Gynecologic Pain

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Author: Dharmesh Kapoor, MBBS, MD, MRCOG, Consultant Gynecologist, Royal Bournemouth Hospital
Coauthor(s): Gamal Mostafa Ghoniem, MD, FACS, Fellowship Program Director, Clinical Professor of Surgery, Head, Section of Voiding Dysfunction, Female Urology and Reconstruction, Cleveland Clinic Florida; Willy Davila, MD, Head, Section of Urogynecology and Reconstructive Pelvic Surgery, Chairman, Department of Gynecology, Cleveland Clinic Florida

Introduction

The uterus, cervix, and adnexa share the same visceral innervation as the lower ileum, sigmoid colon, and rectum. Signals travel via the sympathetic nerves to spinal cord segments T10 through L1. Because of this shared pathway, distinguishing between pain of gynecologic and gastrointestinal origin is often difficult.1

A brief summary of the causes of gynecologic pain with links to other eMedicine articles is included at the end of this article (see Table ).

Acute Pelvic Pain

Acute pain due to ischemia or injury to a viscus is accompanied by autonomic reflex responses such as nausea, vomiting, restlessness, and sweating. The following is a discussion of some of the important gynecologic causes of acute abdominal pain.

Culdocentesis is a useful diagnostic aid for differentiating the cause of acute gynecologic pain. In the absence of a positive pregnancy test result, fresh blood suggests a corpus luteum hemorrhage, old blood suggests a ruptured endometrioma (chocolate cyst), purulent fluid suggests acute pelvic inflammatory disease (PID), and sebaceous fluid indicates a dermoid cyst. However, culdocentesis has largely been superseded by imaging modalities like ultrasonography.

Ectopic pregnancy

An unruptured ectopic pregnancy produces localized pain due to dilatation of the fallopian tube. Once the ectopic pregnancy is ruptured, the pain tends to be generalized due to peritoneal irritation. Symptoms of rectal urgency due to a mass in the pouch of Douglas may also be present. Syncope, dizziness, and orthostatic changes in blood pressure are sensitive signs of hypovolemia in these patients.

Abdominal examination findings include tenderness and guarding in the lower quadrants. Once hemoperitoneum has occurred, distension, rebound tenderness, and sluggish bowel sounds may develop.

Pelvic examination may reveal cervical motion tenderness that is exaggerated on the side of the tubal ectopia.

Initially, a sensitive serum or urine pregnancy test should be performed. Transvaginal ultrasonography should be performed. If an intrauterine gestational sac with a fetal pole is identified, the chances of a coexisting ectopic pregnancy are remote. Such a heterotopic gestation should be considered in patients taking ovulation-inducing drugs. Serial serum beta-human chorionic gonadotropin (hCG) estimations are often helpful in making the diagnosis. In early intrauterine gestations, the doubling time for hCG is usually 48 hours. Only 15% of cases are exceptions to this rule. In the absence of the availability of ultrasonography or in an emergency setting, culdocentesis can be of value to detect unclotted blood. A hematocrit of less than 16% (in the peritoneal blood) excludes hemoperitoneum.

Laparoscopy should be attempted if the patient is hemodynamically stable, a high index of suspicion remains, or the patient complains of increasing pain despite adequate analgesia.

Treatment options for an unruptured ectopic pregnancy include salpingostomy and salpingectomy. These may be performed laparoscopically or by open procedure. Laparoscopic salpingostomy has been found to be less successful than open surgery due to higher persistent trophoblastic rate. Methotrexate, a folic acid antagonist, is also used for the treatment of unruptured ectopic pregnancy, with a variable dose regimen being more successful than a single dose regimen.2 A ruptured ectopic pregnancy requires a laparotomy with removal of blood clots, although it has been reported by the laparoscopic route in experienced hands.

Adnexal masses

Corpus luteum hematoma

This condition develops in the luteal phase of the menstrual cycle. Slow leakage produces minimal pain. Frank hemorrhage can lead to hemoperitoneum and hypovolemic shock. Generalized abdominal pain and syncope are features of such a presentation. Treatment includes laparoscopy or laparotomy, evacuation of clots, and control of ovarian bleeding.

Ruptured ovarian cyst

The most common causes are dermoid cyst, cystadenoma, and endometrioma. Because the amount of blood loss is minimal, hypovolemia does not supervene. Peritoneal irritation due to leakage of cyst fluid can lead to significant tenderness, rebound tenderness, abdominal distension, and hypoperistalsis. Treatment involves cyst removal.

Ovarian torsion

Changes in ovarian axial morphology, which are typically secondary to ovarian cysts (most commonly dermoids), can undergo torsion around the pedicle. Frequently, torsion resolves spontaneously, and the only presenting symptom is lower abdominal pain. Persistent torsion progresses to occlusion of the venous drainage of the ovary, which leads to congestion, ovarian enlargement, thickening of the ovarian capsule, and subsequent infarction. Pain eventually becomes severe and is accompanied by nausea, vomiting, and restlessness. Infarction also leads to fever and mild leukocytosis.

If the ovary appears viable based on laparoscopic examination findings, the pedicle may be untwisted and the cyst removed. An infarcted ovary must be removed.

