2DefinitionFailure 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.
3IntroductionPuberty is a period of transition between childhood life and adult womanhood life during which sexual maturation occursThe hypothalamus is initiator of these pubertal changes in the following order adrenarche, gonadarche and menarche.
5U-shaped LH curve Exercise Anorexia Post-partum High opioid ReversalHigh opioidHigh melatoninLow leptinPre-pubertalstillNeonate Child AdultThis curve is present even in agonadic childThe drop of opioid and melatonin, or rise of leptin allows the release of GnRH
6Two independent events of puberty AdrenarcheGonadarcheStimulusCASHGnRHTimingPrecedes growth spurtFollows growth spurtMediatorDHEAE2ManifestationPubic hairAxillary hairGrowth spurtMenarcheDiseaseNot in Addison’sNot in Turner’s
7Tanner staging of puberty StageAgeBreastsPubic hairE2 Pg/mlI7NippleNil< 10II10Breast budSparse labial10-20III11Smooth contourDark curled hair20-40IV13Secondary moundAdult type hair40-60V14Mature breastAdult distribution> 60NB: Menarche coincides with stage IV
8Second growth spurt It is earlier in females It is higher in males It is related to GH, IGF-1Gonadal steroidsInitiates itTerminates itIncrements inches/yearsGirlsBoysAge in years
9Leveling of amenorrhea 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)
10CategorizationBased on presence or absence of 2ry sexual characteristics:No 2ry sexual characteristicsBreast development, but no pubic and axillary hairNormal 2ry sexual characteristicsIncompletely developed 2ry sexual characteristics
141ry amenorrhea with no 2ry sexual charachteristics centralFSH lowHypogonadotropic hypogonadism:Kallmann’s syndrome: 1ry amenorrhea (lack GnRH)+ AnosmiaCraniopharyngioma: either by damaging the hypothalamus or interferes with the transport o hormonesIf GnRH stimulation test +ve>>> hypothalamusImaging needed for tumors
161ry amenorrhea with no 2ry sexual charachteristics gonadalFSH highHypergonadotropic hypogonadism:Unresponsive end organsDifferential diagnosis:Turner’s syndromeSwyer’s syndromePure gonadal agenesis (46XX & 46XY)Mixed gonadal dysgenesisAbnormal X chromosome
17Turner syndrome Turner’s stigmata Sexual infantilism Short stature Webbed neckSpaced nipplesCubitus valgusShield chestPigmented neviCoarctation of aortaRenal anomalyStreak gonadsTurner’s KaryotypeXOXO/XXXXp-XXr
191ry amenorrhea with breast development and lack of pubic & axillary hairs +ve gonadal secretion, no manifestations of androgen secretionReflects the absence of androgen receptors “complete androgen insensitivity syndrome” (testicular feminization)Genotype : 46XY male intra-abdominal testesPhenotype :female normal contour, no uterus, vaginal dimple….. Due to mullerian-inhibiting substanceGonadectomy,,,, high malignancy rateRaise as female and create new vaginaPsychological counselingIslamic view regarding inheritance
20Morris syndrome (XY female) Male karyotypeFemale phenotypeMale level of testosteroneCompleteReceptor failure5 alpha-reductase defect
211ry amenorrhea with normal 2ry sexual charachteristics Normal gonadal secretionVast majority 46XX, amenorrhea due to anatomical abnormalitiesIn case of absent vagina and/or uterus: Creation of new vagina is the answer (dilators, vaginoplasty)With yterine/vaginal abnormalities always think of renal abnormalitiesWith no uterusMullerian agenesis (Mayer-Rokitansky)XY female (Morris’)With a uterusGynaetresiaImperforate hymenT.S vaginal septumHypoplasia uteriGenital TBSystemic illnessConstitutional delay
25Primary amenorrhea with sexual infantilism ObeseFrohlich’s syndromeLaurance-Moon-Biedl syndromeHand-Schuller-Christian diseasePrader-Willi syndromeCraniopharyngiomaSuprasellar-germinomaThinExercise relatedHigh B-EndHigh catechol estrogenAnorexia nervosaWeight lossSystemic illnessTuberculosisSCDThalassemia
26Primary amenorrhea with sexual infantilism TallPure gonadal agenesisSwyer’s syndromeKallmann’s syndrome17 OHase deficiency17-20 desmolase deficiencyShortPituitary dwarfSexualAsexual (Laron)Turner’s syndromeHypothyroidismConstitutional delay of puberty
27Comparison Item Pure gonadal agenesis Kallmann’s syndrome Karyotype XX or XY (Swyer’s)XXFSHHighLowGonadStreaksOvaryHumegonNo responseGoodAssociationGonadoblastomaAnosmia
28Weight loss amenorrhea SimpleAnorexia nervosaAgeAnyYoungPsychicNoYesWeight lossAdded features20% of IBWMoreDehydrationHormonesNormal GH, rT3, Carotene, DA PRL, LH, T3, E2, ADHGnRH therapyUsefulNotComplicationPossibleAs the fault extends to the pituitary in anorexia, GnRH pulse therapy is not effective in restoring menstruation.
33Management of primary amenorrhea 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.