1、AmenorrhDepartment of Gynecology and ObstetricTongji HospitalCNS-Hypotha lamus-Hypophysenvorderlappen-Ovar-uterus RegelkreisNormale MenstruationNormale Menstruale Zyklus(21-35d)Follikel phase Gn-RH(H)FSH&LHFSH(P)strogen(Ov Fol)strogen endometriale prolif.Dominante FolliKel entwickelt sichEisprungLut
2、ealphaseLH Peak Eisprung Corpus luteum(CL)CL produziert ProgesteroneVeraenderung in Menarche Illustrates the advance in the age at menarche in Western Europe and the United States since 1840 and the slowing of this trend over the last 30 y.Normale MenstruationuNormal 21-35 Tageudauert 2-8 Tageu14 Ta
3、ge luteale PhaseMenarche Alter 129 Jahre15 Jahre13 Jahre(ohne die zweite Geschlechtsmerkmale)Normale MenstruationPhaseDurchschnittliche Start and End Tag(assuming a 28-day cycle)Menstruale Phase1-4Proliferative Phase 5-13Ovulation13-16Secretaere Phase 16-28u Amenorrh ist der Mangel von menstruale Bl
4、utung，ist ein Symptom und keine Erkrankung.u Amenorrh ist die Extremitaet Form von Oligomenorrhu Tatsaechlich ist es haeufig physiologisch.Amenorrh ist normal in prepubertaet,Schwangershaft,and Postmenopause.u Primre Amenorrh Sekundrer AmenorrhDefinitionDefinitionu Primre Amenorrh Failure of menarch
5、e to occur when expected in relation to the onset of pubertal development.u Sekundrer Amenorrh No menarche by age 15 years with signs of pubertal development.No onset of pubertal development by age 13 years.Absence of menstruation for 6 or more months in a previously menstruating women of reproducti
6、ve age.Pathophysiologie of Amenorrhu Inadequate hormonal stimulation of the endomerium “Anovulatory amenorrhea”-Euestrogenic -Hypoestrogenicu Inability of endometrium to respond to hormones“Ovulatory amenorrhea”-Uterine absence -Utero-vaginal agenesis -XY-Females(e.g T.F.S)-Damaged endometrium(e.g A
7、shermans syndrome)Amenorrhprimre AmenorrhOvarian failure 36%Hypogonadotrophic 34%Hypogonadism.PCOS 17%Congenital lesions(other than dysgenesis)4%Hypopituitarism 3%Hyperprolactinaemia 3%Weight related 3%Sekundrer AmenorrhPCOS 30%Premature ovarian failure 29%Weight related amenorrhoea 19%Hyperprolacti
8、naemia 14%Exercise related amenorrhoea 2%Hypopituitarism 2%Etiologie and EinteilungPrimre Amenorrh:selten und haeufige Ursache von Primre Amenorrh sind u chromosomale Missbildung,u intersex Probleme,u genitale Missbildung,u and Gonad Unterentwicklung.Die zweite Geshlechtszeichen existierenu Muelleri
9、an agenesis syndrome,or mayer-rokitansky-kuster syndromeu Testicular feminization or androgen insensitivity syndromeu Resistant ovarysyndrome(Savage syndrome)u genitale Missbildung:transverse Vagina Septa oder Atresia von Hymen und Vaginau True hermaphrodism(真两性畸形）真两性畸形）Muellerian agenesis syndrome,
10、or mayer-rokitansky-kuster syndromeu20%of pubertal primary amenorrhea uNormal breasts and Sexual Hair development&Normal looking external female genitaliauNormal female range testosterone leveluAbsent uterus and upper vagina&Normal ovariesuKaryotype 46-XXu15-30%renal,skeletal and middle ear anomalie
11、suTreatment:STERILE?Vaginal creation (Dilatation VS Vaginoplasty)Androgen insensitivityTesticular feminization syndrome u X-linked trait u Absent androgen receptorsu Normal breasts but no sexual hairu Normal looking female external genitaliau Absent uterus and upper vaginau Karyotype 46,XYu Male ran
12、ge testosterone levelu FSH u Empfindungslosigkeit von Ovar zu fremden strogenu Primre Amenorrh mit die zweiten Geschlechtzeichenu Primordial Follicles and primre Follicles Savage syndrome（对抗性卵巢综合征）对抗性卵巢综合征）u Maennliche und frauliche Keimdruese existieren gleichzeitigu XX;XY;OR XX/XYu Frauliche zweit
13、e geschlechtszeichentrue hermaphrodismGenital AnomaliesCongenital absence of vaginaCongenital absence of uterusu Imperforate hymenu Vaginal diaphragmDie zweite Geshlechtszeichen not existieren1.FSH u kallmanns syndromeu Hypergonadotropic hypogonadism2.FSHu Turners syndrome:which has a 45,XO karyotyp
