Investigations dune aménorrhée secondaire

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Investigations dune aménorrhée secondaire

  1. 1. Menstrual cycle disorders Dr D Chardonnens PD
  2. 2. Definitions Secondary amenorrhea 3 consecutive months without periods Primary amenorrhea No periods after the age of 16 – 17 Hypomenorrhea Periods < 3 days with little bleeding
  3. 3. Definitions Menorrhagia Periods > 7 days & > 80 ml Hypermenorrhea Periods > 80 ml Oligomenorrhea Cycle > 35 days Polymenorrhea Cycle < 21 days
  4. 4. Definitions Primary dysmenorrhea Painful periods before the age of 19 Secondary dysmenorrhea Painful periods after the age of 19
  5. 5. Different levels CNS I Hypothalamus II Pituitary Thyroid Adrenal Ovary III Uterus IV
  6. 6. PFP LFP PLP MLP LLP
  7. 7. Hormonal assays: FSH 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 Pregnancy rate per cycle (%) Delivery 20 15 10 5 0 <15 15 - 24,9 > 25 Basal day 3 FSH (mIU / mL)
  8. 8. Hormonal assays: LH Day 3 LH > 10 IU/L, or LH/FSH > 2.5 infertility spontaneous abortions PCOS
  9. 9. PFP LFP PLP MLP LLP
  10. 10. Basal Body Temperature ↑ basal body temperature ≥ 0.2°C ↑ basal body temperature ≥ 12 days
  11. 11. Basal Body Temperature Inexpensive Repeated in different cycles Not appropriate to time ovulation Poor correlation with P level and endometrial biopsies
  12. 12. Basal body temperature
  13. 13. Basal body temperature
  14. 14. Basal body temperature
  15. 15. Hormonal assays: Progesterone Day 21 2.5 - 5 ng / ml ovulation 10 - 15 ng / ml normal corpus luteal function Day 20, 21, 22 Σ : 15 ≥ ng/ ml
  16. 16. Endometrial biopsy
  17. 17. Different levels 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
  18. 18. Some etiologies of secondary amenorrhea Stress Anorexia… I II Tumors Necrosis… PCO III Menopause… Pregnancy IV Synechiae Stenosis TBC…
  19. 19. Investigating secondary amenorrhea Exclude pregnancy normogonadic amenorrhea E2 > 30 pg/ml Hypogonadic amenorrhea E2 < 30 pg/ml Hypergonadotropic (primary hypogonadism) FSH > 20 – 30 UI/L Hypogonadotropic (secondary hypogonadism) LH < 1 UI/L
  20. 20. Case 1 25 years old athlete with secondary amenorrhea after stopping OC (> 12 months) Investigations Pregnancy test – E2 25 pg/ml FSH = 2 UI/L, LH 0.2 UI/L Prl N Diagnosis: Hypogonadotropic hypogonadism hypothalamic amenorrhea Cave bone mass
  21. 21. Case 2 25 years old athlete with secondary amenorrhea after stopping OC (> 12 months) hot flushes Investigations Pregnancy test – E2 25 pg/ml FSH = 52 UI/L, LH 25 UI/L Prl N Diagnosis Hypergonadotropic hypogonadism: precocious menopause
  22. 22. Case 2 Other investigations Test other endocrine pathways Test for autoimmune diseases Test for genetic diseases (X fragile, Turner….) Counselling THS
  23. 23. Case 3 25 years old athlete with secondary amenorrhea after stopping OC (> 12 months) History of irregular cycles Investigations Pregnancy test – E2 105 pg/ml FSH = 4 UI/L, LH 14 UI/L Prl N Diagnosis « Normogonadic » amenorrhea
  24. 24. Case 3 Investigations T = 0.9 ng/ml 17 OH-P = 250 ng/dl ACTH testing 17 OH-P = 450 ng/dl Ultrasound
  25. 25. PCO ? PCOS • Ultrasound criteria • Infertility 88 % • Insulin resistance 70 % • Hirsutism 62 % • Irregular cycles 50 % • Obesity 38 % • Acne 35 %
  26. 26. PCO and ultrasound criteria ↑ ovarian volume ↑ ovarian stroma > 10 follicles Ø <10 mm at the periphery (necklace sign)
  27. 27. PCO and ultrasound criteria van Santbrink et al. 1997 Fertil Steril ↑ Follicle number (58%) 9 ↑ Ovarian stroma (45%) 10 23 15 3 11 4 ↑ Ovarian volume (41%)
  28. 28. PCO versus PCOS van Santbrink et al. 1997 Fertil Steril Ultrasound criteria (66%) 21 8 5 ↑ Androgens (36 %) 20 17 3 7 ↑ LH (47%)
  29. 29. Androgens 90 % DHEAS 10 % DHEA 60 % Androstenedione 40 % DHEA Peripheral tissue Ovary Adrenal 25 % 50 % 25 % Testosterone
  30. 30. Serum values of androgens 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 pregnancy
  31. 31. Androgens and serious disease Testosterone > 2 ng/ml Look for tumor of the ovary DHEAS > 7000 ng/ml Look for tumor of the adrenal
  32. 32. 17 OH-P and menstrual cycle 3 2 IU/L 1 17 OH-P 0 0 4 8 12 16 20 24 28 Menses Cycle Day