Acute pelvic inflammatory disease

Acute salpingo-oophoritis is a polymicrobial infection that is transmitted sexually. Neisseria gonorrhoeae and Chlamydia trachomatis are usually identified in patients with PID, and both organisms often coexist in the same patient. Gonococcal disease tends to have a rapid onset, while chlamydial infection has a more insidious onset. The US Centers for Disease Control and Prevention (CDC) has recommended strict diagnostic and management guidelines for the treatment of PID in an effort to reduce serious preventable sequelae such as adhesions and infertility. See The 2006 Guidelines for the Treatment of Sexually Transmitted Diseases .3

Diagnostic criteria for PID

All of the following criteria must be present:

  • Lower abdominal tenderness
  • Cervical motion tenderness
  • Adnexal tenderness

Diagnosis may also be supported by any of the following criteria:

  • Temperature greater than 101°F (38.3°C)
  • Abnormal cervical or vaginal discharge
  • Laboratory evidence of C trachomatis or N gonorrhoeae
  • Elevated erythrocyte sedimentation rate or elevated C-reactive protein value

Definitive criteria for diagnosis include the following:

  • Positive findings on transvaginal ultrasound or other imaging technique demonstrating thickened fluid-filled tubes with or without tubo-ovarian abscess or free pelvic fluid
  • Positive endometrial biopsy findings
  • Positive laparoscopy findings

Outpatient management of PID

  • Regimen B includes ceftriaxone at 250 mg IM, cefoxitin at 2 g IM plus probenecid at 1 g PO, or another parenteral third-generation cephalosporin. Add doxycycline at 100 mg PO bid for 14 days to whichever of the above is chosen. Metronidazole 500 mg bid may be added for 14 days.
  • Quinolones are no longer recommended for treatment of infections possibly related to gonococcal infections because of the emergence of resistant strains.4

Inpatient management of PID

  • Regimen A includes cefotetan at 2 g IV q12h or cefoxitin at 2 g IV q6h. Add doxycycline at 100 mg IV/PO q12h to the above choice.
  • Regimen B includes clindamycin at 900 mg IV q8h plus gentamicin at 2 mg/kg IV/IM loading dose followed by 1.5 mg/kg q8h as a maintenance dose.
  • Ampicillin/sulbactam 3 g IV q6h, plus doxycycline 100 mg IV/PO q12h.

Admission criteria for PID

  • Pregnancy
  • Inability to exclude surgical emergencies such as appendicitis
  • Immunosuppression (including HIV infection with low CD4 count)
  • Confirmed or possible pelvic abscess
  • Intrauterine device in situ
  • High fever or severe nausea and vomiting
  • Inability to comply with an outpatient regimen
  • Failed outpatient therapy
  • Adolescence
  • Significant fertility issues

 

Tubo-ovarian abscess

A ruptured abscess can lead to gram-negative endotoxic shock; therefore, this condition is a surgical emergency. The most common presentation is bilateral, palpable, fixed, tender masses. Patients often present with generalized abdominal pain and rebound tenderness caused by peritoneal inflammation. In such cases, the infected tissue must be surgically removed under broad-spectrum antibiotic coverage. Preoperative antibiotic coverage for 24-48 hours is recommended if the patient is stable.

Fibroids

Degenerating fibroid

This may occur during pregnancy when rapid growth of the tumor outstrips its blood supply. This condition is conservatively managed as much as possible.

Twisted subserous fibroid

A pedunculated subserous fibroid may twist and undergo necrosis, causing acute abdominal pain. It may be removed by laparoscopy or an open procedure.

Submucous fibroid

A pedunculated submucous fibroid may present with cramping pain and vaginal bleeding. Hysteroscopic resection is the treatment of choice.

Recurrent Pelvic Pain

Mittelschmerz

Mittelschmerz is midcycle abdominal pain due to leakage of prostaglandin-containing follicular fluid at the time of ovulation. It is self-limited, and a theoretical concern is treatment of pain with prostaglandin synthetase inhibitors, which could prevent ovulation.

Endometriosis

Pain associated with endometriosis may worsen premenstrually or during menses. Patients experience generalized lower abdominal tenderness, and associated complaints include dysmenorrhea, dyschezia, and dyspareunia. Endometriotic deposits in both the uterosacral ligaments and rectovaginal septum contribute to pain during intercourse. Painful defecation is due to infiltration of the bowel wall by endometriotic deposits. Importantly, remember that the pain associated with endometriosis is not correlated with the presence or amount of visible endometriotic tissue. In fact, prevalence of endometriosis is the same in women with and without pain.5 ,6 Rather, pain is related to the chemical mediators of inflammation and neural infiltration.

Ovulation suppression using different drugs has been tried in order to reduce the pain associated with endometriosis. Overall, no difference appears to exist in the efficacy of danazol, gestrinone, oral contraceptives, depot medroxyprogesterone acetate, and gonadotropin-releasing hormone (GnRH) analogs in placebo-controlled trials. However, dydrogesterone was found to be less effective. According to a Cochrane review, ovulation suppression provides no benefit in subfertile women with endometriosis who wish to conceive.7

The absolute benefit for women undergoing surgical ablation of endometriosis is 30-40% over women having only diagnostic laparoscopy, in the short term. This benefit reduced over time, and reoperation rate is as high as 50%.8 In cases of rectovaginal endometriosis, significant short-term pain relief was reported by up to 80%, but at 1-year follow-up, 50% required analgesics or hormones for pain relief. During postoperative treatment, GnRH analogs resulted in significantly reduced pain scores in women who received treatment for 6 months. The evidence for hormone replacement therapy in women with postsurgical menopause for treatment of endometriosis is unclear at present.9

Laparoscopic cystectomy of an endometrioma was found to be superior to simple drainage for treatment of recurring pain; it has recently been shown to result in lower recurrence of signs and symptoms of endometriomas and higher cumulative pregnancy rates.10 ,11

