Chronic Pelvic Pain and Perimenopausal Bleeding

Educational Objectives

The goal of this program is to improve the management of chronic pelvic pain (CPP) and perimenopausal bleeding. After hearing and assimilating this program, the clinician will be better able to:

1.   Distinguish chronic pelvic pain (CPP) from pain associated with overlapping pathologies (eg, endometriosis).

2.   Recognize painful bladder syndrome (PBS) and provide appropriate treatment.

3.   Diagnose neuropathies associated with the abdominal wall and pudendal nerve.

4.   Rule out potential malignancies in patients with noncyclic uterine bleeding.

5.   Prescribe therapy to alleviate anovulatory uterine bleeding in perimenopausal women.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning com­mittee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and the planning committee reported nothing to disclose. In her lec­ture, Dr. Rapkin presents information related to off-label or investigational use of a therapy, product, or device.

Acknowledgments

Dr. Rapkin spoke at 64th Annual Obstetrical and Gynecological Assembly of Southern California, held April 3-4, 2009, in Marina Del Rey, CA. Dr. Hunter-Hicks was recorded at 20th Annual Conference on Focus on the Female Pa­tient, held July 26-30, 2009, in Kiawah Island, SC, and sponsored by the Southern Medical Association. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Management of Chronic Pelvic Pain

Andrea Rapkin, MD, Professor, Department of Obstetrics and Gynecology, David Geffen School of Medicine, and Director, Pelvic Pain Clinic, University of California, Los Angeles

“Red flags”: warning symptoms differentiate chronic pelvic pain syndrome (CPPS) from chronic pelvic pain (CPP); CPPS includes 1) poor response to typically effective conventional therapies, 2) pain disproportionate to degree of pathology, 3) psychosocial and psychologic abnormalities (eg, anxiety, depression), 4) multiple visceral or somatic complaints

Criteria: CPPS categorized as neuropathic disease; frequently presents with sensory abnormalities, exaggerated re­flex response (within end organ area), end organ dysfunction, abnormal muscle contraction (eg, abdominal wall, pelvic floor), and spontaneous firing of dorsal horn neurons; patients frequently display no apparent injuries; allodynia  —  preliminary symptom; attributed to chemical release in dorsal horn; describes abnormal tenderness and disproportionate response to pain; associated with abnormal excitability in spinal cord and brain; hyperalgesia  —  increased sensitivity to pain; pathologic changes to nociceptive systems may become permanent and transfer from pelvic nerves to brain and central nervous system

Neuropathic correlates: visceral hyperalgesia  —  dysmenorrhea, irritable bowel syndrome, interstitial cystitis (IC), and referred neurogenic inflammation (causes vulvodynia in patients with IC; nociceptive signaling within single organ capable of lowering excitatory thresholds throughout pelvic area), visceral muscular reflex, pelvic floor ten­sion myalgia, abdominal wall myalgia (myofascial pain); co-morbidity  —  patients typically present with multiple overlapping conditions; questionnaires valuable for identifying symptoms related to trauma, anxiety, depression, panic, and post-traumatic stress disorder (PTSD); symptoms frequently overlap with those of fibromyalgia or chronic fatigue syndrome (CFS; eg, neuropathy, trigger points); British study  —  found multiple pain generators re­lated to CPP; patients significantly more likely to report dysmenorrhea and dyspareunia; 25% to 50% received mul­tiple diagnoses; multiple organ system involvement associated with moderate to severe pain; potassium instillation study  —  69% of subjects with CPP had positive potassium tests, indicating probable bladder hyperalgesia; 11% dis­played classic IC or biopsy-proven endometriosis

Psychology: patients suffering from CPP frequently report past abuse; Ahnert study  —  PTSD clinically diagnosed in 40% of subjects with CPP (0% in control arm); Heim study  —found changes to responsivity of hypothalamic-pitu­itary-adrenal (HPA) axis in patients with CPP; modulating factors  —depression, anxiety, stress, catastrophic pessi­mism, sensation of loss of control, and reinforcement of pain behavior (eg, by family members); frequently require attention to achieve pain remission

Associated syndromes: endometriosis pain syndrome  — patients with endometriosis may develop pain unresponsive to adhesiolysis; pelvic congestion syndrome  —  infrequently diagnosed in America; myofascial correlates  —  pelvic floor, abdominal wall, generalized fibermyalgia, and vulvodynia; hypogastric ileoinguinal neuropathy  —  more likely to be induced by surgical procedures in patients with CPP (due to neurologic hypersensitivities); inferior hy­pogastric plexus  —  tenderness within area may indicate hyperalgesia; nerve block through hypogastric plexus may alleviate pain when excision of uterus produces no response; focal tenderness and endometriosis  —surgical exci­sion of areas producing tenderness frequently alleviates pain, thus ruling out endometriosis pain; innervation of implants  —  peripheral and central sensitization demonstrated in patients with endometrial implants; sensitization modulates thresholds for nerve excitation in unrelated remote areas (eg, extremities)

