Clinical Review

Endometriosis and pain: Expert answers to 6 questions targeting your management options

OBG Manag. 2015 May;27(5):23-26,28-31

	Robert L. Barbieri, MD, is Editor in Chief of OBG Management; Chair of Obstetrics and Gynecology at Brigham and Women’s Hospital in Boston, Massachusetts; and Kate Macy Ladd Professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School in Boston.
	Tommaso Falcone, MD, is Professor and Chair of Obstetrics and Gynecology at the Cleveland Clinic in Cleveland, Ohio.
	Linda C. Giudice, MD, PhD, is the Robert B. Jaffe, MD, Endowed Professor in the Reproductive Sciences and Chair of Obstetrics, Gynecology, and Reproductive Sciences at the University of California, San Francisco.
	John R. Lue, MD, MPH, is Associate Professor and Chief of the Section of General Obstetrics and Gynecology and Medical Director of Women’s Ambulatory Services at the Medical College of Georgia and Georgia Regents University in Augusta, Georgia.
	Ceana Nezhat, MD, is Director of the Nezhat Medical Center in Atlanta, Georgia, and Medical Director of Training and Education at Northside Hospital in Atlanta.
	Pamela Stratton, MD, is Chief of the Gynecology Consult Service, Program in Reproductive and Adult Endocrinology, at the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Maryland.

References

1. Nezhat C, Nezhat F, Nezhat C. Endometriosis: ancient disease, ancient treatments. Fertil Steril. 2012;98(6S):S1–S62.
2. Giudice LC. Clinical practice. Endometriosis. N Engl J Med. 2010;362(25):2389–2398.
3. Pavone ME, Bulun SE. Aromatase inhibitors for the treatment of endometriosis: a review. Fertil Steril. 2012;98(6):1370–1379.
4. Nothnick WB. The emerging use of aromatase inhibitors for endometriosis treatment. Reprod Biol Endocrinol. 2011;9:87.
5. Chwalisz K, Garg R, Brenner RM, Schubert G, Elger W. Selective progesterone receptor modulators (SPRMs): a novel therapeutic concept in endometriosis. Ann N Y Acad Sci. 2002;955:373–393, 396–406.
6. Duffy JM, Arambage K, Correa FJ, et al. Laparoscopic surgery for endometriosis. Cochrane Database Syst Rev. 2014;(4):CD011031.
7. Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–279.
8. Stegmann BJ, Sinaii N, Liu S, et al. Using location, color, size, and depth to characterize and identify endometriosis lesions in a cohort of 133 women. Fertil Steril. 2008;89(6):1632–1636.
9. Hsu AL, Sinaii N, Segars J, Nieman LK, Stratton P. Relating pelvic pain location to surgical findings of endometriosis. Obstet Gynecol. 2011;118(2 pt 1):223–230.
10. Stratton P, Berkley KJ. Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Hum Reprod Update. 2011;17(3):327–346.
11. Healey M, Ang WC, Cheng C. Surgical treatment of endometriosis: a prospective randomized double-blinded trial comparing excision and ablation. Fertil Steril. 2010;94(7):2536–2540.
12. Healey M, Chang C, Kaur H. To excise or ablate endometriosis? A prospective randomized double-blinded trial after 5-year follow-up. JMIG. 2014;21(6):999–1004.
13. Falcone T, Wilson JR. Surgical management of endometriosis: excision or ablation. JMIG. 2014;21(6):969.
14. Hart RJ, Hickey M, Maouris P, Buckett W. Excisional surgery versus ablative surgery for ovarian endometriomata. Cochrane Database Syst Rev. 2008;(2):CD004992.
15. Nezhat C, Nezhat F, Nezhat CH, Seidman D. Classification of endometriosis: improving the classification of endometriotic ovarian cysts. Hum Reprod 1994;9(12):2212–2216.
16. Roman H, Auber M, Mokdad C, et al. Ovarian endometrioma ablation using plasma energy versus cystectomy: a step toward better preservation of the ovarian parenchyma in women wishing to conceive. Fertil Steril. 2011;96(6):1396–1400.
17. Shakiba K, Bena JF, McGill KM, Minger J, Falcone T. Surgical treatment of endometriosis: a 7-year follow-up on the requirement for further surgery. Obstet Gynecol. 2008;111(6):1285–1292.
18. McAllister SL, McGinty KA, Resuehr D, Berkley KJ. Endometriosis-induced vaginal hyperalgesia in the rat: role of the ectopic growths and their innervation. Pain. 2009;147(1–3):255–264.
19. Parker JD, Leondires M, Sinaii N, Premkumar A, Nieman LK, Stratton P. Persistence of dysmenorrhea and nonmenstrual pain after optimal endometriosis surgery may indicate adenomyosis. Fertil Steril. 2006;86(3):711–715.
20. Abou-Setta AM, Al-Inany HG, Farquar CM. Levonorgestrel-releasing intrauterine device for symptomatic endometriosis following surgery. Cochrane Database Syst Rev. 2006;(1):CD005072.
21. Seracchioli R, Mabrouk M, Manuzzi L, et al. Postoperative use of oral contraceptive pills for prevention of anatomic relapse or symptom recurrence following surgery. Hum Reprod. 2009;24(11):2729–2735.
22. Hornstein MD, Hemmings R, Yuzpe AA, Heinrichs WL. Use of nafarelin versus placebo after reductive laparoscopic surgery for endometriosis. Fertil Steril. 1997;68(5):860–864.
23. Practice Committee of the American Society for Reproductive Medicine. Treatment of pain associated with endometriosis: a committee opinion. Fertil Steril. 2014;101(4):927–935.
24. Dunselman GA, Vermeulen N, Becker C, et al. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014;29(3):400–412.

