The Journal for Nurse Practitioners
Volume 6, Issue 6 , Pages 427-434, June 2010

Endometriosis: Overview and Recommendations for Primary Care Nurse Practitioners

  • Gaylene Altman

      Affiliations

    • Gaylene Altman, RN, PhD, is associate professor at the University of Washington School of Nursing, Seattle, WA.
    • ,
  • Meegan Wolcyzk

      Affiliations

    • Meegan Wolcyzk, MN, ARNP, is a staff nurse at the University of Washington Medical Center, Seattle, WA.

Article Outline

Abstract 

Endometriosis, the presence of endometrial tissue outside the uterine cavity, is a chronic, disabling disease of uncertain etiology, with nonspecific signs and symptoms. Patients often experience chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility, as well as psychosocial stressors. Probable diagnosis may be based on clinical findings; however, laparoscopic surgery is required for definitive diagnosis. Therefore, considerable time may pass before the disease is recognized. This article discusses etiology, clinical presentation, and treatment and reviews typical factors in cases of delayed diagnosis. With a greater understanding of endometriosis, nurse practitioners will be equipped to identify symptoms and diagnose, manage, and refer patients.

Keywords:  chronic pelvic pain , endometriosis , dysmenorrhea , dyspareunia , infertility

 

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Introduction 

Endometriosis, the presence of endometrial tissue outside of the uterine cavity, is prevalent in 6 to 10% of the adult female population.1, 2, 3 In North America, more than 5.5 million women are affected.4 Women with endometriosis experience chronic pelvic pain, dysmenorrhea, dyspareunia, depression, and infertility. These symptoms are associated with missed work or school and impaired familial relationships.

Despite the huge impact that endometriosis has on women and their families, delays in definitive diagnosis (confirmed by surgical biopsy) are common, averaging 11.7 years in the United States.5 As a result, patients often suffer for years without an explanation. Even when their pain is recognized, their signs and symptoms may be mistaken for other diseases, such as pelvic congestion syndrome, pelvic inflammatory disease (PID), or irritable bowel syndrome, further delaying an accurate diagnosis.

With a better understanding of endometriosis, primary care nurse practitioners (NPs) can facilitate prompt clinical diagnosis and initiate treatment to reduce symptoms. This article discusses endometriosis pathogenesis, epidemiology, clinical presentation, and diagnosis. Factors that contribute to diagnostic delay and the potential impact of the disease on women and their families are also explored, and a strategy is provided to help primary care NPs appropriately evaluate, treat, and refer patients with suspected endometriosis.

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Background 

Pathogenesis 

Endometriosis is the growth of endometrial tissue outside of the endometrial cavity and uterine musculature. Endometrial tissue growth is stimulated by estrogen; therefore, the disease is most often found in women of reproductive age and rarely in women with low estrogen levels (i.e., prepubertal or postmenopausal women). Tissue growth is usually predominant in the pelvic area but may occur elsewhere. The most common sites are the ovaries, anterior and posterior cul-de-sac, posterior broad ligaments, uterosacral ligaments, uterus, fallopian tubes, sigmoid colon, and appendix.6, 7

The cause of endometriosis is unclear, and several theories have been proposed to explain its pathogenesis. The most widely accepted is the “implantation theory,” whereby retrograde menstruation of endometrial tissue travels through fallopian tubes and implants in the peritoneal cavity.1, 7 Although it is believed that most women have some degree of retrograde menstruation, women with endometriosis have greater reflux than women without endometriosis. In the context of retrograde menstruation, immunologic, genetic, and environmental factors may predispose women to the disease, causing tissue to adhere and grow.7

Another theory is that women with endometriosis lack adequate peritoneal immune surveillance. Evidence exists to indicate compromised natural killer cell activity in the peritoneal fluid of women diagnosed with endometriosis; this could lead to altered surveillance of ectopic endometrium as well as an increased concentration of leukocytes, macrophages, and cytokine production in the peritoneal cavity. It has been proposed that these immune cells mediate the endometriotic proinflammatory milieu and may possibly facilitate the growth of endometrial tissue. Last, metaplasia of the coelomic endothelium, believed to result from stimulation by menstrual debris, environmental factors, and/or hormonal action, may also play a role in endometriosis pathophysiology.7, 8

