Abnormal uterine bleeding

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Farman Khan, MD, MRCP [2]

Causes

Common Causes


Causes by Organ System

Cardiovascular No underlying causes
Chemical / poisoning No underlying causes
Dermatologic No underlying causes
Drug Side Effect Blood thinners, breakthrough bleeding in women using hormonal birth control, copper intrauterine device , depo-Provera

hormone replacement therapy, tamoxifen, corticosteroids, chemotherapy, clomiphene, dilantin, antipsychotic drugs , antibiotics ( due to toxic epidermal necrolysis or Stevens-Johnson syndrome )

Ear Nose Throat No underlying causes
Endocrine Diabetes, hyperthyroidism, hypothyroidism, Cushing's syndrome, Hormone secreting adrenal and ovarian tumors
Environmental No underlying causes
Gastroenterologic Liver disease
Genetic No underlying causes
Hematologic Clotting disorders, Von Willebrand disease, thrombocytopenia or platelet dysfunction,

acute leukemia ,Some factor deficiencies, Advanced liver disease

Iatrogenic Radiation therapy
Infectious Disease Chlamydia, gonorrhea, uterine infection, genitourinary tract infection, bacterial vaginosis

sexually transmitted diseases, atrophic vaginitis

Musculoskeletal / Ortho No underlying causes
Neurologic No underlying causes
Nutritional / Metabolic No underlying causes
Obstetric/Gynecologic Adenomyosis, atrophy of the tissue lining the vagina and uterus, cervicitis, ectopic pregnancy, endometrial hyperplasia, endometritis, uterine sarcoma, first few months after the first menstrual period, first few weeks after abortion, first few weeks after delivery, intrauterine device, miscarriage, ovarian cysts, placenta previa, polycystic ovarian syndrome, retained products of conception, uterine fibroids, uterine polyps, diseases involving the vulva for example Crohn's disease, Behcet's syndrome , pemphigoid , pemphigus , erosive lichen planus , lymphoma, skin tags, sebaceous cysts, condylomata, angiokerataoma
Oncologic Cancer or precancer of the cervix , cancer or precancer of the endometrium, ovarian cancer, uterine cancer, uterine sarcoma
Opthalmologic No underlying causes
Overdose / Toxicity No underlying causes
Psychiatric No underlying causes
Pulmonary No underlying causes
Renal / Electrolyte Chronic renal disease
Rheum / Immune / Allergy No underlying causes
Sexual Sexual abuse
Trauma Sexual intercourse , sexual abuse , foreign bodies (including IUD) , pelvic trauma, Straddle injuries
Urologic Genitourinary tract infection
Dental No underlying causes
Miscellaneous Foreign body, irritation of the genital area due to bubble baths, soaps, lotions or infection, smoking,

Excessive exercise

Causes in Alphabetical Order


Treatment

Contraindicated medications


Template:Abnormal uterine bleeding Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3] Associate Editor(s)-in-Chief: Nima Nasiri, M.D.[4]

Overview

Abnormal uterine bleeding differential diagnosis

  • Abnormal uterine bleeding differential diagnosis include:[1]
  • Endometrial hyperplasia
  • Cervical polyp
  • Cervical leiomyoma
  • Cervical lymphoma
  • Cervical sarcoma
  • Metastases to the cervix
  • Cervical ectopic pregnancy
  • Cervicitis
  • Cervical erosion ( Ectropion )
  • IUD use
  • Pelvic inflammatory disease
  • Endometriosis
  • Adenomyosis
  • Postcoital bleeding
  • Clear cell adenocarcinoma
  • Hematologic causes:
    • Von willebrand disease
    • Thrombocytopenia
    • Clotting disorder
    • Platelet dysfunction
    • Factors deficiency
Abnormal Uterine bleeidng differential diagnosis
Ob-Gyn neoplasm and diseases Clinical manifestations Para-clinical findings Gold standard
Symptoms Physical exam Lab Findings Imaging Histopathology
Abnormal

vaginal bleeding

Other Genitourinary/ Gastrointestinal symptoms Abdominal pain Pelvic

pain

B symptoms Gynecological examinations Abdominal

mass

HPV

Pap smear

STI panel

Other labs Ultrasound Other

imagings

Cervical cancer[2][3][4][5][6][7][8][9]
  • Postmenopausal
  • Intermenstrual
  • Postcoital
  • Bleeding after pelvic exam
  • Dysuria
  • Urinary hesitancy
  • Dyspareunia
  • Vaginal discharge
  • Itching or burning of the vulva

