Endometriosis
The leading cause of pelvic pain in women
by Catherine Allaire, MD
Vol.17, No.02, February 2009
case presentation

A 25-year-old nulligravid woman has a long-standing history of dysmenorrhea, that she’s managed up to now with NSAIDs. In the last year her dysmenorrhea has worsened, causing her to miss work on a few occasions. There’s also a new onset of deep dyspareunia. She has diarrhea at the time of her menses but no rectal bleeding or pain. Last menstrual period was 2 weeks ago and she’s in no pain today. She’s in a stable relationship but doesn’t want a pregnancy for at least another 3 years. She uses condoms or withdrawal for contraception.

Physical exam

  • appears healthy
  • normal BMI and vitals
  • abdominal exam: benign, no masses or tenderness
  • speculum: normal cervix, no abnormal discharge, no vaginal lesions
  • pelvic: localized tenderness and palpable nodularity (< 1 cm) in the posterior vaginal fornix, palpation reproduces dyspareunia
  • uterus small, retroverted, mobile and non-tender, no adnexal masses or tenderness

Investigations

  • cervical swabs for STIs, Pap smear if due
  • pelvic ultrasound: normal, no adnexal cysts, no cul-de-sac masses

Diagnosis and treatment

The patient is referred to a gynecologist who performs a laparoscopy and discovers mild (Stage 2) endometriosis with deep implants over the uterosacral ligaments. The disease is fully excised and the patient has a levonorgestrel-releasing intrauterine device placed at the time of surgery. Her symptoms are completely relieved.

Making the case

Endometriosis is defined by the presence of endometrial stroma and glands outside the endometrial cavity. This abnormal implantation typically occurs on the pelvic peritoneal surfaces and the pelvic organs, but can sometimes involve distant sites in the body. The ectopic endometrium responds to estrogen stimulation, causing inflammation and scarring. This in turn can lead
to pain and infertility, though not all patients with documented endometriosis are symptomatic.

It’s difficult to estimate the true prevalence of endometriosis as we lack reliable non-invasive tests to diagnose the condition. Studies looking at women undergoing tubal ligation found prevalence rates ranging from 2%-20%. Among infertile women, rates range from 20%-50%. Studies have shown high incidence of the disease (up to 47%) in adolescents with severe pelvic pain. The prevalence of endometriosis appears to have increased over the past few decades. This could simply be due to more accurate diagnosis with increased recognition of subtle or atypical presentations at laparoscopy. But it may also be a consequence of delayed childbearing in combination with contraception methods that don’t suppress ovulation.

The jury’s still out on the exact cause of endometriosis. The most popular current theory holds that retrograde menstruation, in combination with a genetic predisposition or immunological failure, allows implantation and growth of ectopic endometrial cells. A genetic element is supported by studies showing a 6.9% prevalence of endometriosis in first-degree relatives of diagnosed patients, vs 1% in patients’ in-laws.

It was commonly thought that endometriosis is a relentlessly progressive disease, but there’s now good evidence that the lesions can remain stable or recede spontaneously.

Factors that increase risk of endometriosis

  • reproductive age
  • incidence increases with age until menopause
  • most common in Asians and least common in Africans
  • maternal family history
  • greater volume of menstrual flow (short cycles, long heavy flows, early menarche)
  • obstruction of outflow tract (Mullerian anomalies)

Protective factors

  • use of oral contraception
  • smoking
  • low body fat
  • factors that reduce estrogen levels, such as exercise-induced amenorrhea

Symptoms

The most common symptoms are cyclical pelvic pain and infertility. The most frequent pain symptom is dysmenorrhea, which is often unresponsive to anti-inflammatory and oral contraceptive medication. Patients may also suffer from non-menstrual ovarian pain or generalized pelvic pain, which is usually more marked in the luteal phase. Deep dyspareunia is also a common complaint associated with posterior cul-de-sac and uterosacral ligament implants. Some patients may also experience micturition and defecation pain from implants on the bladder or colon. Diarrhea during the menses is a very common complaint of endometriosis patients.

