Clinical Review

Endometriosis: Expert answers to 7 crucial questions on diagnosis

OBG Manag. 2015 April;27(4):38-40,42-46

	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.
	Steven R. Goldstein, MD, is Professor of Obstetrics and Gynecology at New York University School of Medicine; and Director of Gynecologic Ultrasound and Co-Director of Bone Densitometry at New York University Medical Center in New York City. He serves on the OBG Management Board of Editors.
	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.
	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. American College of Obstetricians and Gynecologists. Practice Bulletin #114: Management of endometriosis. Obstet Gynecol. 2010;116(1):223–236.
2. Sanfilippo JS, Wakim NG, Schikler KN, Yussman MA. Endometriosis in association with uterine anomaly. Am J Obstet Gynecol. 1986;154(1):39–43.
3. Taylor HS, Bagot C, Kardana A. HOX gene expression is altered in the endometrium of women with endometriosis. Hum Reprod. 1999;14(5):1328–1331.
4. Berkley KJ, Stratton P. Mechanisms: lessons from translational studies of endometriosis. In: Giamberardino MA, ed. Visceral Pain: Clinical, Pathophysiological and Therapeutic Aspects. Oxford, UK: Oxford University Press; 2009:39–50.
5. Giudice LC. Clinical practice: endometriosis. N Engl J Med. 2010;362(25):2389–2398.
6. Ballard K, Lowton K, Wright J. What’s the delay: a qualitative study of women’s experiences of reaching a diagnosis of endometriosis. Fertil Steril. 2006;86(5):1296–1301.
7. May KE, Conduit-Hulbert SA, Villar J, Kirtley S, Kennedy SH, Becker CM. Peripheral biomarkers of endometriosis: a systematic review. Hum Reprod Update. 2010;16(6):651–674.
8. May KE, Villar J, Kirtley S, Kennedy SH, Becker CM. Endometrial alterations in endometriosis: a systematic review of putative biomarkers. Hum Reprod Update. 2011;17(5):637–653.
9. Tamaresis JS, Irwin JC, Goldfien GA, et al. Molecular classification of endometriosis and disease stage using high-dimensional genomic data. Endocrinology. 2014;155(12):4986–4999.
10. Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod. 2002;17(10):2715–2724.
11. De Graaff AA, D’Hooghe TM, Dunselman GA, et al. The significant effect of endometriosis on physical, mental and social wellbeing: results from an international cross-sectional survey. Hum Reprod. 2013;28(10):2677–2685.
12. Lafay Pillet MC, Huchon C, Santulli P, Borghese B, Chapron C, Fauconnier A. A clinical score can predict associated deep infiltrating endometriosis before surgery for an endometrioma. Hum Reprod. 2014;29(8):1666–1676.
13. Healey M, Cheng C, Kaur H. To excise or ablate endometriosis? A prospective randomized double-blinded trial after 5-year follow-up. J Minim Invasive Gynecol. 2014;21(6):999–1004.
14. Anaf V, El Nakadi I, De Moor V, Chapron C, Pistofidis G, Noel JC. Increased nerve density in deep infiltrating endometriotic nodules. Gynecol Obstet Invest. 2011;71(2):112–117.
15. Stratton P, Berkley KJ. Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Hum Reprod Update. 2011;17(3):327–346.
16. Karp BI, Sinaii N, Nieman LK, Silberstein SD, Stratton P. Migraine in women with chronic pelvic pain with and without endometriosis. Fertil Steril. 2011;95(3):895–899.
17. Berkley KJ. A life of pelvic pain. Physiol Behav. 2005;86(3):272–280.
18. Fauconnier A, Chapron C. Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications. Hum Reprod Update. 2005;11(6):595–606.
19. Vercellini P, Fedele L, Aimi G, Pietropaolo G, Consonni D, Crosignani PG. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients. Hum Reprod. 2007;22(1):266–271.
20. Ling FW. Randomized controlled trial of depot leuprolide in patients with chronic pelvic pain and clinically suspected endometriosis. Pelvic Pain Study Group. Obstet Gynecol. 1999;93(1):51–58.
21. Muzii L, Di Tucci C, Di Feliciantonio M, Marchetti C, Perniola G, Panici PB. The effect of surgery for endometrioma on ovarian reserve evaluated by antral follicle count: a systematic review and meta-analysis. Hum Reprod. 2014;29(10):2190–2198.
22. Muzii L, Luciano AA, Zupi E, Panici PB. Effect of surgery for endometrioma on ovarian function: a different point of view. J Minim Invasive Gynecol. 2014;21(4):531–533.
23. 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.

