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

II Pituitary Thyroid Adrenal III

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

„ „ 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 „ 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 I Anorexia…

II Tumors Necrosis…

PCO III …

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 % • 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 ↑ (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

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 81216202428 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 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 ofof metrorrhagiametrorrhagia duringduring thethe progestationalprogestational phasephase

„ Normal pevic examination „ PAP smear normal CaseCase 88

„ TVS:TVS: endometriumendometrium ofof 4.54.5 mmmm nono uterineuterine pathologypathology EndometrialEndometrial histologyhistology withoutwithout HRTHRT Korhonen et al. CHART 2 1997 AJOG

68. 7 80 60 23. 5 40 20 6. 6 0. 5 0. 6 0. 07

e 0 l e l ia s a ic v y a ua a r b i r s l m a h t o u id a p e s p a t r l r o h r e t c p n t s o e r s e r e i e r f c n d p c O s t i e y r A l e e o p s o S d h a a r M y l C u H n P e a U s ic P p ty A

n= 2964 EndometrialEndometrial histologyhistology withwith sequentialsequential HRTHRT Sturdee et al. 2000 BJOG

Follow up 3,29 years 60 47. 4 40 18 15. 1 7. 6 5. 5 20 2. 7 0. 9 0. 7 0 2. 3

e 0 l e l ia s a ic v y a ua a r b i r s l m a h t o u id a p e s p a t r l r o h r e t c p n t s o e r s e r e i e r f c n d p c O s t i e y r A l e e o p s o S d h a a r M y l C u H n P e a U s ic P p ty A n=1192 EndometrialEndometrial histologyhistology withwith continuouscontinuous HRTHRT Sturdee et al. 2000 BJOG

Follow up 9 months 60 46. 3 27. 9 40 21. 8

20 1. 8 0. 7 0. 4 0 0 0 1. 1

e 0 l e l ia s a ic v y a ua a r b i r s l m a h t o u id a p e s p a t r l r o h r e t c p n t s o e r s e r e i e r f c n d p c O s t i e y r A l e e o p s o S d h a a r M y l C u H n P e a U s ic P p ty A n=1196 First bleeding day from the start of phase in sequential HRT and histology Sturdee et al. 1994 Lancet

60 50 Se c r e t o r y 40 Non A sse ssab le Prolif erativ e 30 Atrophi c Com ple x hy pe rplasia 20 Ot h e r Me n s t r u a l 10 Pse udode cidua l 0 Aty pical h y pe rplasi a 1 3 5 7 9 11131517192123 Endometrial thickness in postmenopausal women Andolf et al. Obstet and Gynecol 1993

Endometrial >> 5mm5mm << 55 mmmm PP thickness

E (pmol/L) E1 (pmol/L) 219219++2020 175175++3535 0.010.01

E (pmol/L) E2 (pmol/L) 3838++1717 1313++2.72.7 0.050.05

P (nmol/L) P4 (nmol/L) 11++0.20.2 0.870.87++0.050.05

BMI 29.129.1++1.21.2 25.625.6++0.30.3 0.020.02 EndometrialEndometrial thicknessthickness inin sequentialsequential therapytherapy Gull et al.

CycleCycle dayday EndometrialEndometrial NN thicknessthickness (mm)(mm) 11--77 4.34.3++1.01.0 44

88--1414 6.86.8++1.21.2 1313

1515--2121 6.06.0++0.30.3 1111

2222--2828 6.26.2++0.60.6 1414 VaginalVaginal sonographysonography andand endometrialendometrial cancercancer Buyuk et al. 1999 Acta Obstet Gynecol Scand

„ 5454 withwith spontaneousspontaneous postmenopausalpostmenopausal bleedingbleeding „ AtrophyAtrophy 55 mmmm „ HyperplasiaHyperplasia 8.68.6 mmmm „ CancerCancer 66 mmmm

„ Out of 9 cancers 3 had an endometrial thickness of 3mm