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Dan C. Martin, MD
UT Medical Group, Inc.

University of Tennessee Health Science Center (UTHSC)

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Daniel Clyde Martin, M.D.
UT Medical Group, Inc.
Infertility and Gynecology
Reproductive Surgery
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Glenn Ann Martin, Ph.D.
Clinical Psychologist

Progression and Regression of Endometriosis

Adapted from "Recognition of Endometriosis" in
Laparoscopic Appearance of Endometriosis, Lecture Supplement
Martin DC (ed), Resurge Press, Memphis, (c)1991

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The human data on changes in endometriosis over time are predominantly from non-randomized studies. Second look laparoscopy is usually in patients with specific problems. An example is Jansen's paper on appearance. (Jansen & Russell, 1986) There was a 100% progression at second look, but only 6 of 77 patients had a second look operation. These data results in a bias toward progressive, persistent, and/or recurrent disease. It is possible that 100% of patients have transient endometriosis at some time in their life. (Evers, 1994; Evers, Dunselman, Land, & Bouckaert, 1991) If 1% to 8% have a surgical diagnosis, (Simpson, Elias, Malinak, & Buttram, 1980) then 92% to 99% of women with endometriosis may regress spontaneously and need limited or no treatment. However, once a diagnosis is made at surgery, the literature becomes more applicable to a patient.

Sampson noted a change from a red raspberry appearance to a blueberry appearance as lesions aged. (Sampson, 1924) Karnaky stated that it required 4 to 10 years for water blister lesions to progress to scarred blue-domed cysts. (Karnaky, 1969) Jansen observed a progressive change to pigmented lesions within 6 to 24 months in all of six of his patients having second look laparoscopy. (Jansen & Russell, 1986) Redwine quantitated these changes and demonstrated a change in the observed appearance from clear to red to scarred black lesions  over 7 to 10 years. (Redwine, 1987) This change was also noted by Koninckx in documenting an increase from 23% to 63% in the occurrence of scarred black lesions over a 20-year age change. (Koninckx, Meuleman, Demeyere, Lesaffre, & Cornillie, 1991) In addition, Koninckx' study demonstrated a decreased occurrence of red and polypoid lesions and an increased occurrence of deep endometriosis over the same time span. Furthermore, Moen (Moen, 1991) documented an increased diagnosis over time in asymptomatic patients with voluntary infertility following tubal ligation. She noted 7.5% at < 5 years, 19.5% at 5 to 9 years and 26.9% in = 10 years. She concluded that endometriosis may be secondary to infertility rather than a cause of infertility.

Progression was more recently suggested by Dmowski. (Dmowski, Lesniewicz, Rana, Pepping, & Noursalehi, 1997) In this study, longer delays in diagnosis from the onset of symptoms were associated with increased stages in patients with pelvic pain. This was not a prominent findings in patients with infertility. This suggests that there may be a specific group in whom progression is more likely. It also suggests a certain degree of complacency with which society and the medical profession deal with pelvic pain when compared to infertility. 

A modification of these changes was seen by Thomas (Thomas & Cooke, 1987) with a 47% progression without therapy and no progression while on suppressive therapy. Similar response was noted by Telimaa. (Telimaa, Puolakka, Ronnberg, & Kauppila, 1987a) Mahmood (Mahmood & Templeton, 1990) confirmed Thomas' and Telimaa's studies and showed progression of endometriosis in 64% of women who had no therapy, 33% of danazol treated patients, 22% of diathermy treated patients and 20% treated with surgery and danazol with 9 to 18 months of followup. There was a small but definite spontaneous regression rate (27%) and regression increased with both medical and surgical treatment. He concluded that endometriosis should be treated even if asymptomatic. The Carter (Carter & Trotter, 1995) algorithm draws on these conclusions in projecting that as many as 50% of patients can avoid laparoscopy if GnRH suppression is used in patients with significant dysmenorrhea. 

