MenstrualMenstrual cyclecycle disordersdisorders DrDr DD ChardonnensChardonnens PDPD DefinitionsDefinitions SecondarySecondary amenorrheaamenorrhea 33 consecutiveconsecutive monthsmonths withoutwithout periodsperiods PrimaryPrimary amenorrheaamenorrhea NoNo periodsperiods afterafter thethe ageage ofof 1616 –– 1717 HypomenorrheaHypomenorrhea PeriodsPeriods << 33 daysdays withwith littlelittle bleedingbleeding DefinitionsDefinitions MenorrhagiaMenorrhagia PeriodsPeriods >> 77 daysdays && >> 8080 mlml HypermenorrheaHypermenorrhea PeriodsPeriods >> 8080 mlml OligomenorrheaOligomenorrhea CycleCycle >> 3535 daysdays PolymenorrheaPolymenorrhea CycleCycle << 2121 daysdays DefinitionsDefinitions PrimaryPrimary dysmenorrheadysmenorrhea PainfulPainful periodsperiods beforebefore thethe ageage ofof 1919 SecondarySecondary dysmenorrheadysmenorrhea PainfulPainful periodsperiods afterafter thethe ageage ofof 1919 DifferentDifferent levelslevels CNS I Hypothalamus II Pituitary Thyroid Adrenal III Ovary Uterus IV PFP LFP PLP MLP LLP HormonalHormonal assays:assays: FSHFSH Prognostic value of day 3 FSH levels in 758 patients undergoing an IVF cycle Adapted from Scott et al. 1989, Fertil. Steril., 51 651 -654 25 Total Delivery 20 er cycle (%) 15 cy rate p 10 5 Pregnan 0 <15 15 - 24,9 > 25 Basal day 3 FSH (mIU / mL) HormonalHormonal assays:assays: LHLH DayDay 33 LHLH >> 1010 IU/L,IU/L, oror LH/FSHLH/FSH >> 2.52.5 infertility spontaneous abortions PCOS PFP LFP PLP MLP LLP BasalBasal BodyBody TemperatureTemperature ↑↑ basalbasal bodybody temperaturetemperature ≥≥ 0.20.2°°CC ↑↑ basalbasal bodybody temperaturetemperature ≥≥ 1212 daysdays BasalBasal BodyBody TemperatureTemperature InexpensiveInexpensive RepeatedRepeated inin differentdifferent cyclescycles NotNot appropriateappropriate toto timetime ovulationovulation PoorPoor correlationcorrelation withwith PP levellevel andand endometrialendometrial biopsiesbiopsies BasalBasal bodybody temperaturetemperature BasalBasal bodybody temperaturetemperature BasalBasal bodybody temperaturetemperature HormonalHormonal assays:assays: ProgesteroneProgesterone DayDay 2121 2.5 - 5 ng / ml ovulation 10 - 15 ng / ml normal corpus luteal function DayDay 20,20, 21,21, 2222 Σ : 15 ≥ ng/ ml EndometrialEndometrial biopsybiopsy DifferentDifferent levelslevels MRI, I FSH & LH indirect evidence of GnRH II FSH, LH, TSH, Prl MRI Thyroid Adrenals E2 P4 A2 T III Echography βhCG Echography IV MRI Hysteroscopy Progestin test SomeSome etiologiesetiologies ofof secondarysecondary amenorrheaamenorrhea Stress I Anorexia… II Tumors Necrosis… PCO III Menopause… Pregnancy IV Synechiae Stenosis TBC… InvestigatingInvestigating secondarysecondary amenorrheaamenorrhea ExcludeExclude pregnancypregnancy normogonadicnormogonadic amenorrheaamenorrhea EE2 >> 3030 pgpg/ml/ml HypogonadicHypogonadic amenorrheaamenorrhea EE2 << 3030 pgpg/ml/ml Hypergonadotropic (primary hypogonadism) FSH > 20 – 30 UI/L Hypogonadotropic (secondary hypogonadism) LH < 1 UI/L CaseCase 11 2525 yearsyears oldold athleteathlete withwith secondarysecondary amenorrheaamenorrhea afterafter stoppingstopping OCOC (>(> 1212 monthsmonths)) InvestigationsInvestigations