Dysfunctional Uterine Bleeding in the Adolescent

1. Dysfunctional Uterine Bleeding in the Adolescent Jennifer E. Dietrich MD, MSc Division of Pediatric and Adolescent Gynecology Department of Obstetrics and Gynecology Baylor College of Medicine

2. Disclosures I the following financial relationships with a commercial interest: CSL Behring Merck Duramed Bayer

3. Basic Terminology can be Confusing Polymenorrhea Oligomenorrhea Amenorrhea Metrorrhagia Menometrorrhagia

4. Polymenorrhea Frequent regular or irregular bleeding at <21 day intervals

5. Oligomenorrhea Infrequent irregular bleeding at >35 day intervals

6. Irregular Menses Bleeding at varying intervals >21 days but <45 days

7. Metrorrhagia Intermenstrual irregular bleeding between regular periods

8. Menorrhagia Excessive amount and increased duration of uterine bleeding >7 days, occurring regularly

9. Menometrorrhagia Frequent irregular, excessive prolonged episodes of uterine bleeding >7 days in duration

10. Pubertal Effects Menses should occur ~2 years after thelarche Expect menses to gradually become more regular Most adolescents should have regular cycles within 2-3 years of menarche

11. What is a normal menstrual cycle for an adolescent just beginning menarche? Average age of first menses is 12.5 years of age Menstrual cycles can be irregular for up to three years after onset of the first cycle Bleeding should occur between every 21-35 days <21 days between cycles? Needs evaluation! >35 days between cycles? Needs evaluation! With each menstrual cycle, bleeding that lasts for more than 7 days? Needs evaluation!

12. General Features of Menses by Gynecologic Year First Gynecologic Year 5 % = 23 days 95 % = 90 days Fourth Gynecologic Year 95 % = 50 days Seventh Gynecologic Year 5 % = 27 days 95 % = 38 days Cycle length more VARIABLE for teens than women 20-40 years of age

13. Menstruation: Additional Practical Points Educate Moms and Daughters about what is normal in the first year: 21-45 days (how to count) </= 7 days of flow 3-6 pads/day is typical Variation in pad/tampon capacity WRITE IT DOWN!

14. Menstrual calendar

15. The most common causes of DUB in an adolescent Annovulation Infections Do not forget to check a pregnancy test!

16. Importance of History Timing Menstrual history Pad/tampon count and size Presence of vaginal discharge Presence of abdominal pain Past medical history Medication exposures Personal and/or family history of easy bruising, gingival bleeding or epistaxis

17. Physical Exam Assess stability—check vitals General- presence of noticeable factors (ie., hirsute features) Thyroid Breast Abdomen Pelvic

18. Differential Diagnosis Annovulation (most common) Due to immaturity of the hypothalamus Hypothalamic dysfunction Polycystic ovarian syndrome

19. Differential Diagnosis Pregnancy-related Miscarriage Ectopic pregnancy Retained products after elective termination

20. Differential Diagnosis Chronic Diseases Renal Liver Thyroid Diabetes

21. Differential Diagnosis Infections Chlamydia PID Shigella

22. Differential Diagnosis Neoplasms Vaginal/cervical tumors Polyps Hemangiomas Leiomyomas Granulosa cell tumor Sertoli-Leydig cell tumor

23. Differential Diagnosis Other Endocrine Disorders (thyroid is most common) Anorexia Nervosa Medications

24. Differential Diagnosis Hematologic Von Willebrand’s Platelet function defects Idiopathic thrombocytopenic purpura Other rare bleeding disorders

25. In the U.S. Over 2-3 million U.S. women have an underlying bleeding disorder. >300,000 hysterectomies/year occur for menorrhagia alone

26. Bleeding Disorders In the general population 1% of individuals worldwide are diagnosed with von Willebrand’s Disease. Bleeding disorders are common in women with menorrhagia with prevalence ranging from 10-50% Von Willebrand’s is the most common of all bleeding disorders with a prevalence of 5-15% among those with bleeding conditions.

27. Give me the stats! Average time to diagnosis for a woman with menorrhagia is 8 years! Distribution 70:30 (female:male) Overall prevalence higher in Northern European countries (18%) Prevalence of severe vWD highest in Sweden (1/200,000)

28. American College of Obstetricians and Gynecologists (ACOG) Recommendations The first adolescent female health care visit should occur between the ages of 13 and 15 Adolescents presenting with menorrhagia should be screened for bleeding disorders

29. How to AVOID missing a bleeding disorder

30. Key elements from history Easy bruising Epistaxis Frequent gum bleeds Family history of menometrorrhagia, post partum hemorrhage, easy bruising, epistaxis, frequent gum bleeds, menorrhagia

31. What types of bleeding disorders are most common? Von Willebrand’s Disease (Prevalence=1%) 3 types Type 1 Type 2—many subtypes Type 3 Platelet function defects

32. Bleeding symptoms in women with vWD

33. NHLBI Testing Recommendations 2008 Primary CBC, PT, PTT, fibrinogen VWF Ag, Ristocetin Cofactor, Factor VIII Values <30 are convincing Values 30-50 may be VWD or simply “low VWF” Secondary Multimers, genetic testing Specialized platelet testing, RIPA, ratios

34. The difficulty… Spectrum of disorders Autosomal Dominant, Autosomal Recessive Variable penetrance Acquired forms No one test is “the best” Repeating tests may be necessary Stress Exercise Pregnancy Hormone use Inflammatory states

35. Correlates of >80ml blood loss… Bleeding heavier than one pad/hour Low serum ferritin Passing clots greater than 1 inch diameter PBAC score >100

36. Morbidity Loss of time from work Psychological effects Loss of time from school Peer interactions Lifestyle modification Focussing ONLY on the bleeding condition

37. The Acute Bleed History and exam are critical! Recommended work-up CBC, TSH, von Willebrand’s panel (vWD Ag, Ristocetin cofactor, Factor VIII), Type and screen, PT, PTT, INR, fibrinogen, PFA 100 Draw labs BEFORE administering hormones Imaging Ultrasound MRI in some cases

38. The Acute Bleed and Treatment Starting Hormones IV Estrogen: recommended for the acute bleeding episode in which patient is unable to tolerate po intake. May be given 25mg IV q6 hours until vaginal bleeding stops. Combination oral contraceptives A 50 mcg pill with ethinyl estradiol has the SAME bioavailability as conjugated equine estrogens administered IV. Pills should be administered every 6 hours until vaginal bleeding stops Tapers are useful-a variety of protocols exist

39. How do hormones work?

40. Hormones Come in Many Shapes and Sizes

41. Differences in Progestins Some are more androgenic than others Low, Medium and High dose Progestins Less breakthrough bleeding reported with levonorgestrel, norgestimate and desogestrel (all are MORE androgenic)

42. Treatment of mild, moderate and severe episodes with known negative pregnancy test

43. Other tips for the acute bleed… May need to premedicate some patients with Phenergan or Odansetron during high dose hormone administration If labs return normal, but you remain clinically suspicious during follow up visits—recheck blood work.

44. Managing the Chronic DUB patient The bleeding may not be quite as heavy, or have lasted quite as long—rest assured it has been just as much of a nuisiance to the patient. MANY options for hormonal management.

45. Summary Dysfunctional uterine bleeding (DUB) is multifaceted in the adolescent patient The most common condition resulting in DUB for the adolescent is annovulation Bleeding is often easily controlled with hormonal manipulation Adolescents have a number of options these days to fit their needs Good evidence for guiding management in women with diagnosed bleeding disorders thus far, but more research is needed.