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

Normal Menstrual Cycle Days 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

Normal Menstrual Cycle Days 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

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 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

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)

Secondary Amenorrhea –No period for 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

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

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

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

Endocrinopaththies Thyroid Disease Cushings Late Onset Congenital Adrenal Hyperplasia –Primarily 21 hydroxylase deficiency

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

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

Secondary Amenorrhea History 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

Secondary Amenorrhea Physical 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

Secondary Amenorrhea Laboratory Evaluation Rule out pregnancy FSH/LH TSH Consider: Prolactin, DHEAS, Testosterone, 17 – OHP, Cortisol

Secondary Amenorrhea Evaluation 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

Secondary Amenorrhea Treatment 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

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

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

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

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

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

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

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

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

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

Moderate DUB in Adolescents Hemoglobin 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

Severe DUB in Adolescents Hemoglobin < 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

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

DUB in Adolescents Goals Correct hemodynamic imbalance Prevent uncontrolled bleeding loss Correct anemia Replace iron storees Encourage contraception for the sexually active teen

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

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

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

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)

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

Primary Amonorrhea Physical 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

Primary Amenorrhea Evaluation FSH/LH Testosterone Karyotype Pelvic Ultrasound

Primary Amenorrhea Treatment 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