This theory suggests that during menstruation, endometrial tissue flows backward through the fallopian tubes into the pelvic cavity instead of leaving the body, leading to the implantation and growth of endometrial cells outside the uterus.
Retrograde Menstruation Theory
Researched by:
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Karen Pendergrass
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Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
Fact-checked by:
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Kimberly Eyer
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Kimberly Eyer
Kimberly Eyer, a Registered Nurse with 30 years of nursing experience across diverse settings, including Home Health, ICU, Operating Room Nursing, and Research. Her roles have encompassed Operating Room Nurse, RN First Assistant, and Acting Director of a Same Day Surgery Center. Her specialty areas include Adult Cardiac Surgery, Congenital Cardiac Surgery, Vascular Surgery, and Neurosurgery.
Retrograde menstruation theory holds that during menstruation, some endometrial tissue reverses through the fallopian tubes into the pelvic cavity. It implants on pelvic organs, thickens, breaks down, and bleeds cyclically, causing inflammation, pain, and scar tissue, characteristic of endometriosis.
Research feed -
Karen Pendergrass
Researched by:
-
Karen Pendergrass
ID
Karen Pendergrass
Fact-checked by:
-
Kimberly Eyer
ID
Kimberly Eyer
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
Overview 
Research Feed Overview
Retrograde menstruation theory suggests that during menstruation, some endometrial tissue flows backward through the fallopian tubes into the pelvic cavity instead of exiting the body. This tissue implants on pelvic organs such as the ovaries, fallopian tubes, and peritoneum. Here, it behaves as usual—thickening, breaking down, and bleeding with each cycle. This can cause inflammation, pain, and scar tissue, typical of endometriosis.
What are the key limitations to the retrograde menstruation theory?
Key Limitations
While the retrograde menstruation theory is a cornerstone in understanding endometriosis, it is not without its limitations:
| Limitations | Observations |
| Prevalence vs. Incidence Dilemma | It is observed that a significant majority of women experience some degree of retrograde menstruation. However, only a subset of these women develop endometriosis. This discrepancy raises questions about the factors that predispose certain individuals to the disease, suggesting that retrograde menstruation alone is insufficient to cause endometriosis. This implies the involvement of other contributory factors, such as genetic predisposition, immune system dysfunctions, and environmental influences, which may affect the body’s ability to clear ectopic endometrial cells. |
| Occurrence Beyond Reproductive Years and Pelvic Area | The theory does not account for endometriosis in individuals who do not undergo menstrual cycles, such as prepubertal girls, postmenopausal women, and men. Additionally, the presence of endometriotic lesions in areas far removed from the pelvic cavity, such as the lungs and nasal passages, challenges the explanation that retrograde menstruation alone is responsible for the dissemination of endometrial tissue. |
| Extrapelvic Manifestations | A significant majority of women experience some degree of retrograde menstruation. However, only a subset of these women develop endometriosis. This discrepancy raises questions about the factors that predispose certain individuals to the disease, suggesting that retrograde menstruation alone is insufficient to cause endometriosis. This implies the involvement of other contributory factors, such as genetic predisposition, immune system dysfunctions, and environmental influences, which may affect the body’s ability to clear ectopic endometrial cells. |
What conditions are associated with retrograde menstruation theory?
Associated Conditions
| Condition | Association with Retrograde Menstruation |
|---|---|
| Endometriosis | Endometriosis related to retrograde menstruation can lead to infertility via inflammation, altered anatomy, and impaired function. |
| Pelvic Inflammatory Disease (PID) | Inflammation exacerbated by retrograde menstruation might increase susceptibility or severity. |
| Adenomyosis | Some theories suggest retrograde menstruation might contribute to its development. |
| Infertility | Endometriosis-related to retrograde menstruation can lead to infertility via inflammation, altered anatomy, and impaired function. |
| Chronic Pelvic Pain | Associated with conditions linked to retrograde menstruation, primarily endometriosis. |
| Endometriomas | Endometriosis can form ovarian cysts known as “chocolate cysts.” |
Conclusion
The retrograde menstruation theory significantly advances our understanding of endometrial cell spread to ectopic sites, potentially causing endometriosis. Yet, it does not fully explain the disease’s origins. Endometriosis is a multifactorial condition. Its development likely stems from a mix of genetic, microbiological, immunological, and environmental influences, along with retrograde menstruation.
