Amenore - Anovulasyon -


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Amenore - Anovulasyon -

  1. 1. Amenorrhea & Anovulation Andrea Chymiy, MD Swedish Family Medicine
  2. 2. Amenorrhea <ul><li>Transient, intermittent, or permanent </li></ul><ul><li>Results from dysfunction of the hypothalamus, pituitary, ovaries, uterus, or vagina </li></ul>
  3. 3. Primary vs. Secondary Amenorrhea <ul><li>Primary: Absence of menarche by the age of 16. </li></ul><ul><li>Secondary: absence of menses for more than three cycle intervals or six months in women who were previously menstruating </li></ul>
  4. 4. Causes of Primary Amenorrhea <ul><li>Chromosomal abnormalities — 45% </li></ul><ul><li>Physiologic delay of puberty — 20% </li></ul><ul><li>Müllerian agenesis — 15% </li></ul><ul><li>Transverse vaginal septum or imperforate hymen — 5% </li></ul><ul><li>Absent hypothalamic production of GnRH - 5% </li></ul><ul><li>Anorexia nervosa — 2% </li></ul><ul><li>Hypopituitarism — 2% </li></ul>
  5. 5. Diagnostic Evaluation for Primary Amenorrhea: <ul><li>Normal pubertal development? </li></ul><ul><li>Was pt’s neonatal/childhood health normal? </li></ul><ul><li>Family history of delayed/absent menarche? </li></ul><ul><li>Any symptoms of virilization? </li></ul><ul><li>Any galactorrhea? (hyperprolactinemia) </li></ul>
  6. 6. More history questions… <ul><li>Any recent increase in stress, or change in weight, diet, or exercise habits? </li></ul><ul><li>Is pt taking any meds or drugs? </li></ul><ul><li>Short stature compared to family members? </li></ul><ul><li>Any symptoms of other hypothalamic-pituitary disease (headaches, visual field defects, fatigue, polyuria or polydipsia?) </li></ul>
  7. 7. Physical Exam: <ul><li>Evaluation of pubertal development - including height, weight, & Tanner staging. </li></ul><ul><li>Pelvic exam to check for presence of cervix, uterus, ovaries (may need ultrasound) </li></ul><ul><li>Check skin for signs of androgen excess (acanthosis nigras, hirsutism, acne, & striae) and vitiligo (thyroid disorders) </li></ul><ul><li>Check for physical features of Turner syndrome (low hair line, web neck, shield chest, and widely spaced nipples) </li></ul>
  8. 8. Tanner staging
  9. 9. Acanthosis nigrans
  10. 10. Striae
  11. 11. Vitiligo
  12. 12. Typical features of Turner Syndrome
  13. 13. If uterus not found on exam… <ul><li>If normal vagina or uterus not obviously present on PE, a pelvic U/S is performed to confirm the presence or absence of ovaries, uterus, and cervix. </li></ul><ul><li>If no uterus found, further evaluation should include a karyotype and measurement of serum testosterone . </li></ul>
  14. 14. If patient does have a uterus… <ul><li>… and no evidence of an imperforate hymen, vaginal septum, or congenital absence of the vagina is found, an endocrine evaluation should be performed. </li></ul><ul><li>Check serum B-HCG, FSH, TSH, & prolactin. </li></ul><ul><li>If signs or symptoms of hyperandrogenism, serum testosterone & DHEA-S should be measured to assess for an androgen-secreting tumor. </li></ul>
  15. 15. Correcting the underlying pathology <ul><li>Surgery is often required in patients with either congenital anatomic lesions or Y chromosome material. </li></ul><ul><li>In those patients with Y chromosome material, gonadectomy should be performed to prevent the development of gonadal neoplasia. Gonadectomy should be delayed until after puberty in patients with complete androgen insensitivity syndrome. </li></ul>
  16. 16. Treatment of PCOS <ul><li>Hirsutism: removal of hair by electrolysis or laser treatment. Slowing of hair growth by administration of an oral contraceptive alone or in combination with an antiandrogen (eg: Sprironolactone) </li></ul><ul><li>Endometrial protection: OCPs </li></ul><ul><li>Anovulation & Infertility: Clomiphene , GnRH, Metformin </li></ul>
  17. 17. Hypothalamic amenorrhea <ul><li>We’ll discuss treatment options after we talk about Secondary Amenorrhea! </li></ul>