A hereditary component to the disease is likely, although specific genes related to pathogenesis have not been identified.7 Studies report a risk for endometriosis in first-degree relatives of women with severe endometriosis that is up to six times higher than for women without relatives with endometriosis.7, 9 Twin studies have also shown an increased prevalence among monozygotic twins, compared with dizygotic twins and non-twin sister pairs.10, 11

Another pathogenic theory is that certain environmental exposures disrupt endocrine and immune response in susceptible individuals. Dioxin is a chemical byproduct found in pesticide manufacturing, bleached pulp and paper products, and medical and municipal waste incineration. Several studies in monkeys have shown a direct, dose-dependent correlation between 2,3,7,8-terachlorodibenzo-p-dioxin (TCDD or dioxin) exposure and endometriosis (confirmed by laparoscopy).12, 13 While studies linking the toxic effects of TCDD in primates have been explicit, similar studies with humans have not shown a convincing link. One limitation is the lack of human markers for endometriosis or dioxin exposure. Currently, the National Institutes of Health is conducting investigations of human exposure to environmental chemicals (including estrogen-like compounds) and the incidence of endometriosis and other diseases.14

Epidemiology 

Estimating the prevalence of endometriosis is difficult, in large part because diagnosis is definitive only by surgical biopsy and many women are asymptomatic. Estimates indicate that endometriosis is prevalent in 6 to 10% of women of reproductive age in the United States and as many as 82% of women with chronic pelvic pain.2, 3

Certain risk and protective factors have been identified. Endometriosis is most common in women 25 to 29 years of age and least common in women more than 44 years of age.2 As noted previously, a strong familial component is apparent. Reproductive health factors are also important. Increased exposure to endometrial material, including shorter menstrual cycles (<28 days) and prolonged flow (>7 days), menorrhagia, metorrhagia, partial or complete obstruction of normal menstrual flow (i.e., cervical stenosis or vaginal septa), and delayed or no parity are all identified risk factors.1, 2 Conditions or activities that decrease the amount or frequency of menstrual bleeding and/or decrease estrogen production appear to be protective; these include exercise, menopause, amenorrhea, oral contraceptive pill (OCP) use, and greater and earlier parity.2, 15

Data are mixed regarding variables such as body mass index (BMI), alcohol consumption, and smoking. Some studies associate smoking with reduced risk (due to relative estrogen deficiency), and others suggest it is a risk factor (possibly due to exposure to dioxin or other chemicals mimicking hormone activity). An evaluation of the prospective cohort for the Nurses Health Study II by Missmer et al.16 found that high BMI at age 18 was modestly and inversely correlated with laparoscopically confirmed endometriosis; however, in the same study, patients with high BMI values maintained a significant inverse association only among individuals with concurrent infertility. Other studies have found lower BMI to be a risk factor.16, 17, 18

Women's Experiences 

The impact of endometriosis on women and their families is profound. Women suffer from physical and psychological symptoms that affect their ability to participate in school, work, and other activities of daily living. The most common symptom of endometriosis is pain, especially immediately prior to and during the menstrual cycle. Many women with endometriosis plan their lives around their menstrual cycle, avoiding any obligations during this time. Patients are at increased risk for insomnia, depression, anemia, and ovarian cancer and are possibly at increased risk for breast cancer as well as autoimmune and atopic disorders, although no conclusive studies are available to verify these hypotheses.7 Last, treatment may bring unwanted side effects associated with medication and repeated surgical procedures.

