Disorders of Menstruation / Abnormal Uterine Bleeding

1. Tory Davis, PA-C Disorders of Menstruation / Abnormal Uterine Bleeding

2. Menstruation Shedding the uterine lining (endometrium) if pregnancy does not occur. Necessary (in the absence of hormonal regulation) to insure the endometrium does not become hyperplastic.

3. Terminology Amenorrhea—lack of menstrual bleeding Primary—no menses by age 16 Secondary—absence of 3 or more expected menstrual cycles ‏ Break-through bleeding (BTB) unexpected bleeding usually occurring while a woman is on exogenous hormonal medication (eg OCPs, patch, or ring)‏

4. Terminology (cont.)‏ Menorrhagia—heavy menstrual bleeding. Prolonged or excessive menstrual blood loss with regular cycles Metrorrhagia—irregular, frequent bleeding Menometrorrhagia—irregular menses with prolonged or excessive blood loss Midcycle bleeding—light menstrual bleeding occurring in ovulatory women at the midcycle estradiol trough

5. Terminology (cont.)‏ Oligomenorrhea-- menstrual bleeding/menses occurring less frequently than 36 days apart Polymenorrhea—frequent menstrual bleeding/menses occurring more frequently than 21 days apart Contact bleeding/post-coital bleeding Dysmenorrhea- painful menstrual bleeding

6. Physiologic Requirement? Hormonal fluctuations of the cycle allow the monthly release of a mature ovum from the ovaries and prepares the endometrium for implantation. Controlled by GnRH from the hypothalamus, FSH and LH from the pituitary, E2 from the ovary, and P4 from the corpus luteum

7. Normal Menstrual Cycles Mature, ovulatory women 28-29 day average 21-36 day range 2-7 days duration 20-80 cc of blood loss per month

8. Cycle Variation Women in their middle reproductive years have the most predictable cycles More pronounced cycle to cycle variability in the 5-7 years after menarche and 6-8 years before menopause

9. Cycle Variation (cont.)‏ Adolescents Majority range 21-48 days Usually anovulatory Mean time from menarche until half the cycles are ovulatory depends upon the age of menarche 12 yrs 1yrs till half cycles are ovulatory 12-13 3yrs >13 4.5 yrs

10. Cycle Variation (cont.)‏ Perimenopause Cycles initially shorten Ultimately (apparently) lengthen, as an entire cycle will be skipped Average age of menopause is 51 Cessation of menses for one year

11. Impact on Health 75% of women experience physical changes associated with menses PMS (Premenstrual syndrome)‏ PMDD (Premenstrual dysphoric disorder)‏ Direct and indirect health care costs Visits to ED, clinic, or office Time lost from work

12. Quality of Life Issues Many women seek healthcare related to menstrual problems National health survey revealed 66% of women sought care 31% had stayed in bed for more than ½ day at least once during the previous year 12% of all ED visits

13. PMS Psychoneuroendocrine d/o with biological, social and psychological impacts Up to 75% of women experience some level of recurrent sx Up to 5% may experience severe sx and distress

14. Common PMS Sx Headache Breast pain Bloating Irritability Fatigue Crying Abd pain Clumsiness Sleep alteration Labile mood Social withdrawal Libido change Appetite change

15. Requisite Symptoms for PMDD Diagnosis Depressed mood Anxiety/tension Mood swings Irritability Decreased interest Concentration difficulties Fatigue Appetite changes/food cravings Insomnia/hypersomnia Feeling out of control Physical symptoms 5/11 symptoms needed for diagnosis and Sx disrupt daily functioning

16. PMS/PMDD Tx Limit caffeine, tobacco, alcohol and sodium Frequent high-complex carb meals CBT, stress management, aerobic exercise

17. PMS/PMDD Tx SSRIs (ie: fluoxetine) 14 days prior to onset of menses OCPs..not really effective Chaste berry and St John’s wort- more effective than placebo but less than fluoxetine

18. Dysmenorrhea Painful menstruation- when pain prevents normal activity and requires medication Pain starts when bleeding starts Prostaglandin activity Emotional/psychological factors

