing endometriosis is laparoscopy with histological confirmation, a procedure that requires surgery and often results in significant diagnostic delays. This invasive nature of laparoscopy, coupled with its risks, low specificity [13], and high cost, emphasizes the need for non-invasive diagnostic methods, particularly for early detection prior to surgery. 

Recent advancements in non-invasive diagnostic techniques, including imaging and biomarker identification, offer promising alternatives. These methods aim to improve early detection and management of endometriosis, thereby enhancing patient outcomes and reducing healthcare burdens. Some key non-invasive approaches include imaging techniques like Transvaginal Ultrasound (TVS) [14], and MRI [15], Symptom-Based Predictive Models [16] and biomarkers. Research into non-invasive biomarkers for endometriosis is ongoing, with promising candidates including glycoproteins, inflammatory markers, and micro RNAs. Although no single biomarker has yet been validated as a reliable diagnostic tool, these studies highlight the potential for biomarkers to play a significant role in non-invasive diagnosis [17].

Menstrual Blood as a Non-Invasive Source of Biomarkers

Menstrual blood testing is emerging as a promising, non-invasive alternative. Research in this area suggests that menstrual blood, which naturally contains endometrial tissue, could be a rich source of novel biomarkers for the early detection of endometriosis [18]. Some studies have already identified several potential biomarkers in menstrual blood that are showing promise as diagnostic markers.

For example:

  • Menstrual blood contains proteins and lipids that differ significantly between women with and without endometriosis. For instance, proteins like CXCL5 and IL1RN have been identified as potential biomarkers due to their increased expression in endometriosis patients [19]. Lipidomic studies have also highlighted specific lipids, such as plasmenylphosphatidylethanolamine and cardiolipin, which show promise in diagnostic models with high sensitivity and specificity [20].

  • Menstrual Blood-Derived Stem Cells (MenSCs) exhibit mesenchymal stem cell properties and are implicated in the pathogenesis of endometriosis. They have been studied for their potential in both diagnosis and treatment. MenSCs from endometriosis patients show distinct characteristics compared to those from healthy individuals, which could serve as biomarkers [21].

Analyzing menstrual blood could significantly reduce the time between symptom onset and diagnosis, offering patients a less invasive and more accessible testing method than current options like laparoscopy. Ongoing research into menstrual blood biomarkers holds the potential to revolutionize endometriosis diagnosis by providing earlier detection and more personalized treatment pathways.

Current Treatment Strategies

While no cure currently exists for endometriosis, treatments focus on managing symptoms and, when necessary, preserving fertility [22]. Treatment options include:

  • Pain Management: Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used to manage pain associated with endometriosis.

  • Hormonal Therapies: These aim to suppress ovulation and estrogen-driven lesion growth. Common treatments include combined oral contraceptives (COCs), progestins, and GnRH agonists or antagonists.

  • Surgical Management: In severe cases, laparoscopic excision to remove lesions is the gold standard. For refractory cases, a hysterectomy may be considered.

  • Fertility Preservation: For women desiring pregnancy, surgical interventions are carefully planned to preserve ovarian function. Assisted reproductive technologies like IVF may be considered when natural conception is challenging.

  • Non-Pharmacologic Approaches: Dietary changes, pelvic floor physical therapy, and stress management can help alleviate symptoms.

The Future of Endometriosis Diagnosis: Why Menstrual Blood Testing is the Key

Despite the availability of treatments, there is a pressing need for more effective, non-invasive diagnostic methods to detect endometriosis early and improve patient outcomes. Current diagnostic tools, including imaging modalities and laparoscopy, have limitations.

This is where menstrual blood testing comes into play. The potential to detect endometriosis through menstrual blood biomarkers is a breakthrough that could transform the way we diagnose and monitor the disease. As research in this area continues to evolve, we could see a future where women have access to easier, faster, and more reliable diagnostic options, ultimately leading to earlier intervention and better treatment outcomes.

The Need for Ongoing Research and Awareness

As endometriosis continues to affect millions of women worldwide, there is an urgent need for increased funding, research, and awareness. Early detection through non-invasive methods such as menstrual blood testing could be the key to improving outcomes for women living with endometriosis.