The theory’s limitations highlight the need for continuous research into endometriosis’s complete pathophysiology. Such work aims to clarify the condition’s complex mechanisms and lead to more effective, targeted treatments. For clinicians and researchers, maintaining an open and critical perspective on the multifaceted nature of endometriosis is essential for advancing care.
Research Feed
Endometriosis and adenomyosis: shared pathophysiology
This study investigates the genetic and epigenetic mechanisms of endometriosis and adenomyosis, highlighting KRAS mutations and abnormal estrogen and progesterone receptor expressions as key factors. It underscores a shared pathophysiology between the conditions, providing insights into treatment targets and the molecular basis of disease progression.
What was studied?
The study focused on the pathophysiology, genetic variants, and epigenetic abnormalities underlying endometriosis and adenomyosis. It emphasized the mechanisms through which these conditions develop, the somatic mutations and epigenetic changes in endometrial and adenomyotic tissues, and the clinical implications of these findings. The primary genetic alterations studied include mutations in the KRAS gene and epigenetic modifications affecting estrogen and progesterone receptor expressions. The role of estrogen in promoting these conditions and the concept of progesterone resistance were also critically evaluated.
Who was studied?
While the published study does not explicitly mention specific patient groups or demographics, it implicitly refers to women diagnosed with endometriosis and adenomyosis. These conditions affect women of reproductive age, with endometriosis symptoms often starting in the adolescent years and extending to menopause and adenomyosis typically being diagnosed later, often in women in their 40s and 50s. The study involves an analysis of endometrial and adenomyotic tissues from these patients, examining genetic mutations and epigenetic changes within these tissues.
What were the most important findings?
Shared Pathophysiology: Both endometriosis and adenomyosis originate from endometrial cells, with KRAS mutations prevalent in both conditions’ epithelial cells. This points to a common genetic predisposition underpinning both diseases.
Epigenetic Abnormalities: Both conditions are characterized by epigenetic defects that lead to abnormal estrogen production and action, particularly through the overexpression of estrogen receptor-β and underexpression of progesterone receptors, resulting in progesterone resistance.
Clinical Implications of Genetic Mutations: The presence of specific genetic mutations, especially in KRAS, not only elucidates the pathogenic pathways of these conditions but also suggests that these mutations provide a survival advantage to ectopic endometrial tissues.
Estrogen’s Role: The study highlights estrogen’s critical role in the establishment and progression of endometriosis and adenomyosis, with implications for treatment strategies aimed at blocking estrogen synthesis.
What are the greatest implications of this study?
Therapeutic Targets: Identifying KRAS mutations and epigenetic markers offers new targets for therapeutic intervention, possibly allowing for more personalized treatment approaches for patients with endometriosis and adenomyosis.
Understanding of Disease Mechanism: Elucidating the genetic and epigenetic mechanisms underlying these conditions helps in understanding their pathogenesis, potentially leading to early detection and preventive strategies.
Progesterone Resistance: The insight into the molecular basis of progesterone resistance opens avenues for addressing this challenge in treating endometriosis and adenomyosis, potentially improving the efficacy of current therapies.
Research Directions: These findings pave the way for future research into the molecular and cellular biology of gynecological disorders, encouraging the development of innovative treatments that can address the root causes of these conditions rather than merely managing symptoms.
Endometriosis
Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (HBOT), Low Nickel Diet, and Metronidazole therapy.
Endometriosis
Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (HBOT), Low Nickel Diet, and Metronidazole therapy.
Infertility
Infertility is the inability to conceive after 12 months of regular, unprotected sex. It affects both men and women and can be due to various physical, hormonal, or genetic factors. Treatments include medication, surgery, assisted reproductive technologies, and lifestyle changes.
Chronic Pelvic Pain (CPP)
Chronic Pelvic Pain (CPP) is persistent pain in the pelvic region lasting six months or longer, often multifactorial, impacting physical and emotional well-being, and associated with various medical conditions.
Endometriomas
An endometrioma is a type of ovarian cyst filled with old blood, arising from endometrial tissue outside the uterus, typically causing pain and potentially impacting fertility.