Amenorrhea

Question 1

Primary amenorrhea definition

Answer 1

14 years with no 2ndary sexual characteristics
OR
16 y with 2ndary sexual characteristics

Question 2

Secondary amenorrhea definition

Answer 2

previous history of menstruation AND no menses for 3 cycles/6 months

Question 3

Endocrinological Hx of amenorrhea

Answer 3

CNS mass symptoms
thyroid
prolactin
androgens
mass symptoms in viscera
adrenal symptoms
outlet
uterus/cervix
ovary/pituitary
hypothalamus (Kallman's - anosmia)

Question 4

Amenorrhea physical examination

Answer 4

Record of growth, Tanner stages, height/weight %
BP
Head to toe - neuro, thyroid, abdominal, genital, skin

Question 5

Primary amenorrhea investigation

Answer 5

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

Question 6

Hypergonadotropic hypogonadism

Answer 6

Ovaries are “failing”
high FSH, low estrogen
look for chromosomal abnormalities

Question 7

Hypogonadotropic hypogonadism

Answer 7

low FSH, low estrogen

CNS is “failing”

Question 8

Eugonadotropic eugonadism

Answer 8

gonads are working

Question 9

hypergonadotropic hypogonadism distribution

Answer 9

46% of amenorrhea
abnormal karyotype - 26%
normal karyotype - 17%

Question 10

Hypogonadotropic hypogonadism distribution

Answer 10

31%
reversible - 18
irreversible - 13

Question 11

Eugonadic distribution

Answer 11

26% of amenorrhea

Question 12

Hypogonadotropic hypogonadism CNS etiology

Answer 12

adenoma, prolactinoma, craniopharyngioma, other CNS lesions
Sheehan’s: acquired insult - reduced perfusion to pituitary
Kallman’s
Idiopathic
FSH beta mutation - defect in FSH receptor

Question 13

Kallman’s syndrome

Answer 13

isolated GnRH deficiency caused by disrupted GnRH neuron migration
anosmia +/- midline facial defects
possible KAL1 gene mutation
never go into puberty on their own

Question 14

Non-CNS etiology of amenorrhea

Answer 14

anorexia
strenuous exercise
stress
primary hypothyroidism
hyperprolactinemia
physiological delay

Question 15

Eugonadotropic eugonadic amenorrhea etiology

Answer 15

PCOS
Hyperprolactinemia - low/normal gonadotropin levels
Structural

Question 16

Hyperprolactinemia etiology

Answer 16

prolactin-inducing medications (antipsychotics, antiepileptics)
hypothyroidism
pituitary tumour
prolactinoma

Question 17

Congenital structural causes of amenorrhea

Answer 17

imperforated hymen
vaginal septum - transverse/longitudinal
cervical agenesis
Mullerian agenesis: MRKH

Question 18

Acquired structural causes of amenorrhea

Answer 18

Asherman’s

Question 19

Mullerian agenesis

Answer 19

normal breasts, normal pubic hair, normal ovaries, no uterus, no cervix, no upper vagina
10-40% have renal abnormality
10-15% have skeletal abnormality

Question 20

Mullerian agenesis tx

Answer 20

psych support/sexual activity, fertility
first line: vaginal dilators
second line: surgical neovagina

Question 21

Special tests for structural causes of amenorrhea

Answer 21

physical exam
TSH, PRL, androgens
progesterone challenge test
ultrasound

Question 22

Progesterone challenge test

Answer 22

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

Question 23

Hypergonadotropic hypogonadism etiology

Answer 23

Primary ovarian insufficiency (POI)
normal karyotype
abnormal karyotype

Question 24

Hypergonadotropic hypogonadism workup

Answer 24

Karyotype
Autoimmune: thyroid, pancreas, adrenals, ovary - look for antibodies, HbA1cC, am cortisol, calcium/phosphate for parathyroid

Question 25

Hypergonadotropic hypogonadism with N karyotype etiology

Answer 25

``` previous ovarian surgery chemotherapy, radiotherapy gonadal dysgenesis autoimmune - Addison's, thyroid, T1DM, myasthenia gravis, SLE receptor mutations - rare idiopathic fragile X premutation ```

Question 26

Fragile X premutations

Answer 26

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

Question 27

Hypergonadotropic hypogonadism with abN karyotype - etiology

Answer 27

Turner - 45XO, mosaics | 46XY - AIS, Swyer syndrome, non-functioning SRY mutation

Question 28

Turner syndrome characteristics

Answer 28

``` 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

Question 29

Turner syndrome treatment

Answer 29

pubertal induction hormone replacement fertility, contraception

Question 30

Turner syndrome investigation/monitoring

Answer 30

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

Question 31

Androgen Insensitivity Syndrome

Answer 31

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

Question 32

Androgen synthesis disorder

Answer 32

5-alpha reductase deficiency (can't convert T --> DHT) autosomal recessive internal male, external female virilize at puberty

Question 33

Hypogonadotropic hypogonadism tx

Answer 33

get back to weight at which you last had menstrual cycle reduce stress for pregnancy - ovulation induction with gonadotropins ($$$$$$)

Question 34

Eugonadotropic eugonadism tx

Answer 34

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

Question 35

Hypergonadotropic hypogonadism treatment

Answer 35

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

Question 36

Causes of amenorrhea with NO breast development with uterus

Answer 36

``` POI Gonadal dysgenesis (Turner, Swyer) Autoimmune oophoritis Fragile X premtutation Iatrogenic - RT, chemo galactossemia Hypothalamus - ED, stress, chronic, Kallman, craniopharyngioma, infection ```

Question 37

Causes of amenorrhea with breast development and uterus

Answer 37

``` outflow obstruction anovulation high PRL hypothyroid PCOS hypothalamic ```

Question 38

Causes of amenorrhea with no breast development/no uterus

Answer 38

XY karyotype agonadism - vanishing testes Enzyme deficiency

Question 39

Causes of amenorrhea with breast development with NO uterus

Answer 39

AIS | MRKH (Mullerian agenesis)