Amenore - www.jinekolojivegebelik.com

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  • Amenore - www.jinekolojivegebelik.com

    1. 1. Amenorrhea Mayurasakorn N.
    2. 2. <ul><li>Not physiologic </li></ul><ul><li>Primary amenorrhea </li></ul><ul><ul><li>Normal secondary sex characteristic </li></ul></ul><ul><ul><li> no manarche by 16 years </li></ul></ul><ul><ul><li> no periods by 2 years after start of secondary sex changes </li></ul></ul><ul><ul><li>If No secodary sex characteristic </li></ul></ul><ul><ul><li>14 years </li></ul></ul><ul><li>Secondary amenorrhea </li></ul>Definitions and Epidemiology <ul><ul><li>If regular menstruation : 3 cycles </li></ul></ul><ul><ul><li>If irregular mrnstruation : 6 months </li></ul></ul><ul><ul><li>Pregnancy </li></ul></ul><ul><ul><li>Breast feeding </li></ul></ul><ul><ul><li>Menopause </li></ul></ul>
    3. 3. <ul><li>Hypothalamic causes </li></ul><ul><li>Pituitary causes </li></ul><ul><li>Premature ovarian failure(<40 years) </li></ul><ul><li>Outflow tract </li></ul><ul><li>Hyperandrogenic anovulation </li></ul>Etiology <ul><li>Hypergonadotropic hypogonadism </li></ul><ul><li>Hypogonadotropic hypogonadism </li></ul><ul><li>Normogonadotropic </li></ul><ul><li>hypogonadism </li></ul>Secondary Amenorrhea
    4. 4. Hypergonadotropic hypogonadism Hypogonadotropic hypogonadism Autoimmune Hemochromatosis Lymphocytic hypophysis Surgery Irradiation Sheehan sd Hyperprolactin Pituitary tumor Empty sella Pituitary TB,syphilis,Encephalitis/menigitis,Sarcoidosis Mump Oophoritis Infection /infiltration Craniopharyngioma, Germinoma,Hamartoma,Teratoma,Metastasis Ovarian tumor Tumor Irradiation Chemotherapy Trauma Anorexia nervosa Stress Exercise Nutrition-related Autoimmune Metabolic Hypothalamus Ovary
    5. 5. <ul><li>Hyperandrogenic anovulation </li></ul><ul><ul><li>PCOS </li></ul></ul><ul><ul><li>Androgen-secreting tumor </li></ul></ul><ul><ul><li>Cushing’s sd </li></ul></ul><ul><ul><li>Nonclassical congenital adrenal hyperplasia </li></ul></ul><ul><ul><li>Thyroid </li></ul></ul><ul><li>Outflow tract </li></ul><ul><ul><li>Asherman syndrome </li></ul></ul><ul><ul><li>cervical stenosis </li></ul></ul>Normogonadotropic hypogonadism
    6. 6. Most common causes
    7. 7. Hypothalamus <ul><li>Stress, wt loss, diet ,exercise, illness </li></ul><ul><li>Chemotherapy,radiation </li></ul><ul><li>Galactorrhea </li></ul><ul><li>Drugs( metoclopramide, </li></ul><ul><li>anti-psychotics?) </li></ul><ul><li>Headaches, visual field defects, fatigue, polyuria, polydipsia </li></ul><ul><li>Chemotherapy,radiation </li></ul><ul><li>Hot flashes, vaginal dryness, poor sleep,decreased libido </li></ul>Hyperprolactinemia Ovary History & Physical examinations Pituitary
    8. 8. <ul><li>Signs of systemic illness ,cachexia </li></ul><ul><li>Breast : galactorrhea </li></ul><ul><li>Bitemporal hemianopia </li></ul>Hypothalamus Hyperprolactinemia Ovary History & Physical examinations Pituitary
    9. 9. <ul><li>Hirsutism, acne, history of irregular menses </li></ul><ul><li>Obstetrical catastrophe, severe bleeding, dilatation and curettage, endometritis </li></ul>PCOS History & Physical examinations BMI,hirsutism, acne, striae, acanthosis nigricans, vitiligo Virilization, clitorial hypertrophy
