Abnormal Uterine Bleeding

Diane M. Flynn COL, MC Chief, Department of Family Medicine Madigan Army Medical Center

BLUF Abnormal Uterine Bleeding

Causes vary across the lifespan Ovulatory status helps to narrow the differential diagnosis in women of reproductive age Rule out cancer in postmenopausal bleeding

Case 1

CC: Irregular menses x 6 months 23 yo G1P1 2 menses in past 6 months, heavier and longer than normal. Menses previously regular since menarche No contraception x 3 years, desires pregnancy 40 lb weight gain since birth of 3 year old daughter

Case 2

CC: Heavy menses x 4 months 44 yo G1P1. Normal, regular menses until 4 months ago PMH: negative PSH: s/p BTL Meds: none

Outline
Normal

menstrual cycle Abnormal uterine bleeding (AUB)

Prior

to menarche During childbearing years Postmenopausal

Amenorrhea
Will

not cover today

Normal Menstrual Cycle

Average

cycle 28 days (range 24-35 days) Median blood loss 30 cc (upper limit of normal 60-80 cc) Lasts 4-6 days

Pituitary hormones

Ovarian hormones

Abnormal Bleeding Patterns

Amenorrhea absence of menses >6 months Oligomenorrhea bleeding at an interval >35 days Menorrhagia (AKA hypermenorrhea) excessive or prolonged menstrual bleeding occurring at regular intervals. Technically, blood loss >80 cc or > 7 days. Polymenorrhea bleeding at intervals <21 days Intermenstrual bleeding bleeding that occurs between regular menses Postmenopausal bleeding bleeding recurs in a menopausal woman at least 1 year after cessation of menses

Ovulatory Status

Ovulatory bleeding cyclic bleeding accompanied by cyclic signs of ovulation Anovulatory bleeding unpredictable, non-cyclic bleeding of variable flow and duration, with absence of signs of ovulation and exclusion of anatomic lesions
Sex

hormones are produced, but not cyclically Common at menarche and in the perimenopausal period

Abnormal Uterine Bleeding (AUB) Across the Age Span

Prior to menarche During childbearing years Postmenopausal

AUB Prior to Menarche differential diagnosis

Must rule out

Malignancy Trauma Sexual

abuse anesthesia

Workup starts with pelvic exam

Consider

AUB in Reproductive Age Women 4 Broad Categories

Pregnancy and pregnancy-related complications Medications and other iatrogenic causes Systemic conditions Genital tract pathology

1. Pregnancy related AUB

Spontaneos abortion Ectopic pregnancy Placental previa Abruptio placenta Trophoblastic disease Puerperal complications, eg, endomyometritis

2. AUB Iatrogenic Causes

Medications
Anticoagulants SSRI Antipsychotics Corticosteriods Hormonal

medications, IUD, tamoxifen

Herbal substances, ie, ginseng, ginkgo, soy supplements

3. Systemic Causes of AUB

Thyroid disease Polycystic ovary disease Coagulopathies Hepatic disease Adrenal hyperplasia and Cushings Pituitary adenoma or hyperprolactinemia Hypothalamic suppression (from stress, weight loss, excessive exercise)

4. Genital Tract Pathology

Infections: cervicitis, endometritis, salpingitis Neoplastic Benign anatomic adenomyosis, leiomyomata, polyps of cervix or endometrium Premalignant lesions cervical dysplasia, endometrial hyperplasia Malignant lesions cervical, endometrial, ovarian, leiomyosarcoma Trauma foreign body, abrasions, lacerations

Abnormal Uterine Bleeding Step 1: History

When did the bleeding start? Were there precipitating factors, such as trauma? What is the nature of the bleeding (temporal pattern, duration, postcoital, quantity) Associated symptoms (pain, vaginal odor, changes in bowel/bladder function) Previous hx or FHx of bleeding disorder? PMH/Meds Sexually active? Weight changes; h/o excessive exercise; h/o eating disorder?

Abnormal Uterine Bleeding Step 2: Physical Examination

General PE to look for systemic illness, signs of hyperandrogenism Careful pelvic exam focus on identifying site of bleeding (vulva, vagina, cervix, uterus, bladder, rectum) Assess size, contour and tenderness of the uterus

Abnormal Uterine Bleeding Step 3: Initial Labs/Studies

HCG Pap smear, biopsy of visible cervical lesions Determine ovulatory status
Menstrual

cycle history Basal body temperature monitoring Serum progesterone Urinary LH excretion Ultrasound evidence of a periovulatory follicle

Abnormal Uterine Bleeding Further Laboratory Evaluation

In addition to HCG and Pap: For heavy or prolonged menses, H/H, platelet count, PT, PTT, consider factor VIII, von Willebrand factor antigen TSH Consider prolactin if oligomenorrhea or galactorrhea present LFTs, lytes if systemic signs of chronic disease Endometrial bx in all women over age 35 yrs or with risk factors of endometrial cancer

Abnormal Uterine Bleeding in Women of Childbearing Age

Treatment of Abnormal Uterine Bleeding in Reproductive-age Women

Medical management

Severe acute bleeding

High dose estrogens

IV
35-mcg pill bid-qid x 5-7 days until menses is stopped, then taper to 1 pill daily until 28-day pack is completed

