- Chronic Pelvic Pain Diagnosis And Management

The findings at laparoscopy have been well documented. In three major studies performed since 1989, the incidence of endometriosis in patients with pelvic pain ranged from 71%⁴ to 83%.²⁸ Findings at laparoscopy for 141 patients with chronic pelvic pain showed endometriosis plus other diseases in 67% and endometriosis alone in 12.7%, leiomyomas alone in 9.2%, adhesions alone in 8.5%, and hernias alone in 1.4%.7 With focal tenderness on pelvic examination, 67% of the patients were found to have endometriosis and with negative chlamydia titers, endometriosis was seen in 83% of these patients.²⁸

Chronic Pelvic Pain Evaluation

In evaluating patients with pelvic pain, a flow chart is helpful (Figure 6). A complete history and physical examination are performed. If the history and physical examination indicate that gynecologic features are not important, she is referred for evaluation of the other five factors involved in pelvic pain. If at the gynecologic exam, abnormal ovarian findings are detected, then ultrasound is performed and the patient is treated accordingly. Laboratory tests are also performed, and if they are abnormal, they are treated accordingly. In addition, empiric antibiotics are given if there is clinical evidence of infection in spite of negative cultures. Following this, if the patient is still in pain, non-steroidal anti-inflammatories are given. The patient is told to take the non-steroidal anti-inflammatories at least 1 day before the pain begins. In this way, the pain receptors are blocked by the non-steroidal anti-inflammatory medication and the patient will feel significantly less pain if the mediators of the pain are prostaglandins.

The patient is then tried on a course of suppressive oral contraceptive therapy for a period of 2 to 3 months. Although there are no studies demonstrating the benefit of oral contraceptive therapy for chronic pelvic pain, this therapy is effective in patients whose major problem is primary dysmenorrhea. If these therapies were not successful, the patient was taken to laparoscopy.

Endometriosis is found in a very high percentage of patients who are carefully screened to eliminate other potential causes of chronic pelvic pain. The question then occurs as to whether it is cost-effective and efficacious to initiate endometriosis specific GnRH agonist therapy prior to laparoscopic diagnosis on the basis of clinical judgement. A cost/benefit analysis comparing GnRH agonist therapy to laparoscopy for clinically diagnosed endometriosis was performed to determine if this is reasonable. A cost comparison of a 2-month trial of GnRH therapy to diagnostic/ therapeutic laparoscopy for all patients who failed treatment with oral contraceptives and non-steroidal anti-inflammatories and for whom a clinical diagnosis of endometriosis had been made was performed.²⁹

Efficacy of GnRH Agonists in Treatment of Endometriosis

For 130 patients in whom a laparoscopic diagnosis of endometriosis was made, 6 months of GnRH therapy was provided as the only treatment.³⁰ After 5 years, 46.6% of treated patients were free of symptoms. These patients were evaluated by laparoscopy for 2 years and then followed very carefully with questionnaires for an additional 3 years. The recurrence rate of pain symptoms in 5 years was evaluated by American Fertility Society (AFS) class. Women with Class I minimal disease had a 25.6% recurrence rate (74.4% response rate) while women with Class II mild disease had a 55.8% recurrence rate, women with Class III moderate disease had a 42.8% recurrence rate and women with Class IV severe disease had a 66.7% recurrence rate (Table 1).

Table 1. RECURRENCE RATE OF PAIN SYMPTOMS IN 5 YEARS BY AFS CLASS
AFS CLASS	RECURRENCE RATE

Class I - Minimal Disease	25.6%
Class II - Mild Disease	55.8%
Class III - Moderate Disease	42.8%
Class IV - Severe Disease	66.7%

53.4% of women treated with GnRH analogs alone had a recurrence of symptoms during the time period of study. 46.6% of women treated with GnRH analogs alone were cured and had no recurrence during the 5-year time period of the study.³⁰
AFS - American Fertility Society

The prevalence of each AFS class of endometriosis in patients with chronic pelvic pain was studied.⁴ Forty-two percent of patients who present with chronic pelvic pain have Class I minimal endometriosis, 36% have Class II mild endometriosis, 28% have Class III moderate endometriosis and 4% have Class IV severe endometriosis (Table 2).

