The Genetics of Endometriosis.

Mapping genetic risk factors for endometriosis continues from early studies on women's health initiated by Nick Martin and Susan Treloar. Their initial recruitment of endometriosis cases and family members received a major boost and became a flagship project within the Cooperative Research Centre (CRC) for the Discovery of Common Human Disease. We extended the study through a formal collaboration with Professor Stephen Kennedy and his group in Oxford. Our first joint scientific meeting was held in Brisbane and was sadly memorable as the day the planes were flown into the Twin Towers in New York. Our initial collaboration expanded into the International Endometriosis Genetics Consortium (IEGC). The IEGC now has 15 groups around the world, and the most recent meta-analysis will be published this year.

Is Endometriosis More Common and More Severe Than It Was 30 Years Ago?

OBJECTIVE: Current estimates of endometriosis prevalence and incidence are highly variable, leading to uncertainty regarding true endometriosis frequency or validity of quantified changes over time. We present a comprehensive review of the prevalence, incidence, and stage of endometriosis worldwide as reported over the past 30 years. DATA SOURCES: We conducted a systematic search of observational studies using the PubMed, Web of Science, EMBASE, and CINAHL databases to identify research papers published in English between January 1989 and June 2019. Search terminologies were limited to titles containing endometriosis and prevalence or incidence, or epidemiology, or frequency, or occurrence, or statistics. METHODS OF STUDY SELECTION: Two independent reviewers screened abstracts for study eligibility, and data from included studies were abstracted. TABULATION, INTEGRATION, AND RESULTS: Overall, 69 studies describing the prevalence and/or incidence of endometriosis met the inclusion criteria. Among these, 26 studies involved general population samples, 17 of which were from regional/national hospitals or insurance claims systems. The other 43 studies were conducted in single clinic or hospital settings. Prevalence estimates for endometriosis widely varied from 0.2% to 71.4% depending on the population sampled. The prevalence reported in general population studies ranged from 0.7% to 8.6%, whereas that reported in single clinic- or hospital-based studies ranged from 0.2% to 71.4%. When defined by indications for diagnosis, endometriosis prevalence ranged from 15.4% to 71.4% among women with chronic pelvic pain, 9.0% to 68.0% among women presenting with infertility, and 3.7% to 43.3% among women undergoing tubal sterilization. A meta-regression was conducted with year as the predictor of prevalence. No trend across time was observed among "general population in country/region" studies (ß = 0.04, p = .12) or among "single hospital or clinic" studies (ß = -0.02, p = .34); however, a decrease over time was observed among general population studies abstracted from health systems or insurance systems (ß = -0.10, p = .005). CONCLUSION: As with all human studies, population sampling and study design matter. Heterogeneity of inclusion and diagnostic criteria and selection bias overwhelmingly account for variability in endometriosis prevalence estimated across the literature. Thus, it is difficult to conclude if the lack of observed change in frequency and distribution of endometriosis over the past 30 years is valid.

An 18th century description of endometriosis : The autopsy of the Countess von Reitzenstein.

Descriptions of endometriosis in 18th century monographs and manuscripts are rare and the recorded macroscopic features of endometriosis seldom support this attribution to the described cases. Recently, we became aware of an anonymous German autopsy report from the 18th century. After transcription, the manuscript was assessed by pathologists with historical expertise. This revealed that the patient died because of a malignant tumor, most probably of a gynecological origin. Furthermore, the described ovarian pathologic findings strongly support the diagnosis endometriotic ovarian cyst. Like Giovanni Battista Morgagni (1668-1772) in his landmark publication De Sedibus et Causis Morborum per Anatomen Indagatis (1761), the author correlated the pathological findings at autopsy with the symptoms of the patient. The identity of the patient could, with high probability, be established as being the Countess of Reitzenstein, the wife of a Prussian general major in the army of Friedrich the Great: Karl Erdmann von Reitzenstein (1722-1789).

Behind the times: revisiting endometriosis and race.

Endometriosis is a common gynecologic condition, affecting approximately 10% of reproductive-aged women. It commonly presents with pelvic pain, painful periods, and infertility and can significantly have an impact on one's quality of life. Early exploration into the pathophysiology of this condition identified race as a risk factor for endometriosis, with the condition predominantly identified in white women. It is still unclear whether there is a biological basis for this conviction or whether it can be explained by methodological and social bias that existed in the literature at that time. Although there is more recent literature exploring the association between endometriosis and race/ethnicity, studies have continued to focus on the prevalence of disease and have not taken into account possible variation in disease presentation among women of different ethnicities. Furthermore, information on diverse populations by race/ethnicity, other than white or black, is quite limited. This paper explores the history of how the association between endometriosis and whiteness was established and whether we still ascribe to a certain stereotype of a typical endometriosis patient today. Furthermore, we discuss the potential implications of such a racial bias on patient care and suggest areas of focus to achieve a personalized and patient focused approach in endometriosis care.

The history of endometriosis.