“Women with uterosacral nodularity, fixed pelvic organs, or severe pain with endometriomas may have deep infiltrating lesions. These lesions, in particular, are not captured well with the current staging system,” says Dr. Stratton. Because they appear to be innervated, “the greatest benefit to the patient is achieved by completely excising these lesions.” Preoperative imaging may help confirm the existence, location, and extent of these deep lesions and help the surgeon plan her approach “based on clinical and imaging findings.”

“Severity of pain or duration of surgical effect does not correlate with stage or extent of disease,” Dr. Stratton says.⁹ “In fact, patients with the least amount of disease noted at surgery experience pain sooner, suggesting that the central nervous system may have been remodeled prior to surgery or that the pain is in part due to some other cause.¹⁰ This observation underscores the principle that, while endometriosis may initiate pain, the pain experience is determined by engagement of the central nervous system.”

For more information on the ASRM revised classification of endometriosis, go to http://www.fertstert.org/article/S0015-0282(97)81391-X/pdf.

4. Which is preferable—excision or ablation?
In a prospective, randomized, double-blind study, Healey and colleagues compared pain levels following laparoscopic treatment of endometriosis with either excision or ablation. Preoperatively, women in the study completed a questionnaire rating various types of pain using visual analogue scales. They then were randomly assigned to treatment of endometriosis via excision or ablation. Postoperatively, they again completed a questionnaire about pain levels at 3, 6, 9, and 12 months. Investigators found no significant difference in pain scores at 12 months.¹¹

Five-year follow-up of the same population yielded slightly different findings, however. Although there was a reduction in all pain scores at 5 years in both the excision and ablation groups, a significantly greater reduction in dyspareunia was observed in the excision group at 5 years.¹²

In an editorial accompanying the 5-year follow-up data, Dr. Falcone and a coauthor called excision versus ablation of ovarian, bowel, and peritoneal endometriosis one of the “great debates” in the surgical management of endometriosis.¹³

“When there is deep involvement of adjacent organs, there is general consensus that excision is best for optimal surgical outcome,” they write. “However, for disease involving the peritoneum alone, there are proponents for either option.”¹³

“This is a very controversial issue,” says Dr. Falcone, “and the debate can sometimes be somewhat inflammatory…. It is hard to understand how a comparative trial could even be accomplished between excision and ablation,” he adds. “In my experience, deep disease typically occurs on the pelvic sidewall over the ureter or in the cul de sac on the bowel or infiltrating the bladder peritoneum. Therefore, ablation would increase the risk of damaging any of these structures. With superficial disease away from critical structures, it should be fine to ablate. Everywhere else and with deep disease you need to excise or leave disease behind.”

“Endometriomas are a special situation,” Dr. Falcone says. “Excision of the cyst has been shown in randomized controlled trials (RCTs) to be associated with less risk of recurrence.¹⁴ Therefore, it should be the treatment of choice. However, in patients interested in future fertility, we must take into consideration the potential damage to ovarian reserve associated with excision.”

Endometriosis of the ovaries has unique manifestations. “My approach to ovarian cysts depends on their classification,” says Dr. Nezhat.¹⁵ In general, primary endometriomas (Type 1) are small, superficial cysts that contain dark “chocolate” fluid. They tend to be firmly adherent to the ovarian tissue and difficult to remove surgically.

Secondary endometriomas (Type 2) are follicular or luteal cysts that have been involved or invaded by cortical endometriotic implants or by primary endometrioma. Secondary endometriomas are further classified by the relationship between cortical endometriosis and the cyst wall. Type 2A endometriomas are usually large, with a capsule that is easily separated from ovarian tissue. Type 2B endometriomas have some features of functional cysts but show deep involvement with surface endometriosis. Type 2C endometriomas are similar, showing extensive surface endometrial implants but with deep penetration of the endometriosis into the cyst wall.¹⁵

“For Type 1 endometriomas, I biopsy the cyst to ensure the lesion is benign, then vaporize the endometrioma,” Dr. Nezhat says. “In cases of type 2A and 2B endometriomas, the cyst capsule is easily enucleated and removed. Type 2C endometriomas are biopsied as well and then I proceed with vaporizing the fibrotic area with a low-power energy source, such as neutral argon plasma, avoiding excessive coagulation and thermal injury.” Recent literature supports the idea of evaluation and biopsy of fibrotic endometriomas to confirm benign conditions, followed by ablation without compromising ovarian function.¹⁶

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Endometriosis and pain: Expert answers to 6 questions targeting your management options

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