Abnormal Uterine Bleeding

Todd May, M.D.

Abnormal Uterine Bleeding

Common in women of all ages ~5% women of reproductive age seek help annually Life phase determines most likely cause, and the likelihood of serious pathology Take your time to properly assess the problem Work-up and treat in a rational manner

Complications of pregnancy Intrauterine pregnancy Ectopic pregnancy Spontaneous abortion Gestational trophoblastic disease Placenta previa Infection Cervicitis Endometritis Trauma Laceration, abrasion Foreign body Malignant neoplasm Cervical Endometrial Ovarian

Systemic disease Hepatic disease Renal disease Coagulopathy Thrombocytopenia von Willebrand's disease Leukemia Medications/iatrogenic Intrauterine device Hormones (oral contraceptives, estrogen, progesterone) Hormonal imbalance Anovulatory cycles Hypothyroidism Hyperprolactinemia Cushings disease Polycystic ovarian syndrome Adrenal dysfunction/tumor Stress Excessive exercise

Benign pelvic lesions Cervical polyp Endometrial polyp Leiomyoma Adenomyosis

Abnormal Bleeding Cause

Pregnancy Hormonal/Dysfunctional Anatomic Coagulopathy/bleeding

disorder

History
Characterize menses Age, parity, past pregnancies, sexual history, contraception, past gyn problems, medications Personal or family history of bleeding disorder Symptoms of thyroid disease History of liver disease

Physical Exam
Orthostatic VS if indicated by Hx Pelvic exam vagina, cervix, uterus, adnexa, PAP Skin ecchymoses, hirsutism Thyroid gland Liver and assoc. stigmata Signs of virulization

Labs
CBC with Plts Urine -HCG if reproductive age

Additional Tests (not routine)

TSH anovulatory LFTs, coagulation studies liver dz or FHx Complete coagulation profile consider for non-pregnant teens GC, Chlamydia if risk or exam suggests Androgen excess free testosterone, DHEA-S (PCOS evaluation) FSH suspect premature ovarian failure Progesterone confirm ovulation, draw in luteal phase

Life Phase

Ovulatory Status

Etiology

R/O Pregnancy Adolescent Likely anovulation Consider bleeding disorder Pregnancy

Reproductive age

Ovulatory (Secretory)

Hormonal DUB Anatomic Coagulopathy

(Usually DUB)

Anovulatory (Proliferative)

Perimenopause

R/O Pregnancy Early EMB/TV Sono

Postmenopause

R/O Endometrial CA

Adolescents
Usually anovulation due to immature Hypothal-Pit axis Rule out pregnancy Consider bleeding disorder Observe or Rx with cyclic MPA or OCs

Consider Bleeding Disorder

von Willebrands Disease

Underdiagnosed; present in 1% of population Autosomal dominant; affects women and men equally Dx: Bleeding time, Factor VIII, vW factor, ristocetin co-factor activity Rx: Desmopressin (ADH) IV or intranasal Increases vW factor, factor VIII, plasminogen activator

Reproductive Age
H&P Check urine -HCG Genital tract lesionBx or refer Enlarged uterus r/o pregnancy sono for anatomic cause

(e.g., fibroids)

Reproductive Age
If not pregnant and normal exam: Usually DUB (i.e., hormonal) Determine ovulatory status key! Treatment: Usually hormonal

Ovulatory Cycles
Regular cycle length Presence of premenstrual symptoms Breast tenderness, dysmenorrhea Mittleschmertz Biphasic temperature curve

Anovulatory Cycles
Unpredictable cycle length Unpredictable bleeding pattern Frequent spotting Infrequent heavy bleeding Monophasic temperature curve

Anovulatory Bleeding
90-95% of reproductive age Cause: systemic hormonal imbalance Always a relative progestindeficient state

Anovulatory Bleeding

Assess for secondary hypothalamic disorder

stress, eating disorder, excessive exercise, wt loss, chronic illness

Check TSH Test for PCOS if indicated

obesity, hirsutism, insulin resistance

Consider chronic anovulation

Anovulatory DUB Treatment

Address underlying disorder Treat with monthly OCs or progesterone withdrawal every 3 months (MPA or DMPA)