GnRH agonists were used for 6 months as the only treatment in patients with documented endometriosis. At 5 years, more than half the patients were symptom-free. The best responses were obtained in patients with mild or moderate disease. Among those with persistent or recurrent pain, an increasing correlation existed with the severity of the endometriosis.12

Primary dysmenorrhea

By definition, primary dysmenorrhea is menstrual pain associated with ovulatory cycles in the absence of structural pathology. It usually manifests in younger women, and a recent study on the natural course of dysmenorrhea found that most women are affected throughout the menstrual years. Improvement is more likely in women who bear children.13 Patients experience suprapubic cramping pain that may radiate to the anterior thigh or sacral region. Pain may be accompanied by autonomic symptoms such as nausea, vomiting, and syncope. The onset of primary dysmenorrhea is a few hours prior to the onset of menses, and pain usually lasts up to 72 hours. More than 80% of patients have an excellent response to treatment with prostaglandin synthetase inhibitors. Oral contraceptives may be used with equal effectiveness in patients who desire simultaneous fertility control.

Smoking was associated with a higher relative risk of severe dysmenorrhea. In a systematic review, naproxen, ibuprofen, and mefenamic acid were more effective for pain relief compared to placebo. The Cochrane reviews have analyzed various studies and found high frequency transcutaneous electrical nerve stimulation (TENS) and acupuncture to be effective for dysmenorrhea.14 Laparoscopic uterine nerve ablation (LUNA) is shown to be effective for women with dysmenorrhea without endometriosis.15 Other drugs that have been reported with some success include nitroglycerin, terbutaline, and guaifenesin.

Secondary dysmenorrhea

Secondary dysmenorrhea is cyclic menstrual pain associated with structural pathology. The most common causes are endometriosis, adenomyosis, and the presence of an intrauterine device. Pain starts 1-2 weeks prior to the onset of menses and persists for a few days after cessation of flow. Hypertonic uterine activity coupled with an excess of prostaglandins is postulated to be the cause of secondary dysmenorrhea. Patients are somewhat less responsive to nonsteroidal anti-inflammatory drugs (NSAIDs) and combination oral contraceptives compared with patients with primary dysmenorrhea. Presacral neurectomy (PSN) has been shown in a single randomized trial to improve severe dysmenorrhea due to endometriosis.16 A Cochrane review found presacral neurectomy to have better pain control in the long term than LUNA, albeit with adverse affects like constipation.17

Adenomyosis

Adenomyosis typically manifests in women in their 40s and is essentially a clinical diagnosis. It coexists with endometriosis and fibroids, and a recent study found that prior uterine surgery was significantly associated with increased risk of adenomyosis.18 Dysmenorrhea is associated with dyspareunia, dyschezia, and acyclical uterine bleeding. The uterus is soft and tender, especially around the time of menstruation. Magnetic resonance imaging shows an enlarged junctional zone and myometrial cysts, whereas ultrasonography shows heterogenous abnormal myometrial echogenicity in patients with adenomyosis. Histopathologic correlation with the clinical diagnosis can be found in only half the cases. For reproductive-aged women, treatment includes NSAIDs, combination oral contraceptives, progesterone-only pills, levonorgestrel intrauterine contraceptive devices, and GnRH agonists. Hysterectomy is a last resort.

Chronic Pelvic Pain

The American College of Obstetrics and Gynecology (ACOG) defines chronic pelvic pain (CPP) as continuous or noncyclical pelvic pain of longer than 6 months duration that localizes to the anatomic pelvis, abdominal wall at or below the umbilicus, lumbosacral back, or the buttocks and is of sufficient severity to cause functional disability or lead to medical care. Nearly 4% of women are thought to have ongoing CPP. It forms the indication for 18% of all hysterectomies and 40% of gynecologic laparoscopies .19 Even the relationship of recurrent pain to menstruation or the presence of dyspareunia is only suggestive.20

Annually, 400,000 laparoscopies are performed on patients with endometriosis and chronic pelvic pain. Negative laparoscopic findings occur in 40% of patients.19

Important nongynecologic causes that must be considered in the differential diagnosis include irritable bowel syndrome (IBS), interstitial cystitis (IC), and pelvic floor myofascial syndrome. Importantly, rule out abdominal wall etiologies that are aggravated by raising of the head or raising of straightened legs while supine.

Dyspareunia as a significant factor

Patients with deep, internal, or thrust dyspareunia often express a feeling that some sort of internal collision is occurring during sexual activity. Any pelvic pathology may be responsible for this discomfort, but abnormalities such as endometriosis, pelvic adhesions, pelvic relaxation, malposition (retroversion), adnexal pathology or prolapse, and uterine fibroids are the most likely causes. IC may cause dyspareunia before it proceeds to chronic unremitting pain. IBS may also cause dyspareunia and pain at the apex of the vagina.

Adhesions

A study using conscious pain mapping during awake laparoscopy found that peritoneal adhesions and filmy adhesions that allowed for movement between 2 structures had the highest pain scores, while dense, fixed adhesions caused less pain.21 Pain is acyclical and not accompanied by vaginal bleeding. Dyspareunia and symptoms suggestive of intermittent subacute bowel obstruction may be associated with adhesions. Adhesiolysis should be recommended with realistic expectations, and a multidisciplinary approach in a pain clinic may be worthwhile prior to attempting surgery. In one study, cure or improvement was reported in two thirds of patients with chronic pelvic pain and nearly half of those with dysmenorrhea.22

In a randomized study, patients with severe adhesions involving the intestinal tract were shown to benefit from adhesiolysis.23 A recent study found adhesions deflecting the sigmoid colon to the pelvic sidewall in 38% of patients with chronic pelvic pain. Among patients without detectable endometriosis, 80% had a significant reduction in symptoms after adhesiolysis on an 18-month follow-up.24 Various agents have been reported to reduce adhesion formation, but none have gained universal acceptance. A recent small randomized study of 25 patients found a significant improvement in right-sided pain in women who underwent paracolic adhesiolysis.25

The issue of prevention of adhesions after pelvic surgery has been an important one. In a recent Cochrane review26 , the authors found that Interceed was the only agent that prevented new adhesion formation and reformation following laparoscopic surgery or laparotomy. However, its use did not lead to an improvement in pregnancy rates.