3. What aspects of the patient history are key?
Dr. Stratton recommends that clinicians begin their evaluation of the patient with pain by asking her to describe that pain—how long she has had it, when it occurs, and which areas are affected.

“Most women with endometriosis-associated pain have chronic pelvic pain,” Dr. Stratton continues.⁵ “Up to 90% of those have dysmenorrhea or cyclic pain with menses.”¹⁰ In addition, women with endometriosis “commonly report having pain with any bleeding or spotting. About 30% of women diagnosed with endometriosis initially present to their gynecologist with dyspareunia.”¹¹

“Episodic pain with menses may become more constant, lasting for many days of the month,” says Dr. Stratton. “Women with dyschezia or dysuria may have endometriosis lesions associated with the bowel or bladder, respectively.¹² When women with these symptoms do not have lesions on bowel or bladder, these pain symptoms may occur because of higher peritoneal hormone and inflammatory factor levels or because adjacent organs share the neural networks.”

Dr. Giudice views the history similarly.

“I believe listening to the patient is essential in evaluating the possibility of her having endometriosis. This involves asking her to describe where her pain is, grading it on a scale of 1 to 10, identifying when in her cycle it occurs, and learning what makes it better or worse,” she says.

“It also is important to assess the quality of the pain,” Dr. Giudice says. “Does it radiate, does it limit her daily activities, does it interfere with her relationships, intercourse, work, school? Is it associated with bowel movements, urination, other pain syndromes?”

“Having a pain questionnaire is a great help so that patients have a chance to reflect on these and other questions that help to frame the pain associated with endometriosis when they come for consultation,” she adds.

By determining if pain is associated with menstruation or spotting, the clinician is better informed about the value of menstrual suppression, says Dr. Stratton. “Determining what makes the pain better or worse can help define triggers which, if treated, can decrease the likelihood of episodes of pain.”

“A detailed history of any medical or surgical treatments and their outcome is helpful in guiding future treatment,” she adds. “While hormonal therapy has been a mainstay of treatment, in some women, some hormonal treatments may worsen pain or have unacceptable side effects like worsening depression or anxiety. In addition, some pain—especially that associated with deep lesions—may be relieved by surgical treatment^13,14; pain that worsened after surgery may suggest neural damage.”

“As there is an engagement of the central nervous system, endometriosis is considered a central sensitivity syndrome in which women may also have other sites of pain,” Dr. Stratton says. “Thus, obtaining a history about current symptoms or prior diagnosis of irritable bowel syndrome, interstitial cystitis/painful bladder, migraines, fibromyalgia, or chronic fatigue syndrome is beneficial.^10,15–17 Facilitating treatment for these comorbidities is a key principle in helping women with endometriosis-associated pain, as any condition that triggers or perpetuates pain warrants treatment.”

4. What should the physical exam entail?
“An abdominal exam and a pelvic exam are essential in evaluating pain in a woman when endometriosis is suspected,” says Dr. Giudice. “Sometimes the latter is challenging in young teens and can be deferred.” Overall, however, “the pelvic exam can give insight into pain triggers, adnexal masses (possible endometriomas) and mobility of pelvic organs. A rectovaginal exam is important in evaluating deep infiltrating disease and to gauge the pelvic pain landscape overall. In addition, palpating the pelvic floor musculature is important to distinguish pelvic floor muscle spasm from endometriosis pain.”

“The challenge for clinicians is to think beyond the endometrial implants, taking into account multiple factors that influence pain perception,” says Dr. Stratton. During the examination, the clinician should begin by mapping the regions of pain in the abdomen and back, “distinguishing musculoskeletal pain from deep pain. Determining whether pains are focused or diffuse is also important.”

Dr. Stratton recommends that the routine pelvic exam be modified because a standard bimanual exam “confuses pain signals from the pelvic floor, abdominal wall, bladder, and other viscera. For this reason, a pain-oriented assessment is mandatory.”

Begin with a single digital examination to map tender areas, Dr. Stratton advises. Then consider the size, shape, and mobility of reproductive and pelvic organs. “A bimanual exam will help identify adnexal masses like endometriomas,” she says.

Endometriomas usually are not associated with pain, she adds, but “they are associated with deep infiltrating lesions. Nodularity along the uterosacral ligaments, limited reproductive organ mobility, and thickening of the rectovaginal septum also suggest deep infiltrating lesions. Importantly, deep infiltrating lesions are the lesion type most associated with pain.”^18,19

References

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Endometriosis: Expert answers to 7 crucial questions on diagnosis

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