1 AMENORREA PRIMARIA Y SECUNDARIA

2 DEFINICIÓN PRIMARIA (AUSENCIA DE MENARCA)ES LA FALTA DE MENSTRUACION . PRIMARIA (AUSENCIA DE MENARCA) SIN CARACTERES SEXUALES DESARROLLADOS DESDE LOS 14 ANOS CON CARACTERES SEXUALES DESARROLLADOS DESDE LOS 16 ANOS SECUNDARIA : FALTA DE MENSTRUACION POR EL PERIODO MAYOR DE 90 DIAS LUEGO DE HABER TENIDO SU MENARCA

3 CORTEZA CEREBRAL-SUPRAHIPOTALAMICO-SISTEMA LIMBICO-EJE HIPOTALAMO-GONADAL-EFECTOR

4 CORTEZA CEREBRAL FEMENINA (RECEP. ESTROG.)SISTEMA LIMBICO- NUCLEOS S. OPT. Y PARAVENT. . ADRENAL (C. R.H.)- HIPOTALAMO (PROCESAMIENTO DE INFORMACION) INHIBICION DE PROCREAR. HIPOFISIS-GONADA UTERO------VIA GENITAL PERMEABLE

5 CAUSAS DE AMENORREAS SECUNDARIASA) HIPOTALAMICA B) HIPOFISARIAS C) OVARICAS D) UTERINAS E) EXTRAGENITAL

6 ESTUDIO DE LA AMENORREA SECUNDARIAPRUEBA DE PROGESTERONA PRUEBA DE ESTROGENOS PRUEBA DEL GNRH

7 DIAGNOSTICAR SI LA FALLA ESTA 1)EN EN EJE HIPOTALAMO-HIPOFISO-GONADAL2)EN EL EFECTOR: UTERO Y PERMEABILIDAD CERVICO-VAGINAL

8 PRUEBA DE PROGESTERONA10 MG. DE MEDROXIPROGESTERONA DURANTE 5 DIAS .DEPRIVACIÓN DE 2 A 10 DIAS POSTERIORES A LA ULTIMA PASTILLA . RESULTADO POSITIVO: ORIENTADOR DE CICLOMONOFASICO RESULTADO NEGATIVO: DESCARTAR EMBARAZO , SE EFECTUA PRUEBA DE ESTRÓGENO. PEDIR TSH, PROLACTINA, ESTROGENO, FSH LH , 17OH PROGESTERONA (3° A 5° DIA DE MENSTRUACION)

9 PRUEBA DE ESTROGENO 0,625 DE ESTROGENO CONJUDADO EQUINO DURANTE 21 DIAS. SE ESPERA DEPRIVACION HASTA 10 DIAS POSTERIOR A LA ULTIMA PASTILLA. RESULTADO POSITIVO: INVESTIGAR EJE HIPOTALAMO-HIPOFISARIO. RESULTADO NEGATIVO: CAUSA UTERINA

10 PRUEBA DE GNRH ADMINISTRACION ENDOVENOSA DE 100 MICROGRAMOS DE GNRHOBTENER MUESTRAS DE SANGRE A LOS 30, 60 Y 90 MINUTOS LA RESPUESTA NORMAL LA FSH DUPLICA SU VALOR BASAL Y LA LH LO TRIPLICA . LA FALTA DE RESPUESTA INDICA QUE LA CAUSA ESTA EN LA HIPOFISIS

11 NEGATIVA: FALLA EL EFECTOR (UTERO) PRUEBA DE PROGESTERONA POSITIVA : CICLO ANOVULATORIO NEGATIVA : PRUEBA DE ESTROGENO PRUEBA DE ESTROGENO NEGATIVA: FALLA EL EFECTOR (UTERO) POSITIVA: FSH,LH,ESTROGENO.PRUEBA DE GNRH PRUEBA DE GNRH NEGATIVA: CAUSA HIPOFISARIA POSITIVA: CAUSA HIPOTALAMICA

12 ESTUDIO HORMONAL FSH LH TSH CORTISOL 17 OH FSH PROGESTERONA PROLACTINAUN BUEN ALGORITMO ILUMINA ESTUDIO HORMONAL FSH LH TSH CORTISOL 17 OH FSH PROGESTERONA PROLACTINA ESTRADIOL GLUCEMIA INSULINA 3° A 5° DIA DEL CICLO

