Intrinsic Potential Factors in Retrograde Menstruation

Retrograde Bleeding and Endometriosis

Key Points

Importance:

•  The cervix, fallopian tubes, and myometrium are key anatomical factors that may significantly influence the risk of developing endometriosis.

Highlights:

• Anatomical variations in the cervix and myometrium are significantly associated with endometriosis risk, reinforcing the need for further research into their role in retrograde menstruation.

What's done here:

• This systematic literature review analyses and evaluates literature concerning the evidence supporting the pathogenic role of uterine anatomical factors in endometriosis development.
• These orifices control the expulsion of menstrual material through narrower structures, including the cervical canal (its diameter, the stenosis of internal or external orifices, and cervical tissue stiffness) and the intramural parts of the fallopian tubes. It also considers anatomical  myometrial abnormalities that may affect the volume of fluid expelled and the force needed for active flow.
• This review concentrates on individuals without clear obstacles to menstrual flow, excluding reports of congenital (Müllerian anomalies) or acquired outflow obstructions. It does not assess the types of refluxing endometrial cells, such as normal versus metabolically or genetically modified cells, or those derived from different uterine layers or bone marrow.

Basic Outlines

• The mechanistic model of endometriosis pathogenesis that links anatomical factors favoring retrograde menstruation, is deemed reasonable and biologically possible.
• There is a strong association between obstructive Müllerian anomalies and endometriosis, suggesting a causal link between refluxed blood and the development of endometriosis.
• Common biological events may not be the same for everyone, and while harmful exposure is linked to adenomyosis and endometriosis, the complex nature of retrograde menstruation indicates it could play an important role in these conditions.
•  When studying the link between etrograde menstruation and endometriosis at least five key aspects should be evaluated: (i) the volume of fluid refluxed, (ii) the mix of blood and endometrial cells, (iii) how often it occurs, (iv) consistency of the event over time, and (v) the influence of medications.
• To accept or reject the role of retrograde menstruation in endometriosis, researchers need to study whether most patients with endometriosis have retrograde menstruation and whether it occurs before the disease develops.
• Current studies provide inconsistent information at one point in time, but the relationship generally meets causation criteria. The lack of increased endometriosis cases with recent reproductive changes is expected, as these changes likely occurred before reliable diagnoses were possible.
• While the myometrium plays a significant role in the development of endometriosis, several important questions still need to be addressed, inclding the proper definition of adenomyosis, apppropriate prospective cohort studies involving healthy adolescents with regular cycles, and no ultrasound-detected adenomyosis to determine if adenomyosis development predicts future pelvic endometriosis.
•  Understanding the nature and course of retrograde menstruation and its determinants will clarify the pathogenesis of both endometriosis and adenomyosis, help define their epidemiological patterns, and enable the development of effective preventive and therapeutic strategies.

Lay Summary

Almost 100 years ago, Sampson suggested that the cervix, the intramural part of the fallopian tubes, and the uterine muscle might influence the amount of menstrual blood that flows backward into the pelvic cavity, potentially leading to endometriosis. The size of the cervical canal, stiffness of cervical tissue, shape of the fallopian tube's intramural portion, and abnormalities in the myometrium could all play a role in the development of endometriosis.

A study published in the Reproductive Biomedicie Online by a team lead by Vercellini et al., reviewed the data from the past 4 decades to determine if cervical, tubal, and myometrial anatomical variants, which may facilitate retrograde menstruation as proposed by Sampson in 1924, are linked to the risk of endometriosis. The authors suggested that if a connection is established, it would reinforce the role of retrograde menstruation in the disease and suggest that medical interventions could be developed to reduce cumulative uteropelvic menstrual exposure over time.

Some studies show that the size of the cervical canal, blockages, and stiffness in cervical tissue could contribute to endometriosis. The strongest evidence points to abnormalities in the uterine muscle as the most consistent factor linked to endometriosis. Early signs of adenomyosis, which may come before endometriosis and contribute to its development by increasing the backward flow of menstrual blood.

Future studies should explore whether a higher number of ovulatory cycles after puberty, along with these anatomical changes, increase the amount of backward menstrual flow and raise the risk of developing endometriosis.

Research Source: https://pubmed.ncbi.nlm.nih.gov/39137508/