Etiology of Endometriosis

Jaroslav J. Marik, M.D.
The Tyler Medical Clinic, Los Angeles. California

Endometriosis, Aspects and Proceedings of a Symposium
Saint John's Hospital and Health Center, Santa Monica, California
Editor: J.J. Marik

The definition of endometriosis by E. Novak(1) quite well defines this disease: "Endometriosis is a condition in which tissue resembling endometrium more or less perfectly is found aberrantly in various locations."
Endometriosis has been known for more than 100 years. The first description of this abnormality in the literature is by Von Rokitansky(2) who described an adenomyoma. The term was misunderstood and other authors reporting later on endometriosis incorrectly called it adenomyoma. (3,4)

The subject of endometriosis was discussed extensively in approximately 25 major scientific publications between 1860 and the early 1940'x. Endometriosis was found in different sites (Table I). The incidence of endometriosis in individual parts of the genital system is shown in Table 2. This disease was also frequently found in association with other pathology: the associations reported by different authors vary significantly (Table 3).

New knowledge led to the formation of numerous theories, some of them still recognized, some of them forgotten. The theories may be divided into three major groups (Table 4), and each can be divided further into several subgroups. Each particular theory had its place in time and was based on clinical findings and current understanding of the problem.

The Implantation Theory was formulated by J.A. Sampson and also by C.T. Javert." Sampson felt that during the menstrual period, fragments of endometrium escape through the fallopian tube and implant in the peritoneal cavity; and that the ovary may be an intermediary host for secondary, more invasive implants.

Numerous authors experimented with Transplantation of endometrium.9-26 In 1942, J.P. Greenhill (27) described 390 cases of operative-scar endometriosis. Table 5 shows the procedures most often related to operative-scar endometri osis.

Metastatic Theory was born after discovery of endometrial fragments in lymphatic channels was reported. (3,8,26,28-35) Also, the possibility of hematogenous spread was discussed. The theory was based on findings and interpretation of Sampson, (7,36) Javert, (8,37) and R. B. Scott, R.W. Te Linde and L.R. Wharton.(26) The work of J.E. Hobbs and M.R. Lazar (38) in 1941 seemed to confirm the hematogenous spread as a possible etiologic mechanism.

A perfect example of Direct Extension of endometrium is, of course, adenomyosis. This condition is also called "endometriosis interna." Endometriosis in extrauterine locations was described and named "endometriosis externa." (6,8,39-43) In these cases, direct extension offered itself to be a good etiologic possibility.

The Celomic Metaplasia theory was considered by N.S. Ivanoff in 1898 (44) and also discussed by other authors. (1,3,6,7,44-48) This theory was substantiated significantly by embryologist A. Maximow49 and by P. Gruenwald, (50-53) who concluded that "Spontaneous endometriosis in all known locations may originate from local tissue." He published extensive studies to prove his conclusion.

A thorough investigation of an ovary, mainly follicles and corpora lutea, led to a formation of the theory of Ovarian Metaplasia. (54-58) This theory was mentioned for the last time in the mid-40's and since that time seems to have been forgotten.

In the 1930's and 1940's, O. Frankl, (31) B.N. Papanicolaou, (59) and O.A. Brines and J.H. Blain (60) presented a Dedifferentiation Theory. According to

these authors, the myometrial cell can dedifferentiate in endometrial stromal cell or the epithelial cell. Dr. Papanicolaou discussed a heteroplasia from stromal to epithelial cells.

Abnormalities in embryonal development and Embryonic Rests were also seen as possible etiologic factors of endometriosis. Both paremesonephric (6,61-63) and mesonephric (64-66) systems were considered.

Some of the above theories were unable to explain the etiology of certain situations or the suggested explanation seemed to be rather too unlikely to be accepted without doubts. This led to a formation of Combination Theories. The Uteronchul Theory describes an extension of endometrium into the tube, the breaking off of healthy endometrium and transplantation to a new site. Composite Theory formed by C.T. Javert (8,67) claims that the endometriosis always originates in the uterine endometrium but can spread by direct extension, exfoliation, implantation, lymphatic or hematogenous spread, or any combination of the above mechanisms.

An important unresolved question was why endometriosis exists only in a certain percentage of women. Why do all women found to have retroverted uterus, endometrial hyperplasia, leiomyomata, cervical stenosis, and menstrual blood in the peritoneal cavity, not develop endometriosis? Several contributing factors were implicated in the etiology of the disease (Table 6).

It is obvious that no single etiological theory is universally accepted. Only very few generalities can be applied to endometriosis. The disease exists in females of menstrual age. It is much more frequently present in women who have difficulties conceiving, and may or may not cause pain. But even these generalities are not truly general. Sampson (6) and B. Ranney (68) described a total of 19 patients well into postmenopausal age with documented endometriosis in the pelvis. And to increase the problem, M.M. Melicow and M.R. Pachter, (69) Melicow and M. Tannenbaum, (70) and A.J. Oliker and A.E. Harris (71) described several cases of endometriosis in the male.

In conclusion, we may say that endometriosis has been known for more than 100 years. The etiology of the disease is not better understood now than it was in the first half of this century, although significant progress has been made in the therapy of this disease. It might be wise to consider endometriosis a multifaceted disease of multiple etiology, multiple symptomatology, and identical or almost identical morphopathology.

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