Endometriosis Saliva Test – Molecular Biomarkers for Non-Invasive and Rapid Diagnostics

At present, the journey from initial symptom manifestation to the diagnosis of endometriosis spans an average of 8 to 12 years [1].

However, a recent breakthrough has emerged, involving collaborative efforts between French and Swiss researchers alongside Ziwig, a pioneering company. They have introduced the “Endotest,” a revolutionary medical innovation designed to identify endometriosis within a mere 14 days [2, 3, 4].

Saliva-Based Detection of Endometriosis Using Chemical Biomarkers

While identifying positive biomarkers is a significant stride, it is crucial to acknowledge that their presence does not universally confirm a diagnosis. False positives and negatives can emerge in scientific testing, underscoring the importance of using many of these markers for secondary observation, rather than primary screening or diagnosis—though PSA stands as a notable, albeit debated, exception.

The current guidelines for endometriosis discourage the use of biomarker determination for diagnosis. Nonetheless, a nod is given to tumor markers (CA 125 and CA 19-9), which might not exhibit relevant elevation, especially in mild cases of endometriosis. Consequently, their applicability for uniform screening is limited due to individual variances [5].

Exploring Altered Gene Regulation via MicroRNAs

In their pursuit of effective endometriosis screening, the French research group employs specific microRNA molecules as biomarkers.

MicroRNA (miRNA) wield the power to modulate gene segments in our DNA, inhibiting them by binding to messenger RNA. This, in turn, impacts certain signaling pathways pivotal to disease development. While familiar signaling pathways have been identified for endometriosis, numerous miRNA molecules—relevant to endometriosis—await exploration [6].

Among the extensively studied miRNA, certain functions have been pinpointed, such as cell growth, and hormone synthesis. By curbing these molecules, endometriosis manifests its hallmark traits, such as aberrant growth beyond the confines of the endometrium  [7, 8].

Good to Know!

Central to the development of this saliva test is the identification of molecular biomarkers.

Biomarkers serve as parameters with diverse applications in the realm of medicine, including disease detection and prognosis assessment. A familiar instance is blood glucose levels, a crucial determinant for diabetes management.

Moreover, molecular biomarkers encompass substances derived from body fluids or extracted tissues.

Certain molecules, like prostate-specific antigen (PSA), have long been employed in urological screenings to detect prostate cancer, highlighting their utility as screening tools.

Identification of Shared MicroRNA Molecules in Endometriosis Patients

The identification of microRNA molecules common in individuals with endometriosis was pursued through an extensive study involving 200 subjects in a French case-control investigation [2].

Of the total participants, 153 individuals (76.5%) were confirmed to have endometriosis through surgical or radiographic validation.

To facilitate control and differentiation, a group of 47 women (23.5%) without endometriosis underwent simultaneous miRNA molecule determination using the same methodology.

The study’s culmination showcased the presence of 109 distinct microRNA molecules co-occurring in an impressive 96% of endometriosis patients, while these specific molecules remained undetectable in saliva samples from the control group.

In total, a comprehensive analysis unveiled 2,561 unique miRNA molecules in both the case and control groups. Notably, 109 of these molecules exhibited selective detection exclusively among the cases afflicted by endometriosis.

Remarkably, among these 109 miRNA, 84 are associated with recognized signaling pathways, with 4 having already been documented in prior endometriosis studies. The remaining 25 miRNA surfaced for the first time through the research spearheaded by Bendifallah’s group, beckoning further fundamental exploration.

These groundbreaking outcomes, achieved within a substantial study cohort, have been effectively translated into practical application. Collaborative efforts with six diverse French hospitals and Ziwig, a pioneering entity, facilitated the development of a novel, non-invasive saliva test that aligns with market demands [4].

With the attainment of a CE-IVD marking, this medical innovation is now accessible for utilization within the EU.  Since October 12, 2022, it has been readily available in the German market, ushering in a new era of diagnostics for endometriosis [3, 4, 9].

Implications for Future Endometriosis Diagnostics

Considering the current scope for optimizing endometriosis diagnosis, this medical innovation could herald a remarkable leap forward in the field.  Unlike the prior necessity of extensive medical history discussions and comprehensive examination, this product has the potential to streamline the diagnostic process.

