ERM2 Menstrual Path

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Author:
jknell
ID:
184355
Filename:
ERM2 Menstrual Path
Updated:
2012-11-19 02:09:16
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Endocrine Reproductive Pathology
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Endocrine and Reproductive Pathology
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  1. Normal Menstrual Cycle


    • -Day 1 = first day of bleeding
    • -Avg cycle length = 28 days
    • -Follicular Phase: variable
    • -Luteal Phase: always 14 days
  2. Amenorrhea
    • cycle length > 6 mo
    • -primary: never experienced bleeding
    • -secondary: previous bleeding experienced
  3. Oligomenorrhea
    -interval 35-180 days
  4. Polymenorrhea
    interval shorter than 21 days
  5. Causes of Amenorrhea
    • 1. Central
    •      -hypothalamus (GnRH)
    •      -pituitary (LH, FSH)

    2. Ovarian

    3. Outflow Tract Causes (uterus)
  6. Functional Hypothalamic Defects
    • 1. Stress (weight loss, exercise)
    • 2. Psychogenic disorders
    • 3. GnRH dysfunction
    • 4. GnRH receptor gene mutation
  7. Weight Loss
    • -at least 22% lean-fat ratio required for normal menses
    • -depends on type of exercise (runners but not swimmers)
    • -critical threshold under which do not menstruate
  8. Psychogenic Disorders
    • 1. Anorexia Nervosa
    • 2. Pseudocyesis
  9. Anorexia Nervosa
    • -wt loss leading to less than 85% expected
    • -not just weight loss that causes amenorrhea
    • -can have hyperkalemia --> death
  10. GnRH Dysfunction (hypogonadotropic hypogonadism)
    • 1. Kallman Syndrome
    • 2. Lawrence-Moon-Biedl-Bardet Syndrome
    • 3. Idiopathic hypergonadotropic hypogonadism
  11. Kallman Syndrome: Symptoms
    • -primary amenorrhea
    • -hyposmia/anosmia
    • -lack of secondary sexual development
    • -color blindness
  12. Kallman Syndrome: Pathophys
    • -GnRH neurons originate in olfactory epithelium and migrate to the hypothalamic region of the brain
    • -in Kallman's the neurons don't migrate and don't get activated

    -two forms: KAL1 and KAL2
  13. KAL1
    • -x-linked
    • -mutation in anosmin
    • -no cleft lip
  14. KAL2
    • -autosomal dominant
    • -mutation in FGFR1
    • -associated with cleft lip
  15. Lawernce-Moon-Beidl-Bardet Syndrome
    • -amenorrhea
    • -retinitis pigmentosa
    • -obesity
    • -mental retardation
    • -lack of secondary sexual development
  16. Anatomic Pituitary Defects
    • 1. Tumors (functional or non-functional, NF more common)
    • 2. Pituitary necrosis (Sheehan's Syndrome: hypotension --> pituitary infarct)
    • 3. Rare: empty sella syndrome, infiltrative diseases, head trauma and irradiation
  17. Functional Pituitary Defects
    • 1. Hormone producing tumors
    •      -PRL (30%)
    •      -GH (18%)
    • 2. Gonadotropin Deficiency (hormone or receptor)
  18. Regulation of Prolactin Secretion in Tumor
  19. Ovarian Causes of Amenorrhea
    • 1. Gonadal Dysgenesis
    •      -Turner's Syndrome
    •      -pure gonadal dysgenesis
    • 2. Premature loss of oocytes
    • 3. Ovarian insensitivity
  20. Turner's Syndrome
    -usually 45XO (46XX)