Regulate cycles, protect against endometrial CA

Clomiphene for ovulation induction in select cases

Ovulatory Bleeding

Usually underlying prostaglandin imbalance (DUB) Defects in local endometrial hormonal hemostasis Structural lesions Leiomyoma, adenomyosis, polyps Systemic disease Liver dz, renal failure, bleeding disorder

Ovulatory Bleeding
Much less common5-10% Consider empiric treatment without further w/u (normal exam)

NSAIDs, OCs, progesterone IUD

If Rx fails, proceed with work up

Metabolic labs Imaging, EMB

Ovulatory DUB Treatment

NSAIDs (prostaglandin synthetase inhibitors) e.g., Ibuprofen, Naproxen, Mefenamic acid First 5d of menses Cyclic OCs x 3-6 mos Progesterone IUD most effective [Tranexamic acid anti-fibrinolytic]

Evaluating endometrial cavity

Consider EMB:
Higher risk women Prolonged exposure to unopposed estrogen Age > 40 Failure to respond to initial management

Evaluating endometrial cavity

Endometrial Biopsy (EMB)
Safe, simple office procedure Rule out endometrial CA Confirm ovulatory status

EMB best done while bleeding Proliferative: confirms anovulation Secretory: confirms ovulation Hyperplasia: chronic unopposed estrogen Atrophy: menopause or continous OCs, HRT, DMPA

Evaluating endometrial cavity

Dilation and Curettage (D&C)
OR procedure, less commonly used

Rule out endometrial carcinoma or hyperplasia

Yield slightly higher than EMB, but still blind sampling technique

Evaluating endometrial cavity

Transvaginal Ultrasonography
(TVSono)

Alternative to EMB to assess endometrium, comparable accuracy Endometrial stripe >5mm EMB for tissue diagnosis Often can detect atrophic endometrium, leiomyomas, and endometrial polyps

Evaluating endometrial cavity

Sonohysterography
(water sono)
TVSono with saline infusion into endometrial cavity Enhances detection of submucosal fibroids and polyps

Evaluating endometrial cavity

Hysteroscopy
Gold standard for endometrial assessment Office procedure Thorough, direct inspection of endometrial cavity Directed biopsy or treatment possible (e.g., polyp excision)

Perimenopause
H&P Check urine -HCG Genital tract lesionBx or refer Enlarged uterus r/o pregnancy TV Sono for anatomic evaluation

(e.g., fibroids)

Perimenopause
If not pregnant and normal exam: Consider early EMB or TV Sono

r/o edometrial hyperplasia, CA

If negative, Rx with low dose OCs or monthly Medroxyprogesterone Sonohysterography or hysteroscopy if Rx fails

r/o anatomic causes

Postmenopause
5-10% endometrial carcinoma Proceed directly to EMB or TV Sono DDx: endometrial hyperplasia, cervical

cancer, cervicitis, atrophic vaginitis, endometrial atrophy, submucosal fibroids, endometrial polyps

Rx specific to cause

Treatment: Acute Bleeding

Conj. Eq. Estrogens x 21d + MPA last 710d

Use Estrogen IV for severe bleeding; hospitalized

High dose OC: 1 QID x 7d; then OC daily x 3 months or MPA x 10d q month x 2-3 more cycles

Surgical Treatment
Therapeutic D+C

fastest method to stop bleeding in unstable patients must follow with hormones to prevent recurrence

Endometrial Ablation/Resection

laser or electrocautery good option if fertility not desired

Surgical Treatment
Hysterectomy

if all else fails or patient prefers subtotal hysterectomy is an option to preserve optimal sexual and bladder function hysterectomy now is rarely necessary solely for uterine bleeding

Life Phase

Ovulatory Status

Etiology

R/O Pregnancy Adolescent Likely anovulation Consider bleeding disorder Pregnancy

Reproductive age

Ovulatory (Secretory)

Hormonal DUB Anatomic Coagulopathy

(Usually DUB)

Anovulatory (Proliferative)

Perimenopause

R/O Pregnancy Early EMB/TV Sono

Postmenopause

R/O Endometrial CA

Adolescents
Most likely anovulatory due to immature Hypothal-Pit axis Rule out pregnancy Consider bleeding disorder Observe or Rx with cyclic MPA or OCs