    10. 10. <ul><li>Hirsutism, acne, history of irregular menses </li></ul><ul><li>Obstetrical catastrophe, severe bleeding, dilatation and curettage, endometritis </li></ul>PCOS History & Physical examinations
    11. 11. <ul><li>PRL </li></ul><ul><li>FBS </li></ul><ul><li>Progesterone estrogen challenge </li></ul><ul><li>Urine BhCG </li></ul><ul><li>Karyotype </li></ul><ul><li>Antithyroid antibody </li></ul><ul><li>FSH </li></ul><ul><li>Progesterone challenge </li></ul><ul><li>DHEA-S and testosterone </li></ul><ul><li>TSH </li></ul>ข้อใดไม่ใช่ Investigations ของ Amenorrhea
    12. 12. Hypothalamus Hyperprolactinemia Ovary Pituitary PCOS Outflow tract Cushing’s sd Thyroid MRI hypothalamus, pituitary FSH,LH, autoimmune MRI pituitary U/S ovary,testosterone Dexamethasone supression test Thyroid function test prolactin Hysterosalpingogram,hysteroscopy Investigations
    13. 13. Pregnancy test TSH ,PRL,FSH TSH Hypothyroid PRL Hyperpro-lactinemia FSH Premature ovarian failure Hypogonadotropic Normogonadotropic PCOS Outflo w Clinical PRL > 40 mg/dL FSH > 40 mIU/mL
    14. 14. <ul><li>High false positive, false negative </li></ul><ul><li>Delay diagnosis </li></ul><ul><ul><li>Primolut-N (Norethisterone acetate) 5-10 mg OD </li></ul></ul><ul><ul><li>Provera (Medroxyprogesterone acetate) 10 mg OD 5 days </li></ul></ul><ul><li>withdrawal bleed within 2 weeks </li></ul>Progesterone challenge test Estrogen progesterone challenge test <ul><ul><li>Premarin (conjugated E)1.25 mg OD </li></ul></ul><ul><ul><li>Progynova(Estradial) </li></ul></ul><ul><ul><li>21 days followed by provera as above </li></ul></ul>
    15. 15. Prog.challenge test Withdrawal bleeding No withdrawal bleeding Chronic anovulation Testosterone, DHEA-S,17 hydroxyprogesterone T,DHEA-S,LH mild PCOS T,DHEA-S marked Androgen-secreting tumor 17-hydroxyprogesterone CAH Idiopathic anovulation
    16. 16. No withdrawal bleeding Est,progest.challenge test Hypothalamic- pituitary failure hypoestrogenic outflow tract. Withdrawal bleeding No Prog.challenge test
    17. 17. <ul><li>1% population </li></ul><ul><li>40% autoimmune ass autoimmune </li></ul><ul><ul><li>Autoimmune thyroiditis </li></ul></ul><ul><ul><li>IDDM </li></ul></ul><ul><ul><li>Parathyroid disease </li></ul></ul><ul><ul><li>MG </li></ul></ul><ul><ul><li>Addison’s disease(1:million) </li></ul></ul><ul><li>Polyglandular sd </li></ul><ul><ul><li>20-40% develop other autoimmune disease </li></ul></ul>Premature ovarian failure <ul><li>TSH, </li></ul><ul><li>thyroid autoAb </li></ul><ul><li>FBS </li></ul><ul><li>Ca,PO4 </li></ul><ul><li>Karyotype : if < 30 for Y chromosome  remove gonad </li></ul>
    18. 18. <ul><li>< 100 ng/mL(µg/L) </li></ul><ul><ul><li>Altered metabolism: liver failure, renal failure </li></ul></ul><ul><ul><li>Ectopic production : BCA,renal cell CA , ovarian dermoid cyst,teratoma </li></ul></ul><ul><ul><li>Hypothyroid </li></ul></ul><ul><ul><li>Drugs: OC,antipsychotic, antidepressant,antihypertensive,opiate,cocain,H2 bloker </li></ul></ul><ul><ul><li>Pituitary stalk irritability </li></ul></ul>Hyperprolactinemia <ul><li>> 100 ng/mL( µg/L) </li></ul><ul><ul><li>Empty sella syndrome </li></ul></ul><ul><ul><li>Prolactinoma </li></ul></ul>
