AMENORRHEA Paul Beck, MD, FACOG, FACS
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  • Before puberty LH/FSH is low. CNS-hypothalmus extremely sensitive to negative feedback of low levels of estrogen. As critical body weight or body composition is approached. CNS hypothalmus becomes less sensitive to negative feedback of estrogen and GNRH secreted in larger amounts causing LH increase FSH less. The initial endocrine change associated with the onset of puberty is the occurrence of episodic pulses of LH occurring during sleep. These pulses absent before onset of puberty. After menstruation, LH pulses occur during sleep and awake. Last endocrinologic event of puberty is activation of the positive gonadotrophic response to increasing levels of estradiol which results in the mid-cycle gonadotrophic surge and ovulation.
  • Largest category, absent breast, uterus present. Second is breast and uterus both present. Third, breast present, uterus absent. Fourth and least common is breast absent, uterus absent. ( Maschchak – 62 cases)
  • Hypothalamic amenorrhea = suppression of pulsatile GNRH. Also note that in estrogen/progesterone withdrawal trial is not entirely necessary, since patients with normal internal genitalia and no specific history regarding uterine invasion are not like to have an outflow tract defect.
  • Thyroid disease is the most common association
  • Associated karyotypes of secondary amenorrhea, 46 xx = most common Mosaics can be 45 X/46XX – can have deletions in x short or long arms Need both x chromosomes
  • Gonadal dysgenesis = absent ovarian due to alterations in sex chromosomes XY gonadal dysgenesis = swyers syndrome – here you have female phenotype, a mullerian system ( no MIf) remove streaks because there is a Y. Gonadal Agenesis – no gonadal function – female – remove streaks Savage syndrome = the resistant ovary syndrome – the ovary fails to respond to FSH/LH. Treatment is Oocyte donation. Premature ovarian failure is about 1%. There is early depletion of ovarian folicles. Specific chromosomes anomalies can sometimes be identified. **Pure gonadal dygenesis/gonadal agenesis/mixed
  • Occasionally can have a pituitary FSH secreting tumor, usually non-functioning as alpha subunit. Treatment for prolactin adenomas- bromocriptine (parlodel 2.5) or cabergoline (dostinex .5) Prolactin inhibits pulsatile GNRH

AMENORRHEA Paul Beck, MD, FACOG, FACS Presentation Transcript

  • 1. AMENORRHEA Paul Beck, MD, FACOG, FACS
  • 2. Incidence of Primary Amenorrhea
    • Less than .1%
    • Puberty
    • Breast: 10.8 +/- 1.10 yrs.
    • Pubic Hair: 11.0 +/- 1.21 yrs.
    • Menarche 12.9 +/- 1.2 yrs.
  • 3. Onset of Puberty and Menstruation
    • Ratio of fat to both total body weight and lean body weight
    • Moderate obesity (20 – 30 % above ideal body weight) = earlier menarch
    • Malnutrition (anorexia nervosa, starvation) = delay
    • Prepubertal strenuous exercise (less total body fat) = delay e.g. ballet dancers, swimmers, runners
  • 4. Diagnostic Evaluation by Compartments
    • I Outflow Tract (uterus – vagina)
    • II Ovary
    • III Anterior Pituitary
    • IV CNS – Hypothalamus (environment and psyche)
  • 5. Evaluation
    • History/Physical
    • Psychiatric, family history-genetic abnormalities, nutritional status, growth/development
    • Secondary sexual characteristics
    • Presence of breasts – normal reproductive tract (uterus, vagina)
  • 6. Evaluation Categories
    • Breast Absent – Uterus Present
    • Breast Present – Uterus Present
    • Breast Present – Uterus Absent
    • Breast Absent – Uterus Absent
  • 7. Initial Tests for Amenorrhea
    • Progesterone challenge
    • TSH
    • Prolactin
    • TSH elevated – hypothyroid
    • Prolactin elevated (MRI – 100 ng/ml)
  • 8. Progesterone Challenge
    • Positive withdrawal bleed
    • Normal prolactin
    • Normal TSH
    • Diagnosis = annovulation
    • Treatment: monthly progesterone/O.C.
  • 9. Progesterone Negative Withdrawal
    • FSH/LH
    • FSH/LH normal – estrogen/progesterone cycle
    • If negative = end organ defect
    • If FSH/LH high = ovarian failure
    • Estrogen – positive withdrawal, FSH normal or low, MRI sella = no path
    • Diagnosis: hypothalamic amenorrhea
  • 10. Chromosome Evaluation for Ovarian Failure
    • If the patient is under age 30 – karyotype
    • Y chromosome/excision of gonadal area
    • Problem – gonadal tumor – malignant
    • 30% do not develop virilization, therefore even normal appearing female needs karyotype to exclude Y
    • After age 30 = premature menopause
  • 11. Selected Blood Test for Autoimmune Disease
    • Calcium, phosphorus
    • Fasting blood sugar
    • A.M. cortisol
    • Free T 4 – TSH
    • Thyroid antibodies
    • CBC – ESR – CRP
    • Total protein A/G ratio
    • Rheumatoid factor
    • Antinuclear antibody
  • 12. Specific Disorders
    • I Outflow - imperforate hymen, ashermans
    • mullerian agenesis, androgen insensitivity syndrome
    • II Ovary - can be primary or secondary amenorrhea
    • 40% of primary amenorrhea have gonadal streaks
    • Of the 40%, 50% = 45,X
    • 25% = mosaics
    • 25% = 46 XX
    • Secondary amenorrhea patients have many karyotypes
  • 13. Specific Disorders (continued)
    • Turner syndrome
    • Gonadal dysgenesis
    • Gonadal agenesis
    • Savage syndrome
    • Premature ovarian failure
    • Radiation therapy
    • Alkylating agents
  • 14. Compartment III
    • Anterior pituitary disorders
    • Tumors – large bitemperal hemianopsia
    • Small tumors – visual defects- rare
    • Craniopharyngioma – calcification x-ray may produce blurring of vision
    • Acromegaly
    • Cushings
    • Pituitary prolactin adenomas (micro/macro)
    • Sheehan’s syndrome
  • 15. Compartment IV
    • CNS disorders
    • Hypothalamic amenorrhea – problem is a GNRH pulsatile secretion
    • Anorexia/Bulemia/weight loss – 25% (onset – 10 – 30 years)
    • Exercise
  • 16. Etiology of Amenorrhea
    • Breast – Absent
    • Breast – Present
    Mullerianagenesis Hypothalamic, pituitary, ovarian pt uterine etiology AIS (T.F.) 3. Pituitary failure 2. Hypothalamic failure 17 a hydroxylase deficiency with 46XX Agonadism Gonadal dysgenisis 17 a hydroxylase deficiency 46xy 1. Gonadal failure turner 45X 17, 20 desmolase deficiency Uterus Present Uterus Absent