Primary and Secondary Amenorrhoea

Question 1

What is primary amenorrhoea? What are the possible causes?

Answer 1

• Definition - absence of menarche by age 15
• Causes
  
  • Hypergonadotrophic hypogonadism (chromosomal - 45X, 46XX, 46XY)
  • Eugonadism (Mullerian agenesis, vaginal septum, imperforate hymen)
  • Low FSH (constitutional delay, GnRH deficiency)

Question 2

Describe how amenorrhoea can occur with reference to the physiology of the normal menstrual cycle

Answer 2

• GnRH pulses from the hypothalamus stimulates LH and FSH secretion from the anterior pituitary
  
  • FSH stimulates follicle growth
  • LH stimulates production of ovarian hormones (oestrogen, progesterone, androgens, inhibin)
  • Inhibin prevents FSH synthesis and secretion, the others are inhibitory at the hypothalamus and pituitary
  • A mature follicle causes an oestrogen surge with the flow-on effect of an LH surge and endometrial proliferation
  • After ovulation, LH causes formation of the corpus luteum (produces progesterone +++ and oestrogen) - converting the endometrium to a secretory form
  • Non-occurrence of pregnancy causes endometrial sloughing (progesterone withdrawal bleed)
  • Pregnancy causes rescue of the corpus luteum by bHCG
• Amenorrhoea can result from disruption at any level here, or a non-responsive endometrium, absence or non-patency of the cervix, vagina and introitus

Question 3

What is secondary amenorrhoea? What are the possible causes?

Answer 3

• Definition - absence of periods for 3 months (regular periods) or 6 months (irregular periods)
• Causes
  
  • Pregnancy
  • ​Low/normal FSH (eating disorders/stress/exercise, PCOS, hypothyroidism, Cushing)
  • High FSH (gonadal failure - 46XX)
  • Hyperprolactinaemia
  • Asherman syndrome
  • Hyperandrogenism (CAH, tumour)

Question 4

Describe the hypergonadotrophic hypogonadal causes of amenorrhoea

Answer 4

• Hypergonadotrophic hypogonadism (high LH/FSH, low oestrogen - ovarian defect)
  
  • Generally inherited or autoimmune

Question 5

Describe the eugonadotrophic causes of amenorrhoea

Answer 5

• Eugonadotrophic amenorrhoea (normal range LH/FSH/oestrogen, lacks cycles - variable defect)
  
  • Inherited - PCOS, adult onset CAH, ovarian tumours
  • Acquired - hyperprolactinaemia, thyroid, Cushing, acromegaly

Question 6

Describe the hypogonadotrophic hypogonadal causes of amenorrhoea

Answer 6

• Hypogonadotrophic hypogonadism (low LH/FSH, low oestrogen - hypothalamus/pituitary defect)
  
  • Hypothalamic
    
    • Inherited - Kallmann, idiopathic
    • Acquired - eating disorders, stress, exercise (B-endorphins), tumour, radiation, infection, infiltration
  • Anterior pituitary
    
    • Inherited - hypoplasia
    • Acquired - prolactinoma, mass (adenoma, mets, radiation, trauma)
  • Chronic disease - ESRD, liver disease, AIDS, malignancy

Question 7

Outline some history and examination considerations you might have in a woman with amenorrhoea

Answer 7

• History approach
  
  • Menstrual (menarche, length, cyclicity, amount)
  • Medical/surgical/radiological/infection intervention around time of change
  • New-onset headaches/visual changes (pituitary)
  • Breast discharge (hyperprolactinaemia)
  • Thyroid symptoms (thyroid)
  • Hot flashes/vaginal dryness (premature ovarian failure)
  • Hirsuitism/acne (PCOS, adult-CAH)
• Examination approach
  
  • Enamel erosion/low BMI (eating disorder)
  • Short/webbed-neck (Turner’s)
  • Visual field defects (pituitary)
  • Acanthosis nigricans, hirsuitism, acne (PCOS, hyperandrogenism, hyperinsulinism)
  • Supraclavicular fat, striae (Cushing’s)
  • Escutcheon (hyperandrogenism/lack of adrenarche)
  • Pink vaginal mucosa and cervical mucus (evidence of oestrogen production)

Question 8

What would be your initial investigations in a woman with primary amenorrhoea?

Answer 8

• FSH and LH with pelvic US
  
  • Consideration of karyotyping based on results

Question 9

What would be your initial investigations in a woman with secondary amenorrhoea?

Answer 9

• TSH, prolactin, bHCG, FSH, LH, TVUS