The earliest known medical description of what we now call endometriosis dates to 1860, when the German pathologist Carl von Rokitansky identified endometrial glands growing in the wrong place inside the uterus and gave the finding a name. But understanding the disease as a distinct condition where tissue similar to the uterine lining grows outside the uterus took decades longer, shaped by competing theories, social biases, and diagnostic technology that lagged behind the biology. The story of endometriosis is less a single eureka moment and more a slow, uneven accumulation of insight spanning nearly two centuries.
Rokitansky’s 1860 Discovery
Carl von Rokitansky, working in Vienna, was the first to document what he saw under the microscope: endometrial glands embedded within the muscular wall of the uterus. He called this finding “cystosarcoma adenoids uterinum,” and the condition was initially grouped under the name “adenomyoma.”1PubMed. History of adenomyosis At the time, the distinction between what we now call adenomyosis (endometrial tissue growing into the uterine wall) and endometriosis (tissue growing outside the uterus entirely) did not exist. Rokitansky was describing something genuinely new, but the conceptual framework to separate these two conditions would not arrive for another half-century.
What made Rokitansky’s contribution possible was advances in microscopy and tissue fixation techniques. Before pathologists could slice, stain, and magnify uterine tissue, the only descriptions of pelvic disease came from what surgeons could see with the naked eye during operations or autopsies. Rokitansky’s era brought a shift toward examining tissue at the cellular level, and that shift turned vague surgical impressions into specific diagnoses. Endometriosis, as a concept, was born in the pathology lab, not the operating room.
The Early 1900s and Expanding the Map
By the turn of the twentieth century, clinicians began recognizing that misplaced endometrial tissue could appear far beyond the uterine wall. In 1912, Hart became the first to document endometriosis in the lungs, a finding that would later be understood as a rare but real manifestation called thoracic endometriosis.2PubMed Central. Catamenial pneumothorax caused by thoracic endometriosis – Section: Discussion A year later, in 1913, the Canadian surgeon Thomas Cullen presented cases of what he called adenomyoma of the rectovaginal septum, describing endometrial tissue growing between the vagina and the rectum.3JAMA. Adenomyoma of the Rectovaginal Septum
These early-twentieth-century reports mattered because they forced a rethinking of what the disease could do. If endometrial-like tissue could show up in the lungs and the rectovaginal septum, it clearly was not just a quirk of the uterine wall. The condition was systemic in a way nobody had anticipated when Rokitansky peered through his microscope in 1860. Each new anatomical site raised the same question: how does this tissue get there?
John Sampson and the Retrograde Menstruation Theory
The person who most shaped our modern understanding of endometriosis was the American gynecologist John Sampson, whose work spanned the 1910s through 1940. Sampson’s research journey began in 1918, when he described how endometrial material could escape the uterine cavity and enter the uterine veins, raising the possibility that endometriosis could spread through the bloodstream.4PubMed. Pathogenesis of endometriosis: Look no further than John Sampson He initially described this as “metastatic” or “embolic” endometriosis, borrowing language from cancer research to explain how tissue could travel from one organ to another.
In 1927, Sampson published two landmark papers. The first laid out evidence that endometrial tissue could spread via the fallopian tubes or venous circulation into the pelvic cavity.5JCI Insight. Endometriosis and ovulatory menstruation: beyond the Sampson principle The second, prompted by what one account describes as “academic banter” from rival gynecologists, shifted focus to a specific version of that idea: retrograde menstruation. The concept is straightforward. During a period, some menstrual blood flows backward through the fallopian tubes instead of out through the cervix. That backflow carries endometrial cells into the pelvis, where they implant and grow. To test this, Sampson deliberately timed his hysterectomies during patients’ menstrual periods so he could observe the process directly.4PubMed. Pathogenesis of endometriosis: Look no further than John Sampson
Sampson’s retrograde menstruation theory became the dominant explanation for endometriosis and remains the most widely cited cause today. Recent genetic studies have strengthened it considerably: researchers have mapped identical DNA mutations in the epithelial cells of the uterine lining and in ectopic endometriotic implants across hundreds of patients, directly demonstrating the connection Sampson proposed nearly a century ago.5JCI Insight. Endometriosis and ovulatory menstruation: beyond the Sampson principle
Why One Theory Was Never Enough
For all its explanatory power, Sampson’s theory has a well-known blind spot. Retrograde menstruation through the fallopian tubes cannot easily account for endometriosis found in locations far from the pelvis, like the lungs, the brain, or surgical scars. Sampson himself acknowledged this limitation. His final publication, in 1940, focused on retrograde tubal menstruation but “clearly fails to explain many types of endometriosis, particularly that located in extra-pelvic sites.”4PubMed. Pathogenesis of endometriosis: Look no further than John Sampson
This gap gave rise to competing theories that have accumulated over the decades. Several pathways have been proposed, including coelomic metaplasia (where cells outside the uterus transform into endometrial-type cells on their own), immune system dysfunction that fails to clear misplaced tissue, hormonal imbalances, involvement of stem cells, and epigenetic changes that alter gene activity without changing DNA itself.6PubMed Central. The Main Theories on the Pathogenesis of Endometriosis None of these theories alone explains every case. The honest state of the science is that we know retrograde menstruation plays a major role in most pelvic endometriosis, but the full picture remains incomplete.
