11.3 Abnormal Uterine Bleeding & Pelvic Inflammatory Disease

FIGO PALM-COEIN Classification of Abnormal Uterine Bleeding

Abnormal Uterine Bleeding (AUB) encompasses any variation from the normal menstrual cycle, including abnormalities in frequency (regular cycle 24 to 38 days), regularity (variation <= 7 to 9 days), duration (bleeding <= 8 days), or volume (patient-perceived heavy flow or blood loss > 80 mL). The International Federation of Gynecology and Obstetrics (FIGO) established the PALM-COEIN classification to standardize clinical evaluation:

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|                        FIGO PALM-COEIN CLASSIFICATION FOR AUB                           |
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                   +-------------------------+-------------------------+
                   |                                                   |
                   v                                                   v
         [ STRUCTURAL (PALM) ]                               [ NON-STRUCTURAL (COEIN) ]
    (Diagnosed by Imaging / Histology)                  (Functional / Systemic / Endocrine)
  - P: Polyp (Endometrial / Endocervical)             - C: Coagulopathy (vWD, ITP)
  - A: Adenomyosis (Endometrial glands in myometrium)  - O: Ovulatory dysfunction (PCOS, Perimenopause)
  - L: Leiomyoma (Fibroids: Submucosal vs Others)     - E: Endometrial (Primary hemostatic defect)
  - M: Malignancy & Hyperplasia (EIN / Carcinoma)     - I: Iatrogenic (IUDs, Drugs, Anticoagulants)
                                                      - N: Not otherwise classified (AVMs, Isthmocele)

Structural Etiologies (PALM)

1. Polyp (AUB-P): Benign localized overgrowths of endometrial glands and stroma surrounding a vascular core. Typically manifest as intermenstrual bleeding, postcoital bleeding, or light menorrhagia. Diagnosed via transvaginal ultrasound (TVS), saline infusion sonohysterography (SIS), or hysteroscopy. Management: hysteroscopic polypectomy.
2. Adenomyosis (AUB-A): Benign penetration of endometrial basal glands and stroma deep into the myometrium, accompanied by reactive myometrial smooth muscle hypertrophy. Classically presents in multiparous women aged 35 to 50 with severe secondary dysmenorrhea and heavy menstrual bleeding. Physical exam reveals a symmetrically enlarged, globular, soft/boggy, and tender uterus (rarely exceeding 12 to 14 weeks size). TVS and MRI demonstrate asymmetric myometrial thickening, subendometrial microcysts, heterogeneous myometrial echotexture, and junctional zone thickness > 12 mm. First-line medical therapy: LNG-IUS; definitive surgical treatment: hysterectomy.
3. Leiomyoma / Fibroids (AUB-L): Benign monoclonal smooth muscle tumors. FIGO types 0–2 protrude into the endometrial cavity. Type 3 is entirely intramural but contacts the endometrium; type 4 is intramural without endometrial or serosal contact. Types 5–7 are subserosal: type 5 has>=50% intramural tissue, type 6<50%, and type 7 is pedunculated. Type 8 includes cervical or parasitic lesions. Exam reveals an irregularly enlarged, firm, nodular, non-tender uterus. Leiomyomas produce heavy prolonged menses, profound iron-deficiency anemia, pelvic pressure, urinary frequency, and constipation.
   • Red (Carneous) Degeneration: An acute complication occurring predominantly during pregnancy or high-estrogen states when the fibroid outgrows its arterial blood supply, leading to hemorrhagic infarction. Presents with acute localized abdominal pain, focal uterine tenderness over the fibroid, low-grade fever, and leukocytosis. Managed conservatively with analgesia and hydration (surgery is contraindicated during acute degeneration due to extreme hemorrhage risk).
4. Malignancy & Hyperplasia (AUB-M): Endometrial hyperplasia (particularly atypical hyperplasia / endometrial intraepithelial neoplasia [EIN]) and endometrial adenocarcinoma. Must be investigated in perimenopausal women and in any woman with postmenopausal bleeding.