14、e.u“pure”gonadal dysgenesis:46XXu Swyers syndrome,46XYkallmanns syndromeu Primary amenorrheau no female secondary sex characteristicu normal inere genigal organu sense of smell dropsHypergonadotrophic Hypogonadism 高促性腺激高促性腺激素性性腺功能减退素性性腺功能减退 Normal height Normal external and internal genital organs(i
15、nfantile)FSH and LH MRI to R/O intra-cranial pathology.30-40%anosmia(kallmanns Syn)Sometimes constitutional delay Treat according to the cause(HRT)Turners syndromeuSexual infantilism and short statureuAssociated abnormalities,webbed neck,coarctation of the aorta,high-arched palate,cubitus valgus,bro
16、ad shield-like chest with widely spaced nipples,low hairline on the neck,short metacarpal bones and renal anomaliesuHigh FSH and LH levelsuBilateral streaked gonadsuKaryotype -80%45X0 -20%mosaic forms(46XX/45X0)uTreatment:HRT Turners syndrome(Classic 45-XO)Mosaic(46-XX/45-XO)Gonadendysgenesieu Binde
17、rgewebige straengende Gonaden(stark unterentwickelte oder fehlende Gonaden)u Unterentwickelte weibliche zweite Geschlechtszeichenu weibliche aeussere GeschlechtsorganeSwyers syndrome(46XY单纯性腺发育不全）单纯性腺发育不全）u 46XYu unterentwickelte weibliche zweite Geschlechtszeichenu bindergewebige straengende Gonade
18、nuSekundrer Amenorrh is commonly a result of central nervous dysfunction,with tumors and hyper or hypofunctional endocrine state playing a significant role,and uterine lesions is too a cause of secondary amenorrhea.u Frequent causes of secondary amenorrhea are hypothalamic dysfunction(55%).then pitu
19、itary(20%),ovarian(20%)and least uterine 5%.Sekundrer AmenorrhEthiology and Classificationu hypothalamische Amenorrhu Hypophysre Amenorrhu Ovarielle Amenorrhu Genitale Amenorrhhypothalamische Amenorrhu Stressu Gewichtsverlust u Anorexia nervosa u Leistungssportu Medikamentu Tumor:drucknekrosen des H
20、ypothalamus(Craniopharyngioma)Weight-related amenorrhoeaAnorexia NervosauAmenorrhea is often first signuA body mass index(BMI)17 kg/m menstrual irregularity and amenorrheauHypothalamic suppression uAbnormal body image,intense fear of weight gain,often strenuous exerciseuLow estradiol uTreatment:body
21、 wt.(Psychiatrist referral)Causes of pituitary amenorrheau Pituitary adenomata is more causes of secondary amenorrhea,may secrete prolactin or the production of gonadotropin ceases or is very inadequateu Empty sella syndromeHypophysre Amenorrhu Ischaemic necrosis of the pituitary gland(often known a
22、s Sheehans disease)u Tumoru Empty sella syndromeSheehans syndromeu Pituitary inability to secrete Gonadotropinsu Pituitary necrosis following massive obstetric hemorrhage is most common cause in womenu Diagnosis:History(The patients had severe postpartum haemorrhage,are lethargic,gain weight and hav
23、e a low metabolic rate,hypotension and amenorrhoea)and E2,FSH,LH +other pituitary deficiencies(thyrotrophic and adrenotrophic hormones)u Treatment:Replacement of deficient hormonesIschaemic necrosis of the pituitary glandEmpty sella as a sequel of pituitary apoplexy in a patient with Sheehan Syndrom
24、e.Ovarielle Amenorrhu Premature ovarian failure u Polycystic ovarian syndromeu Ovarian functional tumorsPrmature Ovarialinsuffizienzu Serum Estradiol 40 IU/ml on repeated occasions u Ovarian failure because of ovarectomy or to do so all the ovarian tissue in both ovaries would have to be destroyed.u
25、 10%of secondary amenorrheau Rarely spontaneous ovulation(resistant ovaries)u Treatment:HRT(osteoporosis,atherosclerosis)Polycystic ovarian syndromeu Polycystic ovarian syndrome is the one most commonly recognized.u secondary amenorrhea u bilateral enlargement of the ovariesu thickened capsules and