One striking piece of evidence that challenges a purely menstruation-based explanation appeared in 2010, when researchers documented endometriosis in a female fetus that had died at 25 weeks of gestation due to placental complications. Since a fetus has never menstruated, retrograde flow cannot be the explanation. The finding suggests that endometrial tissue can be displaced outside the uterine cavity during organ formation in the womb.4PubMed. Pathogenesis of endometriosis: Look no further than John Sampson Cases like this are rare, but they matter: they prove the condition has at least some developmental origins that predate menstruation entirely.
The Long Diagnostic Delay and Its Social Roots
One of the most frustrating aspects of endometriosis history is how long it takes for affected individuals to receive a diagnosis, even today. That delay has deep historical roots. For much of the twentieth century, endometriosis was framed as a disease of white, middle-class women who delayed childbearing for career reasons. Clinicians reported that women who had children later in life seemed more prone to the condition, and the label “career woman’s disease” stuck for decades.7Reproductive BioMedicine Online. The missed disease? Endometriosis as an example of ‘undone science’ – Section: Classificatory ambiguity and the production of non-knowledge The myth was doubly harmful: it suggested women brought the disease on themselves through lifestyle choices, and it rendered Black and minority ethnic women with the same condition largely invisible to the medical establishment.
Scholars who have studied endometriosis through a sociological lens argue that its association with historically specific ideas about menstruation and women’s pain created a legacy of invisibility. The expectation that period pain is normal, combined with the stigma around discussing menstrual symptoms, meant that many patients were dismissed or told their pain was psychological. That legacy shaped not just clinical care but also which research questions got asked and which got ignored, a dynamic some researchers describe as “undone science.”8PubMed Central. The missed disease? Endometriosis as an example of ‘undone science’
The practical consequence is that the average time from symptom onset to diagnosis has historically been measured in years, not months. While awareness campaigns and improved imaging have shortened that gap somewhat, the social and cultural forces that created it have not fully dissipated.
Classification and Staging
As surgical visualization improved through the twentieth century, particularly with the advent of laparoscopy, clinicians needed a way to describe how severe a patient’s endometriosis was and compare cases across studies and treatment centers. Several classification systems were proposed over the decades, but the one that became standard was the revised American Fertility Society (later renamed the American Society for Reproductive Medicine) classification.9PubMed Central. Classification of endometriosis This system assigns a score based on the location, depth, and extent of endometriotic implants and adhesions seen during surgery, grouping patients into stages from minimal to severe.
Research on the system’s reliability found that visual documentation from surgery could be used to determine the stage of disease, lending it some reproducibility.10PubMed. The revised American Fertility Society classification of endometriosis: reproducibility of scoring That said, staging has always been an imperfect tool. A patient with a low stage score can have debilitating pain, while someone with extensive visible disease may have few symptoms. The classification captures the anatomy well but tracks poorly with patients’ lived experience, a disconnect that continues to frustrate clinicians and patients alike.
The Hormonal Treatment Era
For most of the twentieth century, the primary treatments for endometriosis were surgical removal of lesions and, in severe cases, hysterectomy. The development of hormonal therapies opened a fundamentally different approach. The underlying logic is simple: endometriotic tissue responds to the same hormonal signals as the uterine lining, so suppressing those signals can slow the disease’s progression and reduce symptoms.
The main hormonal strategies that emerged include GnRH agonists and antagonists, which act on the brain’s signaling to the ovaries and effectively create a temporary, reversible menopause-like state. Progestins such as dienogest are often used for longer-term management, working through multiple mechanisms to suppress the growth of endometriotic tissue and reduce inflammation. Combined oral contraceptives also play a role by inhibiting ovarian function and thinning the endometrium.11PubMed Central. Hormonal treatments for endometriosis: The endocrine background None of these approaches cure endometriosis. They manage symptoms, and when treatment stops, the disease often returns. But for many patients, hormonal therapy has transformed daily quality of life in ways that surgery alone could not.