Disorders of menstruation are common though non-specific to this group of patients, and can include oligo-ovulation (infrequent periods), metrorrhagia (unsynchronized bleeding) and menorrhagia (heavy menstrual bleeding). Bleeding from another body orifice, if it’s cyclical and coincident with menses, is a rare symptom but one that should raise suspicion for endometriosis.

Numerous theories have been put forward to explain endometriosis-associated infertility but none seems to hold the complete answer. The abnormalities found include disorders of ovulation, luteal function, sperm function, ovum capture, tubal motility, gamete interaction, or implantation as well as altered systemic immune responses, peritoneal fluid prostaglandins, interleukins, macrophages and tumour necrosis factor.

It’s important to note that not all patients with endometriosis have difficulties conceiving but an estimated 40% will be subfertile. Physicians should be careful to present a balanced picture to a newly diagnosed patient.

Signs

The most common physical finding is discomfort during the pelvic examination, particularly with stretching of the uterosacral ligaments and palpation of the posterior cul-de-sac. There may be some induration or nodularity of the uterosacral ligaments and in severe cases there may be a very firm palpable mass in the posterior vaginal fornix. The uterosacral ligaments can be felt in the upper vagina at approximately the 5 and 7 o’clock positions immediately posterior to the cervix. A fixed retroverted uterus can also indicate severe cul-de-sac disease. A patient may present with a tender adnexal mass that appears as a persistent hemorrhagic ovarian cyst on ultrasound (endometrioma). Occasionally, blue-coloured lesions may be seen on the cervix, vulva, vagina or surgical scar (episiotomy or Caesarian).

Differential diagnosis

Endometriosis is the commonest cause of chronic pelvic pain in women of reproductive age. Other causes of pain include pelvic adhesions, chronic PID, pelvic congestion syndrome, pelvic or abdominal neuromuscular problems, interstitial cystitis, irritable bowel syndrome and, more rarely, gynecologic malignancies.

If a woman’s pelvic pain is constant and has no cyclic exacerbations, or is episodic but unrelated to her menstrual cycle, it’s unlikely to be caused by endometriosis.

Diagnosis

The gold standard for diagnosis remains laparoscopy combined with pathological identification of two or more of the following histological criteria on biopsy:

  • endometrial glands
  • endometrial stroma
  • endometrial epithelium
  • hemosiderin-laden macrophages

Because of the wide variety of appearances, a biopsy of the more atypical forms is important as they may look similar to other pathological processes. There is an age-related evolution of endometriosis lesions, from more superficial red or clear lesions to deeper blue-black pigmented lesions. The widely-used Revised American Fertility Society Classification (Stages I-IV) assigns points based on severity of anatomical distortion and depth of the disease. Unfortunately, this staging system has only weak correlation with pain severity and fertility prognosis.

Endovaginal ultrasound can be useful in identifying and evaluating an adnexal mass. Often a pelvic exam may be limited because of patient discomfort or large body habitus. A low threshold should be set for ordering an ultrasound in the setting of pelvic pain, as the finding of an adnexal mass affects the management path taken.

Magnetic resonance imaging (MRI), though not cost-effective in most cases, can occasionally help further delineate the nature of an adnexal mass. Cystoscopy or colonoscopy may confirm suspicions of significant bladder or bowel involvement. Serum measurement of CA-125 antigen is often elevated in patients with moderate to severe endometriosis and particularly in the presence of endometriomas. It can be used to distinguish between endometriomas (which have elevated CA-125 in 78% of cases) and corpus luteum cysts, or in predicting the persistence or recurrence of significant endometriosis. But overall it has low sensitivity and variable specificity and isn’t useful as a screening test.

Treatment

Medical therapy

The primary goals of medical therapy for endometriosis are control of pain and halting disease progression. Medical therapy has never demonstrated improvement in fertility rates. Simple measures can help in providing relief, and an initial therapeutic trial of analgesics, oral contraceptives or progestins is acceptable without a laparoscopic diagnosis, but only if the examination is normal. Endometriomas don’t respond well to medical therapy and require surgery.

