Clinical Review

Endometriosis: Expert answers to 7 crucial questions on diagnosis

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The notorious delay in diagnosis associated with this condition stems in part from its ability to mimic other diseases. The expert answers provided here are designed to help guide your assessment of the patient and achieve a timelier diagnosis.


  • The “why” of endometriosis
  • Is imaging useful?
  • When is diagnostic laparoscopy clearly indicated?
  • Environmental factors, estrogen, and endometriosis



CASE Is her chronic pelvic pain caused by endometriosis?
M.L. is a 32-year-old nulliparous woman who is referred to your office by her primary care provider for chronic pelvic pain. She reports severe dysmenorrhea as her main symptom, but she also mentions dyspareunia. She says these symptoms have been present for several years but have increased in intensity gradually. She asks what you consider to be the most likely diagnosis.

What potential diagnoses do you mention to her? And how do you identify the cause of her pain?

Although endometriosis—the presence of endometrial tissue outside the uterus—affects at least 5 million women of reproductive age in the United States alone, it can be a challenging diagnosis for several reasons.

“Endometriosis is a great masquerader,” says Linda Giudice, MD, PhD. “It presents with a variety of pain patterns, intensities, and triggers. It can also involve symptoms that overlap those of other disorders, including disorders of the gastrointestinal and urinary tracts.”

Although endometriosis falls within the differential diagnosis of chronic pelvic pain, “it is usually not high on the list in the primary care setting (adult and adolescent),” Dr. Giudice adds. She 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, an author of the most recent practice bulletin on endometriosis from the American College of Obstetricians and Gynecologists,1 sees the situation similarly.

“The main challenge in the diagnosis of endometriosis is that its presentation mimics other causes of chronic pelvic pain,” he says. “Pelvic pain due to endometriosis is usually chronic (lasting ≥6 months). It is associated with dysmenorrhea in 50% to 90% of cases, as well as with dyspareunia, deep pelvic pain, and lower abdominal pain with or without back and loin pain. The pain can occur unpredictably and intermittently throughout the menstrual cycle or it can be continuous. In addition, it can be dull, throbbing, or sharp and may be exacerbated by physical activity.2,3 Up to 20% of women with endometriosis have concurrent pain conditions.”4 Dr. Lue is associate professor, 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.

Among other diseases of the female pelvis that have relatively similar presentation, Dr. Lue adds, are pathologies of the:

  • uterus (adenomyosis, fibroids)
  • fallopian tube (hydrosalpinx)
  • ovaries (ovarian cysts)
  • bladder (interstitial cystitis)
  • bowel (irritable bowel syndrome)
  • musculoskeletal system (piriformis syndrome).

Before pelvic pain is attributed to endometriosis, he says, the provider should rule out bowel, bladder, musculoskeletal, and psychiatric causes.

This article focuses on 7 questions, the answers of which are critical to narrowing in on the diagnosis of endometriosis, including essential factors to consider in the patient history, imaging and other diagnostic tools, and considerations in surgical exploration. In the second and third installments of this in-depth series on endometriosis, pain and infertility will be the respective subjects of ­investigation.

Several theories explain the “why” of endometriosis

A dominant theory is that peritoneal endometrial implants arise from retrograde menstruation, during which endometrial tissue passes through the fallopian tubes into the pelvis, says John R. Lue, MD, MPH. Dr. Lue 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.

“Additional theories include immune dysfunction that interferes with clearing of endometrial lesions in the pelvis, as well as genetic alterations that lead to growth dysregulation,” he says.1 “These theories all have merit, and it is likely that the pathogenesis of endometriosis is multifactorial.”

Another strong theory involves the homeobox (HOX) genes, “which mediate embryonic development,” says Dr. Lue.2,3 “These genes are translated into transcription factors that regulate downstream genes necessary for growth and differentiation. It has been demonstrated that HOX genes play an analogous role in endometrial development during the adult menstrual cycle.4 HOX gene expression regulates the growth and development of the human endometrium.5 The expression of HOX genes A10 and A11 varies in response to sex steroids during the menstrual cycle, with dramatic upregulation in the mid-secretory phase,” says Dr. Lue. Recent studies suggest that these genes “play a major role” in endometriosis.6

“Since ovarian endometriomas are clonal and lesions usually have genetic mutations, such somatic mutations with subsequent growth dysregulation may also be etiologic factors,” says Dr. Lue.1,7,8 “Disease at distant sites may be caused by lymphatic or hematogenous spread or metaplastic transformation.”

1. Giudice LC, Swierz LM, Burney RO. Edometriosis. In: Jameson JL, DeGroot LJ, eds. Endocrinology. 6th ed. New York, NY: Elsevier; 2010:2356–2370.
2. Krumlauf R. Hox genes in vertebrate development. Cell. 1992;78(2):191–201.
3. McGinnis W, Krumlauf R. Homeobox genes and axial patterning. Cell. 1992;68(2):283–302.
4. Taylor H, Igarashi P, Olive D, Arici A. Sex steroids mediate HOXA11 expression in the human peri-implantation endometrium. J Clin Endocrinol Metab. 1999;84(3):1129–1135.
5. Taylor H, Vanden Heuvel GB, Igarashi P. A conserved HOX axis in the mouse and human female reproductive system: late establishment and persistent adult expression of the HOXA cluster genes. Biol Reprod. 1997;57(6):1338–1345.
6. 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.
7. Practice Committee of the American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis. Fertil Steril. 2008;90(5 suppl):S260–S269.
8. Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–279.


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