+

+ +
  • Cervical mass on exam
+ ± HPV
  • Atypical cells on Pap smear
  • STI: ±Chlamydia
  • ↑ CA-125
  • Leukomoid reaction
  • Large cervical cancer
  • Angiogenesis on Doppler sonography
  • Bladder involvement
  • Lymph node involvement
T2-weighted MRI :
  • Ovoid, heterogeneous tumor distending the cervical canal with stromal involvement. PET/CT scan:
    • Detect tumor size
    • Lymph node involvement,
    • Metastases to bladder or rectum
  • CIN1: mild dysplasia
  • CIN2: moderate dysplasia
  • CIN3: high degree of dysplasia/metastases
  • Colposcopy/biopsy
Cervical polyp[10]
  • Postcoital
  • Intermenstrual
  • Postmenopausal
  • Bleeding after exam
  • Vaginal discharge
  • Dyspareunia
  • Mass on exam
  • RBC count
  • ↓ Hb, ↓ Hct
  • ↓ Serum Iron
  • Hyper/hypoechogenic masses with or without cysts
  • Filling the endocervical or vaginal canal
  • Epithelial cells with no nuclear atypia/mitoses
  • Hysteroscopy /Biopsy
Cervical leiomyoma[11][12][13][14][15][16][17][18][19]
  • Heavy/prolonged menstrual bleeding
  • Intermenstrual bleeding
+ +
  • Large,irregular pelvic mass
±
  • Well circumscribed hyperechoic mass
T2-weighted MRI:
  • Hypointense masses
  • Homogeneous

enhancement

  • Red degeneration
  • Spindle shaped smooth muscle cells
  • Mature adipocytes
  • Extracellular matrix consist of collagen,fibronectin.
  • Clinical diagnosis/ and
Cervical lymphoma[20][21][22]
  • Difficulty urinating
  • Post-coital pain
+ + +
  • Larrge uterine/cervix mass
  • Irregularity
+ Pap smear:
  • Small round blue cells
  • High nuclear/cytoplasm ratio,
  • Scant cytoplasm
Immunohistochemistry markers:
  • Well-defined, solid, concentric, hypoechoic mass
MRI:
  • Intramyometrial infiltrative nodules
  • Small tumor cells with large nuclei
  • High mitoses and proliferation
Cervical sarcoma[23][24][25][26]
  • Post-coital pain
  • Fullness in pelvic
  • Vaginal discharge
+ + ±
  • Cervical mass
  • Lump protruding from vagina/vulva
+ Leiomyosarcoma markers:
  • Endometrial mass with heterogeneous echogenicity
MRI:
  • Endometrial polypoid mass
  • Hypointense hypervascular solid components
Cervical erosion(Ectropion)[27][28][29][30][31]
  • Light bleeding after pelvic exam
  • Spotting
  • Post-coital pain
  • Painful cramps
+ +
  • Red, glandular area around os of cervix
N/A N/A N/A
Cervicitis[32][33][34][35][36]
  • Intermenstrual bleeding
  • Postcoital
  • Bleeding after pelvic exam
  • Pain during urination
+ +
  • May have fever only
  • Red,inflammed swollen cervix
  • Inflammation/irritation of vulva/vagina
STI panel:
MRI:

May be detected as retention cysts in cervix.

  • Non-specific, lymphocytic infiltration may be seen in microscopic histology.
  • Koilocytic changes in case of HPV as cause of chronic cervicitis.
Endometrial carcinoma[37][38][39][40][41]

bleeding

  • Vaginal discharge
  • Pain during urination
  • Pain during sex
  • Fulness in pelvic
  • Difficulty emptying bladder
+ + ±
  • Often normal
  • Vaginal lump
  • Pelvic mass
+
  • Thickened endometrium
  • Myometrial invasion

T1-weighted MRI:

  • Hypo-to-isointense

T2-weighted MRI:

  • Intermediate signal intensity lower than the normal endometrium
Type I endometrioid endometrial carcinomas (EECs):
  • Moderately differentiated
  • Superficial invasion into the myometrium

Type II non-endometrioid endometrial carcinomas (NEECs):

  • Hysterectomy and biopsy
Endometrial hyperplasia[42][43][44]
  • +
+ N/A
  • Normal or thickened endometrium
±

T1-weighted MRI:

  • Hypo-to-isointense
  • Complex hyperplasia
  • Simple hyperplasia with atypia
  • Complex hyperplasia with atypia (glands are highly irregular in size and shape)
  • Biopsy
Endometriosis[45][46][47][48][49][50][51]
  • Heavy mentrual bleeding
  • Painful menstruation
  • Burning/painful urination
  • Painful bowel movement
  • Pain during or after sex
  • Infertility
  • Watery vaginal discharge
+
  • Pelvic pain
  • Back pain
  • Tender uterosacral nodularity
  • Immobile uterus
  • Cervical motion tenderness
  • Retroverted uterus
+