  18. 18. Secondary Amenorrhea <ul><li>First, second & third cause is pregnancy, followed by…. </li></ul><ul><li>Ovarian disease — 40% </li></ul><ul><li>Hypothalamic dysfunction — 35% </li></ul><ul><li>Pituitary disease — 19% </li></ul><ul><li>Uterine disease — 5% </li></ul><ul><li>Other — 1% </li></ul>
  19. 19. Ovarian causes of amenorrhea <ul><li>Hyperandrogenism (from internal or external sources) </li></ul><ul><li>Ovarian failure due to normal or early menopause </li></ul>
  20. 20. Diagnosing the etiology of secondary amenorrhea <ul><li>Rule out pregnancy! </li></ul>
  21. 21. Pertinent history in work-up of secondary amenorrhea <ul><li>Recent stress, wt loss, diet or exercise changes, or illness? </li></ul><ul><li>Meds (Recent OCP initiation, danazol, meto-clopramide, anti-psychotics?) </li></ul><ul><li>Symptoms of other hypothalamic-pituitary disease, including headaches, visual field defects, fatigue, or polyuria and polydipsia? </li></ul>
  22. 22. Other important stuff in the history… <ul><li>Symptoms of estrogen deficiency, including hot flashes, vaginal dryness, poor sleep, or decreased libido? </li></ul><ul><li>Galactorrhea, hirsutism, acne, and/or a history of irregular menses? </li></ul><ul><li>An history of obstetrical catastrophe, severe bleeding, dilatation and curettage, or endometritis or other infection that might have caused scarring of the endometrial lining ? </li></ul>
  23. 23. Physical exam findings <ul><li>Height & weight, BMI </li></ul><ul><li>Any evidence of systemic illness or cachexia </li></ul><ul><li>Breast exam – check for galactorrhea </li></ul><ul><li>Check for hirsutism, acne, striae, acanthosis nigricans, vitiligo, skin thickness or thinness, and easy bruisability </li></ul>
  24. 24. Initial lab evaluations for secondary amenorrhea <ul><li>Urine or serum B-HCG </li></ul><ul><li>Serum prolactin, TSH, FSH </li></ul><ul><li>DHEA-S and testosterone if indicated </li></ul>
  25. 25. High serum prolactin <ul><li>Screen twice before ordering imaging </li></ul><ul><li>Goal of imaging is to rule out a hypothalamic or pituitary tumor. CT is frequently adequate, but MRI provides a better view of the hypothalamic-pituitary area </li></ul><ul><li>In the case of a prolactinoma, the image will allow determination of whether it is a microadenoma ( < 1 cm) or a macroadenoma (>1 cm) </li></ul>
  26. 26. High serum FSH <ul><li>Indicates the presence of ovarian failure. </li></ul><ul><li>This test should be repeated monthly on three occasions to confirm persistent elevation. </li></ul><ul><li>A karyotype should be considered in most women of secondary amenorrhea age 30 years or younger to r/o complete or partial deletion of the X chromosome, or presence of any Y chromosome material </li></ul>
  27. 27. High serum androgen concentrations <ul><li>A high serum androgen value may solidify the diagnosis of PCOS, or may raise the question of an androgen-secreting tumor of the ovary or adrenal gland. </li></ul><ul><li>initiate evaluation for a tumor if the serum concentration of testosterone is greater than 150 to 200 ng/mL or that of DHEA-S is greater than 700 µg/dL </li></ul>
  28. 28. Normal or low serum gonadotropin concentrations and all other tests normal <ul><li>One of the most common outcomes of laboratory testing in women with amenorrhea. </li></ul><ul><li>Women with hypothalamic amenorrhea have normal to low FSH values, with FSH typically higher than LH </li></ul><ul><li>Cranial MRI is indicated in all women without an a clear explanation for hypogonadotropic hypogonadism </li></ul><ul><li>No further testing is required if the onset of amenorrhea is recent or is easily explained and there are no symptoms suggestive of other disease </li></ul>
  29. 29. Normal serum prolactin & FSH with history of uterine instrumentation <ul><li>Evaluation for Asherman's syndrome should be performed. Many clinicians start with a progestin challenge (Provera 10 mg qD x 10 d) </li></ul><ul><li>If withdrawal bleeding occurs, an outflow tract disorder has been ruled out. </li></ul>
