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 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

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

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

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

• 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

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 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

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

Secondary AmenorrheaLaboratory Evaluation

• Rule out pregnancy

• FSH/LH

• TSH

• Consider: Prolactin, DHEAS, Testosterone, 17 –OHP, Cortisol

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

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

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 AdolescentsHistory

• 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 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

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 Adolescentshemoglobin >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 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

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

Etiology of Acute Menorrhagia Requiring Hospital Admission

DUB-75%Primary Coagulation Disorder-19%

Other7%

DUB in AdolescentsGoals

• Correct hemodynamic imbalance

• Prevent uncontrolled bleeding loss

• Correct anemia

• Replace iron storees

• Encourage contraception for the sexually active teen

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

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 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

Primary AmenorrheaEvaluation

• FSH/LH

• Testosterone

• Karyotype

• Pelvic Ultrasound

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