PregnancyPregnancy testtest –– EE2 2525 pgpg/ml/ml FSHFSH == 22 UI/L,UI/L, LHLH 0.20.2 UI/LUI/L PrlPrl NN DiagnosisDiagnosis:: HypogonadotropicHypogonadotropic hypogonadismhypogonadism hypothalamichypothalamic amenorrheaamenorrhea CaveCave bonebone massmass CaseCase 22 2525 yearsyears oldold athleteathlete withwith secondarysecondary amenorrheaamenorrhea afterafter stoppingstopping OCOC (>(> 1212 monthsmonths)) hothot flushesflushes InvestigationsInvestigations PregnancyPregnancy testtest –– EE2 2525 pgpg/ml/ml FSHFSH == 5252 UI/L,UI/L, LHLH 2525 UI/LUI/L PrlPrl NN DiagnosisDiagnosis HypergonadotropicHypergonadotropic hypogonadismhypogonadism:: precociousprecocious menopausemenopause CaseCase 22 OtherOther investigationsinvestigations TestTest otherother endocrineendocrine pathwayspathways TestTest forfor autoimmuneautoimmune diseasesdiseases TestTest forfor geneticgenetic diseasesdiseases (X(X fragile,fragile, TurnerTurner…….).) CounsellingCounselling THSTHS CaseCase 33 2525 yearsyears oldold athleteathlete withwith secondarysecondary amenorrheaamenorrhea afterafter stoppingstopping OCOC (>(> 1212 monthsmonths)) HistoryHistory ofof irregularirregular cyclescycles InvestigationsInvestigations PregnancyPregnancy testtest –– EE2 105105 pgpg/ml/ml FSHFSH == 44 UI/L,UI/L, LHLH 1414 UI/LUI/L PrlPrl NN DiagnosisDiagnosis «« NormogonadicNormogonadic »» amenorrheaamenorrhea CaseCase 33 InvestigationsInvestigations T = 0.9 ng/ml 17 OH-P = 250 ng/dl ACTH testing 17 OH-P = 450 ng/dl Ultrasound PCOPCO ?? PCOSPCOS • Ultrasound criteria • Infertility 88 % • Insulin resistance 70 % • Hirsutism 62 % • Irregular cycles 50 % • Obesity 38 % • Acne 35 % PCOPCO andand ultrasoundultrasound criteriacriteria ↑ ovarian volume ↑ ovarian stroma > 10 follicles Ø <10 mm at the periphery (necklace sign) PCOPCO andand ultrasoundultrasound criteriacriteria van Santbrink et al. 1997 Fertil Steril ↑ Follicle number (58%) ↑ Ovarian stroma (45%) 9 10 15 23 3 11 4 ↑ Ovarian volume (41%) PCOPCO versusversus PCOSPCOS van Santbrink et al. 1997 Fertil Steril Ultrasound criteria (66%) 21 8 20 5 ↑ Androgens (36 %) 17 3 7 ↑ LH (47%) AndrogensAndrogens DHEAS 90 % 10 % DHEA 60 % Androstenedione 40 % DHEA Ovary Adrenal Peripheral tissue 25 % 50 % 25 % Testosterone SerumSerum valuesvalues ofof androgensandrogens DHEA-S Androstenedione Testosterone ng/ml ng/ml ng/ml Premenopause 1600 1.4 0.4 (500 - 2800) (0.7 - 3.1) (0.2 - 0.8) Menopause 800 0.8 0.15 (0.1 - 2.7) (0.1 - 0.4) Term 320 2.4 4.0 pregnancy AndrogensAndrogens andand seriousserious diseasedisease TestosteroneTestosterone >> 22 ngng/ml/ml Look for tumor of the ovary DHEASDHEAS >> 70007000 ngng/ml/ml Look for tumor of the adrenal 1717 OHOH--PP andand menstrualmenstrual cyclecycle 3 2 IU/L 1 17 OH-P 0 0 4 8 1216202428 Menses Cycle Day BasalBasal valuesvalues forfor 1717 OHOH--PP >> 800800 ngng/dl/dl (24(24 nmolnmol/l)/l) 2121 hydroxylasehydroxylase deficiencydeficiency >> 200200 ngng/dl/dl (6(6 nmolnmol/l)/l) SuspicionSuspicion ofof 2121 hydroxylasehydroxylase deficiencydeficiency TestTest withwith ACTHACTH << 200200 ngng/dl/dl (6nmol/l)(6nmol/l) 2121 hydroxylasehydroxylase