26、contain multiple small follicular in a dense stroma.u Many of these patients are obese,and have an excessive growth of facial and body hair.Polycystic ovary syndromeu The most common cause of chronic anovulationu Hyperandrogenismu Insulin resistance is a major biochemical feature(blood insulin level
27、 hyperandrogenism)u Long term risks:Obesity,hirsutism,infertility,type 2 diabetes,dyslipidemia,cardiovascular risks,endometrial hyperplasia and canceru Treatment depends on the needs of the patient and preventing long term health problems PCOS diagnostic criteria Rotterdam in 2003u Revised 2003 crit
28、eria(2 out of 3)1.Oligo and/or anovulation 2.Clinical and/or biochemical signs of hyperandrogenism 3.Polycystic ovariesu and exclusion of other aetiologies(congenital adrenal hyperplasias,androgen secreting tumours,Cushings syndrome)Polycystic ovary syndromePolycystic ovary syndromeGenitale Amenorrh
29、u Intrauterine adhesions，IUA,(Asherman syndrome)u Endometritis u Following hysterectomy or radiotherapyuterine Amenorrhu Intrauterine adhesions，IUAu the most frequent cause of secondary amenorrhea of anatomic origin.u Dilation and curettage for retained products of pregnancy are at particular risk f
30、or developing scarring of the endometrium.Ashermans syndromeCauses of uterine lesionsu Endometritis:especially destruction of the endometrium by advanced pelvic tuberculosis still occur in some developing countries.u Following hysterectomy or radiotherapyFrequency of tuberculosis in genital organsOr
31、gan Frequency(%)Fallopian tubes 90100Endometrium 5060Ovaries 2030Cervix 515Vulva and vagina 1 Tuberculosis in genital organsDisorders of other endocrine glandsu The adrenal gland.-The adrenogenital syndrome is caused by a tumor or hyperplasia of the adrenal cortex.The symptoms and signs are those of
32、 virilism,with deepening of the voice,hirsutes,acne,amenorrhea and enlargement of the clitoris.-Cushings syndrome,Addisons diseaseu Thyroid gland:in both hypo-and hyperthyroidism,amenorrhea occurs in severe cases.u Diabetes mellitusDiagnostik bei Amenorrh Anamnese Koeperliche Untersuchung Ultraschal
33、l UntersuchungSchwangershaft aussgeschlossenCryptomenorrhea aussgeschlossenCryptomenorrheaOutflow obstruction to menstrual blood-Imperforate hymen-Transverse Vaginal septum with functioning uterus-Isolated Vaginal agenesis with functioning uterus-Isolated Cervical agenesis with functioning uterus-In
34、termittent abdominal pain-Possible difficulty with micturition-Possible lower abdominal swelling-Bulging bluish membrane at the introitus or absent vagina(only dimple)Imperforate hymenAmenorrhea1.Absent or poor 2nd sex Characteristics without uterusKaryotype analysisXXXYCongenital uterine aplasiaand
35、rogen insensitivity syndromeAmenorrhea 3.Absent Uterus/Vagina Karyotype 46-XXMullerian Agenesis(MRKH syndrome)Androgen Insensitivity.Gonadal regression.Testicular enzyme deficiency.Leydig cell agenesis46-XYNormal breasts&sexual hair Normal breasts&absent sexual hairAbsent breasts&sexual hairAmenorrh
36、ea2.Absent or poor 2nd sex Characteristics with normal uterusFSH Serum level Low/Normal High Hypogonadotropichypogonadism Gonadal dysgenesisHypothalamische,Hypophysre Amenorrh45XO;45XO/46XXSekundrer Amenorrh Schwangershaft ausgeshlossen provera+strogenProvera 10 mg PO daily x 5 daysPRLNTSHhypothydis
37、mhyNNbleedingNo bleedingNo bleedinguterusbleedingFSH/LHOvarian failurePCOSLH/FSH3NCT/MRIHyperprolactintumor+-GNRHLow LHhypophyseLHhypothalamushypothalamusAmenorrhea4.Signs of androgen excessTestosterone,DHEAS,FSH,LHDHEAS 500-700 mug/dL DHEAS 700 mug/dLTEST.200 ng/dLSerum 17-OH-PLate CAH Adrenal Hype
38、rplasia/TumorU/S or MRI or CT OvarianOr adrenal tumorLower elevations PCOS (High LH/FSH)Diagnosisu Previous history:u growth and development of body,u previous menstrual history,u obstetric history,u change in the patients environment in her social and emotional environment,u any stress that she has