    19. 19. <ul><li>Discovery and treatment of underlying disorder </li></ul><ul><li>Hormone replacement </li></ul><ul><ul><li>for maintain secondary sex characteristic </li></ul></ul><ul><ul><ul><li>Normal menses every 1-3 months </li></ul></ul></ul><ul><ul><li>reduce risk of osteoporosis </li></ul></ul><ul><ul><ul><li>Adequate caloric intake </li></ul></ul></ul><ul><ul><ul><li>Calcium 1200 to 1500 mg/D </li></ul></ul></ul><ul><ul><ul><li>Vitamin D (400 IU daily) </li></ul></ul></ul><ul><li>Pregnancy </li></ul><ul><ul><ul><li>Ovulation induction </li></ul></ul></ul><ul><ul><ul><li>GnRH pump </li></ul></ul></ul><ul><ul><ul><li>FSH/LH </li></ul></ul></ul>Treatment Goals
    20. 20. Breast 30% High FSH 40% Low FSH 30% <ul><li>gonadal failure is most common cause </li></ul><ul><ul><li>30% have genetic abnormality </li></ul></ul><ul><ul><ul><li>Gonadal dysgenesis, Turner’s syndrome, mosaicism </li></ul></ul></ul><ul><li>uterovaginal agenesis is second most common cause </li></ul><ul><li>Anorexia nervosa </li></ul>Primary Amenorrhea
    21. 21. <ul><li>Normal physical & pubertal development? </li></ul><ul><li>Family history of delayed/absent menarche? </li></ul><ul><ul><li>Short stature compared to family members? </li></ul></ul><ul><li>Neonatal/childhood health normal? any recent increase in stress, or change in weight, diet, or exercise habits? </li></ul><ul><li>Hypothalamic-pituitary disease (headaches, visual field defects, fatigue, polyuria or polydipsia?) </li></ul><ul><li>Drugs? </li></ul>History
    22. 22. Physical examination <ul><li>Height, weight </li></ul><ul><li>Secondary sex characteristic (Tanner staging) </li></ul><ul><li>PV for cervix, uterus, ovaries (may need ultrasound) </li></ul><ul><li>Androgen excess (acanthosis nigras, hirsutism, acne, & striae) </li></ul><ul><li>Turner syndrome (low hair line, web neck, shield chest, and widelyspaced nipples) </li></ul><ul><li>Galactorrhea? </li></ul>
    23. 23. <ul><li>Thelarche (breast devel): average age 10.8 yrs </li></ul><ul><ul><li>estrogen exposure </li></ul></ul><ul><li>Adrenarche (pubic/axillary hair development): average 11 yrs </li></ul><ul><ul><li>ovarian,adrenal androgen production ,end organ response </li></ul></ul><ul><li>Decreased breast size or vaginal dryness </li></ul><ul><li>decreasing estrogen exposure (or increasing androgens) </li></ul>Secondary sex characteristic
    24. 24. Tanner Staging Stage 1 : prepubertal Stage 2 : breast bud Stage 3 : further enlarge of breast & areolar ,no seperation Stage 4: areolar & papilla form second mound Stage 5 : mature, only projection of papilla
    25. 25. Tanner Staging Stage1 : villus hair Stage 2 : Sparse growth of slightly pigmented hair along labia (11.9 years) Stage 3 : C oarser, curled and pigmented; spreads across pubes (12.7 years) Stage 4 : Adult-type hair but no spread to medial thigh (13.4 years) Stage 5 : Adult-type hair with spread to medial thigh but not up linea alba (14.6 years)
    26. 26. Secondary sex characteristic No Yes Pubic hair Yes Uterus No Androgen insentivity syndrome Imperforate hymen Yes No Mullerian agenesis As secondary amenorrhea PV
