Anovulation and Amenorrhea 2

Question 1

What is are the major roles of FSH?

Answer 1

• Stimulates proliferation of granulosa cells
• Stimulates aromatase and estradiol
• Increases granulosa cell FSH and LH receptors
• Produces autocrine-paracrine factors, especially activin and inhibin

Question 2

What is the role of LH in the early and late follicular phase?

Answer 2

• Early on, triggered by estradiol positive feedback to induce ovulation
• Late follicular phase:
  
  • final follicular maturation and continued steroidogenesis in the face of declining FSH
  • initiates luteinization and progesterone production in granulosa cells

Question 3

What are the most common hypothalamic causes of secondary amenorrhea?

Answer 3

• Stress
• Weight loss
• Exercise

Question 4

What do the causes of hypothalamic amenorrhea have in common?

Answer 4

• Increase opioid activity of the hypothalamic-pituitary-adrenal axis
• Inhibits the GnRH pulse generator

Question 5

What are common findings in hypogonadotropic hypogonadism?

Answer 5

• Low/normal FSH and LH
• Hypoestrogenic
  
  • thin endometrial stripe
  • failure to withdraw to progestins
  • immature vaginal cytology
  • low estradiol level

Question 6

What is the most common pituitary cause of secondary amenorrhea and what are its characteristics?

Answer 6

• Hyperprolactinemia
  
  • rises throughout pregnancy in response to high levels of estrogens
  • elevated prolactin inhibits pulsatile GnRH release, in part via hypothalamic opioid activity
  • always check TSH to rule out primary hypothyroidism
  • take a careful drug history
  • MRI to evaluate for tumor

Question 7

What are the common causes of hyperprolactinemia?

Answer 7

• Pharmacologic agents
  
  • drugs that inhibit dopamine synthesis, release, or action
  • antipsychotics
    
    • phenothiazines and haloperidol - 4x increase until drug is stopped
    • Clozapine and olanzapine - transient before normalizing
    • Risperidone - effect similar to phenothiazines
• Prolactin-secreting microadenoma/macroadenoma
• Idiopathic
• Primary hypothyroidism

Question 8

What are the common ovarian causes of amenorrhea?

Answer 8

• PCOS
  
  • anovulation
  • androgen excess
  • polycystic ovaries
    
    • 12 or more follicles 2-9 mm in diameter
    • ovarian volume more than 10.5 cc
• Premature ovarian failure
  
  • ovarian fialure with elevated FSH (two above 40 mIU/mL one month apart) before 40
  • result of premature depletion of oocyte-follicle complex
  • Causes:
    
    • chromosomal
    • autoimmune
    • idiopathic
    • iatrogenic (oophrectomy, chemotherapy, radiation therapy)
  • 50% have evidence of follicles
  • 20% have evidence of ovulation
  • Pregnancy reported in 8%

Question 9

What are the chromosomal abnormalities that result in premature ovarian failure?

Answer 9

• Mosaics and deletions of the X chromosome
• Pubertal development and menstruation occurs in about 3% of 45X and in about 12% of 45,X/46,XX individuals
• Menstruation occurs in over half of individuals with X chromosome deletions
• If 45,X/46,XX mosaicism is present, patient should be evaluated for cardiovascular abnormalities
  
  • deletions of the X chromosome may result in familial POF
  • recommend peripheral blood karyotype

Question 10

What are the findings in autoimmune causes of POF?

Answer 10

• Patients with concomitant Addison’s disease
• Evidence of autoimmune disease in 15% to 30% of women with POF
• 20% hypothyroid and 2% had diabetes

Question 11

What are the genetic causes of POF?

Answer 11

• Genes responsible are unkown
• 10-15% of cases associated with FMR1 gene premutation

Question 12

What are the tests done for an individual with POF?

Answer 12

• Karyotype for individuals under 30, risk for CV disease and X chromosome deletions
• Fragile X analysis in all under 40

Question 13

What effect does POF have on bone mineral density?

Answer 13

• 43% noromal
• 44% osteopenia
• 14% osteoporosis
• primary amenorrhea, BMI, and duration of POF associated with BMD

Question 14

What is Asherman syndrome?

Answer 14

• Result of partial or complete obliteration of uterine cavity by adhesions
• Only common uterine cause of secondary amenorrhea
• Causes:
  
  • curettage for a spontaneous or induced abortion or for postpartum hemorrhage
  • uterine survage
  • pelvic tuberculosis
• Only common non-anovulatory cause of secondary amenorrhea

Question 15

How does primary hypothyroidism result in hyperprolactinemia?

Answer 15

TRH stimluates prolactin as well as TSH