19. Dysmenorrhea tx NSAIDs, starting a day before period Ibuprofen, naproxen Anti-prostaglandins much less effective after pain is established Continuous heat to abd OCPs for 6-12 months have lasting benefit

20. Abnormal Uterine Bleeding Menorrhagia Oligomenorrhea Metrorhhagia Polymenorhhea Menometrorhhagia Oligomenorrhea Contact bleeding

21. Ddx of Abnormal Uterine Bleeding Blood Dyscrasias Anatomic causes of bleeding, including pregnancy Anovulation Malignancy Non-uterine causes of bleeding

22. AUB work-up Hx PE with cytology Pelvic ultrasound Endometrial biopsy Hysteroscopy D & C

23. Blood Dyscrasias Von Willebrand Idiopathic thrombocytic purpura (ITP)‏ Leukemia Clotting factor deficiencies

24. Anatomic causes Pregnancy—cessation of menstrual bleeding for 40 weeks 1 in 5 pregnancies end in spontaneous abortion First symptom is usually bleeding Gestational trophoblastic disease (molar pregnancy)‏ Non-viable pregnancy with a large, grapelike placenta that sloughs off and causes heavy bleeding Infection Cervicitis—leads to bleeding from the cervix Endometritis—leads to sloughing off of endometrial blood and mucous

25. Anatomic causes (cont.)‏ Endocervical or endometrial polyps Esp post-coital bleeding IUD Bleeding likely with Paragard, extremely rare with Mirena (progestin-containing)‏ Leiomyoma (fibroids)‏ Subserosal (in wall of myometrium)‏ Intramural (most common “bump on top”)‏ Submucosal (can be pedunculated)‏

27. Leiomyomas (Fibroids)‏ Benign neoplasms arising from uterine wall smooth muscle cells 20-25% of reproductive age women Can be small to quite large, single or multiple. Surrounded by pseudocapsule. Often asx, but can cause metrorrhagia, menorrhagia, dysmenorrhea and infertility Cause unknown, but hormone responsive

28. Fibroid Sx Prolonged, heavy bleeding, can cause anemia (which type?)‏ Pain- from vascular compression Sensation of fullness, heaviness in pelvis Infertility or spontaneous abortion PE: Distorted uterine contour Confirm with ultrasound

29. Fibroid Tx Depends on sx, age, parity, reproductive plans, general health, and size/location of leiomyomas GnRH agonists- to shrink fibroid OCPs control bleeding but do not treat the fibroid Progestin-releasing IUD for multiple small leiomyomata

30. Fibroid Tx - Surgical Myomectomy- preserves fertility, high risk for fibroid recurrence Hysterectomy- eliminates sx and chance of recurrence. Also eliminates uterus. Uterine fibroid embolization (UFE)‏ Embolic occlusion of uterine arteries As effective as above, few recurrences, few major complications

31. Anovulation Patient History—very important to diagnosis Ovulatory cycles—consistent number of days from beginning of one cycle to the next, breast tenderness, and dysmenorrhea usually present Anovulatory cycles—variation in number of days per cycle, no breast tenderness, and dysmenorrhea is not consistent from one cycle to the next

32. Anovulation Hypothalmic disorder related to: Stress Diet Exercise Body fat Pituitary-ovarian axis very sensitive to any bodily changes

33. Anovulation: Endocrinopathies Thyroid Both hypo- and hyperthyroidism may present with AUB TSH

34. Anovulation, endocrinopathies Prolactin Pepperell evaluated 304 patients with oligoamenorrhea and found 7.6% had increased prolactin Interrupts menstrual function by inhibiting pulsatile release of GnRH Note: causes for falsely elevated prolactin levels Recent breast exam or breast stimulation Recent pelvic exam

35. Anovulation: POF Premature Ovarian Failure (Early Menopause)‏ Diagnosed if woman of child-bearing age develops amenorrhea and FSH level is found to be greater than 35 This is an indication that the ovaries are no longer producing sufficient hormone levels to allow ovulation to occur

