Amenorrhea

Question 1

Define primary amenorrhea

Answer 1

• No menses by 15 with normal growth/secondary sex characteristics
• No menses by 13 with absent puberty

Question 2

Define secondary amenorrhea

Answer 2

• No menses for at least 3 months after previously having regular menses
• No menses for at least 6 months after a history of irregular menses

Question 3

Primary amenorrhea ddx

Answer 3

Hypothalamus/Pituitary
- Cranial mass (craniopharyngioma)
- TBI
- Brain irradiation
- Inflammatory/infiltrative disease
- Kallman
- Isolated GnRH deficiency
- Functional hypothalamic (weight loss, anorexia, excessive exercise, stress, critical illness)

• Pituitary infarct
• Empty sella syndrome
• Hypothyroidism
• Hyperprolactinemia
• Acromegaly
• Cushing disease

Ovary
- Gonadal dysgenesis
- POI (Fragile X, Turner, iatrogenic chemo/radiation)
- PCOS
- CAH

Outflow tract
- Imperforate hymen
- Transverse septum
- Mullerian anomaly
- AIS

Question 4

Primary amenorrhea - history

Answer 4

1. H&P: signs of puberty?
   Other: recent stress/weight/exercise changes, hair/skin changes, cyclical pain (outflow tract obstruction), family history (constitutional delay), anosmia (Kallman), cognitive/learning impairment?
2. Uterus present?

Question 5

Primary amenorrhea - labs

Answer 5

1. hCG - exclude pregnancy!
2. FSH, LH, E2 - hyper/hypo vs hypo/hypo
3. TSH, PRL
4. Karyotype - AIS?
5. Testosterone, DHEA-S, 17-OHP: PCOS, CAH

Question 6

Primary amenorrhea - imaging

Answer 6

1. Pelvic US
2. Pituitary MRI

Question 7

Primary amenorrhea ddx - absent uterus?

Answer 7

1. Get a karyotype:
   - If XX: Mullerian agenesis
   - If XY: AIS vs 5 alpha reductase deficiency

Question 8

Primary amenorrhea ddx - present uterus?

Answer 8

1. Get an FSH:
   If high = ovarian failure
2. Get a karyotype:
   - If XX: POI (why? fragile X, chemo/radiation)
   - If XO - Turner inc mosaics
   - If XY: gonadal dysgenesis
3. Get an FSH:
   If normal:
   - Outflow tract disorder
   - PCOS, CAH
   If low:
   - Constitutional puberty delay
   - Functional hypothalamic
   - Congenital GnRH deficiency
   - Brain mass/empty sella

Question 9

Primary amenorrhea ddx - most common by incidence?

Answer 9

1. Gonadal dysgenesis (43%)
2. Mullerian agenesis (15%)
3. Constitutional delay (more common in boys) (14%)

Question 10

Secondary amenorrhea ddx - most common by incidence?

Answer 10

1. Hypothalamic/pituitary (~50%)
2. Ovarian (40%)
3. Uterine (7%)
   *Pregnancy
   *Medications

Question 11

Secondary amenorrhea ddx

Answer 11

1. Hypothalamic/Pituitary
   - Acquired hypothalamic amenorrhea
   - Hyperprolactinemia
   - Hypothyroidism
   - Pituitary apoplexy (Sheehan)
   - Injury
2. Ovarian
   - POI
   - PCOS
3. Uterine
   - Asherman

Don’t forget pregnancy and medications!

Question 12

Secondary amenorrhea - history

Answer 12

1. Menstrual history - menarche, AUB
2. Pregnancy/postpartum history
3. Exercise habits
4. Medication history
5. PMH: comorbid diseases

Question 13

Secondary amenorrhea - labs

Answer 13

1. HCG
2. FSH, LH, E2, P4
3. TSH, PRL
4. DHEAS, testosterone, 17-OHP

Question 14

Secondary amenorrhea - imaging

Answer 14

Pelvic US (possibly with saline)
Pituitary MRI

Question 15

Secondary amenorrhea - algorithm

Answer 15

1. Check hCG to exclude pregnancy
2. Check prolactin
   - If high: repeat fasting in absence of stimulating triggers (sex, exercise), if still high > MRI to evaluate for prolactinoma
3. Check TSH
   - If high: get free T4, if high > treat
4. Check FSH (and E2, LH):
   - If high: POI (why?)
   - If low: MRI for mass vs functional
   - If normal: PCOS vs uterine factor