13 OTROS ESTUDIOS PROGESTERONA 21° TESTOSTERONA SHBGDEHIDROEPIANDROSTERONA SULFATO (DHEAS) ESTUDIOS CROMOSOMICOS EN AMENORREAS PRIMARIAS

14 ALGORITMO Figure 1. Flow diagram f

15 CAUSAS DE AMENORREAS 1)HIPOTALAMICAS POR STRESS ANOREXIASOBREENTRENAMIENTO FISICO AMENORREA MAS TRATORNOS OLFATORIOS 2)HIPOFISARIAS ADENOMA PROLACTINICO CRANEOFARINGIOMA SINDROME DE SHEEHAN HIPOFISITIS

16 CAUSAS DE AMENORREA 3)OVARICAS 4) UTERINAS FALLA OVARICA PRECOZPOLIQUISTOSIS DE OVARIO DISGENESIAS GONADALES 4) UTERINAS SINEQUIAS UTERINAS TUBERCULOSIS 5) EXTRAGONADALES A) ENDOCRINAS HIPOTIROIDISMO INSUFICIENCIA SUPRARRENAL . HIPERPLASIA SUPRARENAL CONGENITA B) METABOLICAS DIABETES. OBESIDAD INSUFICIENCIA HEPATICA

17 OTRA CLASIFICACION 1) CAUSA ANATOMICA 2) CAUSA FALLA OVARICAAnomalías de la vía de eliminación de la menstruación 2) CAUSA FALLA OVARICA Alteración citogenética del cromosoma X Mutación específica de gen Defectos en las enzimas de la esteroideogénesis Defectos en la secreción o acción de las gonadotrofinas Disfunción inmunológica Agresiones físico-química 3) AMENORREA CRONICA Hipotalámica Hipofisaria Falla en la retroalimentación negativa Otros desordenes endócrinos 4) Relación con el hiperandrogenismo

18 Anatomic Causes a. Pregnancy b. Müllerian agenesis or dysgenesis (uterine, cervical, or vaginal) c. Imperforate hymen d. Cervical stenosis e. Various disorders of sexual differentiation f. Intrauterine adhesions (Asherman syndrome

19 2. Tentative Classification of Premature Ovarian Failureproducing androgens or estrogens iv. Neoplasms producing hCG (including trophoblastic disease) v. Liver and renal disease vi. Obesity 2. Tentative Classification of Premature Ovarian Failure A) Citogenetic Alterations of the X Chromosome i. Absence of an X chromosome ii. Trisomy X with or without mosaicism iii. Structural abnormalities of the X chromosome B) Mutations of Specific Genes i. Premutation of FMRl gene (Fragile X; 6% of cases) ii. INHA (inhibin alpha) iii. FOXL2 (a forkhead transcription factor associated with the blepharophimosis/ptosis/epicanthus inverse syndrome) iv. ELF2B (a family of genes associated with CNS leukodystrophy and ovarian failure) v. BMP15 (bone morphogenetic factor 15, involved with folliculogenesis) vi. PMM2 (phosphomannomutase) vii. AIRE (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome))

20 2. Tentative Classification of Premature Ovarian Failurec) Enzymatic Defects Steroidogenic enzyme defects A. 17α-Hydroxylase or 17,20-lyase deficiency B. 20,22-Desmolase deficiency C. c. Aromatase deficiency ii. 2. Galactosemia D) Defects in Gonadotropin Secretion or Action i. Receptor and post-receptor defects A. FSH receptor (FSHR) mutations B. LH receptor (LHR) mutations C. G-protein alterations ii. Secretion of biologically inactive gonadotropin iii. α- or β-Subunit defects E) Immune Dysfunction i. Association with other autoimmune disorders (15-20% of cases, 4% with steroidogenic cell autoimmunity) ii. Isolated iii. In association with congenital thymic aplasia F) Physical Insults i. Chemotherapeutic (especially alkylating) agents ii. Ionizing radiation iii. Viral agents iv. Surgical extirpation g. Gonadotropin-Secreting Pituitary Tumors (Extremely Rare) h. Idiopathic