Infertility is also common among women suffering from endometriosis. An estimated 20 to 50% of women with infertility may have endometriosis, and 30 to 40% of women with endometriosis are infertile.4 This may result from a number of processes, including distorted pelvic anatomy (adhesions) that impair oocyte release, pickup, or transport, and substances released from implants that affect ovulation, fertilization, and implantation. It has also been postulated that endocrine and ovulatory disorders may contribute to infertility by affecting the luteal phase and follicular growth.19

Consideration of childbearing potential is extremely important when working with women who have endometriosis. The desire for pregnancy, either now or in the future, may greatly influence treatment choice. While medical treatment can help manage symptoms, there is no evidence that symptom control improves fertility.19 Young women may want to consider earlier childbearing, before the disease progresses. For women who suffer from infertility, education as well as referral to a reproductive endocrinologist is recommended. Treatment options for infertility secondary to endometriosis include surgical ablation of endometriotic implants, medication to stimulate ovulation combined with intrauterine insemination (IUI), and in vitro fertilization.

Delay of Diagnosis 

The average delay preceding definitive diagnosis of endometriosis in the United States is 11.7 years.5 This is likely due to a number of individual and medical factors. In one study of 32 women with confirmed endometriosis, Ballard et al.20 found that women often normalized their menstrual experiences and/or were embarrassed to share their experiences with others; this led to delays in seeking care.20 In their survey of approximately 650 women with endometriosis, Cox et al.21 found an average of 3.8 years of delay from symptom onset to seeking help.21 Some women indicated painful pelvic examinations deterred them from seeking care. Others experienced pain with intercourse but were embarrassed to discuss this. Some said they thought they might have endometriosis but became scared when they read more about it and decided they did not want to know. In another study, Arruda et al.22 found that younger women took a significantly longer time to report their symptoms (2 years for women <19 years of age vs. 0.2 years for women >30 years of age) and experienced a longer time to diagnosis (12.1 vs. 3.3 years, respectively).

At the medical level, Ballard et al.20 found that diagnosis delay occurred due to pain being normalized by family doctors or intermittent hormonal suppression of symptoms (via birth control pills or other hormonal contraceptives). Women in this study reported referral delays from primary to secondary care ranging from 1 month to 22 years (median, 36 months). The length of time from referral to secondary care to diagnosis was 0 to 84 months (median, 9 months). In a retrospective study, Pugsley and Ballard3 looked at the most common symptoms reported by 101 women with a definitive endometriosis diagnosis, most of whom had required multiple provider visits before diagnosis. The women most likely to be referred to specialists and to receive shorter delays in diagnosis were those presenting with infertility (85% of 20 women) and dyspareunia (72% of 29 women). This is consistent with the findings of Arruda et al.22, who found greater delay for patients presenting with pelvic pain than those reporting infertility or dyspareunia. Another reason identified by Ballard et al.20 is nondiscriminatory delay (the use of diagnostic tools that are not reliable for endometriosis).

Ultrasonography is often performed for patients presenting with chronic pelvic pain but is not a useful tool for endometriosis diagnosis. All but 3 of the women in this study were referred for transvaginal ultrasonography. It was found that a false-negative ultrasound examination raised further doubt with providers regarding the genuineness of their patient's symptoms.

Many women feel incredibly isolated as they struggle to obtain an accurate diagnosis. In a study by Cox et al.21, women often felt that their general practitioners did not ask the right questions and left the extent of their symptoms and experience unrevealed. Others were refused a referral to a specialist. More women were satisfied with care received from specialists (gynecologists), but others felt they were diagnosed with little compassion or education.

The physical and psychological benefits from even a clinical diagnosis (vs. definitive) can be profound. In a qualitative interview-based study Ballard et al.20 found four themes in the benefit of diagnosis: (1) relief from social and work responsibilities; (2) provides a language with which to discuss the problem; (3) provides a sense of control over symptoms; and (4) relief that symptoms were not due to cancer. Following diagnosis, women reported a sense of increased control over their symptoms because they could now identify treatment options and make treatment decisions.