Chronic pelvic inflammatory disease

Pain is thought to be due to infection or adhesions that exacerbate the baseline condition. However, a recent animal study failed to show adhesions following direct bacterial inoculation.27 Infection may be accompanied by fever, leukocytosis, and gonococcal or chlamydial infection. Laparoscopy and peritoneal fluid cultures help confirm the diagnosis in most cases. Empiric treatment with antibiotics should be commenced prior to laparoscopy.

Ovarian remnant syndrome

Following a total abdominal hysterectomy and bilateral salpingo-oophorectomy, the ovarian remnant can undergo cystic changes that cause pain. Hormonal suppression with danazol, combined oral contraceptive pills, high-dose progestins, and GnRH agonists are possible treatment options. Diagnosis may be aided by ultrasonography. Finding the ovarian tissue may be challenging. As with all laparoscopic surgery, operator expertise is vital in the success of the procedure, because of the dense adhesions that are often present. Otherwise, a laparotomy maybe indicated.

Irritable bowel syndrome

IBS is one of the most common functional intestinal disorders. It is defined as a group of functional disorders in which abdominal discomfort or pain is associated with defecation or a change in bowel habits. IBS also involves features of disordered defecation.

Rome criteria for IBS28

Recurrent symptoms (2 of 3) present for at least 12 weeks in the preceding year

  • Abdominal pain relieved with defecation
  • Onset associated with change in frequency of stool
  • Onset associated with change in stool appearance

Symptoms supportive of diagnosis

  • Abnormal stool frequency
  • Abnormal stool form
  • Abnormal stool passage
  • Passage of mucus
  • Bloating

History plays an important role in excluding causes such as lactose intolerance, which present with similar symptoms. Upon examination, a tender sigmoid colon is often palpable. Fiber supplementation has not been shown to have significant benefits and should be reserved for patients with hard stools. Patients with recurrent severe abdominal cramps may benefit from antispasmodics such as dicyclomine and hyoscyamine, although this treatment has not been substantiated in controlled studies. Patients with severe IBS need a multifaceted approach that includes psychiatric evaluation because symptoms may be a part of a somatization disorder.29

Low-dose antidepressants such as amitriptyline and selective serotonin reuptake inhibitors may have an adjunctive role. Alosetron (Lotronex) has been reintroduced to the US market and is approved for severe chronic diarrhea-predominant IBS, but only after other treatment modalities are unsuccessful, because of the risk of serious adverse gastrointestinal events (eg, ischemic colitis, serious complications of constipation). These adverse effects have resulted in hospitalization, blood transfusion, surgery, and death.

Tegaserod (Zelnorm), which is a partial agonist of the 5-hydroxytryptamine receptor that helps symptoms of IBS, alleviates constipation and accelerates intestinal transit. A recent meta-analysis found tegaserod to have significant benefits in women with constipation-predominant IBS.

Tegaserod was temporarily withdrawn from the US market in March 2007; however, as of July 27, 2007, restricted use of tegaserod is now permitted via a treatment IND protocol. The treatment IND will allow tegaserod treatment of irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC) in women younger than 55 years who meet specific guidelines. Its use is further restricted to those in critical need who have no known or preexisting heart disease.

Earlier this year, tegaserod marketing was suspended because of a meta-analysis of safety data pooled from 29 clinical trials that involved more than 18,000 patients. The results showed an excess number of serious cardiovascular adverse events, including angina, myocardial infarction, and stroke, in those taking tegaserod compared with placebo. In each study, patients were assigned at random to either tegaserod or placebo. Tegaserod was taken by 11,614 patients, and placebo was taken by 7,031 patients. The average age of patients in these studies was 43 years, and most patients (ie, 88%) were women. Serious and life-threatening cardiovascular adverse effects occurred in 13 patients (0.1%) treated with tegaserod; among these, 4 patients had a heart attack (1 died), 6 had unstable angina, and 3 had a stroke. Among the patients taking placebo, only 1 (0.01%) had symptoms suggesting the beginning of a stroke that went away without complication.

 

Loperamide was also found to be useful for women with painless diarrhea. It is now available on the US market. Fedotozine (investigational in the United States) is a kappa-opioid agonist that decreases intestinal hypersensitivity and may help decrease bloating pain. Substance P antagonists are currently being evaluated for the treatment of IBS. Patient support groups can also be useful.

Approximately 60% of patients with chronic pelvic pain may have IBS as a primary or coexistent diagnosis. The Rome criteria for diagnosis should be used in routine clinical practice. Early diagnosis allows the formulation of a management plan that includes counseling and nonpharmacologic interventions, which play important roles in alleviating patient symptoms.