Table 2. DISTRIBUTION BY AFS CLASSIFICATION OF ENDOMETRIOSIS IN PATIENTS WITH PELVIC PAIN
AFS CLASS	RECURRENCE RATE

Class I - Minimal Disease	42%
Class II - Mild Disease	36%
Class III - Moderate Disease	28%
Class IV - Severe Disease	4%

Total Class Iand II	78%
Total Class III and IV	32%

AFS - American Fertility Society

Once a determination has been made that a patient has a gynecologic cause for disease, endometriosis is the most prevalent disease and minimal to mild endometriosis is most frequently found at laparoscopy. Minimal or mild disease is also that disease which most completely responds to GnRH agonist alone.

GnRH Agonist as Diagnostic-Therapeutic Trial vs Laparoscopy

Table 3. COST ANALYSIS OF LAPAROSCOPY vs GNRH AGONIST THERAPY
Average cost of laparoscopy	$6,000
1 month of GnRH agonist therapy	$300
Class III - Moderate Disease	$1,800

The average cost of therapeutic laparoscopy varies, but $6,000 is a reasonable estimate. One month of GnRH therapy is approximately $300 and 6 months is approximately $1,800 (Table 3). Two months of GnRH therapy can be provided as a therapeutic trial for relief of pain at a cost of approximately $600 per patient for 100 patients who present with chronic pelvic pain and who are diagnosed with endometriosis. The total cost for determining therapeutic appropriateness for these 2 months will be $60,000 for all 100 patients. The cost of laparoscopic treatment for non-responders after 2 months of GnRH therapy would be approximately $6,000 per laparoscopy for diagnosis and treatment. Fifty patients would be non-responders³⁰ so this cost would be $300,000. The cost of completing the GnRH therapy for 4 more months for the responding patients would be $60,000 (50 patients x $300 x 4 months) (Table 4). The total cost of GnRH therapy involving a 2-month trial for all patients with laparoscopic surgery reserved for those patients who did not respond to GnRH therapy would be $420,000.

Table 4. USE OF 2 MONTHS OF GNRH AGONIST FOR DIAGNOSIS OF RELIEF OF PAIN AT COST OF $600 PER PATIENT FOR 100 PATIENTS
Total cost for determination of therapeutic appropriateness (2 months of GnRH agonist for all patients)	$ 60,000
Cost for laparoscopic treatment of failures after 2 months of GnRH agonist therapy (50 patients x $6,000)	$ 300,000
Cost for completion of GnRHa therapy for 4 more months for the successful patients (50 patients x $1,200)	$1,800

Total cost of GnRH agonist therapy for 2-month trial with laparoscopic surgery for patients who do not respond	$420,000

If the same 100 patients are treated immediately by laparoscopic therapy at $6,000 per patient, this would be a total cost of $600,000 ($6,000 x 100 patients). Laparoscopy is successful in approximately 70% of patients.¹¹ Therefore retreatment of laparoscopic failures must occur which will cost an additional $180,000 (30 patients x $6,000 per patient). The total cost for this is $780,000 (Table 5). The savings for 100 patients by using GnRH therapy for 2 months as a diagnostic therapeutic trial followed by completion of therapy for responders and therapeutic laparoscopy for non-responders vs laparoscopic treatment only is $360,000, which is a 46% savings.

Table 5. LAPAROSCOPIC TREATMENT
100 patients at $6,000 per laparoscopic therapy	$ 600,000
Retreatment of laparoscopic failures (approximately 30%)	$ 180,000

Total cost	$ 780,000

GnRH agonist as a diagnostic/therapeutic modality will save almost one half the total cost of treatment of endometriosis as a cause of pelvic pain. In addition, as a diagnostic/ therapeutic modality it will save 50% of the patients the need for an operative procedure. GnRH therapy saves 50% of the patients a laparoscopy and saves 50% of the money spent for the evaluation and treatment of the patients in whom the gynecologic condition of endometriosis is associated with pelvic pain.

Risks of GnRH Agonists

The risks of the use of GnRH agonists include bone loss and onset of menopausal symptoms. Bone loss and menopausal symptoms can be treated by the use of add-back therapy with low-dose estrogen replacement. If it is desired to avoid the use of estrogen replacement as add back, then the use of aledronate 10 mg orally a day 30 minutes prior to the first meal with 500 mg of calcium a day to prevent osteoclastic activity and provide for bone growth to the extent of 1.5% - 3% over that period.³¹ For menopausal symptoms, norethindrone 5 mg orally each day is frequently sufficient.

Risks of Laparoscopy

The benefit of laparoscopy is that other diseases besides endometriosis can be identified and treated.¹¹ However there are risks of laparoscopy including trocar injuries and bowel perforations. Trocar injuries to the vessels are now the most frequent occurrence in laparoscopy in terms of risk. Bowel injuries such as perforation can result in death.³²