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AMENORREA

AMENORREA. PRIMARIA Y SECUNDARIA. DEFINICIÓN. 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

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AMENORREA

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  1. AMENORREA PRIMARIA Y SECUNDARIA

  2. DEFINICIÓN • 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 SECUNDARIAS • A) HIPOTALAMICA • B) HIPOFISARIAS • C) OVARICAS • D) UTERINAS • E) EXTRAGENITAL

  6. ESTUDIO DE LA AMENORREA SECUNDARIA • PRUEBA DE PROGESTERONA • PRUEBA DE ESTROGENOS • PRUEBA DEL GNRH

  7. DIAGNOSTICAR SI LA FALLA ESTA 1)EN EN EJE HIPOTALAMO-HIPOFISO-GONADAL • 2)EN EL EFECTOR: UTERO Y PERMEABILIDAD CERVICO-VAGINAL

  8. PRUEBA DE PROGESTERONA • 10 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 GNRH • OBTENER 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. 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. UN 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 • SHBG • DEHIDROEPIANDROSTERONA SULFATO (DHEAS) • ESTUDIOS CROMOSOMICOS EN AMENORREAS PRIMARIAS

  14. ALGORITMO Figure 1. Flow diagram f

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

  16. 3)OVARICAS FALLA OVARICA PRECOZ POLIQUISTOSIS 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 CAUSAS DE AMENORREA

  17. OTRA CLASIFICACION • 1) CAUSA ANATOMICA • Anomalías 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. 1. 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. producing 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 Failure c)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) Defectsin 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 • a) 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 Hyperandrogenism • Common • Polycystic Ovary Syndrome80% • IdiopathicHirsutism15%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 System 1) 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 Amenorrhea • Single 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 Nervosa Preoccupation 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

  27. Neuroendocrine Abnormalities Associated with Anorexia Nervosa • Diminished 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

  28. EXERCISE-INDUCED HYPOTHALAMIC AMENORRHEA • Ballet (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.

  29. AMENORREA

  30. Regulation 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.

  31. . 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. • \

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

  33. CON Y SIN TRATAMIENTO

  34. AMENORREA PRIMARIA • 1)SINDROME DE KALLMANN • 2)SINDROME DE TURNER • 3)INSENSIBILIDAD AL RECEPTOR ANDROGENICO • 4)AGENESIA UTERO-VAGINAL • 5)HIPERPLASIA ADRENAL CONGENITA

  35. 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

  36. 2)SINDROME DE TURNER • PATRON X0 • FALTA DE DESARROLO CARACTERES SEXUALES SECUNDARIOS • ESTATURA BAJA • INFANTILISMO • COARTACION DE AORTA • CINTILLAS OVARICAS : GONADOBLASTOMA • MOSAICISMOS

  37. 3) INSENSIBILIDAD AL RECEPTOR ANDROGENICO • PATRON 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

  38. 4)AGENESIA DE UTERO-VAGINA • PATRON XX • VAGINA CORTA (PROCESO CLOACAL) • PRESENCIA DE VELLO AXILAR Y PUBIANO • DIAGNOSTICO DIFERENCIAL CON TESTICULO FEMINIZANTE

  39. 5)HIPERPLASIA ADRENAL NO CLASICA • DEFECIT ENZIMATICO 17 ,3 Y 21 • HIRSUTISMO • SIGNOS DE DEFIMINIZACION • VIRILIZACION

  40. AMENORREA

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