Currently, the definitive diagnosis hinges on laparoscopy and subsequent tissue examination according to medical guidelines [5].

This abdominal endoscopy, commonly known as laparoscopy, often involves subsequent inpatient care.

To illustrate the financial implications, a study showcased average operation costs ranging from 747 to 939 euros, dependent on the endometriosis stage [10]. These costs are exclusive of subsequent inpatient expenses.

Conversely, the Endotest Diagnostic test kit, available from Eluthia in Germany, is priced at 799 Euros [3].

Presently, health insurance coverage for this procedure remains unregulated in Germany. It falls under individual health services, warranting individual application and potential reimbursement based on the decision [2].

Insurance companies can fund both recognized and non-recognized treatments. In the case of newly developed methods like the Endotest, replicability stands as a vital factor for broader acceptance.

Replicability involves reproducing study outcomes in independent studies, often involving a larger subject pool than the original study, which bolsters the method’s credibility [14].

Ziwig, the manufacturer, asserts a test sensitivity of 97% and specificity of 100% for the saliva test based on the original study and initial clinical application [4].

Sensitivity indicates the ability to detect actual endometriosis cases, while specificity highlights the test’s accuracy in correctly identifying healthy individuals.

In comparison, laparoscopic diagnostics exhibit high sensitivity but varying specificity based on symptom patterns. A 2012 study demonstrated a sensitivity of 85% and a specificity of just 44% [11].

However, it is essential to underline that laparoscopy provides not only diagnostic insight but also showcases the extent and pattern of endometriosis involvement, which a saliva test cannot replicate.

Moreover, laparoscopy encompasses both diagnostic and therapeutic roles, distinguishing between purely diagnostic and extended therapeutic interventions. Consequently, the diagnostic and therapeutic value of a laparoscopy surpasses that of a saliva screening test.

Lastly, time emerges as a pivotal factor for patients seeking a diagnosis. Early detection plays a pivotal role in shaping the severity and trajectory of endometriosis due to its implications for treatment. While conventional surgical or medical examinations may span several months, the Endotest remarkably shortens the diagnosis timeline to just 14 days [4, 9].

Outstanding Queries Regarding MicroRNA-Based Salivary Testing

Amidst the media buzz surrounding the Endotest, pertinent questions have surfaced, underscoring areas that could be elucidated through further studies or broader market deployment [2, 4, 12, 13]:

  1. The initial study featured 200 female participants whose shared molecular outcomes formed the basis of the test. The logical question arises: To what extent might the reported test probabilities and the overall test validity alter when a more extensive cohort of women undergoes testing?
  2. Analogously, the potential for confirming the methodology’s validity through replication studies presents itself as a crucial consideration.
  3. The participants enrolled in the study had not undergone surgical therapy during the study’s duration. An intriguing query emerges: How will the test outcomes change post-surgical excision of endometriosis lesions?
  4. This raises the question of the test’s applicability in monitoring potential recurrences after surgical intervention.
  5. The discussion within the research group’s study publication already broaches the subject of hormonal therapy’s impact on test results. The extent of this influence and its potential ramifications warrant thorough exploration.

The realm of endometriosis research is undergoing an exciting phase, bolstered by the decision of the German parliament to actively advance endometriosis research within Germany and neighboring France.

MicroRNA molecules, particularly their role in diagnostics and their potential as therapeutic targets, beckon extensive research, adding to the anticipation surrounding endometriosis’s ongoing scientific progress.

Free Endometriosis Self-Test

Are you grappling with concerns about whether your menstrual and post-period symptoms are within the realm of normalcy, or if an underlying condition might be at play?

Introducing EndoAI – your gateway to the preliminary evaluation of the potential presence of endometriosis. By reflecting upon your symptoms, you can gain valuable insights. Simply click on the link provided and embark on your self-assessment journey!


