Week 3: Primary amenorrhea

Question 1

Who would we evaluate for primary amenorrhea?

Answer 1

• Age 16, no menses, regardless of secondary sex characteristics
• Age 14, no menses and no secondary sex characteristics
• No period 5 years after breast development

Question 2

Patient with breasts and uterus with amenorrhea

Answer 2

1. Hypothalamus/Pituitary
   - thyroid: hypo or hyperthyroidism (TSH)
   - hyperprolactinemia: prolactin levels can disrupt pulsatility of GnRH
2. Vagina/Uterus
   - outflow obstruction: imperforate hymen, transverse vaginal septum. Suspect with cyclic ab pain
   - Ashermans Syndrome: scarring of uterine cavity. seen in secondary amenorrhea, due to multiple surgeries, e.g. abortions, or infection that caused scarring

Question 3

Patients with breast present and uterus absent

Answer 3

• know that they have estrogen because of breast. Gold standard is to do karyotype.
• can test testosterone levels to distinguish between the two. If male range, it is AIS.
  1. 46 XY – Androgen Insensitivity syndrome
• external female, no axillary/pubic hair
• male range testosterone
  2. 46 XX –Mullerian Agenesis aka Mayer Rokatansky Hauer Syndrome (MRKH)
• pubic hair present, female range testosterone

Question 4

Androgen Insensitivity Syndrome

Answer 4

• X linked recessive, mutation in androgen receptor so that it is unresponsive to testosterone
• have intra ab gonads and no uterus due to SRY gene and AMH (anti mullerian hormone)
• testes secreting testosterone, but no response so testicles don’t descend and no pubic/axillary hair
• have external female genitalia
• large breast from aromatase in adipose that converts testosterone to estrogen

Question 5

Mullerian Agenesis

Answer 5

• unknown etiology
• congenital absence of internal vagina
• has ovary to make estrogen
• some have uterine remnant with blind vaginal pouch–>sloughing endometrium has nowhere to go and can cause endometriosis
• full secondary sex characteristic w/ pubic/axillary hair
• have associated abnormalities: renal, cardiac, skeletal
• 15% of primary amenorrhea

Question 6

Differential for Patients with no breast, has uterus present

Answer 6

• know that estrogen is low, don’t know if its ovary, hypothalamus
  1. FSH/LH < 5 IU: hypogonadotropic hypogonadism
  2. FSH >20, LH> 40
• hypergonadotropic hypogonadism
• problem in ovary

Question 7

GnRH stimulation test

Answer 7

• to distinguish between hypothalamic or pituitary origin of hypogonadotropic hypogonadism
• not actually done
• give IV GnRH and measure LH response.
• if LH response > 20, its a hypothalamic problem since have adequate pituitary response

Question 8

Hypogonadotropic hypogonadism causes

Answer 8

HYPOTHALAMIC causes:
-constitutional delay: common, family hx. no treatment needed
-hypothalamic dysfunction: exercise induced, anorexia, severe stress
-Kallman’s syndrome: failure of GnRH neurons to migrate. Anosmia
-CNS tumors
PITUITARY causes:
-pituitary tumor: craniopharyngiomas, adenomas
-isolated gonadotropin def. Rare

Question 9

Hypergonadotropic hypogonadism causes

Answer 9

• must get a karyotype
  1. 46 XX -premature ovarian failure
• gonadal dysgenesis- unclear etiology. Perrault syndrome-assoc. deafness
• autoimmune cause
• resistant ovary syndrome: rare, absent/defective gonadotropin receptors
• galactosemia: disorder of galactose metabolism, will have other problems
• hx of chemo/radiation
  2. 45 X- Turner’s syndrome
• most common form of gonadal dysgenesis in females. Accelerated oocyte loss without 2nd X chromosome
• phenotype: short, shield chest, webbed neck, cardiac and skeletal abnormalities.
• needs surrogate in pregnancy b/c risk of aortic dissection
  3. 46 XY - Swyer’s syndrome
• absent SRY region. Streak gonads. normal internal and external female genitalia. Doesn’t have normal ovary development because only 1 X.

Question 10

Differential for patient with no breast and no uterus

Answer 10

• very rare
  1. XY 18 hydroxylase deficiency
• blind vaginal pouch: has AMH but lacks testosterone and estrogen
• regression of internal males structures. No internal male/female genitalia.
• normal female external genitalia
• no hormones, no breasts
• HTN, hypokalemia from buildup of hormone precursors-cortisol and mineralocorticoids