Non-Structural Etiologies (COEIN)

1. Coagulopathy (AUB-C): Underlying systemic disorders of hemostasis. Present in up to 20% of adolescents presenting with severe menorrhagia at menarche. Von Willebrand Disease (vWD) is the most common inherited bleeding diathesis. Screen with: heavy menses since menarche, history of postpartum hemorrhage, bleeding after dental work, or recurrent epistaxis/gingival bleeding.
2. Ovulatory Dysfunction (AUB-O): Absence of cyclical luteal progesterone production due to anovulatory cycles. Chronic unopposed estrogen drives sustained, disorganized endometrial proliferation without secretory stabilization, leading to fragile, asynchronous breakdown and heavy, unpredictable bleeding. Common at the extremes of reproductive life (adolescents post-menarche and perimenopausal women). Pathological causes include Polycystic Ovary Syndrome (PCOS), hypothyroidism, hyperthyroidism, hyperprolactinemia, hypothalamic amenorrhea, and extreme physical stress.
3. Endometrial (AUB-E): Primary disorder of the local endometrial hemostatic mechanisms, manifesting as predictable, cyclical heavy menstrual bleeding in women with normal ovulatory function and no structural pathology. Pathophysiology involves local deficiencies in vasoconstrictors (endothelin-1, PGF2-alpha) and excessive local vasodilators (PGE2, prostacyclin) or accelerated endometrial fibrinolysis.
4. Iatrogenic (AUB-I): Caused by medications or intrauterine devices. Copper IUDs frequently cause menorrhagia and dysmenorrhea; progestin implants and injections cause unscheduled breakthrough spotting; psychotropics altering dopamine cause hyperprolactinemia (e.g., risperidone, haloperidol); and oral anticoagulants exacerbate flow.
5. Not Otherwise Classified (AUB-N): Rare conditions such as uterine arteriovenous malformations (AVMs) and caesarean scar defects (isthmocele).

Diagnostic Workup & Endometrial Sampling Guidelines

Initial Diagnostic Assessment

• Pregnancy test (urine or serum beta-hCG) is mandatory in every reproductive-age female presenting with AUB.
• Complete blood count (hemoglobin, hematocrit, platelet count) and serum ferritin to evaluate iron deficiency.
• Targeted laboratory workup: Thyroid-stimulating hormone (TSH), serum prolactin, coagulation profile (PT, aPTT, vWF antigen, and Ristocetin cofactor if heavy menses since menarche).
• Pelvic transvaginal ultrasound (TVS) to measure double-wall endometrial thickness (ET), uterine size, and detect leiomyomas, adenomyosis, or adnexal masses.

Mandatory Indications for Endometrial Biopsy (Pipelle Sampling)

Endometrial tissue sampling is required to exclude atypical endometrial hyperplasia and endometrial carcinoma in the following patient cohorts:

1. All women aged >= 45 years presenting with abnormal uterine bleeding.
2. Women aged < 45 years with persistent AUB and clinical risk factors for chronic unopposed estrogen exposure:
   • Obesity (BMI >= 30 kg/m2; peripheral aromatization of androstenedione to estrone)
   • Polycystic Ovary Syndrome (PCOS) / chronic anovulation
   • Nulliparity, early menarche, or late menopause
   • Diabetes mellitus and hypertension
   • Family history of endometrial, ovarian, or colorectal cancer (Lynch syndrome / HNPCC)
   • Tamoxifen therapy
   • Failure of first-line medical therapy with persistent bleeding
3. Any postmenopausal female presenting with uterine bleeding and an endometrial thickness > 4 mm on TVS.

Evidence-Based Medical Management of AUB

Medical therapy is the first-line intervention for AUB without malignant pathology:

Pelvic Inflammatory Disease (PID): Pathogenesis & Clinical Diagnosis

Pelvic Inflammatory Disease (PID) is an acute, ascending infection of the female upper genital tract involving any combination of the endometrium (endometritis), fallopian tubes (salpingitis), ovaries (oophoritis), and pelvic peritoneum (peritonitis).