    27. 27. Secondary sex characteristic No ( normal cervix and uterus not include ambiguous) FSH E Primary Gonodal failure Constitutional delay Kallman sd Hypothalamus-pituitary Karyotype XX,XY,XO
    28. 28. <ul><li>Gonodal dysgenesis </li></ul><ul><ul><li>less than 30y  karyotype </li></ul></ul><ul><ul><li>if Y chromosome exists, excise gonads </li></ul></ul><ul><ul><li>if 46XX, r/o 17a-hydroxylase deficiency </li></ul></ul><ul><ul><li>If XO  Turner sd </li></ul></ul>Primary gonodal failure <ul><li>Premature ovarian failure </li></ul><ul><ul><li>Time </li></ul></ul><ul><ul><ul><li>Before thelarche </li></ul></ul></ul><ul><ul><ul><li>Before menarche </li></ul></ul></ul><ul><ul><ul><li>After menopause </li></ul></ul></ul><ul><li>Autoimmnue </li></ul><ul><li>Laboratory evidence of autoimmune is much more prevalent than clinically significant disease </li></ul>
    29. 29. <ul><li>CNS, hypothalamic, or pituitary failure </li></ul><ul><ul><li>Constitutional delay </li></ul></ul><ul><ul><li>Hypothalamic dysfunction </li></ul></ul><ul><ul><ul><li>Kallmann syndrome </li></ul></ul></ul><ul><ul><ul><li>Anorexia nervosa, exercise induced; </li></ul></ul></ul><ul><ul><ul><li>Space-occupying lesion of CNS </li></ul></ul></ul><ul><ul><li>Pituitary damage (surgery/radiation) </li></ul></ul><ul><ul><li>Hyperprolactinemia </li></ul></ul>Hypogonadotropic hypogonadism
    30. 30. Mullerian agenesis <ul><li>normal gonad  hormone </li></ul><ul><li>but no uterus and upper vagina </li></ul><ul><li>Embryonal activation of antimullerian hormone </li></ul><ul><li>15-30% ass. urogenital malformation : unilateral renal agenesis, pelvic kidney, horseshoe kidney, hydronephrosis  IVP </li></ul><ul><li>Cyclic breast tenderness or pain in rudimentary uterus </li></ul><ul><li>karyotype R/O male pseudohermaphrodism </li></ul>
    31. 31. <ul><li>1:60,000, XR mutation of androgen receptor </li></ul><ul><li>Karyotype 46, XY </li></ul><ul><li>Male range testosterone level </li></ul><ul><li>Normal breasts but no sexual hair </li></ul><ul><li>Normal looking female external genitalia </li></ul><ul><li>Occasional present of inguinal mass </li></ul><ul><li>Absent uterus and upper vagina by AMH </li></ul><ul><li>Risk gonodal malignancy 20% </li></ul><ul><li>Raised as girls (XY) </li></ul><ul><ul><li>remove gonads after breast development and epiphyseal closure </li></ul></ul><ul><ul><li>replace estrogen </li></ul></ul>Complete androgen insensitivity syndrome
    32. 32. Imperforate hymen
    33. 33. <ul><li>Discovery and treatment of underlying disorder </li></ul><ul><li>Remove gonadal streaks if XY or mosaic </li></ul><ul><ul><li>Increased (52%) risk of gonadoblastomas, dysgerminomas, and yolk sac tumors </li></ul></ul><ul><li>Hormone replacement for maintain secondary sex characteristic and reduce risk of osteoporosis </li></ul><ul><li>adolescent: low dose E  breast augmentation </li></ul><ul><li>Then progestin  normal menses every 1-3 months </li></ul><ul><li>Pregnancy </li></ul><ul><ul><li>Ovulation induction </li></ul></ul><ul><ul><li>Pulsatile GnRH </li></ul></ul><ul><ul><li>FSH/LH </li></ul></ul>Treatment Goals