  1. Pugsley Z, Ballard K. Management of endometriosis in general practice: the pathway to diagnosis. Br J Gen Pract. 2007 Jun;57(539):470-6. PMID: 17550672; PMCID: PMC2078174. Available from: https://pubmed.ncbi.nlm.nih.gov/17550672/
  2. Bendifallah S, Suisse S, Puchar A, Delbos L, Poilblanc M, Descamps P, Golfier F, Jornea L, Bouteiller D, Touboul C, Dabi Y, Daraï E. Salivary MicroRNA Signature for Diagnosis of Endometriosis. J Clin Med. 2022 Jan 26;11(3):612. doi: 10.3390/jcm11030612. PMID: 35160066; PMCID: PMC8836532. Available from: https://pubmed.ncbi.nlm.nih.gov/35160066/
  3.  Endotest Diagnostic- Ein Endometriosetest für die frühe und zuverlässige Diagnose {Internet} {cited 2022 Oct 24} Available from: https://www.eluthia.com/endotest/
  4. Diagnostic {cited 2022 Oct 24} Available from: https://ziwig.com/en/endotest/
  5. AWMF Leitlinie: Diagnostik und Therapie der Endometriose {Internet} {cited 2022 Oct 22}Available from: https://www.awmf.org/leitlinien/detail/ll/015-045.html
  6.  Ghafouri-Fard S, Shoorei H, Taheri M. Role of Non-coding RNAs in the Pathogenesis of Endometriosis. Front Oncol. 2020 Aug 4;10:1370. doi: 10.3389/fonc.2020.01370. PMID: 32850438; PMCID: PMC7417625 Available from: https://pubmed.ncbi.nlm.nih.gov/32850438/
  7. Nasu K, Aoyagi Y, Zhu R, Okamoto M, Yano M, Kai K, Kawano Y. Role of repressed microRNAs in endometriosis. Med Mol Morphol. 2022 Mar;55(1):1-7. doi: 10.1007/s00795-021-00303-8. Epub 2021 Aug 31. PMID: 34463829. Available from: https://pubmed.ncbi.nlm.nih.gov/34463829/
  8. Azam INA, Wahab NA, Mokhtar MH, Shafiee MN, Mokhtar NM. Roles of microRNAs in Regulating Apoptosis in the Pathogenesis of Endometriosis. Life (Basel). 2022 Aug 26;12(9):1321. doi: 10.3390/life12091321. PMID: 36143357; PMCID: PMC9500848. Available from: https://pubmed.ncbi.nlm.nih.gov/36143357/
  9. Endometriose mittels Speicheltest diagnostizieren? {Internet} {cited 2022 Oct 22} Available from: https://www.endometriose-vereinigung.de/aktuell.html
  10. Klatt, Franziska: Ist die Betreuung von Endometriosepatientinnen in der Praxis gesundheitsökonomisch sinnvoll? – Klinische und gesundheitsökonomische Analyse der Endometriosebehandlung in der gynäkologischen Praxis und ihrem ambulant- operativen Bereich 2017. Medizinische Fakultät Charité, Universitätsmedizin Berlin. {Internet} {cited 2022 Oct 22} Available from: https://refubium.fu-berlin.de/handle/fub188/28446
  11. Agarwal SK, Chapron C, Giudice LC, Laufer MR, Leyland N, Missmer SA, Singh SS, Taylor HS. Clinical diagnosis of endometriosis: a call to action. Am J Obstet Gynecol. 2019 Apr;220(4):354.e1-354.e12. doi: 10.1016/j.ajog.2018.12.039. Epub 2019 Jan 6. PMID: 30625295. Available from: https://pubmed.ncbi.nlm.nih.gov/30625295/
  12. Endotest- ein Speicheltest auf Endometriose??? {Internet} {cited 2022 Oct 22} Available from: https://babybauchblog.de/endotest-speicheltest-endometriose/
  13. Findeklee, Sebastian: Endo-Test – Endometriose Diagnostik Speicheltest {Internet} {cited 2022 Oct 24} Available from: https://endo-dialog.de/endo-test-endometriose-diagnostik-speicheltest/
  14. Suchbegriff Replikationsstudie {Internet} {cited 2022 Oct 26} Available from: https://dorsch.hogrefe.com/stichwort/replikationsstudie

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