Menstrual Abnormalities

    .. beginning of document
    • Bottom Line:
      • If LH + FSH is high = primary gonadal failure
      • If LH + FSH is low
        • either gonadal hyperproduction and LH/FSH inhibition (estrogen present)
        • or gonads are normal and pituitary not producing LH/FSH (estrogen absent)
        • Test for estrogen with progesterone challenge test. (if withdrawal bleed = estrogen present)
        • Can also do estrogen + progesterone challenge test to see if uterus able to produce menses.
    EXCELLENT AAFP article on amenorrhea:
    Another way to think about this.... (My old diagram)


    Primary Amenorrhea

    Some Causes:

    • Mullerian agenesis (congenital, failure of mullerian ducts to develop: missing uterus+fallopian tubes, variable malformed vagina)
    • Androgen Insensitivity (Normal breast, absent uterus; Androgen resistance (mutation in receptor), so phenotypical male 46XY appears as a female.  Testicles secrete anti-mullerian hormone presents development of mullerian duct, thus upper vagina and uterus do not develop.  Ectopic testes must be removed to avoid neoplasm and hormones HRT required). 
    • Vaginal Septum
    • Imperforate Hymen
    • Constitutional Delay
    • Polycystic Ovarian Syndrome (PCOS)
    • Gonada Dysgenesis
      • Turner's Syndrome - Abnormal sex chromosomes (Turner's 45X)
      • Gonadal Failure -  Normal Sex chromosomes (46XX or 46 XY)  --- Most common

    Secondary Amenorrhea

    1.  Pregnant?  B-HCG
    2.  TSH/Prolactin? Is this a TSH or prolactin thing? (treat thyroidism or MRI for prolactin tumor  (other sx headache, vision changes, galactorrhea).
    3.  Progestin challenge: Are the hormones normal? (withdrawal bleed then hormones normal - normogonadotropic)
    4.  Check LH+FSH: If normones abnormal (no withdrawal bleed) then check LH + FSH to see if it's hypogonadotropic or hypergonadotropic

    Abnormal Uterine Bleeding

    AUB in Menarche

    Dysfunctional Uterine Bleeding (DUB)
    • Dx of exclusion'
    • Anovulatory heavy irregular bleeding
    • Either at menarche or at perimenopause
    • Must exclude other causes:
    Hematologic Causes
    • Coagulopathy (vWD)
    • Iron def??
    • Platelet abnormalities
    • Leukemia
    Endocrine Disorders
    • PCOS
    • Adrenal: CAH, Cushings Syndrome
    • Hypothalamic/Pituitary Dysfunction - eating disorder, excessive exercise, stress, idiopathic
    • Thyroid Disorders: hypothyroidism
    • Ovarian Tumors: secreting estrogens or androgens (very rare)
    • Threatened, missed, incomplete abortion
    • Ectopic pregnancy
    • Molar pregnancy

    Local Lesions

    • Endometrial Polyps
    Incorrect Use of OCP
       - CBC
       - BhCG?
       - TSH, Prolacting
       - Free testosterone, 17-hydroxy progesterone and DHEA (r/o PCOS, CAH0
       - Coag profile +/- vWF activity assay
       - ABCs
       - ESTROGEN (premarin 25mg iv q4h x24hrs) - causes nausea (use gravol)
       - OCP (monophasic prep) - ont tablet po tid x3-4d then bid for 3-4d, then od x21d.
    Need to keep on OCP until HPA axis matures.

    AUB in Perimenopausal

    Benign Conditions
    • Pregnancy
    • Leiomyomas (40% over 40 have them)
    • Adenomyosis - 
    • Endometriosis
    • PID
    Pre-malignant conditions
    • Cervix - Dysplasia, squamous cell ca., adenocarcinoma
    • Endometrium - Endometrial hyperplasia +/- atypia; endometrial adenocarcinoma
    • Coagulation vWB (10-15% due to vWB not detected in youth)
    • Thrombocytopenia (ITP)
    • Leukemia
    • Liver-disease - estrogen not metabolized
    • Hypothalamic - prolactinomas, sstress, wt loss
    • Hypothyroidism
    • Adrenal - Cushing's, CAH
    • Ovarian - hormone secreting tumors (rare), PCOS
    • Forgotten IUD
    • OCP/HRT incorrect
    • Neuroleptics - Dopamine and prolactin
    • Tubal ligation is NOT a cause.  Usually people get TL in perimenopause, which is around the time of AUB
    Dysfunctional Uterine Bleeding (DUB)
    • Dx of exclusion
    • No organic causes, anovulation
      - Labs: CBC, ferritin, TSH, PRL, BhCG, coag profile if vWD suspected
      - Sonohysterogram: polyps/fibroids
      - U/S 0.5-1cm normal?  1.4cm if about to menstruate
      - Hysteroscopy: done under GA, not commonly used

    Drug Mechanism  % decr flow  other benefits
    NSAID  inhibits COX  20-50  decr dysmen
     Cyclokapron  anti-fibrinolytic  40  
     Danazol inh. steroidogenesis, testosterone derivative   up to 80  15% amenorrhea, good tx for endometriosis
     Progestin Decidualizes endometrium   50  regulates cycle
     OCP inh steroidogenesis   50  decr. dysmen
     Mirena IUD  decidualizes endometrium  up to 80  treats endom. hyperp.
          - Hysteroscopic resection: fibroids and polyps
          - Hysteroscopic endometrial ablation: treats 80% over 5y, but comes back due to tubal origin?
          - Hysterectomy

    Congenital Adrenal Hyperplasia (CAH)

    • Over 95 percent of cases of congenital adrenal hyperplasia (CAH) are due to 21-hydroxylase due to CYP21A2 mutations. It is one of the most common known autosomal recessive disorders.
    • Can present as:
      • Virilizing form
      • Salt wasting form (adrenal crisis - hypotension, hyponatremia, hyperkalemia)
    • Females
      • Born with ambiguous genitalia
    • Males
      • Appear unaffected at birth, but later
    • Both
      • Early onset puberty
      • Rapid growth + premature completion of growth (short stature) if not treated early
      • Milder forms can present in adulthood
    • Adults
      • Early puberty and fertility problems
      • Females can have excessive body hair, irregular menses, or acne. 


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