(limited value)

  • Ground glass echogenicity of the cyst fluid (Endonetrioma)
  • Cysts are unilocular
  • MRI findings is variable, depending upon the sites of endometriosis such as peritoneal implants, ovarian endometrioma, pelvic endometriosis.
  • Endometrial type glands and stroma presence is charracteristic histology findings, suggestive for endometriosis.
Pelvic inflammatory diseases[52][53][54]
  • Bleeding after sex
  • Intermenstrual bleeding
  • Pelvic pain
± +
  • Oral temperature >101F
  • Vaginal/vulvar tender lesion depending on microbial causes
STI panel: Non-specific lab values:
  • WBC
  • Oral temperature >101F
Ultrasound:
  • Thickened, fluid-filled tubes with or without free pelvic or tuboovarian complex
MRI findings:
  • Inflammation in pelvic soft tissue
  • Hydrosalpinx
  • Tubo-ovarian abscess in chronic PID.
  • Clinical diagnosis is gold standard for diagnosing PID
Adenemyosis[55][56][57][58][59][60]
  • Abnormal uterine bleeding
  • Painful menstruation
+ +
  • Polypoid mass protruding into the endocervical canal.
  • Enlarged uterus may present as abdominal mass
  • Subendometrial striations
  • Myometrial cysts
  • Asymetrical thickness in myometrium walls
  • Heterogenous exhotexture of myometrum
MRI:
  • Thickened junctional zone
  • Presence of ectopic endometrial glands into the myometrium.
  • Histology findings post hysterectomy
Cervical ectopic pregnancy[61][62] +
  • Soft and disporportionally enlarged uterus.
±
  • Empty uterine
  • Thickened endometrium
T2-weighted MRI:
  • Hypointense large mass

T1-weighted MRI:

  • Partially hyperintense mass
  • Necrotic hemorrhagic mass with chorionic villus
Vaginal cancer[63][64][65][66]
  • Postcoital bleeding
+ + ±
  • Ill-defined vaginal ulcer
  • In case of metastases to internal organs
Ultrasound: MRI:
  • Isointense on T1-weighted images
  • Soft-tissue mass with intermediate-to-high signal intensity on T2-weighted images
Biopsy findings:
  • Biopsy
Paget's disease of vulva to cervix[67][68][69][70][71]
  • Bleeding from lesion
  • Oozing
  • ±Vaginal discharge
  • Pain in vulva
  • Itching or burning sensation in vulva
  • Scaly eczematoid lesion in vulva.
  • Erythematous plaques with white scaling.
  • Inguinal lymphadenopathy in case of metastases.
  • Positive for cytokeratins(CK7)
  • Negative for S-100 and Melan-A
N/A MRI:
  • Hyperintense on diffusion weighted imaging
  • Thick vulvar skin
  • "Cake-icing effect", pathognomic for vulvar paget's disease
  • Intraepidermal adenocarcinoma which involves epidermis
  • Biopsy of lesion
Nabothian cyst[72][73][74][75]
  • Postcoital bleeding
  • In very rare cases depending upon the size of cyst it can cause abdominal pain and amenorhea
  • Majority of them are asymptomatic due to their small size( few milimeters)
N/A
  • Anechoic well defined cystic lesions
T1-weighted
  • Intermediate or slightly high signal intensity T2-weighted
  • High signal intensity on T2-weighted images
  • Benign cystic lesion
  • Multiple benign cystic masses, usually few milimieters in diameter.
  • Histopathological exam if large cystic masses
IUD use[76][77]
  • Heavy bleeidng
  • Painful menstruation
  • ±Vaginal discharge
+
  • In cases of uterine rupture and far migration of IUD, it can cause adhesion, bowel obstruction, perforation.
+
  • Normal


Pregnancy and pregnancy related conditions Clinical manifestations Para-clinical findings Gold standard Additional findings
Symptoms Physical examination
Lab Findings Imaging Histopathology
Abnormal uterine bleeding Other symptoms
Miscarriage[78][79] +
  • Enlarged uterus
  • Blood clot in cervical os.
Ultrasound:
  • ‘Sliding sign’ on transvaginal ultrasound
  • Embryo with increase in crown-rump length without visible embryo heart activity
  • Absence of embryo heart activity
Abruptio placenta[80][81] +
  • Pelvic/back pain
  • Abdominal pain
  • Vaginal bleeding
  • Painful uterine contractions
  • Uterine tenderness
  • ↓ Fetal heart rate
  • ↓ Fetal movement

Ultrasound:

  • Uterine hypertonicity
  • Non-reassuring fetal heart
  • Villous infarctions
  • Decidual destruction, hemorrhage
Placenta previa[82][83][84] +
  • Uterine contraction
  • Blood clot or spotting
Ultrasound:
  • Low lying placenta, less than 1cm from cervical os.
Ectopic pregnancy[85][86] +
  • Pelvic pain which is worse on one side
Ultrasound:
  • Absence of "Sliding sign" on gentle pressure of cervix
  • Tubal rupture
Molar pregnancy[87][88][89] +
  • Heavy vaginal bleeding
  • Uterine size larger than date
Ultrasound:
  • Complex and echogenic intrauterine mass
  • Containing many small cystic spaces
  • Classical "snow storm" appearance
  • Hydropic villi
  • Empty uterus
  • Fetal tissue in partial hydatiform mole.
  • Histological confirmation post-curettage
Hematologic conditions Clinical manifestations Para-clinical findings Gold standard Additional findings
Symptoms Physical examination
Lab findings Imaging Histopathology
Abnormal uterine

bleeding

Other symptoms
Von willebrand disease[90][91][92] +
  • Easy bruising
  • Gum/dental bleeding
  • Heavy menses
  • Fatigue
  • Blood in stool
  • Blood in urine
  • GI bleeding in rare cases
N/A N/A
  • Current gold standard diagnostic testing includes:
Factors deficiencies[93][94] +
  • Easy bruising
  • Gum/dental bleeding
  • Heavy menses
  • Fatigue
  • Blood in stool
  • Blood in urine
  • Intramuscular hematoma
N/A N/A
Platelet dysfunction[95][96] ±
  • Skin bruises
  • Epistaxis
  • Excessive bleeding after surgery
  • Menorrhagia
  • Bruises on skin
N/A
Metabolic conditions Clinical manifestations Para-clinical findings Gold standard Additional findings
Symptoms Physical examination
Lab findings Imaging Histopathology
Abnormal uterine bleeding Other symptoms
Hyperthyroidism[97][98] +
  • Wet skin/hair thinning
  • Low TSH
  • TSH receptor antibodies (TRAb)
Ultrasound:
  • Homogenous hypo-echogenicity
Microscopic histology:
  • Lymphocytic infiltration in follicles
  • Enlarged colloids
  • Total T4

For Grave's disease:

  • TSH receptor antibody
Associated conditions:
Hypothyroidism[99][100][101][102][103] +
  • Dry skin
  • Hair loss
  • Normal/ low TSH
  • ↑ Total cholesterol
  • LDL
  • VLDL
Ultrasound:
  • Homogenous hypo-echogenicity
Microscopic histology:
  • Follicular atrophy
Associated conditions with Hashimoto thyroiditis:
Adrenal hyperplasia[104][105][106][107][108] +
  • Irregular menses
  • Percocious puberty
  • Muscle weakness
  • Fatigue
Depending upon deficient enzyme:

Depending upon enzyme deficiencies may include the following:

CT-Scan:
  • Enlargement of glands
  • Cosyntropin stimulation test (250 μg cosyntropin intravenously):
Cushing's disease[109][110] +
  • Weight gain
  • Moon facies
  • Skin bruising
  • Abdominal striae
  • Facial plethora
  • Ecchymosis
  • Violacious striae
  • Muscle weakness
  • Slow deep tendon reflex relaxation
  • Emotional lability
T1-weighted MRI:
Polycystic ovarian syndrome[111][112][113][114][115] +
  • Prolactin in some women
  • LH/ Normal or ↓ FSH
  • ↑ Serum Anti-mullerian hormone
Ultrasound:
  • ↑ Number of follicles
  • ↑ Ovarian volume
  • Fluid filled ovaries
  • Multiple cysts in ovaries bilaterally.
Associated conditions:
  • Insulin resistance
Medication side effects/ Iatrogenic Clinical manifestations Para-clinical findings Gold standard Additional findings
Symptoms Physical examination
Lab Findings Imaging Histopathology
Abnormal uterine bleeding Other symptoms
Anticoagulants[116][117][118]
  • +
  • Heavy menstrual bleeding
  • Pallor
  • Heavy menstrual bleeding
N/A N/A
  • Complete medication history
Antipsychotics[119] +
  • Sexual dysfunction
N/A N/A
  • Complete medication history
  • Serum prolactin test
Oral contraceptive pills[120]
  • Break through bleeding
  • Menstrual irregularity
  • Mood swings
  • Heavy bleeding
  • Depressed mood
N/A N/A
  • Ruling out organic cause, complete history of medication use
Herbal supplements[121][122] +
  • Heavy menstrual bleeding
  • Menstrual irregularity
  • Amenorrhea
  • Menorrhagia
Ultrasound: N/A

References

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