© 2012. Last updated 2018.
‘Sampson’s Theory’ dates back to the early 1920s and is based on the extensive works of John Sampson, MD, an Albany gynecologist who became fascinated with endometriosis after encountering it in many of his patients. Despite the passage of nearly a century, ‘retrograde menstruation’ remains the most persistent – yet flawed – theory of disease origin, leading to continued confusion about, poor health literacy on, and failed treatments for endometriosis.
Initially, Dr. Sampson assumed endometriosis resulted from “seedlings” from the ovaries. He later proposed that the disease actually results from backwards (“reflux” or “retrograde”) menstruation, ‘wherein endometrium is showered monthly onto the peritoneum and ovaries.’ Throughout his life’s work, he maintained that “[f]ragments of endometrial tissue, at times, are disseminated into the venous circulation during menstruation, from the mucosa lining the uterine cavity and also from ectopic endometrial foci; [that] metastatic or embolic endometriosis arises from the implantation of these emboli in nearby veins; [and that] endometrial tissue set free by menstruation, therefore, is sometimes not only alive – but may actually continue to grow if transferred to situations favorable to its existence.” Essentially: he considered endometriosis simply to be normal endometrial cells located in abnormal places.
This flawed concept has persisted for nearly 100 years, despite being debunked by much of the literature over the past 3 decades. If Sampson’s theory was correct, endometriosis would not be possible until a girl’s first period occurred – yet there has long been abundant evidence to disprove this. It also fails to account for the presence of disease in males and others who have never menstruated. Moreover, endometriosis is not simply ‘bits of rogue endometrium implanted as a result of backflow menstruation’ as many press articles, patient foundations and even “academic leaders” incorrectly describe. Normal endometrium is profoundly, histologically different from the functional glands and stroma that comprise endometriosis. The tissue does somewhat resemble – but is not identical to – ‘normal’ endometrium. Studies have revealed that the eutopic and ectopic endometrial stromal cells in indivduals with endometriosis exhibit fundamental differences in invasive, adhesive and proliferative behaviors from those who do not have the disease; thus it simply cannot be ‘normal endometrium showered back onto the pelvis’.
Further, when we review a patient’s videotapes of multiple previous surgeries, we rarely see disease in new areas. For example, if bladder disease is present at Surgery A, it may persist through subsequent operations if it was not completely removed. On the other hand, if bladder disease is not present at Surgery A, it does not just suddenly appear at surgeries B, C, D, etc. According to Sampson’s Theory, it would be reasonable to expect to see new disease in new areas all the time, growing like daisies in a field. Yet, in our surgical experiences in over 8,000 procedures across more than 5,000 patients, this simply does not happen.
It has also been our personal experience across literally thousands of cases that if all endometriosis is completely removed at surgery (true excision), an individual has a very low chance of recurrence. This evidence, then, would favor a metaplastic or congenital theory, because it suggests endometriosis is a finite disease. That is to say, a person has as much endometriosis as they have – whether a little or a lot – and that if it is completely excised, the disease does not just always, hopelessly “grow back” wildly like weeds in a garden over and over again. Also, because most of the menstrual flow involves the vagina and vulva, a logical extension of Sampson’s Theory would predict a high incidence of endometriosis in those locations – yet vaginal and vulvar endometriosis are actually uncommon [Albee et. al.]. There is now ongoing research revisiting the role of reflux menses; again investigating the potential link to endometriosis, but now in the neonate [see also: Perinatal Origin of Endometriosis Revisited]. It is too preliminary to draw any definitive conclusions on this data as yet.
Nevertheless, we have also long known that retrograde menstruation is a very common phenomenon among many women – yet not all women develop endometriosis. There are many various flaws with Sampson’s ideology, but the continued propagation of his theory has led to countless cases of poorly treated disease, the promotion of pharmaceutical treatment as a front line option, clinical (vs. confirmed) diagnosis, and ongoing ‘excuses’ for poor surgical treatment and other failed therapies.
Additional theories of origin exist apart from Dr. Sampson’s, each singularly failing to account for all forms of endometriosis in all those affected. See also David Redwine, MD’s excellent article on this topic: Is endometriosis an autotransplant? Researchers do agree that endometriosis is polygenic and multifactorial, though the exact pathogenic mechanism(s) are still unclear. However, without question: there are many factors contributing to disease pathophysiology and pathogenesis outside of Sampson’s ‘backflow’ notion, and although his work in endometriosis was important, it should not be the guiding concept by which today’s treatments are rendered.
Additional reading of interest:
Was Sampson wrong?
Unus pro omnibus, omnes pro uno: A novel, evidence-based, unifying theory for the pathogenesis of endometriosis
Invisible Microscopic Endometriosis: How Wrong Is the Sampson Hypothesis of Retrograde Menstruation to Explain the Pathogenesis of Endometriosis?
Potential role of endometrial stem/progenitor cells in the pathogenesis of early-onset endometriosis
Neonatal uterine bleeding as antecedent of pelvic endometriosis
Is neonatal uterine bleeding involved in the pathogenesis of endometriosis as a source of stem cells?
Stem cell theory for the pathogenesis of endometriosis
Interplay between Misplaced Müllerian-Derived Stem Cells and Peritoneal Immune Dysregulation in the Pathogenesis of Endometriosis
The role of the Hoxa10/HOXA10 gene in the etiology of endometriosis and its related infertility
Embryologic origin of endometriosis: analysis of 101 human female fetuses
Genetic, epigenetic and stem cell alterations in endometriosis: new insights and potential therapeutic perspectives
Stem cells: are they the answer to the puzzling etiology of endometriosis?
Endometriosis and genetics: what responsibility for the genes?
Epithelial to mesenchymal transition-like and mesenchymal to epithelial transition-like processes might be involved in the pathogenesis of pelvic endometriosis
Mutations in the PTEN tumor gene and risk of endometriosis: a case-control study
Eutopic and ectopic stromal cells from patients with endometriosis exhibit differential invasive, adhesive, and proliferative behavior
NME1 suppression promotes growth, adhesion and implantation of endometrial stromal cells via Akt and MAPK/Erk1/2 signal pathways in the endometriotic milieu
RHOC: a key gene for endometriosis