Menstrual Disorders: Excessive Vaginal Bleeding, Secondary Amenorrhea and Primary Amenorrhea

1. Menstrual Disorders:Excessive Vaginal Bleeding, Secondary Amenorrhea and Primary Amenorrhea Betsy Pfeffer MD Assistant Professor Clinical Pediatrics Columbia University Morgan Stanley Children’s Hospital of New York Presbyterian

2. Normal Menstrual CycleDays 1-13 • Hypothalmus-Pituitary • Increased GnRH, FSH • Ovary-Follicular Phase • Estrogen produced by granulosa cells • Development of primary follicle • Feedback of E2 (+ to decrease FSH, - to increase LH) • Uterus-Proliferative Phase • Increased glandular cells and stroma

3. Normal Menstrual CycleDays 15-28 • Hypothalmus-Pituitary • Decreased GnRH, FSH, LH • Ovary • Primary follicle becomes corpus luteum • Corpus luteum secretes progesterone x 14 days • Uterus-Secretory Phase • Coiling of endometrial glands • Increased vascularity of stroma • Increased glycogen in endometrial cells

5. Normal Menstrual Cycle • Average age of Menarche is 12.7 (Tanner 4) • Ovulation occurs in 50% of girls one year post menarche and in 80% by two years • 21-40 days long • 2-8 days of bleeding • 20-80cc blood loss • Once cylic menses established it is still normal to have an occasional anovulatory cycle

6. Anovulatory Cycles • Normal up to gynecologic age of 2-3 years • Cycles may be long (8-12 weeks) • If sexually active may be worried about pregnancy • Cycles often short (2-3 weeks)

8. Secondary Amenorrhea • Secondary Amenorrhea • No period for 12-18 months after menarche • Absence of three menstrual cycles in the teen who has already established regular cyclic menses • Oligomenorrhea • Uterine bleeding at prolonged intervals (41days –3months) with normal flow/duration and quantity • Same differential/evaluation for secondary amenorrhea and oligomenorrhea

9. Normal Menses • Dependant on an intact hypotalamic-pituitary-ovarian-uterine axis • Disruption of this axis at any level can lead to amenorrhea/oligomenorrhea

10. Hypothalamic causes of Secondary Amenorrhea • Pregnancy • Medications • Endocrinopathies • Eating disorders • Tumors/Infiltrative process/Infections • Chronic disease • Exercise • Stress • Idiopathic: abnormal GnRH, Kallman’s syndrome: hypogonadotropic hypogonadism (low FSH/LH) anosmia

11. Endocrinopathies • PCOS: chronic anovulation/hyperandrogenism • HAIR-AN Insulin LH FSH Normal/Low Estrogen Theca Cells Androgen

12. Endocrinopaththies • Thyroid Disease • Cushings • Late Onset Congenital Adrenal Hyperplasia • Primarily 21 hydroxylase deficiency

13. Pituitary causes of Secondary Amenorrhea • Tumor • Infiltrative • Nonneoplastic lesions • Sheehan’s Syndrome: pregnancy related • Simmonds Disease: non pregnancy related • Aneurysm

14. Ovarian and Uterine causes of Secondary Amenorrhea • Premature Ovarian Failure • Menopause before age 35 • Associated with autoantibodies • Increase in thyroid/adrenal disease • Post chemotherapy/radiation • Asherman’s Syndrome

15. Secondary AmenorrheaHistory • Menstrual History • Sexual History • Past Medical History/Surgical History • Family History • Headaches • Galactorrhea • Nutritional Status/Dietary History • Androgen excess/Symptoms of Thyroid Disease • Stress • Exercise • Medications

16. Secondary AmenorrheaPhysical Exam • Vital Signs/Ht/Wt/BMI • Tanner Stage • Goiter • Signs of androgen excess: hisuitism, cliteromegly, acne, hair loss • Galactorrhea • Anosmia • Signs of systemic disease • Consider pelvic in sexually active teen

17. Secondary AmenorrheaLaboratory Evaluation • Rule out pregnancy • FSH/LH • TSH • Consider: Prolactin, DHEAS, Testosterone, 17 –OHP, Cortisol

18. Secondary AmenorrheaEvaluation • If HCG is negative give progesterone challenge • + withdrawl bleed • endometrium has been primed with estrogen • Suggests anovulation/does not identify the cause • - withdrawl bleed • Hypoestrogenemia : CNS lesion, Ovarian failure, anorexia, Turner’s mosaic • Endometrial damage: Asherman’s

19. Secondary AmenorrheaTreatment • Treat precipitating cause if it is identified • If due to anovulation induce uterine bleeding every 6-8 weeks or place on birth control because of increased risk of endometrial cancer and anemia secondary to DUB • Encourage need for birth control if sexually active • Refer to specialist when indicated

20. Etiology of Excessive Vaginal Bleeding in Teens • Dysfunctional Uterine Bleeding -Etiology of >95% excessive vaginal bleeding in perimenarchal teens w/ normal hemoglobin and normal physical exam • Usually due to anovulation • Diagnosis of exclusion

21. Dysfunctional Uterine Bleeding • Irregular, prolonged, excessive, unpatterned painless bleeding • Anovulatory cycle • Endometrial in origin • No structural or organic pathology