36. Other Causes of Anovulation Any medication that affects the cytochrome P-450 cycle, eg psychotropic drugs Ovarian tumors that produce steroids: Granulosa cell tumors Sertoli Leydig cell tumors

37. Malignancy as a Cause of AUB Uterus—endometrial cancer Cervix--severe dysplasia, carcinoma in situ, or invasive cancer will lead to bleeding. Fallopian tubes—much less common Ovarian—not usually associated with bleeding

38. DUB “Dysfunctional uterine bleeding” Abnormal uterine bleeding with pathologic causes ruled out So..you’ve done all that stuff, and it’s all okay Usually tx with hormones (ie OCPs) to control bleeding

39. Non-uterine causes Genital neoplasms of the vulva or vagina To avoid missing vaginal lesions, stainless steel speculum blades should be rotated on removal to fully evaluate the vaginal mucosa Better: use plastic speculum with good light source Genital trauma/foreign objects Rectal bleeding or urinary tract source

40. Evaluation History Menstrual pattern (duration, changes in quality, color of menses)‏ Dysmenorrhea, mittleschmerz, breast changes Post-coital spotting Dietary practices, change in weight, exercise, stress Evidence of systemic disease

41. Evaluation (cont.)‏ Physical Exam Vital signs, height, weight, body phenotype, BMI Skin, hair (acne, hirsutism pattern)‏ Fat distribution, striae Thyroid Breast exam to check for galactorrhea Complete pelvic exam Tanner stage for teens

42. Evaluation--testing All patients: Pregnancy test CBC with platelets Recent Pap Over 35 yrs: Endometrial sample Documented drop in hgb <10 PT, PTT Bleeding time As indicated: TSH Prolactin Testosterone LH/FSH 17-OH progesterone Overnight dexamethasone suppression test or 24 hr urinary free cortisol Hysteroscopy or ultrasound

43. Proposed Treatment Scheme Begin evaluation and diagnostic testing, rule out pregnancy, check hgb Hospitalize for low hgb (<7), and strongly consider blood dyscrasia, submucosal fibroid, or malignancy

44. Acute Bleeding: Control Oral progestins: Micronized Progesterone 200 mg (Prometrium) or Medroxyprogesterone 10 mg (Provera) or Norethindrone 5 mg (Aygestin)‏ 1 po q4 hrs or until bleeding stops, then 1 qid x 4 days 1 tid x 3 days 1 bid x 2 weeks, then Cycle monthly with progestin or low dose oral contraceptive

45. AUB Long Term Control Cycle with low dose OCP, patch, or vaginal ring Cycle with a progestin, eg Prometrium Use of progestin-containing IUD (Mirena)‏ Choice depends upon: Contraceptive need Smoking status Medical history Patient preference

46. Long Term Control Danazol or other androgen agents will shut down the hypothalamic-pituitary-ovarian axis GnRH analogs (Lupron, Nafarelin) (x 6 months)‏ Ibuprofen and other NSAIDs decrease bleeding and cramping Endometrial thickness of 4 mm or less is needed to eliminate intermenstrual bleeding

47. Endometrial Ablation Uterine thermal balloon Out-patient procedure Regional anesthesia (spinal or epidural)‏ Balloon catheter inserted into uterus Very hot fluid (87C) is inserted for 8 minutes Post-Procedure Cramping, bleeding for 1 week, serous discharge for 4-6 weeks Amenorrhea is the intended result

48. Endometriosis Abnormal growth of endometrial tissue in locations other than the uterine lining 3-10% of women of reproductive age 30% of infertile women

49. Pathogenesis Cause unknown, but theories: Retrograde menstruation Viable endometrium shed during menses, flows thru fallopian tubes to peritoneal cavity Solid theory that does not explain all cases (ie: endometriosis in non-menstruating women or in non-peritoneal endometriosis)‏

50. Pathology This is a SURGICAL diagnosis Characteristic diagnostic surgical gross appearance Small petechial lesions to larger “powder burn” lesions 5-10 mm Multiple lesions On ovary, can enlarge to several centimeters Endometriomas, or “chocolate cysts”