Myofascial pain

Myofascial etiologies occur in 15% of patients with chronic pelvic pain. Trigger points are hyperirritable spots usually within a taut band of skeletal muscle or in muscle fascia. These are painful upon compression and can give rise to characteristic referred pain, tenderness, and autonomic phenomena. Women may experience pain from trigger points (areas overlying muscles that induce spasm and pain) in the myofascial layers of the pelvic sidewall or pelvic floor. The obturator internus and levator ani are common sites and should be palpated. A recent study found levator pain in 87% of women with diagnosed interstitial cystitis (IC).30 Coexisting symptoms, such as frequent headaches, nonrestorative sleep, diffuse tender points, and fatigue, may be suggestive of systemic disorders such as fibromyalgia.

Treatment for trigger points usually involves hyperstimulation analgesia (eg, stretching, cold spray), local injection of anesthetic agents, TENS, and acupuncture. All of these treatments act as counterirritants that alter the central gate or threshold control and result in the prolonged response. The action of an injected local anesthetic has the effect of blocking the central response.31 A recent small study of 18 women found improvement in 72% with trigger point injections combining anesthetic agents and triamcinolone.32 A randomized placebo-controlled trial from Australia found significant improvements in nonmenstrual pelvic pain and pelvic floor spasms in women treated with botulinum toxin type A.33

Myofascial pain may manifest as focal lower abdominal pain due to entrapment of the genitofemoral or ilioinguinal nerves, which is a sequela of Pfannenstiel incisions. A bupivacaine nerve block is both a diagnostic and therapeutic measure. Cryoneurolysis or surgical removal of the involved nerve should be reserved for recalcitrant cases. Manual therapy of pelvic floor myofascial trigger points is also reported to improve pain in women with IC and in women with frequency-urgency syndrome.34

Interstitial cystitis

Considerable overlap exists in symptomatology in patients with IC and IBS. Although some authorities believe that the National Institute of Diabetes and Digestive and Kidney Diseases criteria are too rigid, the criteria still serve as a useful clinical guide for understanding the complex nature of the problem.

Required findings

  • Hunner ulcer or diffuse glomerulations (ie, small bleeding points on the bladder surface seen after hydrodistension of the bladder)
  • Pain associated with the bladder or urinary urgency

Automatic exclusions

  • Age younger than 18 years
  • Duration of symptoms less than 9 months
  • Urinary frequency fewer than 8 times per day
  • Absence of nocturia
  • Benign or malignant tumors
  • Radiation cystitis
  • Vaginitis
  • Cyclophosphamide cystitis
  • Urethral diverticulum
  • Genital cancer
  • Active herpes infection
  • Bladder or lower ureteric calculi
  • Involuntary bladder contractions
  • Bladder capacity less than 350 mL while awake
  • Symptoms relieved by antibiotics, urinary antiseptics, analgesics, anticholinergics, or muscle relaxants

A recent study found evidence of IC on cystoscopy findings in 38% of patients who underwent laparoscopy for chronic pelvic pain.35 In a longitudinal study of a cohort of IC patients, the most common sites of pain were lower abdominal (80%), urethral (74%), and lower back (65%).36

Two different etiologic mechanisms have been suggested for IC. The classic or ulcerative variant is inflammatory in origin, and the nonulcer variant is neuropathic in origin. This has implications for choice of therapy. An evidence-based therapeutic algorithm for treatment does not exist.37

Treatment options

Hydroxyzine is a histamine receptor antagonist with effects on the central and peripheral nervous systems. Hydroxyzine is suggested to have a good clinical effect in patients with IC. The dose is 25-50 mg bid for 14 days.

Amitriptyline is a tricyclic antidepressant that also blocks the H1 histamine receptor. Amitriptyline acts via blockade of acetylcholine receptors, including inhibition of reuptake of released serotonin and norepinephrine. It also has a sedating action via the H1 receptors. A recent placebo-controlled, randomized trial showed significant improvement in patients with IC who were treated with amitriptyline.38

Corticosteroids are not widely used because of adverse effects such as fluid retention and osteoporosis. However, a recent study reported improved pain control and overall satisfaction with oral prednisone in a cohort of women with severe refractory IC.39

Pentosan polysulfate sodium (PPS) (Elmiron) is claimed to restore the depletion in the glycosaminoglycan (GAG) layer. A double-blind placebo-controlled trial revealed subjective improvements in pain, urgency, frequency, and nocturia. Patients also demonstrated objective improvement in average voided volume. However, no objective demonstration of improvement was noted in urinary frequency. Another study found that the classic subtype of IC responds better than the nonulcer form. In a placebo-controlled trial, one quarter of the patients reported more than 25% improvement. A good response is expected after 4-12 months of treatment, and 50% of patients demonstrate improvement in this time. The dose is 150-200 mg bid between meals. A later study evaluating PPS and hydroxyzine failed to show improvement in most women.40 Chondroitin sulfate is another drug that replenishes the GAG layer. The dose is 50 mL twice a week, then decreasingtoonceweeklyfor4weeks.Remissionismaintainedwithmonthlyinstillations.