Endometriosis in Other Primates
One of the more illuminating discoveries in the history of endometriosis research is that the disease occurs spontaneously in nonhuman primates, and only in nonhuman primates among non-human animals. Monkeys and apes that menstruate can develop endometriosis on their own, without any experimental induction.12PubMed. Nonhuman primate models for translational research in endometriosis This finding reinforced the link between menstruation and endometriosis: species that do not menstruate do not get the disease spontaneously.
Researchers have used this to build animal models for studying the condition. Baboons with spontaneous or surgically induced endometriosis have become a key model for investigating how the disease develops, how it progresses over time, and how new treatments perform before human trials. Studies tracking cynomolgus monkeys by monthly laparoscopy found that endometriosis developed in all monitored animals, but the speed and severity varied widely among individuals, likely influenced by differences in how much retrograde menstruation occurred and by genetic factors.13PubMed. The Natural History of Spontaneously Occurred Endometriosis in Cynomolgus Monkeys by Monthly Follow-Up Laparoscopy for Two Years The individual variation in primates mirrors what clinicians see in humans: some people develop severe disease rapidly, while others with similar exposure to retrograde flow never develop significant lesions.
An Evolutionary Perspective
In recent years, some researchers have begun framing endometriosis not just as a disease to be treated but as a consequence of evolutionary trade-offs. The argument goes like this: in primates, the uterine lining evolved to undergo spontaneous decidualization, a process where the endometrium thickens and prepares for pregnancy on its own hormonal schedule rather than waiting for an embryo to trigger the change. This adaptation allowed better quality control over which embryos implanted, improving reproductive outcomes. But the flip side of spontaneous decidualization is menstruation: when no embryo arrives, the prepared lining sheds. And menstruation, as Sampson showed, creates the conditions for retrograde flow and potential endometriosis.14PubMed. Is endometriosis due to evolutionary maladaptation?
This perspective gains additional weight from a modern demographic reality. For most of human evolutionary history, women spent the majority of their reproductive years either pregnant or breastfeeding, experiencing relatively few menstrual cycles in a lifetime. In industrialized societies, the average person with a uterus now experiences hundreds of periods over their lifetime, a situation without precedent in our species’ history. Endometriosis, along with related conditions like adenomyosis and dysmenorrhea, can be understood as vulnerabilities that come with this mismatch between our evolved biology and our modern reproductive patterns.15PubMed. The significance and evolution of menstruation The evolutionary framing does not change how the disease is treated today, but it reframes the question of “why does this happen?” in a way that moves the conversation beyond individual pathology. Endometriosis is not a malfunction so much as a predictable consequence of a reproductive system being used in a way evolution never anticipated.
The Persistent “Career Woman” Myth and Racial Bias
It is worth dwelling on the “career woman’s disease” label because its influence extended well beyond casual prejudice. For decades, the assumption that endometriosis preferentially affected affluent white women who postponed motherhood actively shaped clinical practice. Doctors were less likely to consider the diagnosis in younger patients, in women who already had children, and especially in Black and minority ethnic women. The related silencing of the experiences of these groups “added to the misperception of endometriosis as a white career woman’s illness.”7Reproductive BioMedicine Online. The missed disease? Endometriosis as an example of ‘undone science’ – Section: Classificatory ambiguity and the production of non-knowledge
The demographic myth became self-reinforcing. If clinicians did not look for endometriosis in certain populations, they did not find it, and the absence of diagnoses was taken as evidence that the disease did not occur in those populations. This feedback loop only began to crack as patient advocacy organizations and more diverse research cohorts revealed that endometriosis occurs across all racial and socioeconomic groups. Awareness that the historical picture was distorted by clinical bias rather than biology has been one of the most consequential shifts in how the medical community understands the disease.
Fetal Endometriosis and What It Means for Theories of Origin
The 2010 report of endometriosis in a 25-week female fetus deserves its own space because it poses a genuinely hard question for every mainstream theory. A fetus has no menstrual cycle, no ovarian hormonal surges, and no immune system in the adult sense. Yet the misplaced endometrial tissue found in this case had the same histological and immunohistochemical features as endometriosis seen in adults.4PubMed. Pathogenesis of endometriosis: Look no further than John Sampson The researchers concluded that the most likely explanation was dislocation of primitive endometrial tissue outside the uterine cavity during organogenesis, which is a fancy way of saying that some endometrial cells ended up in the wrong spot while the organs were still forming.
If even a small fraction of endometriosis cases begin before birth, then the disease is not exclusively a consequence of menstruation, immune failure, or hormonal environment. It may be, in some cases, a developmental error that lies dormant until puberty activates it. This does not overturn Sampson’s theory for the majority of cases, but it complicates any account that tries to identify a single cause. The history of endometriosis research keeps returning to this theme: every time a unifying explanation gains acceptance, an outlier case reminds us the disease is more varied than the theory.