    34. 34. 17 yo female with primary amenorrhea <ul><li>Normal pubertal development </li></ul><ul><li>Normal health </li></ul><ul><li>No family history of delayed puberty </li></ul><ul><li>Not involved in athletics </li></ul><ul><li>Does well in school </li></ul><ul><li>Not taking any meds </li></ul>Case 1:
    35. 35. Physical Examination <ul><li>Thin young woman (10% below IBW) </li></ul><ul><li>Normal genitalia </li></ul><ul><li>No galactorrhea </li></ul><ul><li>Tanner stage 4 </li></ul><ul><li>Laboratory values </li></ul><ul><li>Urine and serum B-HCG negative </li></ul><ul><li>Prolactin, FSH, TSH all normal </li></ul>
    36. 36. Further history Patient’s parents concerned about her eating habits (very low fat intake and restricting calories) Diagnosis : hypothalamic amenorrhea <ul><li>Etiology is most likely inadequate caloric and fat intake. </li></ul><ul><li>referred for evaluation for an eating disorder. </li></ul>
    37. 37. <ul><li>Psychological stress, weight changes,exercise </li></ul><ul><li>Chronic debilitating disease </li></ul><ul><li>Competitive sport : 3-fold risk of amenorrhea </li></ul><ul><ul><li>Esp: long distance runners </li></ul></ul><ul><li>Rx </li></ul><ul><ul><li>correct causes </li></ul></ul><ul><ul><li>Adequate intake </li></ul></ul><ul><ul><li>Less exercise </li></ul></ul><ul><ul><li>OC??? </li></ul></ul>Hypothalamic amenorrhea
    38. 38. 24 yo woman with secondary amenorrhea <ul><li>Menarche at age 12 </li></ul><ul><li>Periods have always been irregular </li></ul><ul><li>Now amenorrhea x 10 months </li></ul><ul><li>Overweight </li></ul><ul><li>Wants to get pregnant </li></ul>Case 2:
    39. 39. Physical Examination <ul><li>Obese female </li></ul><ul><li>Acne </li></ul><ul><li>Normal genitalia </li></ul><ul><li>Mild hirsutism </li></ul>
    40. 40. <ul><li>Urine B-HCG negative </li></ul><ul><li>TSH, FSH and Prolactin : WNL </li></ul><ul><li>Testosterone 180 ng/dL </li></ul><ul><li>Pelvic U/S </li></ul>Laboratory findings
    41. 41. <ul><li>Etiology unknown </li></ul><ul><ul><li>Reduce insulin sensitivity 30-40% : </li></ul></ul><ul><ul><li>Increase secretion LH </li></ul></ul><ul><li>Hyperinsulin or LH  Theca cell  androgen  disturb hypothalamus& ovary  anovulation </li></ul>PCOS : Polycystic Ovarian Syndorme
    42. 42. PCOS : Polycystic Ovarian Syndorme
    43. 43. <ul><li>Menstrual disturbance </li></ul><ul><ul><li>(DUB,oligomenorrhea (76%), amenorrhea(24%) </li></ul></ul><ul><li>Symptom onset at menarche but sign androgen excess obvious several years later </li></ul><ul><li>Differential diagnosis : </li></ul><ul><ul><li>Androgen-secreting tumor(ovarian or adrenal) </li></ul></ul><ul><ul><li>Cushing’s sd </li></ul></ul><ul><ul><li>Nonclassical congenital adrenal hyperplasia </li></ul></ul><ul><ul><li>Thyroid </li></ul></ul><ul><ul><li>Excess estrogen </li></ul></ul><ul><li>Increased risk endometrial cancer threefold </li></ul>Hyperandrogenic anovalation
    44. 44. Metabolic complication <ul><li>Impaired glucose tolerance:31% </li></ul><ul><li>Impaired fasting glucose 7.5% </li></ul><ul><li>DM : 2-5 folds test  OGTT </li></ul><ul><li>Cardiovascular risk 2 folds </li></ul><ul><li>Metabolic syndrome 43% </li></ul>