Analgesics

Prostaglandin production may account for some of the symptoms of endometriosis, particularly dysmenorrhea and gastrointestinal disturbances. NSAIDs inhibit prostaglandin synthesis and have been shown to provide relief of primary dysmenorrhea. But a literature review finds no conclusive evidence that they help relieve pain in endometriosis patients. Being generally safe and inexpensive, NSAIDs can be included in the first line of therapy for symptom relief, though they won’t halt disease progression. They should be started immediately at the first onset of pain or even before cyclical pain begins. Other less conventional methods of pain relief may be helpful, including acupuncture and biofeedback. Narcotic preparations can improve quality of life when used under close supervision for short periods, once a diagnosis has been made. There’s little risk in a patient with no history of addictive behaviour.

Hormonal therapy

The most commonly used hormonal endometriosis treatments are listed in Table 2. If referral isn’t immediately warranted (see Table 1) the primary care physician may begin menstrual suppression for their patient’s symptoms without a confirmed diagnosis. The usual contraindications apply. Depo-Provera should be used with caution in the adolescent population due to concerns about its effects on bone. The levonorgestrel-releasing IUD has shown efficacy in the treatment of dysmenorrhea associated with endometriosis and may also cause regression of cul-de-sac disease.

Surgical therapy

The surgical management of endometriosis can be conservative or radical. With conservative surgery, the goal is to remove all the diseased tissue while restoring normal pelvic anatomy. The surgery can be performed by laparoscopy or by laparotomy. Both approaches offer similar outcomes, but laparoscopic surgery leads to quicker recovery and less discomfort.

There’s good evidence that surgical treatment of even mild or minimal endometriosis can improve fertility and reduce pelvic pain. In general, surgical treatment seems to have better success than medical therapy, with lower recurrence rates. But the evidence doesn’t justify multiple conservative surgeries for pain or infertility. If surgery alone fails to achieve pregnancy, consider fertility medications (clomiphene, gonadotropins) and/or assisted reproductive technologies. If pain recurs, particularly within a short time-frame after surgery, medical management is the best option.

Radical or “definitive” surgery is the closest thing to a cure, although it can only be offered once fertility is no longer desired. If all the endometriosis tissue is excised and ovaries, tubes and uterus are removed, the risk of ongoing pain is low. But if the ovaries are retained, studies show that two-thirds of women will have recurrence of symptoms and up to one-third will require further surgery. Following pelvic clean-out the patient can be started on HRT immediately; it’s recommended that continuous combined estrogen-progestin regimens be used to prevent stimulation of possible residual disease by unopposed estrogen.

Though progress has been made, we still have much to learn. Avenues for research abound, and luckily many are currently being explored by good clinical studies.

Catherine Allaire MDCM, FRCSC is Clinical Associate Professor at UBC in the Division of Reproductive Endocrinology and Infertility.

Tips to manage menstrual suppression

Continuous OCP

  • Use monophasic pill
  • Breakthrough bleeding: take 1 pill bid until bleeding stops; if bleeding continues, stop for a week and have a full withdrawal bleed
  • Moodiness: change pills until you find one better tolerated
  • Nausea: try vaginal administration using double dose or NuvaRing

Provera/Depo Provera

  • Start with oral Provera (20-30 mg) for 6-8 weeks; if well tolerated, can switch to Depo-Provera 150 mg IM every 6-10 weeks (cheaper and easier)
  • Breakthrough bleeding: add low dose of estrogen until bleeding stops

Levonorgestrel-releasing IUD

  • Likely needs to be replaced more frequently (q2-3 years) for pain control
  • Add back low dose estrogen if breakthrough bleeding beyond first 3 months
When to refer to a gynecologist
  • Pelvic pain not responding to first-line medical management
  • Non-cyclical chronic pelvic pain
  • Clinical finding suggestive of advanced disease (cul-de-sac nodules, adnexal mass)
  • Delayed fertility
  • Recurrence of symptoms in previously treated patients

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