21 3 Chronic anovulation Psychogenic, including pseudocyesisa) HIPOTALAMIC Psychogenic, including pseudocyesis ii Exercise-associated iii. Eating disorders, nutritional iv. 2° to systemic illness v. Hypothalamic neoplasms b. Pituitary i. Isolated gonadotropin deficiency (including Kallmann syndrome) ii. Hypopituitarism iii. Pituitary neoplasms, including mucroadenomas c. With inappropriate steroid feedback i. Functional androgen excess (PCOS) ii. Adrenal Hypoplasia iii. Neoplasms producing androgens or estrogens iv. Neoplasms producing hCG (including trophoblastic disease) v. Liver and renal disease vi. Obesity d.Other endocrine disorders i. Thyroid dysfunction ii. Adrenal hyperfunction

22 . Causes of HyperandrogenismCommon Polycystic Ovary Syndrome80% Idiopathic Hirsutism15%UncommonLate-Onset 21-Hydroxylase Deficiency1-5% Rare< 1% Steroidogenic Enzyme Deficiencies3b-hydroxysteroid dehydrogenase17-ketosteroid reductasearomataseAndrogen Secreting Tumors of Ovary or Adrenal-Ovarian Hyperthecosis (a PCOS variant) Other Endocrine Hyperprolactinemia Cushing syndrome Defects in cortisol metabolism Acromegaly

23 . Classification of Anovulation Associated with the CNS Hypothalamic-Pituitary System1) Functional Hypothalamic Anovulation Exercise-related factors Nutritional factors Psychogenic or stress factors 2) Physiologic Anovulation Prepubertal phase Postpartum phase Breastfeeding phase 3) Pharmacologic-Associated Anovulation Opiate agonist Dopaminergic agonist 4) Psychiatric-Associated Disorders Pseudocyesis Anorexia nervosa Bulimia 5) Organic Defects of the Hypothalamic-Pituitary Unit Kallmann syndrome Isolated gonadotropin deficiency Pituitary tumors Sheehan syndrome Pituitary apoplexy/aneurysm Empty sella syndrome Inappropriate prolactin secretion Infection (human immunodeficiency virus, tuberculosis) Post-radiation effects Head trauma

24 Common Features of Women with Psychogenic Hypothalamic AmenorrheaSingle marital status Obsessive-compulsive habits History of significant stressful life events History of sexual abuse History of prior irregular menstrual cycles Normal or thin habitus Tendency to use sedatives or hypnotic drugs Involved in professional occupations High intelligence

25 Associated Neuroendocrine Abnormalities in Hypothalamic Amenorrhea.Increased daytime cortisol secretion Increased amplitude and duration of nocturnal melatonin secretion Increased nocturnal secretion of GH Elevated CRH levels in cerebral spinal fluid Blunted elevation of PRL, ACTH, and cortisol during the noon meal

26 Common Features of Anorexia NervosaPreoccupation with handling of food Bulimic behavior Calorie counting Distortion of body self-image Hyperactivity-Obsessive-compulsive personality Increased incidence of past sexual abuse Amenorrhea Constipation Coarse, dry skin Soft, lanugo-type hair Hypothermia with defective thermoregulation Mild bradycardia Cardiac arrhythmias Hypotension Hypokalemia secondary to diuretic or laxative abuse Osteopenia Increased serum beta-carotene levels AnemiaLeukopenia Elevated hepatic enzymes

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30 Neuroendocrine Abnormalities Associated with Anorexia NervosaDiminished GnRH-LH pulsatile frequency and amplitude Low blood LH and FSH levels Impaired ACTH response to CRH stimulation testing Resistance to dexamethasone suppression Increased ACTH levels Increased 24 hour urinary free cortisol levels Low prolactin levels Low TSH levels High reverse T3 and low T3 levels Elevated GH levels Decreased IGF-1 levels Diabetes insipidus

31 EXERCISE-INDUCED HYPOTHALAMIC AMENORRHEABallet (6-43%) and middle and long distance running (24-26%). The incidence appears to be less frequent in bicycling (12%) and swimming (12%) . Pulsatility is not disrupted by the stress of exercise but rather LH pulsatility is disrupted because of reduced energy availability . It is important to emphasize that for so many of these athletes the "female athlete triad" of amenorrhea, osteoporosis, and eating disorders coexist.