This Endometriosis Awareness Month, let’s advocate for a future where no woman has to suffer in silence, where early diagnosis and personalized care are the norms. It’s time to push for better research, innovation, and awareness - especially for non-invasive diagnostic tools that could close the gender health gap and improve the lives of countless women.

Key Takeaways:

✔️ Endometriosis affects 1 in 10 women and involves ectopic endometrial-like tissue.

✔️ Symptoms include chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility.

✔️ Menstrual blood biomarkers show promise as a non-invasive diagnostic tool for endometriosis.

✔️ Research is needed to validate menstrual blood testing as a reliable diagnostic method.

✔️ A focus on non-invasive diagnostics could dramatically reduce diagnostic delays and improve patient care.

References & Further Reading

  1. Neto, J., Abrão, M. S., Schor, E., & Silva, J. C. R. e. (2022). Surgical Classification of Endometriosis. Revista Brasileira de Ginecologia e Obstetrícia, 44(08), 737–739. https://doi.org/10.1055/s-0042-1755588

  2. Miszczyk, K., Gonet, M., Kania, A., Lazar, M., Maj, P., Maternia, J., Mozer, P., Sergiel, N., Serwik-Trandasir, A., & Włodarczyk-Cybulska, K. (2023). Endometriosis as very common cause of chronic pelvic pain – overview of actual knowledge. Journal of Education, Health and Sport, 46(1), 368–381. https://doi.org/10.12775/jehs.2023.46.01.026

  3. Fernando, R. (2024). The effect of endometriosis on the fertility of women. World Journal of Biology Pharmacy and Health Sciences, 19(1), 320–331. https://doi.org/10.30574/wjbphs.2024.19.1.0441

  4. De Corte, P., Klinghardt, M., von Stockum, S., & Heinemann, K. (2024). Time to Diagnose Endometriosis: Current Status, Challenges and Regional Characteristics—A Systematic Literature Review. Bjog: An International Journal Of Obstetrics And Gynaecology. https://doi.org/10.1111/1471-0528.17973

  5. Bulun, S. E. (2022). Endometriosis caused by retrograde menstruation: now demonstrated by DNA evidence. Fertility and Sterility, 118(3), 535–536. https://doi.org/10.1016/j.fertnstert.2022.07.012

  6. Signorile, P. G., Viceconte, R., & Baldi, A. (2022). New Insights in Pathogenesis of Endometriosis. Frontiers in Medicine, 9. https://doi.org/10.3389/fmed.2022.879015

  7. Tresso, A., Thota, N., James, C., Borash, N., Brennan, E., Bayat, S., Vollenhoven, B., & Tapmeier, T. (2024). The over-activated peritoneal immune environment in endometriosis is characterised by a lack of PD-1 inhibition. https://doi.org/10.1101/2024.08.30.610573

  8. Liu, H., Li, J., Guan, C., Gao, W., Li, Y., Wang, J., Yang, Y., & Du, Y. (2024). Endometriosis is a disease of immune dysfunction, which could be linked to microbiota. Frontiers in Genetics, 15. https://doi.org/10.3389/fgene.2024.1386411

  9. Dymanowska-Dyjak, I., Terpiłowska, B., Morawska-Michalska, I., Michalski, A., Polak, G., Terpiłowski, M., Rahnama-Hezavah, M., & Grywalska, E. (2024). Immune Dysregulation in Endometriomas: Implications for Inflammation. International Journal of Molecular Sciences, 25. https://doi.org/10.3390/ijms25094802

  10. Liu, H., Li, J., Guan, C., Gao, W., Li, Y., Wang, J., Yang, Y., & Du, Y. (2024). Endometriosis is a disease of immune dysfunction, which could be linked to microbiota. Frontiers in Genetics, 15. https://doi.org/10.3389/fgene.2024.1386411

  11. Afolabi, M. A. (2022). The Concept of Clinical Endometriosis: A Paradigm Shift in Africa. 2(1). https://doi.org/10.53902/pwhcij.2022.02.000509