Anovulatory Adults
Identify secondary causes of Hypothal-Pit dysfunction, thyroid disease, PCOS Address underlying cause Manage bleeding with cyclic MPA, DMPA, or OCs

Ovulatory Adults

Causes: endometrial modeling defect, structural lesions, systemic disease Consider empiric Rx without further w/u if history and exam are normal

NSAIDs, OCs, Progesterone IUD

If Rx fails, w/u with metabolic labs, imaging, and EMB if indicated

Perimenopause
Progressive anovulation due to declining ovarian function Rule out pregnancy Consider early EMB or TVSono
(esp. with endometrial CA risk factors)

Rx with OCs or monthly MPA

Postmenopause

Rule out endometrial CA (5-10%)

Proceed directly to EMB or TVSono endometrial hyperplasia, cervical cancer, cervicitis, atrophic vaginitis, endometrial atrophy, submucosal fibroids, endometrial polyps

Evaluate for other causes

Rx specific to underlying cause

Summary
Abnormal uterine bleeding is very common Life phase and detailed menstrual history are key Employ rational evaluation and treatment strategy You can manage it!

Cervical Cancer Screening

Todd May, MD

Cervical Cancer
12,800

cases/yr 50% never screened Death rate 70% since 1940s

Pap introduced

Natural History
HPV

acquired in teens, 20s Prolonged pre-malignant phase Spontaneous HPV clearing common CIN peaks 20s-30s Small number progress to invasive cancer

Risk Factors for Neoplasia

Multiple HPV Smoking HIV

sexual partners

Routine Screening Recs

Start:

3yrs after first vaginal intercourse Age 21 (unless virginal?) Annually age <30 Age >30 q2-3yrs if normal x 3 annuals Age 65-70 if consistently normal After hysterectomy for benign condition

Interval:

Stop:

High-Risk Screening Recs

Pap every 6 months x 2, then annually for: HIV positive Immunocompromised by organ transplant, chemoRx, chronic steroid use Prior Rx for CINII/III or cancer Rationale: Progression to HSIL and CA more common and more rapid

Essentials of Pap Sampling

Collect cells before bimanual exam Gently remove cervical mucus/dc Visualize entire portio of cervix Use scraper for ectocervix; brush for endocervical specimen Fix slide immediately (<3-4sec)

Cytologic Interpretation
Adequacy

of specimen diagnosis

Satisfactory or unsatisfactory Bethesda 2001

Descriptive

Presence/absence

endocervical cells

of

Negative for IEL or Malig.

Benign cellular changes

Trichomonas Fungus c/w candida sppNo action Floral shift/BVNo action Suspect Chlamydiacall back to test HSVnotify patient HPV/koilcytosismanage as LSIL Actinomyces (IUD)Rx with Amox

Negative for IEL or Malig.

Reactive changes

InflammationNo action Atrophy w/ inflam. (atrophic vaginitis)Rx w/ topical estrogen, repeat if no ECC RadiationNo action Reactive/reparative AtypiaNo action Squamous metaplasiaNo action

Squamous Cell Abnormalities

ASCUSundetermined significance ACS-Hcannot exclude HSIL LSILlow gradeincludes HPV, mild dysplasia/CINI HSILhigh gradeincludes modsevere dysplasia, CINII/III, CIS Invasive SCCa

Glandular Cells
Endometrial cellsconsider EMB if age>40 or abnormal bleeding Atypical Endocervical cellscolpo, Bx, ECC Atypical Endometrial cellsEMB, D&C, or hysteroscopy Endocervical, Endometrial, or Extrauterine Cadefinitive Rx

ASC US

HIV

Repeat 4-6 months

> ASC US

HPV DNA Testing

HPV Positive (for high risk types)

Negative

HPV Negative

Colposcopy
Routine Screening
Repeat PAP 12 months

ASCH / LSIL

Colposcopy

Neg or CIN 1

CIN 2 or 3, CIS

PAP q6 mos x 2

RX

HSIL

Colposcopy + ECC

Satisfactory

Unsatisfactory

No CIN or CINI Diagnostic Excision

CIN 2, 3

Diagnostic Excision

Rx

Bottom Line
When to refer for colposcopy:
ASC-US x 2 (x1 if HIV+) ASC-H LSIL HSIL