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Evaluation of Women with Possible Endometriosis 

History 

Whenever a woman presents with dysmenorrhea, chronic pelvic pain, dyspareunia, or possible infertility, endometriosis should be considered. Primary dysmenorrhea can be distinguished from secondary dysmenorrhea because the latter is caused by an underlying pathology (i.e., endometriotic implants on the uterus, fallopian tubes, or ovaries). Evaluation should begin with a thorough inquiry about symptoms, health history (including menstrual history, medication use, and psychosocial history), and lifestyle factors. Questioning about reproductive health should include age at menarche, menstrual cycle patterns (cycle length, duration of flow, quantity of flow, and symptoms with menses), pregnancy history, presence of infertility, and history of PID or sexually transmitted diseases. Women should also be asked about the presence of chronic pelvic pain, dyspareunia (especially with deep penetration), back pain, dyschezia, rectal pain, diarrhea, constipation, dysuria, hematuria, infertility, and chronic fatigue. It is also helpful to evaluate symptom timing. Symptoms of endometriosis tend to be strongest premenstrually and with menses, when estrogen levels are highest, and subside after menses cessation. However, women with endometriosis may also be asymptomatic and present with concerns regarding infertility. Last, it is critical to inquire about family history, including known endometriosis or potentially indicative symptoms (e.g., a mother or sister with menorrhagia, metorrhagia, dysmenhorrhea, or a hysterectomy for unknown reasons).

Physical Examination 

A complete physical evaluation should include an abdominal, pelvic, and rectal examination. Signs of endometriosis found on physical examination may include palpable tender nodules in the cul-de-sac or uterosacral ligaments; localized tenderness in the cul-de-sac, uterosacral ligaments, or rectovaginal septum; pain with uterine movement; enlarged or tender adnexal masses; and fixation of adnexa or uterus in a retroverted position.1, 15, 23 Red, blue, or hemorrhagic nodules may also be visualized on the external genitalia, vagina, or cervix.15 Just as with subjective symptoms, women with endometriosis may have no signs on physical examination or signs may be inconclusive.24 Furthermore, the severity of symptoms does not necessarily correlate with disease severity (number and size of implants).

Clinical Diagnosis 

History and physical examination should guide the differential for a woman presenting with dysmenorrhea. A differential diagnosis may include primary dysmenorrhea, intrauterine or ectopic pregnancy, PID, tuboovarian abscess, uterine fibroids, ovarian cysts, appendicitis, inflammatory bowel disease or obstruction, cancer (cervical, uterine, and ovarian), urinary tract infection, pyelonephritis, kidney stones, or ruptured endometrioma.15 Appropriate tests to rule out these conditions include a Pap smear, pelvic ultrasonography, urine or serum human chorionic gonadotropin level, screening for gonorrhea and chlamydia infections, urine culture, and complete blood count. A transvaginal ultrasound may help to rule out ovarian cysts.

A primary care NP can diagnose endometriosis clinically based on history, physical examination, and appropriate exclusion of other pathology. According to the American Academy of Family Physicians, “Empiric diagnosis and treatment of endometriosis is reasonable, based on clinical suspicion and presentation. Patients with persistent symptoms after empirical treatment should be referred for laparoscopy, the preferred method for diagnosis.”1 For many patients with mild to moderate disease, a clinical diagnosis is sufficient to provide psychosocial relief and enables patients to make appropriate choices regarding treatment and fertility.

Currently no laboratory tests or diagnostic imaging exist that can be reliably used to diagnose endometriosis. Ultrasound, computed tomography, and magnetic resonance imaging are generally not effective unless ureteral, bladder, or bowel involvement is suspected. Ultrasonography may be effective in visualizing endometriomas of the ovaries, but it is overall a poor diagnostic tool. Cancer antigen 125 (CA-125) blood levels may be elevated with endometriosis, with the best correlation seen in women with more severe disease (by staging).24, 25 However, while this may be helpful in monitoring treatment response, it is generally not diagnostically reliable. Laparoscopic surgery is required for definitive diagnosis. Implants appear as small blue, purple, or red tissue growths, with biopsy performed to confirm the disease. Classification is based on the site(s) and severity (size and depth) of endometrial implants and adhesions.23

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Primary Care NP Management of Endometriosis 

Treatment 

Primary care NPs are in a position to manage endometriosis treatment, depending on the severity of symptoms and disease, patient tolerance to medications, and patient preference, therapeutic goals, age, and desire for current or future pregnancy. Treatment may include psychosocial evaluation and support for the individual and the family; education; pharmacologic management; follow-up; and referrals to a gynecologist, women's health NP, or reproductive endocrinologist. A recommended endometriosis treatment pathway can be found at http://www.aafp.org/afp/2006/0815/p594.html.