Microbial Etiology

PID is overwhelmingly an ascending, sexually transmitted polymicrobial infection:

• Primary Initiating Pathogens:
  • Chlamydia trachomatis: Responsible for 30-50% of cases. Characterized by an insidious, indolent, subacute presentation. Lower-genital chlamydial infection is often asymptomatic and may ascend to cause PID. Upper-genital infection can also be subtle or asymptomatic while causing tubal damage; a positive cervical test alone does not diagnose PID.
  • Neisseria gonorrhoeae: Responsible for 20-40% of cases. Characterized by an acute, fulminant presentation with high-grade pyrexia, copious purulent cervical discharge, and severe pelvic pain.
• Mycoplasma genitalium: A sexually transmitted pathogen associated with cervicitis and PID.
• Other Polymicrobial Flora: Endogenous vaginal anaerobes and opportunists superinfect the damaged mucosa, including Bacteroides fragilis, Prevotella species, Peptostreptococcus, Ureaplasma urealyticum, and enteric Gram-negative rods (Escherichia coli).

Clinical Presentation & The Low-Threshold Empiric Diagnostic Rule

Symptoms include: bilateral lower abdominal and pelvic pain (dull, aching, constant, exacerbated by walking and coitus), abnormal mucopurulent vaginal discharge, deep dyspareunia, postcoital bleeding, and irregular intermenstrual bleeding. Severe cases display high spiking fevers, chills, nausea, and vomiting.

CDC & International Empiric Diagnostic Standard: Because the risk of permanent tubal damage and subsequent infertility increases exponentially with every day treatment is delayed, clinicians must maintain a low threshold for initiating empiric antibiotic therapy. Empiric treatment for PID must be started immediately in any sexually active young woman presenting with lower abdominal or pelvic pain if no other cause is apparent and at least ONE of the following minimum clinical criteria is present on bimanual pelvic examination:

1. Cervical Motion Tenderness (CMT / 'Chandelier Sign'): Severe, sharp pain elicited by gentle lateral and vertical rocking of the cervix during examination.
2. Uterine Tenderness: Marked tenderness upon direct bimanual palpation and compression of the uterine corpus.
3. Adnexal Tenderness: Tenderness upon palpation of one or both fallopian tubes and ovaries.

Supportive Criteria: Oral temperature > 38.3°C (101°F); abnormal cervical mucopurulent discharge or cervical friability; abundant white blood cells on saline wet mount of vaginal fluid; elevated C-Reactive Protein (CRP) or ESR; and laboratory confirmation of cervical infection with N. gonorrhoeae or C. trachomatis via Nucleic Acid Amplification Testing (NAAT).

Antimicrobial Regimens, Complications & Long-Term Sequelae

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|                        OUTPATIENT vs INPATIENT PID MANAGEMENT                           |
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                   |                                                   |
                   v                                                   v
         [ OUTPATIENT REGIMEN ]                              [ INPATIENT REGIMEN ]
  - Indications: Mild to moderate disease,            - Indications: Tubo-ovarian abscess, surgical
    tolerating oral intake, reliable follow-up          emergency uncertain, pregnancy (specialist regimen), severe illness
  - Ceftriaxone 500 mg IM single dose                   (high fever/vomiting), failed oral therapy
    + Doxycycline 100 mg PO BD x 14 days              - If nonpregnant: Ceftriaxone 1-2 g IV daily
    + Metronidazole 400-500 mg PO BD x 14 days          + Doxycycline 100 mg IV/PO BD
  - Mandatory clinical review at 48 to 72 hours         + Metronidazole 500 mg IV/PO BD
                                                        (Or Clindamycin 900mg IV q8h + Gentamicin)

Standard Outpatient Regimen

Indicated for mild-to-moderate PID without systemic toxicity or signs of peritonitis:

• Ceftriaxone 500 mg IM as a single dose (covers N. gonorrhoeae; use 1 g if patient weighs >= 150 kg) PLUS
• Doxycycline 100 mg orally twice daily for 14 days (covers C. trachomatis) PLUS
• Metronidazole 400 to 500 mg orally twice daily for 14 days (provides essential anaerobic coverage and treats bacterial vaginosis, preventing anaerobic tubal destruction).
• Crucial Rule: The patient must be clinically re-evaluated at 48 to 72 hours. Failure to demonstrate substantial clinical improvement (reduction in fever, abdominal pain, and pelvic tenderness) mandates immediate hospital admission.

