Anovulation and Amenorrhea 2 Flashcards
Describe how the normal function of the hypothalamic pituitary-ovarian axis is altered with the common causes of anovulation/amenorrhea.
What is are the major roles of FSH?
- Stimulates proliferation of granulosa cells
- Stimulates aromatase and estradiol
- Increases granulosa cell FSH and LH receptors
- Produces autocrine-paracrine factors, especially activin and inhibin
What is the role of LH in the early and late follicular phase?
- 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
What are the most common hypothalamic causes of secondary amenorrhea?
- Stress
- Weight loss
- Exercise
What do the causes of hypothalamic amenorrhea have in common?
- Increase opioid activity of the hypothalamic-pituitary-adrenal axis
- Inhibits the GnRH pulse generator
What are common findings in hypogonadotropic hypogonadism?
- Low/normal FSH and LH
- Hypoestrogenic
- thin endometrial stripe
- failure to withdraw to progestins
- immature vaginal cytology
- low estradiol level
What is the most common pituitary cause of secondary amenorrhea and what are its characteristics?
- 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
What are the common causes of hyperprolactinemia?
-
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
What are the common ovarian causes of amenorrhea?
-
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%
What are the chromosomal abnormalities that result in premature ovarian failure?
- 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
What are the findings in autoimmune causes of POF?
- Patients with concomitant Addison’s disease
- Evidence of autoimmune disease in 15% to 30% of women with POF
- 20% hypothyroid and 2% had diabetes
What are the genetic causes of POF?
- Genes responsible are unkown
- 10-15% of cases associated with FMR1 gene premutation
What are the tests done for an individual with POF?
- Karyotype for individuals under 30, risk for CV disease and X chromosome deletions
- Fragile X analysis in all under 40
What effect does POF have on bone mineral density?
- 43% noromal
- 44% osteopenia
- 14% osteoporosis
- primary amenorrhea, BMI, and duration of POF associated with BMD
What is Asherman syndrome?
- 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
How does primary hypothyroidism result in hyperprolactinemia?
TRH stimluates prolactin as well as TSH