Non-steroidal-anti-inflammatory drugs (NSAIDs) are the first-line treatment for women with dysmenorrhea without proven endometriosis. A typical regimen consists of ibuprofen, 600 to 800 mg orally, four times per day, or naproxen, 550 mg orally, twice per day. NSAIDs should be initiated with the onset of premenstrual symptoms and continued for at least 3 days.26 To minimize gastrointestinal upset, women should take the medication with food or after meals. In patients with mild to moderate endometriosis, hormonal suppression is indicated. Progestins, such as medroxyprogesterone acetate (MPA; Depo-Provera; Pfizer), MPA (Provera; Pfizer), levonorgestrel-releasing intrauterine devices (Mirena; Bayer HealthCare Pharmaceuticals), or implantable contraceptives (Implanon; Schering Corporation) can be used to inhibit ovarian estrogen production. A typical dose of MPA would be 100 mg, by intramuscular injection every 2 weeks for four doses, followed by 200 mg intramuscularly monthly for 4 additional months.26, 27 Intermenstrual bleeding, headache, weight gain, breast tenderness, delayed fertility, and decreased libido are common side effects of progestin therapy.

Combination OCPs, taken either cyclically or continuously, may be used with mild disease to promote endometrial tissue atrophy, provide relief from dysmenhorrhea, and ideally delay disease progression. For women who are not seeking pregnancy, this may be a good option because of the low incidence of side effects.28 The recommended initial treatment is 35 mcg of ethinyl estradiol and a progestin. This dosage can be decreased for headaches or increased for breakthrough bleeding. Side effects are similar to progestin therapy and include bloating, nausea, weight gain, and increased risk of deep vein thrombosis.26 If symptoms are not controlled after 3 months, it is recommended that other therapies (such as gonadotropin-releasing hormone [GnRH] agonists) be considered.15

When treating women with NSAIDs, progestins, or OCPs it is important to explain that the medications provide symptom control, not a cure. With cessation of therapy, prior symptoms will likely recur. Other modalities for pain management may include pelvic floor relaxation, massage therapy, biofeedback, exercise, stress management, antidepressant therapy, or herbal teas; however, limited research is available regarding the efficacy of these approaches.

Education 

Education is imperative for patients with suspected endometriosis. Armed with knowledge, women are better able to cope with the disease and make informed decisions regarding care. Nurse practitioners should educate patients regarding the condition's prevalence, pathogenesis, and known risk and protective factors. They should also discuss treatment options and their associated risks and benefits. Because fertility is often affected, patients should be encouraged to consider present or future desire for childbearing.

Patients and their families also require education about the psychosocial aspects of the disease. This may include coping strategies such as exercise, support groups, counseling, management of depression (pharmacologic and nonpharmacologic), and complementary therapies for symptom relief.15 Ongoing discussion about the disease, coping mechanisms, treatment effectiveness and side effects, and desire for pregnancy should be included in follow-up encounters. Frequency of appointments will be determined by a woman's individual situation and needs.

Referral 

Referral to a gynecologist or women's health NP should be considered upon patient request or when conservative pharmacologic therapy is not effective in managing symptoms. If treatment with progestins or OCPs fail, referral is warranted. Furthermore, if a woman is experiencing severe symptoms, extensive disease, or infertility, referral to a gynecologist is indicated. A patient may also choose to go directly to a reproductive endocrinologist for assisted reproductive technologies.