deficiencydeficiency 1717 OHOH--PP postpost ACTHACTH >> 15001500 ngng/dl/dl LateLate onsetonset adrenaladrenal hyperplasiahyperplasia 10001000--15001500 ngng/dl/dl SuspicionSuspicion ofof latelate onsetonset hyperplasiahyperplasia GeneGene 21B21B analysisanalysis << 10001000 ngng dldl HeterozygoteHeterozygote carriercarrier CaseCase 33 CaveCave InfertilityInfertility DevelopmentDevelopment ofof diabetesdiabetes typetype 22 IncreaseIncrease inin cardiovascularcardiovascular eventsevents ?? HyperplasiaHyperplasia andand endometrialendometrial carcinomacarcinoma CaseCase 44 2525 yearsyears oldold athleteathlete withwith secondarysecondary amenorrheaamenorrhea afterafter stoppingstopping OCOC (>(> 1212 monthsmonths)) HistoryHistory ofof headachesheadaches andand visualvisual disturbancesdisturbances InvestigationsInvestigations PregnancyPregnancy testtest –– EE2 2828 pgpg/ml/ml FSHFSH == 44 UI/L,UI/L, LHLH 11 UI/LUI/L PrlPrl 150150 ngng/ml/ml DiagnosisDiagnosis HypogonadicHypogonadic amenorrheaamenorrhea withwith hyperprolactinemiahyperprolactinemia CaseCase 44 DDDD ofof hyperprolactinemiahyperprolactinemia StressStress MedicationMedication (neurotropes,(neurotropes, estrogenesestrogenes…….).) HypothyroidHypothyroid statestate NeurogenicNeurogenic ((breastbreast palpation,palpation, intercostalintercostal zona..)zona..) HypothalamicHypothalamic disordersdisorders PituitaryPituitary disordersdisorders CaseCase 55 2525 yearsyears oldold athleteathlete withwith secondarysecondary amenorrheaamenorrhea afterafter stoppingstopping OCOC (>(> 1212 monthsmonths).). HistoryHistory ofof postpartumpostpartum hemorrhagehemorrhage withwith retainedretained placentaplacenta InvestigationsInvestigations PregnancyPregnancy testtest –– EE2 174174 pgpg/ml/ml FSHFSH == 2525 UI/L,UI/L, LHLH 5858 UI/LUI/L PrlPrl NN DiagnosisDiagnosis NormogonadicNormogonadic hypergonadotropichypergonadotropic amenorrheaamenorrhea CaseCase 55 UltrasoundUltrasound PP4 == 6,26,2 ngng/ml/ml CaseCase 55 HysterosalpingographyHysterosalpingography HysteroscopyHysteroscopy CaseCase 66 2525 yearsyears oldold athleteathlete withwith secondarysecondary amenorrheaamenorrhea afterafter stoppingstopping OCOC (>(> 1212 monthsmonths).). HistoryHistory ofof postpartumpostpartum hemorrhagehemorrhage withwith retainedretained placenta.placenta. SheShe couldcould notnot breastfeedbreastfeed.. InvestigationsInvestigations Pregnancy test – E2 10 pg/ml FSH = 1 UI/L, LH 0.2 UI/L Prl 4 ng/mL DiagnosisDiagnosis Hypogonadic hypogonadotropic amenorrhea CaseCase 66 SheehanSheehan SyndromeSyndrome TestTest thethe endocrineendocrine axisaxis CNSCNS MRIMRI HormonalHormonal substitutionsubstitution accordingaccording toto thethe endocrineendocrine deficitsdeficits CaseCase 77 4242 yearyear oldold ladylady complainingcomplaining ofof menorrhagiamenorrhagia andand secondarysecondary dysmenorrheadysmenorrhea sincesince 22 yearsyears Normal pelvic examination PAP smear normal TVSTVS andand HTVSHTVS HTVSHTVS vsvs hysteroscopyhysteroscopy TVSTVS HTVSHTVS HysteroscoppyHysteroscoppy CaseCase 88 5959 yearyear oldold womenwomen onon sequentialsequential HRTHRT complainigcomplainig