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The degree of surgery and approach to surgery appear important. Mahmood's (Mahmood & Templeton, 1990) progression rates for diathermy and combined diathermy and danazol are greater than Redwine's (Redwine, 1991) recurrence rate (6.7%) at two years following laparoscopic excision or Wheeler's (Wheeler & Malinak, 1987) recurrence rate of 6.6% at one to two years following laparotomy. It is noted that Redwine had a 19.4% recurrence rate at five years and Wheeler a 19.5% recurrence rate. However, Redwine's recurrent did not include all patients undergoing surgery. His reoperation rate was 55% with 35% having no evidence of endometriosis. Laser vaporization and/or excision appear to improve the prognosis. (Chang, Chou, Soong, Chang, Lee, & Lai, 1997; Martin, 1985; Martin, 1986)

Hoshiai (Hoshiai, Ishikawa, Sawatari, Noda, & Fukaya, 1993) noted not only progression and regression but also documented that this could be an intermittent phenomenon in specific patients. One of his patients who had initial spontaneous regression had subsequent progression at third-look laparoscopy. Of interest, he noted that danazol had a greater effect on adhesion scores and postulated this may be related to fibrinolytic enhancing activity. On the other hand, Buserelin (GnRH analog) had a greater effect on the lesion appearance and on suppressing estrogen levels. Wiegerinck(Wiegerinck, Van Dop, & Brosens, 1993) suggested that since peritoneal lesions show a changing pattern of activity and appearance, there is an ongoing need for reclassification with aging. This suggestion reinforces concerns about the inadequacy of staging for the study of endometriosis. (Hornstein, Gleason, Orav, Haas, Friedman, Rein, et al., 1993; Palmisano, Adamson, & Lamb, 1993) 

D'Hooghe (D'Hooghe, Bambra, Isahakia, & Koninckx, 1992; D'Hooghe, Bambra, Raeymaekers, & Koninckx, 1996) demonstrated similar changes in baboons. They demonstrated that 91% of baboons had additional lesions at secondlook laparoscopy whereas 52% had regression at the sites of original lesions. In the control, none of which had endometriosis at first look, 70% had developed endometriosis by secondlook. All endometriosis was stage I. They also documented changes in specific changes in lesion colors. He noted white vesicles becoming white plaques, red vesicles becoming black spots, organ zones becoming white plaques and black spots becoming white plaques.

Davis (Davis, Thillet, & Lindemann, 1993) found red lesions in 86% of adolescents with an average age of 16.6 as opposed to 20% of patients undergoing LAVH with an average of 37.4. This was statistically significant (p = 0.04). Of interest, red lesions were significantly associated with bowel symptoms such as diarrhea and vomiting. 

This age related change in appearance may be due to a uniform progression in individual patients, the result of more than one type of progression of lesions or the result of some other factor. However, as a general rule, the appearance is different at varying ages. Perhaps more important is that there was significant overlap and age does not appear to be the only factor in appearance. Furthermore, the observation that some lesions regress does not negate the observation that some patients progress to extensive forms of disease with multiple organ involvement. (Vercellini, Vendola, Presti, & Bolis, 1993) Patient management anticipates progression as well as regression. 