22. Differential Diagnosis of Excessive Vaginal Bleeding • Complications of Pregnancy • ectopic, threatened abortion, hydatiform mole • Infections • cervicitis, PID • Endocrine Disorders • hypothyroidism, PCOS, late onset CAH, cushings, androgen producing tumor, prolactinoma

23. Differential Diagnosis of Excessive Vaginal Bleeding • Blood Dyscrasias • ITP, VWD, Glanzman’s disease, SLE, leukemia liver/renal failure, inherited clotting deficiencies, vit K deficiency • Ovarian Masses • hormonally active cysts, tumor, polyps • Trauma/foreign body • Medications • contraception

24. DUB in Adolescents • History often unreliable • Hormonal therapy almost always works • Curettage rarely necessary

25. DUB in AdolescentsHistory • Gynecological Age • Menstrual History • Sexual Activity • Method of Contraception • Presence of Pain • Nausea/breast tenderness • Dizziness • Symptoms of endocrinopathies • Other Bleeding History • Medications

26. DUB in Adolescentsphysical exam • Vital signs • Pallor • Bruising/Petechiae • Murmur/Tachycardia • Evaluation for endocrinopathies-hirsuitism, acne,cliteromegaly, goiter, visual fields, acanthosis, galactorrea • Pelvic exam if sexually active

27. Lab Evaluation • HCG • CBC: hemoglobin and platlets • GC/Chlamydia • LH/FSH, TSH, 17- OHP, Prolactin, Testosterone, DHEAS • If Hemoglobin less than 10 • PT/PTT, Von Willebrand’s Ag, Ristocetin Cofactor, Factor X111 and 1X, Platlet aggregation studies • Referral to Hematology

28. Mild DUB in Adolescentshemoglobin >11 • Reassure • Iron supplementation • Menstrual calendar • Phone follow-up in one week • Follow-up 3 months unless continues bleeding • Contraception if sexually active

29. Moderate DUB in AdolescentsHemoglobin 9-11 • Low dose monophasic OCP • 2-4 tabs a day until bleeding stops • Then once a day • Allow withdrawal bleed when Hemoglobin >11 • Cycle for at least 6 months • Iron when on one OCP/day • Progesterone only pills: Aygestin better than Provera • Close follow-up

30. Severe DUB in AdolescentsHemoglobin < 9 and/or Massive Hemmorhage • Hospitalize • Fluid resuscitation • Blood transfusion rarely needed • Premarin 25mg IV q 4-6 hours (max 4 doses) • Monophasic OCP q6h then tapered to qd • Iron • Continue OCP 6 months

31. Etiology of Acute Menorrhagia Requiring Hospital Admission Other 7% DUB-75% Primary Coagulation Disorder-19%

32. DUB in AdolescentsGoals • Correct hemodynamic imbalance • Prevent uncontrolled bleeding loss • Correct anemia • Replace iron storees • Encourage contraception for the sexually active teen

33. Primary Amenorrhea • Primary Amenorrhea • No uterine bleeding by age 16 • No secondary sex characteristics by age 14 • SMR5 for one year and no uterine bleeding • No uterine bleeding four years after breast development

34. Etiology of Primary Amenorrhea • Primary amenorrhea w/o breast development but w/ normal genitalia • Turner’s Syndrome/Mosaicism • Structurally abnormal X chromosome • Gonadal dysgenesis • 17 alpha hydroxylase deficiency (normal stature,hypertension, hypokalemia, sexually infantile) • Hypothalamic failure due to inadequate GnRH

35. Etiology of Primary Amenorrhea • Primary amenorrhea w/ breast development (SMR 4) but absent uterus • Testicular Feminization • Congenital absence of the uterus (Rokitansky Syndrome). Associated with renal and skeletal anomolies

36. Etiology of Primary Amenorrhea • Primary amenorrhea w/o breast development and w/o uterus • RARE • Usually male karyotype w/ elevated gonadotropin levels and low testosterone. Produce enough MIF to inhibit develpoment of female internal genital structures (17,20-lyase deficiency, agonadism, 17 alpha hydroxylase deficiency w/ 46XY karyotype)

37. Etiology of Primary Amenorrhea • Primary amenorrhea w/breast development (SMR4) and w/ uterus • Same evaluation as for secondary amenorrhea • Imperforate Hymen • Turner’s Mosaic

38. Primary AmonorrheaPhysical exam • Blood Pressure/Height/Weight • Tanner stage • Signs of gonal dysgenesis: Webbed neck, low set ears, broad shieldlike chest, short fourth metacarpal • Pelvic exam • Imperforate hymen • Transverse vaginal septum • Absent uterus

39. Primary AmenorrheaEvaluation • FSH/LH • Testosterone • Karyotype • Pelvic Ultrasound

40. Primary AmenorrheaTreatment • Turner’s Syndrome • growth hormone first • estrogen replacement later • Rokitansky Syndrome • vaginoplasty • Testicular Feminization • remove gonads • Estrogen replacement • Vaginoplasty • Enzyme Defects • hormone replacement • remove gonads if Y chromosome is present