Primary amenorrhea

1. Primary amenorrhea

2. Failure to initiate spontaneous menses by the age of 16 or evidence of pubertal onset by age of 14. It is a rare condition seen in less than 0.1% of the general population. Definition

3. Puberty is a period of transition between childhood life and adult womanhood life during which sexual maturation occurs The hypothalamus is initiator of these pubertal changes in the following order adrenarche, gonadarche and menarche. Introduction

4. Hypothalamus Oxytocin PVN ADH SON Hypothalamus Pituitary Stalk Pituitary gland GnRH Satiety center VMN Chiasma

5. Exercise Anorexia Post-partum U-shaped LH curve Reversal High opioid High melatonin Low leptin Pre-pubertal still Neonate Child Adult This curve is present even in agonadic child The drop of opioid and melatonin, or rise of leptin allows the release of GnRH

6. Two independent events of puberty

7. Tanner staging of puberty NB: Menarche coincides with stage IV

8. Second growth spurt • It is earlier in females • It is higher in males • It is related to GH, IGF-1 • Gonadal steroids • Initiates it • Terminates it Increments inches/years 1 2 3 4 Girls Boys 0 2 4 6 8 10 12 14 16 18 20 Age in years

9. For proper menses to occur there should be a nice integration between the hypothalamus, pituitary, ovary and responsive uterus as well as a patent effluent genital tract. We have four levels; Level 1 (Uterus and outflow tract), Level II (Ovary), Level III (Pituitary), Level IV (Hypothalamus) Leveling of amenorrhea

10. Categorization • Based on presence or absence of 2ry sexual characteristics: • No 2ry sexual characteristics • Breast development, but no pubic and axillary hair • Normal 2ry sexual characteristics • Incompletely developed 2ry sexual characteristics

12. Primary amenorrhea

13. LDL-c P450SCC 21OHase 21OHase 3HSD 3HSD 3HSD 11HSD 17HSD P450arom P450arom Acetate Cholesterol 11OHase 17OHase 17OHase DOC Corticosterone • 5P 4P Aldosterone Desmolase 11 desoxy cortisol or compound S • 17 OH5P 17OH4P Desmolase 11OHase • DHEA AD Cortisol E1 Te Cortisone E2

14. 1ry amenorrhea with no 2ry sexual charachteristics central FSH low • Hypogonadotropic hypogonadism: • Kallmann’s syndrome: 1ry amenorrhea (lack GnRH)+ Anosmia • Craniopharyngioma: either by damaging the hypothalamus or interferes with the transport o hormones If GnRH stimulation test +ve>>> hypothalamus Imaging needed for tumors

15. Squamous epithelium Calcification Enamel-like Cystic spaces Craniopharyngioma Rathke’s pouch tumor • GH (Dwarf, obese) • Gn (Delayed puberty) • ADH (DI) ICT Stalk section Optic chiasm

16. 1ry amenorrhea with no 2ry sexual charachteristics gonadal FSH high • Hypergonadotropic hypogonadism: • Unresponsive end organs • Differential diagnosis: • Turner’s syndrome • Swyer’s syndrome • Pure gonadal agenesis (46XX & 46XY) • Mixed gonadal dysgenesis • Abnormal X chromosome

17. Turner syndrome Turner’s stigmata • Sexual infantilism • Short stature • Webbed neck • Spaced nipples • Cubitus valgus • Shield chest • Pigmented nevi • Coarctation of aorta • Renal anomaly • Streak gonads • Turner’s Karyotype • XO • XO/XX • XXp- • XXr

18. Turner syndrome Cystic hygroma Fetal hydrops Cystic hygroma

19. 1ry amenorrhea with breast development and lack of pubic & axillary hairs • +ve gonadal secretion, no manifestations of androgen secretion • Reflects the absence of androgen receptors “complete androgen insensitivity syndrome” (testicular feminization) • Genotype : 46XY male intra-abdominal testes • Phenotype :female normal contour, no uterus, vaginal dimple….. Due to mullerian-inhibiting substance • Gonadectomy,,,, high malignancy rate • Raise as female and create new vagina • Psychological counseling • Islamic view regarding inheritance

20. Morris syndrome (XY female) Male karyotype Female phenotype Male level of testosterone Complete Receptor failure 5 alpha-reductase defect

21. With no uterus Mullerian agenesis (Mayer-Rokitansky) XY female (Morris’) With a uterus Gynaetresia Imperforate hymen T.S vaginal septum Hypoplasia uteri Genital TB Systemic illness Constitutional delay 1ry amenorrhea with normal 2ry sexual charachteristics • Normal gonadal secretion • Vast majority 46XX, amenorrhea due to anatomical abnormalities • In case of absent vagina and/or uterus: Creation of new vagina is the answer (dilators, vaginoplasty) • With yterine/vaginal abnormalities always think of renal abnormalities

23. 1ry amenorrhea with incomplete 2ry sexual charachteristics

24. Comparison

25. Obese Frohlich’s syndrome Laurance-Moon-Biedl syndrome Hand-Schuller-Christian disease Prader-Willi syndrome Craniopharyngioma Suprasellar-germinoma Thin Exercise related High B-End High catechol estrogen Anorexia nervosa Weight loss Systemic illness Tuberculosis SCD Thalassemia Primary amenorrhea with sexual infantilism

26. Tall Pure gonadal agenesis Swyer’s syndrome Kallmann’s syndrome 17 OHase deficiency 17-20 desmolase deficiency Short Pituitary dwarf Sexual Asexual (Laron) Turner’s syndrome Hypothyroidism Constitutional delay of puberty Primary amenorrhea with sexual infantilism

27. Comparison

28. Weight loss amenorrhea As the fault extends to the pituitary in anorexia, GnRH pulse therapy is not effective in restoring menstruation.

29. Comparison Can Turner cases got pregnancy? Yes

30. Primary amenorrhea

31. History Personal history Family history Past history Physical examination Secondary sex characteristics Virile manifestations Weight, height, span Sonographic assessment Laparoscopy Gonadal biopsy Evaluation of primary amenorrhea

32. Buccal smear Karyotying Endocrine evaluation FSH/LH, PRL/TSH Estrogen (PWT, C.I, E2 assay) Androgen (Te, DHEAS) Investigation

33. The aim of treatment is to attain maximum physiologic function of which an individual can attain. No treatment until the diagnosis is solid. The majority will be able to achieve satisfactory sexual life but the prospect of fertility may be poor. HRT may be needed for life. Management of primary amenorrhea