Inpatient Admission Criteria & Parenteral Regimens

Indications for Inpatient Admission:

1. Surgical emergencies cannot be excluded (e.g., acute appendicitis, ovarian torsion, ectopic pregnancy).
2. Tubo-Ovarian Abscess (TOA) suspected or confirmed on imaging.
3. Pregnancy (PID in pregnancy is exceptionally rare but carries severe risk of maternal sepsis and fetal loss).
4. Severe illness, high fever (> 38.5°C), nausea, vomiting, or peritonitis.
5. Inability to tolerate or absorb oral medications.
6. Clinical failure of oral outpatient therapy after 48 to 72 hours.
7. Severe immunocompromise (advanced HIV disease).

Inpatient Parenteral Regimens (nonpregnant patients): In pregnancy, select IV antibiotics with an infectious-disease specialist.

• Regimen A: Ceftriaxone 1 to 2 g IV once daily PLUS Doxycycline 100 mg IV or orally twice daily PLUS Metronidazole 500 mg IV twice daily.
• Regimen B: Clindamycin 900 mg IV every 8 hours PLUS Gentamicin 2 mg/kg IV loading dose followed by 1.5 mg/kg IV every 8 hours (or once-daily 5 mg/kg).
• Parenteral therapy is maintained until the patient exhibits sustained clinical improvement for at least 24 to 48 hours (resolution of fever, leukocytosis, and tenderness), after which oral therapy (Doxycycline 100 mg BD + Metronidazole 400 mg BD) is continued to complete the full 14-day course.

Complications & Long-Term Reproductive Sequelae

1. Fitz-Hugh-Curtis Syndrome (Perihepatitis): Occurs in 5% to 15% of PID cases. Represents transperitoneal or lymphatic dissemination of C. trachomatis or N. gonorrhoeae to the liver capsule and subdiaphragmatic space. Clinically presents with sharp, pleuritic right upper quadrant (RUQ) abdominal pain radiating to the right shoulder, frequently mimicking acute cholecystitis or pleurisy. Laparoscopy reveals characteristic 'violin-string' fibrinous adhesions between the anterior hepatic capsule and the parietal peritoneum. Liver function tests are characteristically normal or only mildly deranged.
2. Tubo-Ovarian Abscess (TOA): A life-threatening loculated inflammatory mass involving the fallopian tube, ovary, and adjacent bowel. TVS demonstrates a complex, multilocular, thick-walled adnexal mass with internal echoes and septations. Unruptured TOA is treated with inpatient parenteral antibiotics; masses >= 8 cm or those refractory to 48-72 hours of IV therapy require percutaneous or laparoscopic drainage. Ruptured TOA requires urgent resuscitation, broad-spectrum IV antibiotics and operative source control. Laparotomy or laparoscopy provides drainage and washout; salpingo-oophorectomy may be necessary for nonviable or extensively destroyed tissue, but is not mandatory in every case.
3. Long-Term Reproductive Morbidity:
   • Tubal Factor Infertility: Directly proportional to the number of PID episodes: approximately 10% to 12% after one episode, 20% to 25% after two episodes, and > 50% after three or more episodes.
   • Ectopic Pregnancy: The risk of extrauterine gestation is increased 7- to 10-fold following PID due to loss of tubal ciliated epithelium and luminal plical adhesions.
   • Chronic Pelvic Pain: Affects approximately 30% of patients due to chronic pelvic adhesions and nerve entrapment.
   • Partner Tracing: All sexual partners within the preceding 60 days must be evaluated, tested, and empirically treated regardless of symptoms, with strict sexual abstinence until all partners have completed their antimicrobial regimens.