39、 undergone,u any attempt at severe dieting.Diagnosisu General and pelvic medical examination u Any history of recent or long-standing illness is sought,and a general examination is made(including observation of the body build and hair distribution)to exclude any general illness.u The breasts and pel
40、vic organs are examined.Once Pregnancy and cryptomenorrhea are excluded:The patient is a bioassay for Endocrine abnormalities Four categories of patients are identified 1.Amenorrhea with absent or poor secondary sex Characters2.Amenorrhea with normal 2ry sex characters3.Amenorrhea with signs of andr
41、ogen excess4.Amenorrhea with absent uterus and vaginaDiagnosisu Advanted diagnostic methodsu Examination of uterine function -Curettage of the uterine cavity and endometrial biopsy -Hysterosalpingography -Hysteroscopy u Hormone test -Progestin test -Estrogen-progestin testDiagnosisu Examination of o
42、varian function -Basal body temperature -Serum hormone assays:FSH,LH,E2,P,T -Ultrasonography can also help known development of follicle and ovulation -Ovarian stimulating test:HMG 75-150U/d intramuscular 4 days,since 6th day ovarian hormones can be measuredDiagnosisu Examination of pituitary functi
43、on -LH,FSH,PRL,TSH assays -Head CT-scan or MRIDiagnostic proceduresTreatmentu Cause treatment it is essential to first establish a cause for the amenorrhea.u Surgical managementu Women with genital tract obstruction require surgery to create a vagina or to restore genital integrity.u Pituitary tumor
44、su Ovariantumors u Ashermans syndromeTreatmentu Ashermans syndrome-treatment involves lysis of the sunchiae and postoperative treatmnt with large doses of estrogen to facilitate endometrial proliferation.u Conjugated estrogen,1.25mg P.O.two to four times per day for several weeksThrapie u Tuberculos
45、is u Stress or emotional problem-spontaneous recovery is to be expected if the problem can be removed or alleviated by the passage of time.u Nutritional deficiency must be treated or removed.Hormone treatmentAmenorrheaovarian functionFSHLHEPtreatmentovarianno follicle develops，anovulation-E+Ppituita
46、ryno follicle develops，anovulation-E+PCNS-Hypothalamusno follicle develops，anovulation-E+Pfollicle develops，anovulation+-PTreatmentu Hormone treatment u Hypergonadotrophic amenorrhea:hormone replacement therapyu Hypogonadotrophic amenorrhea:if the uterus is present,sequential treatment with estrogen
47、-progestin preparations.If the uterus absent,only estrogen therapy.Treatmentu If the patient does wish for a pregnancy-therapy should be directed to restore ovulation by the administration of ovulation-inducing agents.the most frequently used therapy isu Clomiphene citrate.50 to 100 mg are given fro
48、m day 5 to day 9.u If a woman fails to respond to clomiphene citrate,follicle-stimulating hormone can be administered directly to stimulate follicular growth.HMG,pure FSH+hCGu GnRH-a Treatmentu Thyroid gland:hypothyroidism-Levothyroxine u The adrenal gland.The adreno-genital syndrome is caused by a
49、tumor or hyperplasia of the adrenal cortex-hydrocortisone or dexamehtasone 0,25-0,5mg orally q.i.dHormonal treatmentPrimary Amenorrhea with absent secondary sexual characteristicsu To achieve pubertal development Premarin 5mg D1-D25+provera 10mg D15-D25 X 3 months;2.5mg premarin X 3 months and 1.25m
50、g premarin X 3 monthsu Maintenance therapy 0.625mg premarin+provera OR ready HRT preparation OR 30g oral contraceptive pillTreatmentu Bromocriptine:the hyperprolactinemia associated with some pituitary adenomas results in amenorrhea and galactorrhea.u About 80%of all pituitary tumors secrete prolact