Intravesical instillation therapy can be performed using agents that are cytoprotective or cytodestructive. Cytoprotective agents include heparin, which may be given in a dose of 20,000 IU in 10 mL of sterile water. Some authors have used methylprednisolone in combination with heparin. A combination of heparin with alkalinized lidocaine was shown to provide better symptom relief than heparin alone.41

Cytodestructive agents include dimethyl sulfoxide (DMSO), silver nitrate, and bacille Calmette-Guérin (BCG) vaccine. DMSO is a scavenger for intracellular hydroxy free radicals. It is an anti-inflammatory agent and a local anesthetic. It is instilled twice as 50 mL of 50% solution. It may be given with a cocktail of gentamicin, lidocaine, sodium bicarbonate, and heparin. DMSO provides relief in about two thirds of cases, and it increases bladder compliance and inhibits detrusor contractions.42 BCG is thought to modulate immune responses. It is instilled as 12.5 mg (50 mL) weekly for 4-6 weeks. A recent placebo-controlled trial failed to show significant benefit with BCG.43

Capsaicin is another drug that has been successful in patients with IC. Capsaicin is a selective neurotoxin for small myelinated class C afferent neurons. It reflexly inhibits bladder contractions, decreases their amplitude, and increases the residual volume. Patients with urgency and frequency due to idiopathic diabetes insipidus or sensory urgency have not responded as well to capsaicin. Also, 40 mL of 2% lidocaine is given to effect anesthesia from the initial excitation. The dose of capsaicin is 50 mL instilled over a 4-week period. Approximately 44% patients were content with this treatment, and an additional 36% had a decrease in the frequency of urge incontinence. Capsaicin requires reinstillation after 6 months.

Resiniferatoxin is an agent that works on a similar principle. A recent study showed it to be a promising agent for the treatment of IC.

A Cochrane review of intravesical treatments for IC found that the evidence was most promising for BCG and oxybutynin.44

Cystectomy and ileal conduit was the most frequently used major surgical procedure. A review of prescribed treatments in the IC database revealed that cystoscopy with hydrodistension is the most popular treatment. Sacral neuromodulation, hyperbaric oxygen, botulinum toxin (BTX-A), and cyclosporine A are among the newer modalities in the treatment of IC and have been tried with some success. Long-term results are needed before these should be recommended as primary measures.

Urethral syndrome

Patients with urethral syndrome present with classic symptoms of urinary tract infection, but urinary culture results are negative for infection. Symptoms include frequency, urgency, and pressure in the absence of nocturia. Physical examination reveals a tender ropelike urethra. The clinical course is marked by remissions and exacerbations. Causes include chlamydia, mycoplasma, herpes simplex, urethral trauma, atrophy, stenosis, and functional obstruction. Female prostatitis is believed to be due to inflammation of the paraurethral glands and is believed to be a frequent cause of urethral syndrome. Clinical examination reveals localization of tenderness to these glands.45 Treatment of urethral syndrome should be tailored to the individual cause. Patients with sterile pyuria respond to a 2- to 3-week course of doxycycline or erythromycin. All postmenopausal women should also receive a trial of local estrogen therapy. Urethral dilatation and biofeedback have been used for resistant cases.

Posthysterectomy syndrome

Posthysterectomy syndrome is pain due to a low-grade cuff cellulitis, seroma or hematoma of the cuff, or neuralgia related to transection of the nerve tissue. Resection of a portion of the vaginal cuff occasionally helps relieve the pain.46

Hysterectomy for chronic pelvic pain

Long-term studies have shown that success with hysterectomy is disappointing when the only indication is pain. If the pain has persisted for more than 6 months, has not responded to analgesics, and is causing significant distress and impairment, then hysterectomy may be considered an option after counseling the patient that the pain may persist after surgery.

Idiopathic pain

Newer treatment modalities like percutaneous tibial nerve stimulation have shown initial promise.47 Because of their noninvasive nature, they are likely to be tried in women with unexplained pelvic pain.

Vulvar Pain

Vulvovaginitis may be due to allergic reaction (eg, contact vaginitis), infection (eg, bacterial, parasitic, fungal), or hypoestrogenism (ie, atrophic). Symptoms include burning, discomfort, dyspareunia, and abdominal vaginal discharge. Localizing the pain is important in order to determine the diagnosis.

Contact vulvitis

The patient usually complains of itching or burning that involves the vulva but not the vagina. Elimination of the possible agent and administration of topical steroids for 7-10 days usually result in resolution of symptoms.

Atrophic vaginitis

Primary complaints include burning, dyspareunia, and vaginal spotting. The patient may also experience burning during micturition, urinary urgency, and urinary frequency. Topical estrogen cream is the first-line treatment. Incidence of systemic absorption is low with low-dose topical estrogens. Estradiol-releasing vaginal rings have the highest continuance and efficacy rates among all topical preparations.48

Microbial vaginitis

The usual complaints are accompanied by vaginal discharge. Appropriate treatment results in resolution of symptoms.

Vulvodynia

Vulvodynia is defined as chronic vulvar burning and/or pain without clear medical findings. Specific treatable causes, such as dermatoses or group B streptococci infection, should be ruled out in the first instance. Essential (dysesthetic) vulvodynia is a diffuse unremitting vulval burning that may radiate to the inner thigh, buttocks, and perineum. Associated complaints include urethral and rectal burning or discomfort. This condition is commonly found in postmenopausal women. Physical examination reveals findings of hyperalgesia in the affected areas. Pudendal nerve damage or compression is a possible contributory factor. Urinary frequency, urgency, and incontinence may develop as a consequence, and chronic constipation may also develop.

Vulvar vestibulitis (provoked vulvodynia) is severe pain upon vestibular touch or attempted vaginal entry during coitus, tenderness to pressure localized within the vulvar vestibule, and physical examination findings limited to vestibular erythema of various degrees.

Because both the vestibule of the vulva and the bladder are derived from the urogenital sinus, a common etiology has been suggested for these conditions. Standard therapy for vulvodynia includes amitriptyline and, more recently, gabapentin. Additional therapies include estrogen cream, nitroglycerin cream (0.2%), interferon-alpha, and pelvic floor rehabilitation with surface electromyography (EMG) biofeedback.