  30. 30. Evaluating for Asherman’s syndrome <ul><li>If bleeding does not occur, estrogen and progestin should be administered (conjugated estrogen x 35 d with medroxyprogesterone for last 10 d) </li></ul><ul><li>failure to bleed upon cessation of this therapy strongly suggests endometrial scarring. </li></ul><ul><li>In this situation, a hysterosalpingogram or direct visualization of the endometrial cavity with a hysteroscope can confirm the diagnosis of Asherman syndrome </li></ul>
  31. 31. Treatment for functional hypothalamic amenorrhea <ul><li>For athletic women, adequate caloric intake to match energy expenditur e is often followed by resumption of menses (70-80%) </li></ul><ul><li>All women athletes with amenorrhea should be encouraged to take 1200 to 1500 mg of calcium daily and supplemental vitamin D (400 IU daily) </li></ul>
  32. 32. Basal BMI vs probability of resumption of menstruation
  33. 33. Treatment for functional hypothalamic amenorrhea <ul><li>Nonathletic women who are underweight or who appear to have nutritional deficiencies </li></ul><ul><li>- should have nutritional counseling </li></ul><ul><li>- Can be referred to a multidisciplinary team specializing in the assessment and treatment of individuals with eating disorders. </li></ul>
  34. 34. Hyperprolactinemia <ul><li>Can be corrected with a dopamine agonist in most women (cabergoline, bromocriptine, pergolide) </li></ul><ul><li>Other options include surgery, radiation therapy and estrogen </li></ul>
  35. 35. Treatment of ovarian causes of secondary amenorrhea <ul><li>No treatment available for primary ovarian failure, but women should take supplemental calcium and vitamin D. All the texts and journal articles also recommend HRT… </li></ul><ul><li>PCOS can be treated as described previously </li></ul>
  36. 36. Treatment of Asherman’s syndrome <ul><li>Therapy consists of hysteroscopic lysis of adhesions followed by long-term estrogen administration to stimulate regrowth of endometrial tissue </li></ul>
  37. 39. Case 1: 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>
  38. 40. Case 1: Physical Exam <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>
  39. 41. Case 1: Further history <ul><li>Patient’s parents concerned about her eating habits (very low fat intake and restricting calories) </li></ul>
  40. 42. Diagnosis: Hypothalamic Amenorrhea <ul><li>Etiology is most likely inadequate caloric and fat intake. </li></ul><ul><li>Patient should be referred for evaluation for an eating disorder. </li></ul><ul><li>Chances of normal menstruation are very good if patient takes in adequate calories. </li></ul>
  41. 43. Case 2: 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 c/o amenorrhea x 10 months </li></ul><ul><li>Overweight </li></ul><ul><li>Wants to get pregnant </li></ul>
  42. 44. Case 2: Physical Exam <ul><li>Obese female </li></ul><ul><li>Acne </li></ul><ul><li>Normal genitalia </li></ul><ul><li>Mild hirsutism </li></ul>
  43. 45. Case 2: Laboratory findings <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 findings show polycystic ovaries </li></ul>
  44. 46. U/S findings in PCOS
  45. 47. Case 3: 29 yo woman with 18-month h/o amenorrhea <ul><li>Normal development </li></ul><ul><li>No family history of amenorrhea </li></ul><ul><li>Does not exercise excessively or restrict diet </li></ul><ul><li>Denies galactorrhea </li></ul><ul><li>Has h/o SAB with subsequent D & C </li></ul>
  46. 48. Case 3: Physical Exam <ul><li>WDWN young woman </li></ul><ul><li>Normal exam </li></ul><ul><li>No galactorrhea </li></ul>
  47. 49. Case 3: Laboratory findings <ul><li>Urine B-HCG negative </li></ul><ul><li>Prolactin wnl </li></ul><ul><li>TSH, FSH, LH all wnl </li></ul>
  48. 50. Case 3: Further work-up <ul><li>Fails Provera challenge </li></ul><ul><li>Fails 1-month trial of estrogen + progesterone </li></ul><ul><li>Pelvic U/S shows no uterine stripe </li></ul><ul><li>Hysteroscope confirms diagnosis of…Asherman’s Syndrome </li></ul>
  49. 51. <ul><li>Thank you ! </li></ul>