A dispute has recently emerged whether early descriptions exist of the condition we name endometriosis. A first question is: 'Who identified endometriosis?' To respond, two non-complementary methods have been employed: searching for ancient descriptions of symptoms associated with endometriosis or, alternatively, identifying researchers who described pathological features we associate with the presence of endometriosis in its various forms. We opted for the latter and found no evidence that in older times anyone delineated the macroscopic features of endometriosis; descriptions of menstrual or cyclic pain cannot be taken as proof of knowledge of what caused it. During the mid-part of the 19th century, Rokitansky had a great intuition: endometrial glands and stroma can be present in ovarian and uterine neoplasias. However, using histological parameters of endometrial structure and activity, the first scientist to delineate peritoneal endometriosis under the name 'adenomyoma' was Cullen. On the other hand, Rokitansky was the first to describe a form of adenomyosis (an adenomatous polyp). Early descriptions of ovarian endometrioma as 'haematomas of the ovary' or 'chocolate cysts' date back to the end of the 19th century. The first mention of an 'ovary containing uterine mucosa' was published in 1899 by Russel, but Sampson was the first to demonstrate specific endometrial activities, such as desquamation at the time of menstruation and decidualization in pregnancy; subsequently, he presented a theory on its pathogenesis.

Endometriosis, a modern syndrome.

The identification of endometriosis has been a subject of intense debate over the last decade. There is, however, no doubt that Thomas Cullen was the first to describe endometriosis and adenomyosis as one disease characterized by the presence of endometrium-like tissue outside the uterine cavity. With the introduction of laparoscopy in the early 1960s three different clinical presentations of endometriosis were distinguished: peritoneal, deep adenomyotic and cystic ovarian. As soon as synthetic steroids became available, pioneer clinicians started utilizing these in an attempt to replace radical surgery by a medical treatment. While medical therapy may resort in relief, in most cases the current approach consists of a combination of medical and surgical therapy. While the pathogenesis of endometriosis is still enigmatic and complex, there is increasing evidence that endometriosis is part of a uterine reproductive dysfunction syndrome. For prevention of complications, it is very important that diagnosis is made as early as possible in a woman's life.

Progestins and medical treatment of endometriosis - physiology, history and society.

The transitory effect of hormonal treatment is the alleged main reason to criticize progestins (PGS) and combined pills (OP) in the managment of endometriosis. To the contrary their poor efficacy in the long run is often underlined. As a result, medical treatment is too seldom advised in endometriosis. In this article, we shall focus on the analysis of the reasons of the paucity of the medical interest given to progestins, reasons, which are not of a scientific or objective nature. The ultimate aim of this analysis is to develop arguments in favour of continuous administration of hormones as to obtain not simply an anovulation but a state of prolonged amenorrhea much more efficacious than the simple suppression of ovulation too often advised. And, with an emphasis on the fundamental role of surgery in the treatment of endometriosis, to give the greatest consideration to the specific nature of this disease, which is a chronic disease, justifying the long duration of hormonal administration.

History of adenomyosis.

Although the claim has been made that there are early descriptions of what today we call endometriosis and adenomyosis in theses presented in Europe in the late 17(th) and during the 18(th) centuries, the first description of the condition initially named 'adenomyoma' is that provided in 1860 by the German pathologist Carl von Rokitansky, who found endometrial glands in the myometrium and designated this finding as 'cystosarcoma adenoids uterinum'. Over the following 50 years 'adenomyoma' (and endometriosis) were considered pathologies separate from the so-called 'haemorrhagic ovarian cysts', and it was not until 1921 that this condition was recognized to be of endometriotic origin. The first systematic description of what is today known as adenomyosis was the work of Thomas Stephen Cullen who, at the turn of the 19(th) century, fully researched the 'mucosal invasion' already observed by a number of investigators in several parts of the lower abdominal cavity. Cullen clearly identified the epithelial tissue invasion as being made of 'uterine mucosa' and defined the mechanism through which the mucosa invades the underlying tissue. In 1925, 2 years before Sampson created the term 'endometriosis', Frankl created a name for the mucosal invasion of the myometrium and clearly described its anatomical picture; he called it 'adenomyosis uteri' and explained that 'I have chosen the name of adenomyosis, which does not suggest any inflammatory genesis as do terms like adenometritis, adenomyositis, adenomyometritis, still employed'. The current definition of adenomyosis was finally provided in 1972 by Bird who stated: 'Adenomyosis may be defined as the benign invasion of endometrium into the myometrium, producing a diffusely enlarged uterus which microscopically exhibits ectopic non-neoplastic, endometrial glands and stroma surrounded by the hypertrophic and hyperplastic myometrium'.

How old is endometriosis? Late 17th- and 18th-century European descriptions of the disease.

UNLABELLED: DESIGN OF THE PROJECT: This study is the result of a detailed examination of numerous historical documents as well as several contemporary works describing endometriosis. The historic texts are housed in the National Library of Medicine in Bethesda, Maryland, and had not been unearthed previously. Those primary sources date from 1690 to 1797 and repeatedly describe the organic damage and constitutional symptoms currently identified with endometriosis. The biologic research for this study was done during 1997 and 1998 in the Pathology Department of the Canton-Potsdam Hospital located in Potsdam, New York. CONCLUSION(S): Endometriosis was described in European history approximately 300 years ago.

Endometriosis then and now. Evolution of surgical techniques and treatment.

Surgical techniques and practices for conservative endometriosis surgery began developing in the U.S. They led naturally to contemporary concepts and to the rationale for use of the techniques.

Who identified endometriosis?

Although uterine adenomyoma and endometriosis were described around the turn of the 19th century, the history of the identification of endometriosis has remained controversial and continues to confuse recent literature affecting the management of the disease. Using histologic parameters of endometrial structure and activity, the first scientist to identify the condition, under the name "adenomyoma," was Thomas Cullen. John Sampson was the first to identify the pathogenesis of the condition.