    45. 45. <ul><li>2/3 </li></ul><ul><ul><li>Chronic anovulation </li></ul></ul><ul><ul><li>Hyperandrogenism </li></ul></ul><ul><ul><li>U/S : polycystic ovaries </li></ul></ul><ul><li>Exclude other causes </li></ul><ul><li>20% of woman with regular menses have polycystic ovary </li></ul><ul><li>LH/FSH> 2 , not useful in diagnosis </li></ul>NIH criteria
    46. 46. Treatment <ul><li>Short-term management </li></ul><ul><ul><li>Infertility </li></ul></ul><ul><ul><li>Hirsutism </li></ul></ul><ul><ul><li>Acne </li></ul></ul><ul><ul><li>Obesity </li></ul></ul><ul><ul><li>Miscarriage </li></ul></ul><ul><li>Long-term management </li></ul><ul><ul><li>Cardiovascular risks </li></ul></ul><ul><ul><ul><li>Cholesterol </li></ul></ul></ul><ul><ul><ul><li>Diabetes </li></ul></ul></ul><ul><ul><ul><li>blood pressure </li></ul></ul></ul><ul><ul><li>Endometrial Cancer </li></ul></ul>
    47. 47. <ul><li>weight reduction </li></ul><ul><ul><li>lower androgen level , improve hersutism, normalize menses , decrease insulin resistance </li></ul></ul><ul><li>Anovulation & Infertility: Clomiphene , GnRH, Metformin </li></ul><ul><li>RCOG guidline 2003 </li></ul><ul><li>Protection endometrial CA: Oral contraceptive or Cyclic progestin to prevent : monthly 10-14 day regimen </li></ul><ul><ul><li>Antiandrogen </li></ul></ul><ul><ul><ul><li>Cyproterone acetate (Diane-35) </li></ul></ul></ul><ul><ul><ul><li>Drospirenone ( Yasmin) </li></ul></ul></ul>
    48. 48. 34 Years with secondary amenorrhea 19 years <ul><li>Menarche at age 15 </li></ul><ul><li>Only 2 cycles </li></ul><ul><li>Short stature </li></ul>Case 3:
    49. 50. Turner Syndrome
    50. 51. <ul><li>Classic 45,X </li></ul><ul><li>other : </li></ul><ul><ul><li>46,X ,i(Xq) </li></ul></ul><ul><ul><li>46,X,Xq- </li></ul></ul><ul><ul><li>46,X,Xp- </li></ul></ul><ul><ul><li>46,X,r(X) </li></ul></ul><ul><ul><li>45,X/46,XX </li></ul></ul><ul><li>Time of diagnosis </li></ul>
    51. 52. <ul><li>Ischemic heart disease </li></ul><ul><li>Type 2 DM </li></ul><ul><li>osteoporosis </li></ul><ul><li>Cirrhosis </li></ul><ul><li>Type 1 DM </li></ul><ul><li>Dilated ascending aorta </li></ul><ul><li>Thyroiditis </li></ul>ข้อใดไม่ใช่ Risks ของผู้ป่วย turner syndrome <ul><li>Hypothyroidism </li></ul><ul><li>Coartation of aorta </li></ul><ul><li>Fracture </li></ul><ul><li>Type 1 </li></ul><ul><li>CA colon </li></ul><ul><li>Hypertension </li></ul><ul><li>Horseshoe kidney </li></ul>
    52. 53. <ul><li>Cardiovascular </li></ul><ul><ul><li>Record BP, BMI </li></ul></ul><ul><ul><li>Echocardiogram q 3-5 years </li></ul></ul><ul><ul><li>FBS </li></ul></ul><ul><ul><li>Fasting lipid </li></ul></ul><ul><li>Renal ultrasound </li></ul><ul><li>Renal and liver function </li></ul><ul><li>Thyroid status & antibody </li></ul><ul><li>BMD </li></ul><ul><li>Aortogram </li></ul>
    53. 54. Treatment <ul><li>Children : Growth hormone </li></ul><ul><li> adequate height, phychological demand, may spontaneous mense </li></ul><ul><li>Estrogen  maintian secondary sex characteristic </li></ul><ul><li>Bone mass </li></ul><ul><li>Cycle progesterone </li></ul><ul><li>Fertility </li></ul><ul><ul><li>Oocyte donation </li></ul></ul><ul><ul><li>Oocyte implantation from cryopreservation </li></ul></ul>

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