30 cc foley catheter in endometrial cavity can be used

Surgery -- when medical management fails

Endometrial ablation Uterine artery embolization Myomectomy Hysterectomy

Treatment of Abnormal Uterine Bleeding in Reproductive-age Women

Chronic or less severe acute bleeding Anovulatory bleeding
Oral

contraceptives (reduce blood loss by 50%) Cyclic progesterone after acute episode
Ovulatory
NSAIDs

bleeding

(reduce loss by 20-50%) Progesterone-releasing IUDs (reduce loss by 80-90%)

Polycystic Ovary Syndrome

Common hyperandrogenic disorder, affects at least 6% of women Wide spectrum of manifestations Skin changes: acne, hirsuitism Gynecologic disorders such as anovulatory uterine bleeding, oligomenorrhea, recurrent miscarriages, infertility

Case Definition of PCOS -- Rotterdam

Two of the following three:
Oligo- and/or anovulation Clinical or biochemical signs of hyperandrogenism Hirsuitism, acne, or male pattern balding High serum androgens Polycystic ovaries (by ultrasound) Presence of 12 or more follicles in each ovary, measuring 2-9 mm in diameter, or increased ovarian volume

Biochemical Findings

Elevated serum free testosterone is most sensitive test for hyperandrogenemia LH may be elevated Estradiol and estrone are normal OGTT recommended in women with PCOS and obesity or family history T2 DM

Acanthosis Nigricans

Associated with insulin resistance

PCOS Treatment Recommendations

Base on individual patient goals For hirsuitism or other androgenic symptoms:

Weight loss if overweight OCPs endometrial protection Consider spironolactone Hirsuitism can be treated mechanically (shaving, electrolysis) Evaluation of couple, including semen analysis Weight loss Clomid can be used to induce ovulation If clomid resistant, metformin x 8-12 weeks, then repeat clomid

If pregnancy is desired:

Endometrial Cancer

Age-associated Risk of Endometrial Cancer

Age Group 19-39 yrs 30-34 35-39 40-49 Endometrial Cancer Rate per 100,000 10.2 2.8 6.1 36.5

Sensitivity and Specificity of Studies to Diagnose Endometrial Cancer

Test Endometrial bx Transvaginal US (5mm cutoff) Sonohysterography (SHG) Sensitivity Specificity 99.6% 92% 95% 91% 81% 88%

Postmenopausal Bleeding

Women started on hormone therapy within previous year

Observe

bleeding for one year before diagnosing abnormal uterine bleeding

Women on no hormone therapy or on hormone therapy for >12 months

Rule

out endometrial cancer

Postmenopausal Bleeding Workup

Which test is best?

Cochrane comparison of TVUS, sonohysterography, and hysteroscopy with biopsy revealed no clearly superior test Transvaginal US If endometrial stripe >5 mm, do endometrial bx If bleeding persists despite reassuring workup, need additional evaluation, such as dilatation and curettage, sonohysterography or hysteroscopy with biopsy

One approach

Case 1

23 yo G1P1 Oligomenorrhea 40 lb weight gain Desires fertility

Case 1
PMH: negative ROS: otherwise normal SH: husband in Iraq, due to return in 3 months

Physical Exam

BP 136/82, Wt 183 lb, BMI 31kg/m2 Normal HEENT, neck, heart, lung, abdominal exam Normal breast, pelvic exam No signs hyperandrogenism Skin: normal, no acne, no hirsuitism, no acanthosis nigricans Differential?

Differential Diagnosis

Pregnancy Polycystic Ovary Disease Thyroid disease Prolactinoma

Labs/studies?

Labs

HCG negative TSH 2.9 Prolactin normal LH/FSH normal DHEA sulfate normal Testosterone not done CBC normal GC/chlamydia negative Normal Pap within previous year

Ultrasound

Normal uterus At least 10 small follicles in the R ovary, multiple small follicles in L ovary Dominant follicle left ovary, 15 mm Diagnosis?

Case 1 Working diagnosis: PCOS

Management and Course
Nutritional

counseling for weight loss No medications, since patient trying to conceive Could consider clomiphene and/or metformin Patient succeeded in losing 5 lbs and regular menses returned

Case 2

44 yo G1P1 Heavy menses x 4 months Differential Diagnosis?

Physical Exam
BP

118/56, BMI 25.7 Neck, Heart, Lungs, Abdomen normal Breasts: normal Pelvic normal Labs?

Labs

HCG neg Hgb 10, Hct 32, Platelets normal, low-normal RBC indices FSH/LH normal TSH normal Pap normal Endometrial biopsy: normal, no hyperplasia

Case 2 Diagnosis?

Case 2: Diagnosis and Management

Perimenopausal anovulatory bleeding FeSO4, repeat Hct in 4-6 weeks Consider OCPs if menorrhagia persists

Summary AUB

After H&P, remainder of workup is directed by patients age and ovulatory status Reproductive age

Rule out pregnancy Determine ovulatory status

Women age >35 (or risk factors for cancer), do endometrial biopsy Postmenopausal women

Transvaginal US may be best first step Consider also endometrial bx and/or refer for other diagnostic studies