  12. Sridhar, S., Gallant, T., & Brunn, E. (2022). Overview of Pathogenesis, Symptoms, Diagnosis, Management, and Prognosis of Endometriosis and Its Role in Infertility. Journal of Gynecologic Surgery, 38(1), 3–6. https://doi.org/10.1089/gyn.2021.0160

  13. Diagnosis of Endometriosis at Laparoscopy: A Validation Study Comparing Surgeon Visualization with Histologic Findings. (2022). Journal of Obstetrics and Gynaecology Canada, 44(2), 135–141. https://doi.org/10.1016/j.jogc.2021.08.013

  14. Ferrero, S., Barra, F., Perrone, U., Paudice, M., & Vellone, V. G. (2024). Ultrasound diagnosis of bowel endometriosis. Gynecologic and Obstetric Investigation, 1–24. https://doi.org/10.1159/000542563

  15. Avery, J., Deslandes, A., Freger, S., Leonardi, M., Lo, G., Carneiro, G., Condous, G., Hull, M. L., Hull, L., Carneiro, G., Avery, J., O’Hara, R., Condous, G., Knox, S., Leonardi, M., Panuccio, C., Sirop, A., Abbott, J., Gonzalez-Chica, D., … Jenkins, M. (2023). Non-invasive Diagnostic Imaging for Endometriosis Part 1: A Systematic review of recent developments in Ultrasound, Combination Imaging and Artificial Intelligence. Fertility and Sterility. https://doi.org/10.1016/j.fertnstert.2023.12.008

  16. Samanta, N., Schiller, E., López-Molini, I., Martin, M., Flores, I., Meyer, A. S., & Chen, N. (2024). An accessible, non-invasive tool for endometriosis diagnosis reveals an association between age at symptom onset and endometriosis symptom prevalence. Journal of Endometriosis and Pelvic Pain Disorders, 16(2), 71–78. https://doi.org/10.1177/22840265241257295

  17. Encalada Soto, D. (2024). Navigating towards precision: evaluating the clinical value of non-invasive biomarkers for the diagnosis of endometriosis. Minerva Obstetrics and Gynecology. https://doi.org/10.23736/s2724-606x.23.05313-7

  18. Amanda, C., Hestiantoro, A., & Asmarinah, A. (2024). Menstrual Blood Biomarkers for the Noninvasive Diagnosis of Endometriosis: A Review. https://doi.org/10.21203/rs.3.rs-4923540/v1

  19. Ji, S., Liu, Y., Yan, L., Zhang, Y., Li, Y., Zhu, Q., Xia, W., Ge, S., & Zhang, J. (2023). DIA-based analysis of the menstrual blood proteome identifies association between CXCL5 and IL1RN and endometriosis. Journal of Proteomics, 104995. https://doi.org/10.1016/j.jprot.2023.104995

  20. Starodubtseva, N., Chagovets, V., Tokareva, A., Dumanovskaya, M. R., Kukaev, E., Новоселова, А. В., Frankevich, V., Павлович, С. В., & Сухих, Г. Т. (2024). Diagnostic Value of Menstrual Blood Lipidomics in Endometriosis: A Pilot Study. Biomolecules, 14(8), 899. https://doi.org/10.3390/biom14080899

  21. Cordeiro, M. R., Carvalhos, C. A., & Figueiredo-Dias, M. (2022). The Emerging Role of Menstrual-Blood-Derived Stem Cells in Endometriosis. Advances in Cardiovascular Diseases, 11(1), 39. https://doi.org/10.3390/biomedicines11010039

  22. Konal, M. (2024). Medical Treatment for Endometriosis. https://doi.org/10.5772/intechopen.1007680

Dr Amy Whitbread

Lead Scientist at theblood.

https://www.linkedin.com/in/dr-amy-whitbread-240852240/
Zurück

Understanding Heavy Menstrual Bleeding: Causes, Symptoms, and Solutions
Weiter

What Do Menstrual Blood Clots Say About Your Health?