Vestibulodynia is an entity that may be a combination of vestibulitis and constant spontaneous vulvodynia. Patients have a higher incidence of dysuria, and even the contact of urine on the vestibular skin evokes a sensation of pain. Perineoplasty is associated with a higher failure rate in these patients. Further, a higher frequency of human papilloma virus DNA is found in tissue samples of patients with vestibulodynia.49

Pain Due to Complications of Gynecologic Surgery

Thermal bowel injury is a serious complication of surgery. It occurs in 0.5-3.2 per 1000 cases, and symptoms may not develop for days or weeks. Patient presentation includes bilateral lower quadrant pain, tenderness, fever, leukocytosis, and peritonitis. Ileus or free gas under the diaphragm may be noted on a plain abdominal radiograph.

Peritonitis may occur as a consequence of undetected bowel perforations. Other complications include abscess, enterocutaneous fistula, and septic shock.

Thermal injury to the bladder or ureter may manifest up to 14 days postoperatively with abdominal or flank pain, fever, and peritonitis. Findings from an intervenous pyelogram demonstrate extravasation of urine or urinoma. Patients with mechanical obstruction may present in 1 week with a similar clinical picture.

Incisional herniae rarely become incarcerated. Patients present with abdominal pain and signs of bowel obstruction or perforation.

Hysteroscopy commonly leads to uterine perforation, which may involve the bowel. Such a possibility should be kept in mind when evaluating a patient.

Following a vaginal hysterectomy, patients may present with pelvic pain due to vaginal cuff hematoma, cellulitis, or ovarian abscess. Wound complications such as dehiscence, renal angle pain due to ureteric injury, and retention should be considered.

Osteitis pubis is a possibility in patients who undergo a Marshall-Marchetti-Krantz procedure and operations for vaginal vault prolapse and urinary incontinence that use bone-anchoring systems.

Summary

Causes of Gynecologic Pain

 

Table

Acute pelvic pain

Complications of pregnancy
  • Ectopic pregnancy, ruptured or unruptured (see Ectopic Pregnancy )
  • Abortion (see Threatened Abortion and Abortion, Incomplete )
  • Degenerating fibroid (see Fibroids )
Acute infection
  • Endometritis (see Endometritis )
  • Acute pelvic inflammatory disease (see Pelvic Inflammatory Disease )
  • Tubo-ovarian abscess
  • Pelvic thrombophlebitis
  • Ovarian vein thrombosis (see Ovarian Vein Thrombosis )
Adnexal mass
  • Corpus luteum hematoma (see Corpus Luteum Rupture )
  • Ovarian torsion (see Ovarian Torsion )
  • Ruptured ovarian cyst (see Ovarian Cysts )
  • Paratubal cyst
  • Endometriosis (see Endometriosis )
  • Ovarian hyperstimulation syndrome

Chronic pelvic pain

Gynecologic
  • Extrauterine
    • Adhesions
    • Chronic ectopic pregnancy (see Ectopic Pregnancy )
    • Chronic pelvic inflammatory disease (see Pelvic Inflammatory Disease )
    • Endometriosis (see Endometriosis )
    • Ovarian remnant syndrome
  • Uterine
    • Adenomyosis
    • Chronic endometritis (see Endometritis )
    • Fibroids (see Fibroids )
    • Intrauterine device
    • Pelvic congestion
    • Pelvic support defects
    • Polyps
Urologic
  • Chronic urinary tract infection (see Urinary Tract Infection, Females )
  • Overactive bladder
  • Interstitial cystitis (see Interstitial Cystitis )
  • Bladder stones (see Bladder Stones )
  • Suburethral diverticulitis (see Urethral Diverticulum )
  • Urethral syndrome (see Urethral Syndrome )
  • Trigonitis (see Trigonitis )
Gastrointestinal
  • Constipation (very common in elderly persons) (see Constipation )
  • Diverticular disease
  • Inflammatory bowel disease (see Inflammatory Bowel Disease )
  • Enterocolitis
  • Irritable bowel syndrome (see Irritable Bowel Syndrome )
  • Neoplasia
  • Chronic appendicitis (see Appendicitis )
  • Cholelithiasis (see Cholelithiasis )
Musculoskeletal
  • Coccydynia
  • Disk problems
  • Degenerative joint disease
  • Fibromyositis (see Fibromyalgia )
  • Hernia
  • Herpes zoster (see Herpes Zoster )
  • Lower back pain (see Mechanical Low Back Pain )
  • Levator ani syndrome (pelvic floor spasm)
  • Myofascial pain (see Myofascial Pain )
  • Nerve entrapment syndromes (see Nerve Entrapment Syndromes )
  • Osteoporosis (see Osteoporosis )
  • Posture-related pain
  • Scoliosis (see Scoliosis ), lordosis, kyphosis
  • Strains, sprains
Other
  • Physical or sexual abuse, prior or current (see Domestic Violence )
  • Lead or mercury toxicity (see Toxicity, Lead and Toxicity Mercury )
  • Hyperparathyroidism (see Hyperparathyroidism )
  • Porphyria (see Porphyria, Acute Intermittent )
  • Somatization disorders (see Somatoform Disorders )
  • Substance abuse, ie, cocaine (see Substance Abuse )
  • Sickle cell disease (see Sickle Cell Anemia )
  • Sympathetic dystrophy
  • Tabes dorsalis