  33. 33. Basal values for 17 OH-P > 800 ng/dl (24 nmol/l) 21 hydroxylase deficiency > 200 ng/dl (6 nmol/l) Suspicion of 21 hydroxylase deficiency Test with ACTH < 200 ng/dl (6nmol/l) 21 hydroxylase deficiency
  34. 34. 17 OH-P post ACTH > 1500 ng/dl Late onset adrenal hyperplasia 1000-1500 ng/dl Suspicion of late onset hyperplasia Gene 21B analysis < 1000 ng dl Heterozygote carrier
  35. 35. Case 3 Cave Infertility Development of diabetes type 2 Increase in cardiovascular events ? Hyperplasia and endometrial carcinoma
  36. 36. Case 4 25 years old athlete with secondary amenorrhea after stopping OC (> 12 months) History of headaches and visual disturbances Investigations Pregnancy test – E2 28 pg/ml FSH = 4 UI/L, LH 1 UI/L Prl 150 ng/ml Diagnosis Hypogonadic amenorrhea with hyperprolactinemia
  37. 37. Case 4 DD of hyperprolactinemia Stress Medication (neurotropes, estrogenes….) Hypothyroid state Neurogenic (breast palpation, intercostal zona..) Hypothalamic disorders Pituitary disorders
  38. 38. Case 5 25 years old athlete with secondary amenorrhea after stopping OC (> 12 months). History of postpartum hemorrhage with retained placenta Investigations Pregnancy test – E2 174 pg/ml FSH = 25 UI/L, LH 58 UI/L Prl N Diagnosis Normogonadic hypergonadotropic amenorrhea
  39. 39. Case 5 Ultrasound P4 = 6,2 ng/ml
  40. 40. Case 5 Hysterosalpingography Hysteroscopy
  41. 41. Case 6 25 years old athlete with secondary amenorrhea after stopping OC (> 12 months). History of postpartum hemorrhage with retained placenta. She could not breastfeed. Investigations Pregnancy test – E2 10 pg/ml FSH = 1 UI/L, LH 0.2 UI/L Prl 4 ng/mL Diagnosis Hypogonadic hypogonadotropic amenorrhea
  42. 42. Case 6 Sheehan Syndrome Test the endocrine axis CNS MRI Hormonal substitution according to the endocrine deficits
  43. 43. Case 7 42 year old lady complaining of menorrhagia and secondary dysmenorrhea since 2 years Normal pelvic examination PAP smear normal
  44. 44. TVS and HTVS
  45. 45. HTVS vs hysteroscopy
  46. 46. TVS
  47. 47. HTVS
  48. 48. Hysteroscoppy
  49. 49. Case 8 59 year old women on sequential HRT complainig of metrorrhagia during the progestational phase Normal pevic examination PAP smear normal
  50. 50. Case 8 TVS: endometrium of 4.5 mm no uterine pathology
  51. 51. Un 0 20 40 60 80 as se ss ab le 6.6 At n= 2964 rop hic Pr oli 68.7 fer ati ve Se cre 23.5 tor y Me 0.5 ns tru al Ps eu do de cid ua Hy pe rpl At as yp ia ica lh yp 0.6 erp Korhonen et al. CHART 2 1997 AJOG las Ca rci no ma Endometrial histology without HRT 0.07 Ot he r
  52. 52. Endometrial histology with sequential HRT Sturdee et al. 2000 BJOG Follow up 3,29 years 47.4 60 40 18 15.1 20 7.6 5.5 2.7 0.9 0.7 0 2.3 0 le ua las ia ve ma y hic al ab r as tor cid tru he ati erp no rop ss rpl cre Ot fer ns de rci yp se pe At oli do Me Se Ca as lh Hy Pr eu Un ica Ps yp n=1192 At
  53. 53. Endometrial histology with continuous HRT Sturdee et al. 2000 BJOG Follow up 9 months 60 46.3 27.9 40 21.8 20 1.8 0.7 0 0.4 0 0 1.1 0 le ua las ia ve ma y hic al ab r as tor cid tru he ati erp no rop ss rpl cre Ot fer ns de rci yp se pe At oli do Me Se Ca as lh Hy Pr eu Un ica Ps yp n=1196 At
  54. 54. First bleeding day from the start of progestogen phase in sequential HRT and endometrium histology Sturdee et al. 1994 Lancet 60 50 Secretory 40 Non Assessable Proliferative 30 Atrophic Complex hyperplasia 20 Other Menstrual 10 Pseudodecidual Atypical hyperplasia 0 1 3 5 7 9 11 13 15 17 19 21 23
  55. 55. Endometrial thickness in postmenopausal women Andolf et al. Obstet and Gynecol 1993 Endometrial > 5mm < 5 mm P thickness E1 (pmol/L) 219+20 175+35 0.01 E2 (pmol/L) 38+17 13+2.7 0.05 P4 (nmol/L) 1+0.2 0.87+0.05 BMI 29.1+1.2 25.6+0.3 0.02
  56. 56. Endometrial thickness in sequential therapy Gull et al. Cycle day Endometrial N thickness (mm) 1-7 4.3+1.0 4 8-14 6.8+1.2 13 15-21 6.0+0.3 11 22-28 6.2+0.6 14
  57. 57. Vaginal sonography and endometrial cancer Buyuk et al. 1999 Acta Obstet Gynecol Scand 54 with spontaneous postmenopausal bleeding Atrophy 5 mm Hyperplasia 8.6 mm Cancer 6 mm Out of 9 cancers 3 had an endometrial thickness of 3mm

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