It is helpful for the primary care NP to be aware of other treatment options available to women with a clinical or definitive diagnosis of endometriosis. Specialists may opt to treat with GnRH agonists or danazol. GnRH agonists (nafarelin, leuprolide, goserelin) inhibit pituitary gonadotropin secretion, decreasing ovarian estrogen production to create a temporary type of menopause. They are administered either intramuscularly, subcutaneously, or as a nasal spray. These medications are costly and can be prescribed for only 3 to 6 months due to the risk of decreased bone density and total body calcium. Side effects include vasomotor symptoms due to the low estrogen environment; these include hot flashes, vaginal dryness, decreased libido, insomnia, breast tenderness, depression, and headaches. Barrier contraception is recommended during treatment.1

Danazol works by increasing androgen levels and decreasing estrogen, thereby inhibiting endometriotic implant growth. It is prescribed as 400 mg, orally, twice per day, for 6 to 9 months, beginning on the fifth day of menses. Side effects are very common (dose-dependent), are primarily due to increased androgen levels, and include weight gain, muscle cramps, fluid retention, decreased breast size, acne, hirsutism, oily skin, decreased high-density lipoprotein cholesterol, increased liver enzymes, hot flashes, mood changes, and depression. Importantly, danazol is teratogenic; therefore, patients receiving this therapy must have a reliable form of birth control.26

Surgery may be indicated for severe or advanced disease, infertility, or if there is anatomic distortion of the pelvic organs or obstruction of the bowel or urinary tract. Laparoscopy is often performed to diagnose endometriosis and to ablate implants and adhesions. Ablation may help with pain relief, as well as treat secondary infertility problems. Definitive surgery includes abdominal hysterectomy with bilateral salpingo-oopherectomy. This may be appropriate for women with severe disease or who do not desire future fertility.26

For infertility, recommended treatment is a combination of expectant management, surgery, and assisted reproduction techniques. Because medical therapy has not been shown effective in enhancing fertility, medical management is not recommended for women desiring pregnancy or with severe endometriosis. Surgery may be effective in improving fertility for women with mild to moderate disease, while in vitro fertilization may be the best option for women with severe endometriosis.19

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Summary 

Primary care NPs need to be informed about endometriosis in order to identify signs, symptoms, and risk factors. They need to make accurate clinical diagnoses, provide appropriate treatment, and refer to specialists when indicated. Secondary care referrals will often be necessary for definitive diagnosis, management of severe disease, and treatment for infertility. The benefits of accurate and timely diagnosis are tremendous. Symptoms may be better managed and fertility is maintained, and women will have the benefit of an explanation for their physical and psychosocial pain.

At the primary care level, reported pelvic pain or painful menstruation must be recognized as potentially indicative of endometriosis. Even though pain is a subjective symptom, women with endometriosis are often able to distinguish “normal pain” (responsive to over-the-counter analgesia) from the pain of endometriosis.29 Given the high prevalence of dyspareunia and the embarrassment women may experience discussing this issue, primary care NPs also need to ask directly about this symptom.

Diagnostic delay is a common problem, and evidence-based practice guidelines to facilitate an accurate clinical diagnosis would be beneficial. Current research of endometriosis includes efforts to identify less invasive, more accessible diagnostic tools. The identification of genes associated with endometriosis, for example, would be tremendously valuable. Additionally, research needs to be performed to identify specific ways to detect women who may have endometriosis.

In addition to physical pain, endometriosis carries psychosocial ramifications; therefore, NPs should not focus solely on the biomedical aspects of the disease. Women need reassurance and explanations. How are these symptoms affecting her life, relationships, or work? What does this illness mean for her? How is she coping? Does she experience depression? How does treat the pain? What is her support system? What are her fears related to the illness? This holistic, patient-centered approach is a fundamental strength of many NPs and needs to be applied with patients who present with possible or certain endometriosis.

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References 

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 In compliance with national ethical guidelines, the authors report no relationships with business or industry that would pose a conflict of interest.

PII: S1555-4155(09)00424-3

doi:10.1016/j.nurpra.2009.07.022

The Journal for Nurse Practitioners
Volume 6, Issue 6 , Pages 427-434, June 2010

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