Recurrent pelvic pain

Gynecologic
  • Mittelschmerz (see Mittelschmerz )
  • Primary or secondary dysmenorrhea (see Dysmenorrhea )
Differential diagnosis
  • Gastrointestinal
    • Gastroenteritis (see Gastroenteritis, Bacterial and Gastroenteritis, Viral )
    • Appendicitis (see Appendicitis )
    • Bowel obstruction (see Obstruction, Small Bowel )
    • Diverticulitis (see Diverticulitis )
    • Inflammatory bowel disease (see Inflammatory Bowel Disease )
    • Irritable bowel syndrome (see Irritable Bowel Syndrome )
    • Mesenteric ischemia (see Mesenteric Artery Ischemia )
  • Urologic
    • Cystitis (see Cystitis, Nonbacterial )
    • Acute pyelonephritis (see Pyelonephritis, Acute )
    • Ureteric calculus
  • Abdominal wall
    • Hematoma
    • Strangulated or incarcerated hernia (see Abdominal Hernias )
  • Miscellaneous
    • Acute porphyria (see Porphyria, Acute Intermittent )
    • Pelvic thrombophlebitis
    • Aneurysm (see Aneurysms, Abdominal )
    • Abdominal angina (see Abdominal Angina )

Acute pelvic pain

Complications of pregnancy
  • Ectopic pregnancy, ruptured or unruptured (see Ectopic Pregnancy )
  • Abortion (see Threatened Abortion and Abortion, Incomplete )
  • Degenerating fibroid (see Fibroids )
Acute infection
  • Endometritis (see Endometritis )
  • Acute pelvic inflammatory disease (see Pelvic Inflammatory Disease )
  • Tubo-ovarian abscess
  • Pelvic thrombophlebitis
  • Ovarian vein thrombosis (see Ovarian Vein Thrombosis )
Adnexal mass
  • Corpus luteum hematoma (see Corpus Luteum Rupture )
  • Ovarian torsion (see Ovarian Torsion )
  • Ruptured ovarian cyst (see Ovarian Cysts )
  • Paratubal cyst
  • Endometriosis (see Endometriosis )
  • Ovarian hyperstimulation syndrome

Chronic pelvic pain

Gynecologic
  • Extrauterine
    • Adhesions
    • Chronic ectopic pregnancy (see Ectopic Pregnancy )
    • Chronic pelvic inflammatory disease (see Pelvic Inflammatory Disease )
    • Endometriosis (see Endometriosis )
    • Ovarian remnant syndrome
  • Uterine
    • Adenomyosis
    • Chronic endometritis (see Endometritis )
    • Fibroids (see Fibroids )
    • Intrauterine device
    • Pelvic congestion
    • Pelvic support defects
    • Polyps
Urologic
  • Chronic urinary tract infection (see Urinary Tract Infection, Females )
  • Overactive bladder
  • Interstitial cystitis (see Interstitial Cystitis )
  • Bladder stones (see Bladder Stones )
  • Suburethral diverticulitis (see Urethral Diverticulum )
  • Urethral syndrome (see Urethral Syndrome )
  • Trigonitis (see Trigonitis )
Gastrointestinal
  • Constipation (very common in elderly persons) (see Constipation )
  • Diverticular disease
  • Inflammatory bowel disease (see Inflammatory Bowel Disease )
  • Enterocolitis
  • Irritable bowel syndrome (see Irritable Bowel Syndrome )
  • Neoplasia
  • Chronic appendicitis (see Appendicitis )
  • Cholelithiasis (see Cholelithiasis )
Musculoskeletal
  • Coccydynia
  • Disk problems
  • Degenerative joint disease
  • Fibromyositis (see Fibromyalgia )
  • Hernia
  • Herpes zoster (see Herpes Zoster )
  • Lower back pain (see Mechanical Low Back Pain )
  • Levator ani syndrome (pelvic floor spasm)
  • Myofascial pain (see Myofascial Pain )
  • Nerve entrapment syndromes (see Nerve Entrapment Syndromes )
  • Osteoporosis (see Osteoporosis )
  • Posture-related pain
  • Scoliosis (see Scoliosis ), lordosis, kyphosis
  • Strains, sprains
Other
  • Physical or sexual abuse, prior or current (see Domestic Violence )
  • Lead or mercury toxicity (see Toxicity, Lead and Toxicity Mercury )
  • Hyperparathyroidism (see Hyperparathyroidism )
  • Porphyria (see Porphyria, Acute Intermittent )
  • Somatization disorders (see Somatoform Disorders )
  • Substance abuse, ie, cocaine (see Substance Abuse )
  • Sickle cell disease (see Sickle Cell Anemia )
  • Sympathetic dystrophy
  • Tabes dorsalis

Recurrent pelvic pain

Gynecologic
  • Mittelschmerz (see Mittelschmerz )
  • Primary or secondary dysmenorrhea (see Dysmenorrhea )
Differential diagnosis
  • Gastrointestinal
    • Gastroenteritis (see Gastroenteritis, Bacterial and Gastroenteritis, Viral )
    • Appendicitis (see Appendicitis )
    • Bowel obstruction (see Obstruction, Small Bowel )
    • Diverticulitis (see Diverticulitis )
    • Inflammatory bowel disease (see Inflammatory Bowel Disease )
    • Irritable bowel syndrome (see Irritable Bowel Syndrome )
    • Mesenteric ischemia (see Mesenteric Artery Ischemia )
  • Urologic
    • Cystitis (see Cystitis, Nonbacterial )
    • Acute pyelonephritis (see Pyelonephritis, Acute )
    • Ureteric calculus
  • Abdominal wall
    • Hematoma
    • Strangulated or incarcerated hernia (see Abdominal Hernias )
  • Miscellaneous
    • Acute porphyria (see Porphyria, Acute Intermittent )
    • Pelvic thrombophlebitis
    • Aneurysm (see Aneurysms, Abdominal )
    • Abdominal angina (see Abdominal An

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