Understanding Abnormal Uterine Bleeding Patterns Across Ages

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

2. 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

3. 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

4. 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

5. Outline • Normal menstrual cycle • Abnormal uterine bleeding (AUB) • Prior to menarche • During childbearing years • Postmenopausal • Amenorrhea • Will not cover today

6. 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

7. Pituitary hormones Ovarian hormones

8. 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

9. 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

10. Abnormal Uterine Bleeding (AUB)Across the Age Span • Prior to menarche • During childbearing years • Postmenopausal

11. AUB Prior to Menarche differential diagnosis • Must rule out • Malignancy • Trauma • Sexual abuse • Workup starts with pelvic exam • Consider anesthesia

12. AUB in Reproductive Age Women – 4 Broad Categories • Pregnancy and pregnancy-related complications • Medications and other iatrogenic causes • Systemic conditions • Genital tract pathology

13. 1. Pregnancy related AUB • Spontaneos abortion • Ectopic pregnancy • Placental previa • Abruptio placenta • Trophoblastic disease • Puerperal complications, eg, endomyometritis

14. 2. AUB Iatrogenic Causes • Medications • Anticoagulants • SSRI • Antipsychotics • Corticosteriods • Hormonal medications, IUD, tamoxifen • Herbal substances, ie, ginseng, ginkgo, soy supplements

15. 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)

16. 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

17. 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?

18. 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

19. 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

20. 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

21. 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

22. 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 bleeding • NSAIDs (reduce loss by 20-50%) • Progesterone-releasing IUDs (reduce loss by 80-90%)

23. 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

24. 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

25. 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

26. Acanthosis Nigricans Associated with insulin resistance

27. 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) • If pregnancy is desired: • 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

28. Endometrial Cancer

29. Age-associated Risk of Endometrial Cancer

30. Sensitivity and Specificity of Studies to Diagnose Endometrial Cancer

31. 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

32. Postmenopausal Bleeding Workup • Which test is best? • Cochrane comparison of TVUS, sonohysterography, and hysteroscopy with biopsy revealed no clearly superior test • One approach • 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

33. Case 1 • 23 yo G1P1 • Oligomenorrhea • 40 lb weight gain • Desires fertility

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

35. 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?

36. Differential Diagnosis • Pregnancy • Polycystic Ovary Disease • Thyroid disease • Prolactinoma

37. Labs/studies?

38. 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

39. 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?

40. 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

41. Case 2 • 44 yo G1P1 • Heavy menses x 4 months • Differential Diagnosis?

42. Physical Exam • BP 118/56, BMI 25.7 • Neck, Heart, Lungs, Abdomen normal • Breasts: normal • Pelvic normal • Labs?

43. 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

44. Case 2 Diagnosis?

45. Case 2: Diagnosis and Management • Perimenopausal anovulatory bleeding • FeSO4, repeat Hct in 4-6 weeks • Consider OCPs if menorrhagia persists

46. Summary AUB • After H&P, remainder of workup is directed by patient’s 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