Treating symptoms of endometriosis: cyclical pain frequently indicates relationship to endometriosis; approxi­mately one-third of patients with mild or moderate disease do not respond to treatment; hormone therapy  —  considered first-line treatment for CPP with cyclic exacerbation or dysmenorrhea; Cochrane database oral contra­ceptive (OC) studies  —  suggest OCs may be as effective as gonadotropin-releasing hormone (GnRH) analogues, and that continuous OCs superior to cyclic OCs; combination evaluation  —  27 trials evaluated efficacy of various progestins; only 9% nonresponders; similar efficacy demonstrated in 4 randomized control trials (RCTs) compar­ing progestins to danazol or GnRH; progestins produce high response rates, but tolerated poorly; add-back regi­mens improve tolerability of GnRH analogues; intrauterine progesterone study  —  subjects receiving intrauterine devices (IUDs) reported greater relief of dysmenorrheal symptoms and higher patient satisfaction; danazol  —  vaginal dosing (with contraceptive) may improve tolerability; GnRH analogues  —  well-studied; outcomes equal to those of danazol; substantially superior to placebo for dysmenorrhea; add-back regimens not shown to reduce pain; aromatase inhibitors  —letrozole used by speaker in severe cases (eg, unresponsive pulmonary endometriosis); surgical management  —  ovary-sparing procedures significantly more likely to require reoperation; estrogen re­placement should be delayed until 6 mo postsurgery (consider progestin alone); surgical modalities significantly as­sociated with pain recurrence over 5 yr; nonresponsive patients typically report pain within 3 to 5 mo; adhesions  —  infertility and CPP not typically related to location of adhesions; 2 RCTs suggest surgery does not affect outcomes; Swank study  —  laparoscopy with adhesiolysis not superior to laparoscopy alone (subject-blinded placebo)

Painful bladder syndrome (PBS): highly specific subgroup of patients with severe end organ disease; cystoscopy frequently normal; suprapubic pain most common complaint; vaginal, urethral, or perineal pain not uncommon; po­tassium sensitivity test  —  losing favor due to potential for significant pain, even in patients with healthy bladders; urinary tract infections (UTIs)  —  lack of response to treatment may indicate false positive; voiding abnormalities occasionally respond to pelvic floor physical therapy; vulvodynia and dyspareunia may relate to increased sensiti­zation or pelvic floor trigger points; etiology  —  currently unestablished; no correlation between lesions and out­come; phantom pain  —  bladder removal frequently relieves urgency and frequency, but not pain; diet  —  liquids restricted to water and chamomile tea; bland foods recommended; agents to balance bladder acidity and bladder training behavior modification frequently effective; pentosan polysulfate  —requires 6 mo to produce response; may cause alopecia; cannot be combined with nonsteroidal anti-inflammatory drugs (NSAIDs; hydroxyzine due to antico­agulant effect); intravesical placement improves response rates; hydroxyzine  —  oral antihistamine; produces mast cell degranulation; elevated histamine concentrations observed in bladders of patients with PBS; amitriptyline  —  acts as antihistamine, sodium channel blocker, and anticholinergic (reduces voiding); nerve blocks  —  pudendal, caudal, and epidural blocks used to downregulate hyperactive systems; implantable sacral nerve stimulator (SNS)  —  small studies show promise

Neuropathic abdominal wall pain: differentiated into 2 types; 1) nerve injury  —  produced by surgical complications or induced by exercise or trauma (associated with neurovascular herniation), 2) myofascial trigger points  —  primary or secondary to previous visceral inflammation; ileohypogastric (IH) and ileoinguinal (IL) neuropathy  —  typically presents with dysesthesia (described as burning or aching) over L1 and L2 nerve distribution; frequently reported as ovarian pain; pain referred to hip, labia (with IL neuropathy), or anterior thigh; movement or leaning forward often reported as source of pain; physical examination (PE) should focus on localizing pain; Carnett test  —  have patient lift both legs straight up and repalpate area; persisting pain indicates abdominal wall pain (rather than visceral); aspiration and local anesthetization of affected nerves produces immediate relief; 50% decrease in pain over 2 wk confirms diagnosis of neuropathy; trigger points  —  hyperalgesias associated with viscerosomatic re­ferred pain; injecting trigger points with local anesthetic yielded 89% success rate at 6-mo follow-up; nonlocalized abdominal wall pain may indicate trigger points in muscle (rather than visceral pain)

Pudendal neuropathy: frequently arises from viscerosomatic referral or entrapment of pudendal nerve (rare); nerve entrapment  —  patients may display motor signs (altered bowel and bladder function) or severe pain alleviated by standing; clitoral, vestibular, perineal, and rectal pain frequently classified as pudendal neuropathy; examinations should evaluate tenderness across entire distribution and individual branches of pudendal nerve; palpate nerve at is­chial spine area; pudendal nerve motor latency test  —  of limited use (pudendal nerve must be severely damaged to exhibit motor neuropathy); postpartum  —  42% of patients exhibit trauma; risk factors include forceps, prolonged second stage, and high birth weight; mesh placement for posterior repair  —  may compromise pudendal nerve; re­vised Food and Drug Administration (FDA) guidelines warn of risk for persistent pain (£5%)

