1. Emad R. Sagr, MBBS, FRCSC, FACOG Consultant Obstetrics & Gynecology and Gynecology Oncology Security Forces Hospital

2. Definitions Primary amenorrhea Failure of menarche to occur when expected in relation to the onset of pubertal development.  No menarche by age 16 years with signs of pubertal development.  No onset of pubertal development by age 14 years. Secondary amenorrhea  Absence of menstruation for 3 or more months in a previously menstruating women of reproductive age.

3. CNS-Hypothalamus-Pituitary Ovary-uterus Interaction Neural controlChemical control Dopamine (-) Norepiniphrine (+) Endorphines (-) Hypothalamus Gn-RH Ant. pituitary FSH, LH Ovaries Uterus ProgesteroneEstrogen Menses –± ?

4. Incidence of Primary Amenorrhea  Less than.1%  Puberty Breast: 10.8 +/- 1.10 yrs. Pubic Hair:11.0 +/- 1.21 yrs. Menarche12.9 +/- 1.2 yrs.

5. Onset of Puberty and Menstruation  Ratio of fat to both total body weight and lean body weight  Moderate obesity (20 – 30 % above ideal body weight) = earlier menarch  Malnutrition (anorexia nervosa, starvation) = delay  Prepubertal strenuous exercise (less total body fat) = delay e.g. ballet dancers, swimmers, runners

6. Diagnostic Evaluation by Compartments IOutflow Tract (uterus – vagina) IIOvary IIIAnterior Pituitary IVCNS – Hypothalamus (environment and psyche)

7. Evaluation  History/Physical  Psychiatric, family history-genetic abnormalities, nutritional status, growth/development  Secondary sexual characteristics  Presence of breasts – normal reproductive tract (uterus, vagina)

8. Evaluation Categories  Breast Absent – Uterus Present  Breast Present – Uterus Present  Breast Present – Uterus Absent  Breast Absent – Uterus Absent

9. Initial Tests for Amenorrhea  Progesterone challenge  TSH  Prolactin TSH elevated – hypothyroid Prolactin elevated (MRI – 100 ng/ml)

10. Progesterone Challenge  Positive withdrawal bleed  Normal prolactin  Normal TSH  Diagnosis = annovulation  Treatment: monthly progesterone/O.C.

11. Progesterone Negative Withdrawal  FSH/LH  FSH/LH normal – estrogen/progesterone cycle  If negative = end organ defect  If FSH/LH high = ovarian failure  Estrogen – positive withdrawal, FSH normal or low, MRI sella = no path  Diagnosis: hypothalamic amenorrhea

12. Chromosome Evaluation for Ovarian Failure  If the patient is under age 30 – karyotype  Y chromosome/excision of gonadal area  Problem – gonadal tumor – malignant  30% do not develop virilization, therefore even normal appearing female needs karyotype to exclude Y  After age 30 = premature menopause

13. Specific Disorders IOutflow- imperforate hymen, ashermans mullerian agenesis, androgen insensitivity syndrome IIOvary - can be primary or secondary amenorrhea 40% of primary amenorrhea have gonadal streaks Of the 40%, 50% = 45,X 25% = mosaics 25% = 46 XX Secondary amenorrhea patients have many karyotypes

14. Specific Disorders (continued)  Turner syndrome  Gonadal dysgenesis  Gonadal agenesis  Savage syndrome  Premature ovarian failure  Radiation therapy  Alkylating agents

15. Compartment III  Anterior pituitary disorders  Tumors – large bitemperal hemianopsia  Small tumors – visual defects- rare  Craniopharyngioma – calcification x-ray may produce blurring of vision  Acromegaly  Cushings  Pituitary prolactin adenomas (micro/macro)  Sheehan’s syndrome

16. Compartment IV CNS disorders  Hypothalamic amenorrhea – problem is a GNRH pulsatile secretion  Anorexia/Bulemia/weight loss – 25% (onset – 10 – 30 years)  Exercise

17. Etiology of Amenorrhea Breast – Absent Breast – Present Uterus Absent Uterus Present 17, 20 desmolase deficiency 1. Gonadal failure turner 45X 17 a hydroxylase deficiency 46xy Gonadal dysgenisis Agonadism 17 a hydroxylase deficiency with 46XX 2. Hypothalamic failure 3. Pituitary failure AIS (T.F.) Hypothalamic, pituitary, ovarian pt uterine etiology Mullerianagenesis