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bulletCarter, J. E., & Trotter, J. P. (1995). GnRH analogs in the treatment of endometriosis: clinical and economic considerations. Female Patient, 20(12), 13-20.
bulletChang, F.-H., Chou, H.-H., Soong, Y.-K., Chang, M.-Y., Lee, C.-L., & Lai, Y.-M. (1997). Efficacy of isotopic 13CO2 laser laparoscopic evaporization in the treatment of infertile patients with minimal and mild endometriosis: a life table cumulative pregnancy rates study. J Am Assoc Gynecol Laparoscopists, 4, 219-223.
bulletD'Hooghe, T. M., Bambra, C. S., Isahakia, M., & Koninckx, P. R. (1992). Evolution of spontaneous endometriosis in the baboon (Papio anubus, Papio cynocephalus) over a 12-month period. Fertil Steril, 58, 409-412.
bulletD'Hooghe, T. M., Bambra, C. S., Raeymaekers, B., & Koninckx, P. (1996). Serial laparoscopies over 30 months show that endometriosis in captive baboons (Papio anubis, Papio cynocephalus) is a progressive disease. Fertil Steril, 65, 645-9.
bulletDavis, G. D., Thillet, E., & Lindemann, J. (1993). Clinical characteristics of adolescent endometriosis. J Adolesc Health, 14, 362-368.
bulletDmowski, W. P., Lesniewicz, R., Rana, N., Pepping, P., & Noursalehi, M. (1997). Changing trends in the diagnosis of endometriosis: a comparative study of women with pelvic endometriosis presenting with chronic pelvic pain or infertility. Fertil Steril, 67, 238-43.
bulletEvers, J. L. H. (1994). Endometriosis does not exist; all women have endometriosis. Human Reproduction, 9(12), 2206-2209.
bulletEvers, J. L. H., Dunselman, G. A. H., Land, J. A., & Bouckaert, P. X. J. M. (1991). Is there a solution for recurrent endometriosis? Brit J Clin Pract (Suppl 72), 72(3), 45-50.
bulletHornstein, M. D., Gleason, R. E., Orav, J., Haas, S. T., Friedman, A. J., Rein, M. S., Hill, J. A., & Barbieri, R. L. (1993). The reproducibility of the revised American Fertility Society classification of endometriosis. Fertil Steril, 59(5), 1015-1021.
bulletHoshiai, H., Ishikawa, M., Sawatari, Y., Noda, K., & Fukaya, T. (1993). Laparoscopic evaluation of the onset and progression of endometriosis. Am J Obstet Gynecol, 169, 714-719.
bulletJansen, R. P. S., & Russell, P. (1986). Nonpigmented endometriosis: clinical, laparoscopic, and pathologic definition. Am J Obstet Gynecol, 155, 1154-1159.
bulletKarnaky, K. J. (1969). Theories and known observations about hormonal treatment of endometriosis-in-situ, and endometriosis at the enzyme level. Arizona Medicine, January, 37-41.
bulletKoninckx, P. R., Meuleman, C., Demeyere, S., Lesaffre, E., & Cornillie, F. J. (1991). Suggestive evidence that pelvic endometriosis is a progressive disease, whereas deeply infiltrating endometriosis is associated with pelvic pain. Fertil Steril, 55, 759-765.
bulletMahmood, T. A., & Templeton, A. (1990). The impact of treatment on the natural history of endometriosis. Hum Reprod, 5, 965-970.
bulletMartin, D. C. (1985). CO2 laser laparoscopy for the treatment of endometriosis associated with infertility. J Reprod Med, 409-412.
bulletMartin, D. C. (1986). CO2 laser laparoscopy for endometriosis associated with infertility. J Reprod Med, 31, 1089-1094.
bulletMoen, M. H. (1991). Is a long period without childbirth a risk factor for developing endometriosis. Hum Reprod, 6(10), 1404-1407.
bulletPalmisano, G. P., Adamson, G. D., & Lamb, E. J. (1993). Can staging systems for endometriosis based on anatomic location and lesion type predict pregnancy rates? Int J Fertil, 38(4), 241-249.
bulletRedwine, D. B. (1987). Age-related evolution in color appearance of endometriosis. Fertil Steril, 48, 1062-1063.
bulletRedwine, D. B. (1991). Conservative laparoscopic excision of endometriosis by sharp dissection: life table analysis of reoperation and persistent or recurrent disease. Fertil Steril, 56, 628-634.
bulletSampson, J. A. (1924). Benign and malignant endometrial implants in the peritoneal cavity, and their relation to certain ovarian tumors. Surg Gynecol Obstet, 38, 287-311.
bulletSimpson, J. L., Elias, S., Malinak, L. R., & Buttram, V. C. J. (1980). Heritable aspects of endometriosis. I. Genetic studies. Am J Obstet Gynecol, 137, 327.
bulletTelimaa, S., Puolakka, J., Ronnberg, L., & Kauppila, A. (1987a). Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis. Gynecol Endocrinol, 1, 13-23.
bulletThomas, E. J., & Cooke, I. D. (1987). Impact of gestrinone on the course of asymptomatic endometriosis. Brit Med J, 294, 272-274.
bulletVercellini, P., Vendola, N., Presti, M., & Bolis, G. (1993). Multifocal endometriosis: a case report. J Reprod Med, 38, 815-819.
bulletWheeler, J. M., & Malinak, L. R. (1987). Recurrent endometriosis. Contr Gynecol Obstet, 16, 13-21.
bulletWiegerinck, M. A. H. M., Van Dop, P. A., & Brosens, I. A. (1993). The staging of peritoneal endometriosis by the type of active lesion in addition to the revised American Fertility Society classification. Fertil Steril, 60(3), 461-464.

Adapted from "Recognition of Endometriosis" in
Laparoscopic Appearance of Endometriosis, Lecture Supplement
Martin DC (ed), Resurge Press, Memphis, (c)1991

The color illustrations that accompanied this paper are in the Color Atlas.

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