Medications for neuropathic pain: tricyclic antidepressants   —  amitriptyline (most sedating); desipramine (least se­dating); topical agents  —  used for vulvar, vestibular, perirectal, and abdominal wall pain; selective serotonin reup­take inhibitors (SSRIs)  —  not typically effective for neuropathic pain; serotonin-norepinephrine reuptake inhibitors  —  addition of norepinephrine component improves response rates significantly (over SSRIs); anticonvulsants  —  patients unresponsive to gabapentin may respond to pregabalin (or vice versa); slow dosage es­calation advised due to associated sedation and dizziness; compounding  —  amitriptyline or gabapentin may be added to lidocaine for abdominal wall pain; 10% dimethyl sulfoxide may help compounds penetrate tissues; local anesthetic nerve blocks  —  given in series

Patient evaluation: thorough history critical; pain questionnaires valuable; daily pain rating  —  documents potential relationships between pain and menstrual bleeding and differentiates between types of pain; recording mood rat­ings and pain triggers gives information about relationship to depression and stress; pain-mapping PE  —  start with abdominal wall and check for vulvar and vestibular pain; should include examination of urethra and palpation of bladder, pelvic floor muscles (separately), paracervical region, and inferior hypogastric plexus; block trigger points and neuropathies before pelvic examination; rectovaginal examination also recommended; early multimodal therapy  —  look for and remove (or isolate) original insult and all triggers; treats all sources of pain and dysfunction (beyond gynecologic origin); physical therapy  —  can reduce nervous system irritability by relieving muscles con­tracted around nerves; psychologists  —  should be familiar with cognitive-behavioral modalities and determination of optimal stress-reduction technique

Perimenopausal Bleeding: What’s the Work-up?

Verda Hunter-Hicks, MD, Resource Center For Gynecologic Oncology, Kansas City, MO

Noncyclic uterine bleeding: anovulation  —  primary pathophysiology associated with abnormal bleeding; absence of corpus luteum causes failure of ovaries to secrete progesterone; continued estrogen release stimulates growth of uterine lining; lack of progesterone inhibits normal menstruation and enables continuous endometrial proliferation; patients frequently present with irregular, unpredictable, or inconsistent menstruation; similar abnormal changes may occur during adolescence or postpartum; anovulatory uterine bleeding  —  risk escalates as women approach menopause; onset represents decline in ovarian function; educating patients about normal changes during peri­menopausal period critical; follicle-stimulating hormone, luteinizing hormone, or estradiol  —serum levels unreli­able during perimenopausal period (due to sporadic resumption of ovarian function); possibility of pregnancy should be considered; coagulopathies  —  more prevalent in younger patients

Diagnosis: should focus on ruling out cancer and associated atrophic changes; obesity  —  primary risk factor for en­dometrial cancer; induces unopposed estrogen production and potentiates formation of endometrial hyperplasia; differential  —  begins with typical history and PE plus gynecologic examination; ultrasonography (US) determines if biopsy or sampling of endometrium indicated; endometrial assessment  —  uniformly indicated in perimenopausal women due to high prevalence of endometrial cancer; disposable suction piston devices  —  most common method of endometrial assessment; few studies have evaluated in-office sampling vs dilation and curettage (D&C); office-based devices yield false negatives in approximately one-third of patients; D&C  —  misses 10% of lesions; in 20% of procedures, only 20% of endometrium sampled; transvaginal US  —applies high-frequency transducers in close proximity to targeted structures and produces magnification; visualizes interface between 2 sides of atrophic basal endometrium; endometrial echo of £4 mm associated with diminished rates of endometrial cancer (>1 in 100,000; biopsy not required); common irregularities in uterine shape may obscure results, rendering transvaginal US unreli­able; sonohysterography  —  viable alternative to D&C and procedures requiring general anesthesia; thickened endometrium  —  clinical significance remains unclear; literature does not support requisite biopsy when detected

Medications: anovulatory uterine bleeding classified as endocrine disorder; medical management preferred; primary goal  —  eliminate bleeding and prevent anemia; therapies require significant time to correct changes in endometrial lining; patients should attempt regimens for minimum of 2 to 3 mo; cyclic progestins  —  advised for patients with semi-regular menstrual cycles (intermittent anovulation); therapy for 10 to 15 days per month may induce regular menstrual cycles; low-dose contraceptives  —  generally preferred treatment (except in patients who smoke); cyclic hormone replacement therapy  —recommended for patients closer to true postmenopause (few or absent ovulatory cycles); perimenopausal women frequently experience withdrawal bleeding

Surgical therapy: indicated when excessive anovulatory bleeding unresponsive to medication; hysterectomy  —  not considered ideal due to association with high rates of mortality and morbidity; endometrial ablation  —  thermal ab­lation typically preferred; yields high patient satisfaction rates; risk for amenorrhea low; laser abalation associated with greater perioperative risks

Suggested Reading

Cagnacci A et al: Cyclic progestin administration increases energy expenditure and decreases body fat mass in perimeno­pausal women. Menopause