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34 AMENORREA

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36 Regulation of germ cell migration. A: 4-week embryoRegulation of germ cell migration. A: 4-week embryo. Differentiation of primordial germ cells (PGC) occurs from epiblast-derived cells pressent in the yolk sac near the base of the allantois. PGcs express alkaline phosphatase (AP), Oct4 and c-kit. Stem cell proteins, like fibronectin and laminin, are expressed along the PGC pathway. B: 5-week embryo. PGCs migrate along the dorsal mesentery of the hind gut to the gonadal ridges.

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39 Undifferentiated reproductive tract. Undifferentiated reproductive tract. Both Wolffian and Müllerian ducts are present. Müllerian ducts open in the urogenital sinus at the level of the Müllerian tubercle between the orifices of the Wolffian duct. \ { "@context": "http://schema.org", "@type": "ImageObject", "contentUrl": "http://slideplayer.es/3226922/11/images/39/Undifferentiated+reproductive+tract.jpg", "name": "Undifferentiated reproductive tract", "description": ". Undifferentiated reproductive tract. Both Wolffian and Müllerian ducts are present. Müllerian ducts open in the urogenital sinus at the level of the Müllerian tubercle between the orifices of the Wolffian duct. \", "width": "800" }

41 . Diagrams representing five degrees of virilization affecting the urogenital sinus and external genitalia in females.

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43 CON Y SIN TRATAMIENTO

44 AMENORREA PRIMARIA 1)SINDROME DE KALLMANN 2)SINDROME DE TURNER3)INSENSIBILIDAD AL RECEPTOR ANDROGENICO 4)AGENESIA UTERO-VAGINAL 5)HIPERPLASIA ADRENAL CONGENITA

45 1)SINDROME DE KALLMANN_AMENORREA ASOCIADA A ANOSMIA RECESIVA LIGADA AL X AUSENCIA DEL DESARROLO PUBERAL UTERO Y OVARIOS HIPOPLASICOS QUE CONSERVAN FOLICULOS PRIMORDIALES CON RESPUESTA AL GNRH TIENEN VELLO AXILAR Y PUBIANO

46 2)SINDROME DE TURNER PATRON X0FALTA DE DESARROLO CARACTERES SEXUALES SECUNDARIOS ESTATURA BAJA INFANTILISMO COARTACION DE AORTA CINTILLAS OVARICAS : GONADOBLASTOMA MOSAICISMOS

47 3) INSENSIBILIDAD AL RECEPTOR ANDROGENICOPATRON XY INSENSIBILIDAD DE LOS RECEPTORES A LOS ANDROGENOS TESTICULOS ECTOPICOS: DESARROLLO DE LOS CARACTERES SEXUALES SECUNDARIOS Y LA POSIBILIDAD DE TRANSFORMARSE UN SEMINOMA FALTA DE VELLO AXILAR Y PUBIANO VAGINA CORTA (PROCESO CLOACAL) FALTA DE UTERO Y VAGINA

48 4)AGENESIA DE UTERO-VAGINAPATRON XX VAGINA CORTA (PROCESO CLOACAL) PRESENCIA DE VELLO AXILAR Y PUBIANO DIAGNOSTICO DIFERENCIAL CON TESTICULO FEMINIZANTE

49 5)HIPERPLASIA ADRENAL NO CLASICADEFECIT ENZIMATICO 17 ,3 Y 21 HIRSUTISMO SIGNOS DE DEFIMINIZACION VIRILIZACION

50 AMENORREA

51 AMENORREA SECUNDARIA (- ) P. ESTROGENO: (-) EFECTOR (utero-canal). P.PROG.(+)ANOVULACION: LABORATORIO (- ) P. ESTROGENO: (-) EFECTOR (utero-canal) (+) EJE HT-HF-GONADAL TSH FSH LH PRL Gluc./Ins 17OHPRO Hipotiroidismo Falla PCO Tumor HOMA HSC ovarica IMC CARIOTIPO HIPERANDROGENISMO ANOREXIA X/0 X/Y TESTO DHEAS VIRILIZACION ANOVULACION HIPOTALAMICA

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53 UN BUEN aDIAGNOSTICO QUE ILUMINEUN BUEN ALGORITMO ILUMINA