    • Clinical Features
    •      -short stature
    •      -broad chest
    •      -low set ears
    •      -web neck
    •      -congenital heart disease
    •      -hypothyroidism
  21. Pure Gonadal Dysgenesis
    • -46XX
    • -fleshy streak instead of ovaries
    • -can be 46XY
  22. Outflow Tract Causes of Amenorrhea
    • 1. Muellarian Anomalies (congenital)
    • 2. Androgen Insensitivity Syndrome (46XY)
    • 3. Vaginal Agenesis
    • 4. Imperforate hymen
    • 5. Intrauterin adhesions (instrumentation)
  23. PCOS: Epidemiology
    -5-10% of reproductive aged women
  24. PCOS: Clinical Features
    • 1. Reproductive Disruption
    •      -androgen excess --> hirsutism
    •      -chronic anovulation (oligomenorrhea)
    •      -polycystic ovaries
    • 2. Metabolic Abnormalities
    •      -insulin resistance (diabetes)
    •      -obesity
  25. PCOS: Pathophysiology
    -follicles are arrested in midantral stage --> cysts

    -theca cell layer hyperplasia (excessive androgens: maybe due to abnormal enzyme activity)

    -increased GnRH activity --> increased LH --> more androgen
  26. PCOS and obesity
    • -increased free FAs --> hyperinsulinemia
    • -increased theca cell production of androgen
    • -decreased SHBG (increase free T)
    • -lower IGFBP (increase theca cell production of androgen)
    • -inflammatory cytokines
  27. PCOS: Management
    • 1. OCPs: anovulation, hair
    • 2. Anti-androgens (Spironolactone): blocks T signaling, hair
    • 3. Progesterone: anovulation
    • 4. IVF/Ovulation induction (aromatase inhibitor): infertility
  28. Endometriosis: Etiology Theories
    • 1. Retrograde Menstruation
    • 2. Hematologic Spread
    • 3. Lymphatic Spread
    • 4. Coelomic Metaplasia
    • 5. Genetic Factors
    • 6. Immune Factors
  29. Endometriosis: Diagnosis
    -laparscopy
  30. Edometriosis: Medical Therapy
    • -estrogen suppression (control pain)
    • -NSAIDs
    • -OCPs (continuous)
    • -Progestins
    • -Danazol
    • -GnRH-agnoist (with add back therapy)
  31. Inflammation in Endometriosis
    • -in women with endometriosis the endometrium expresses COX2 and aromatase inhibitors
    • -PGs have a positive effect on aromatase
    • -estrogens active COX2

    -positive feedback
  32. Side Effects of OCPs
    • -breakthrough bleeding
    • -weight gain
    • -breast tenderness
    • -bloating
    • -nausea
  33. Danazol
    • -testosterone derivative
    • -anovulation, hyperandrogenic, hypoestrogenic

    -use in mild endometriosis

    -adverse effects: acne, edema, wt gian, hirsutism, flushes, spotting, atrophic vaginitis

    rarely used
  34. GnRH agonists
    • -initially stimulate FSH/LH release (flare)
    • -downregulate GnRH receptors ("pseudomenopause")
    • -expensive
    • -risk of osteoporosis
  35. GnRHa add back therapies
    • -estrogens +/- porgestins
    • -progestins
    • -progestins + bisphosphonate
    • -tibolone (synthetic steroid with E and P activity)
  36. Endometriosis: Surgical Therapy
    • -vaporization with laser
    • -excision
  37. Adenomyosis
    • -presence of endometrial tissue within the myometrium
    • -enlarged, tender, uterus
    • -dysmenorrhea

    • Management:
    • -analgesics
    • -OCPs
    • -GnRHa
    • -hysterectomy
  38. Leiomyomata: Epidemiology
    • <0.5% become malignant
    • -benign smooth muscle tumors of the uterus
    • -mroe common in African American
  39. Leiomyomata: Types
    • -Intramural
    • -Subserosal (outer)
    • -Submucosal (cavity)
  40. Leiomyomata: Symptoms
    • -asymptomatic
    • -menorrhagia
    • -infertility
    • -pregnancy complications
    • -pain
    • -degeneration (lose blood supply)
    • -parasitic fibroids
  41. Leiomyomata: Treatment
    • -watch and wait
    • -anagelsics/OCPs
    • -medical shrinkage with GnRHa (temporary)
    • -radiological (uterine artery embolization)
    • -myomectomy
    • -hysterectomy

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