Amenorrhea Flashcards
Primary amenorrhea definition
14 years with no 2ndary sexual characteristics
OR
16 y with 2ndary sexual characteristics
Secondary amenorrhea definition
previous history of menstruation AND no menses for 3 cycles/6 months
Endocrinological Hx of amenorrhea
CNS mass symptoms thyroid prolactin androgens mass symptoms in viscera adrenal symptoms outlet uterus/cervix ovary/pituitary hypothalamus (Kallman's - anosmia)
Amenorrhea physical examination
Record of growth, Tanner stages, height/weight %
BP
Head to toe - neuro, thyroid, abdominal, genital, skin
Primary amenorrhea investigation
bHCG FSH, LH, estradiol PRL, TSH Progesterone challenge test - if negative, consider head imaging - if estrogen is present, progesterone would cause sheeding Androgens if symptoms are present pelvic ultrasound Karyotype MRI head
Hypergonadotropic hypogonadism
Ovaries are “failing”
high FSH, low estrogen
look for chromosomal abnormalities
Hypogonadotropic hypogonadism
low FSH, low estrogen
CNS is “failing”
Eugonadotropic eugonadism
gonads are working
hypergonadotropic hypogonadism distribution
46% of amenorrhea
abnormal karyotype - 26%
normal karyotype - 17%
Hypogonadotropic hypogonadism distribution
31%
reversible - 18
irreversible - 13
Eugonadic distribution
26% of amenorrhea
Hypogonadotropic hypogonadism CNS etiology
adenoma, prolactinoma, craniopharyngioma, other CNS lesions
Sheehan’s: acquired insult - reduced perfusion to pituitary
Kallman’s
Idiopathic
FSH beta mutation - defect in FSH receptor
Kallman’s syndrome
isolated GnRH deficiency caused by disrupted GnRH neuron migration
anosmia +/- midline facial defects
possible KAL1 gene mutation
never go into puberty on their own
Non-CNS etiology of amenorrhea
anorexia strenuous exercise stress primary hypothyroidism hyperprolactinemia physiological delay
Eugonadotropic eugonadic amenorrhea etiology
PCOS
Hyperprolactinemia - low/normal gonadotropin levels
Structural
Hyperprolactinemia etiology
prolactin-inducing medications (antipsychotics, antiepileptics)
hypothyroidism
pituitary tumour
prolactinoma
Congenital structural causes of amenorrhea
imperforated hymen
vaginal septum - transverse/longitudinal
cervical agenesis
Mullerian agenesis: MRKH
Acquired structural causes of amenorrhea
Asherman’s
Mullerian agenesis
normal breasts, normal pubic hair, normal ovaries, no uterus, no cervix, no upper vagina
10-40% have renal abnormality
10-15% have skeletal abnormality
Mullerian agenesis tx
psych support/sexual activity, fertility
first line: vaginal dilators
second line: surgical neovagina
Special tests for structural causes of amenorrhea
physical exam
TSH, PRL, androgens
progesterone challenge test
ultrasound
Progesterone challenge test
provides an estimate of estrogen concentration and confirms presence of an estrogen primed uterus
- daily progesterone for 5-10 d
Positive response: normal withdrawal bleeding (3-5 d of menses) usually occurring 2-3 days after end of progestin, but up to 10%
will be positive in 90% of women with E2 > 50 pg/ mL
Hypergonadotropic hypogonadism etiology
Primary ovarian insufficiency (POI)
normal karyotype
abnormal karyotype
Hypergonadotropic hypogonadism workup
Karyotype
Autoimmune: thyroid, pancreas, adrenals, ovary - look for antibodies, HbA1cC, am cortisol, calcium/phosphate for parathyroid
Hypergonadotropic hypogonadism with N karyotype etiology
previous ovarian surgery chemotherapy, radiotherapy gonadal dysgenesis autoimmune - Addison's, thyroid, T1DM, myasthenia gravis, SLE receptor mutations - rare idiopathic fragile X premutation
Fragile X premutations
FMR1
increased CGG repeats in FMR1 gene
most common inherited cause of mental retardation and autism
family history of autism, mental retardation, developmental delay
14% in familial PO1, 1-7% in sporadic
Hypergonadotropic hypogonadism with abN karyotype - etiology
Turner - 45XO, mosaics
46XY - AIS, Swyer syndrome, non-functioning SRY mutation
Turner syndrome characteristics
short stature webbed neck low set ears/hairline wide spaced nipples/shield chest short 4th metacarpal wide carrying angle absent sexual development
mosaic: 50%’ XY: 5%
15% begin puberty
Turner syndrome treatment
pubertal induction
hormone replacement
fertility, contraception
Turner syndrome investigation/monitoring
Renal ultrasound (Dx, q3-5 y): 36-70%, horseshoe kidney, solitary, rotational, duplicated
echo (Dx, 1x 12-15 y, then q5 y): 33%, bicuspid aortic valve, coarctation of aorta, aortic valve disease
Autoimmune (Dx q1-2 y): screen for DM, thyroid, hepatitis, celiac, thrombocytopenia
Hearing loss: audiometry x 1
ophthalmology
osteoporosis: up to 90%, BMD
Gonadectomy: if Y present
Androgen Insensitivity Syndrome
X-linked recessive
mutation in androgen receptor
inguinal testes (no spermatogenesis), breast development (peripheral conversion of androgen –> estrogen), no pubic hair, blind vagina, no uterus
Complete AIS: gonadectomy at puberty
Incomplete AIS: may be virilized, gonadectomy at diagnosis
Androgen synthesis disorder
5-alpha reductase deficiency (can’t convert T –> DHT)
autosomal recessive
internal male, external female
virilize at puberty
Hypogonadotropic hypogonadism tx
get back to weight at which you last had menstrual cycle
reduce stress
for pregnancy - ovulation induction with gonadotropins ($$$$$$)
Eugonadotropic eugonadism tx
Hypothyroidism/hyperthyroidism: correct/synthroid
PCOS: health weight, treat concerning symptom (hirsutism/acne), cyclic progestin
for pregnancy - ovulation induction: clomiphene citrate, mesormin, laparoscopic ovarian drilling, gonadotropins
Hypergonadotropic hypogonadism treatment
psych support
hormonal replacement until age of menopause
-if delayed puberty, may need induction
- hormone replacement with estrogen/cyclic progestin, or combined OCP
15% can resume ovulation, 5-10% may become pregnant - counsel on contraception
fertility: oocyte donation, adoption
Causes of amenorrhea with NO breast development with uterus
POI Gonadal dysgenesis (Turner, Swyer) Autoimmune oophoritis Fragile X premtutation Iatrogenic - RT, chemo galactossemia Hypothalamus - ED, stress, chronic, Kallman, craniopharyngioma, infection
Causes of amenorrhea with breast development and uterus
outflow obstruction anovulation high PRL hypothyroid PCOS hypothalamic
Causes of amenorrhea with no breast development/no uterus
XY karyotype
agonadism - vanishing testes
Enzyme deficiency
Causes of amenorrhea with breast development with NO uterus
AIS
MRKH (Mullerian agenesis)
