Endocrine Regulation of Female Fertility

Question 1

Define primary amenorrhoea [1]

Answer 1

never had a period

Question 2

List the causes of primary amenorrhoea under the following headings:

1. genitourinary abnormalities [3]
2. chromosomal abnormalities [1]
3. secondary hypogonadism [3]

Answer 2

1. Genitourinary abnormalities
   
   • Congenital absence of uterus, cervix or vagina
     
     • Rokitansky syndrome
     • Androgen insensitivity syndrome
2. Chromosomal abnormalities
   
   • Turner’s syndrome
3. Secondary hypogonadism (pituitary/hypothalamic causes)
   
   • Kallmann syndrome
   • Pituitary disease
   • Hypothalamic amenorrhoea (characterised by low BMI, stress, illness)

Question 3

Define secondary amenorrhoea [1]

Answer 3

no periods for 6 months

Question 4

List the causes of secondary amenorrhoea under the following headings:

1. uterine [1]
2. ovarian [2]
3. pituitary [2]
4. hypothalamic [3]

Answer 4

1. Uterine
   
   • Ashermans syndrome
2. Ovarian
   
   • Polycystic ovarian syndrome (PCOS)
   • Premature ovarian failure
3. Pituitary
   
   • Prolactinoma
   • Pituitary tumour
4. Hypothalamic
   
   • Weight loss
   • Stress
   • Drugs (e.g. opiates)

Question 5

List the other causes of amenorrhoea [7]

Answer 5

1. Physiological
   
   • Pregnancy
   • Lactation
2. Iatrogenic
   
   • Oral contraceptive pill (or other hormonal contraceptives)
3. Thyroid dysfunction
4. Hyperandrogenism
   
   • Cushing’s syndrome
   • Congenital adrenal hyperplasia (CAH)
   • Adrenal or ovarian tumour

Question 6

Define hirsutism [1]

Answer 6

excess hair growth in a male pattern due to increased androgens and increased skin sensitivity to androgens

Question 7

What are the causes of hirsutism? [5]

Answer 7

1. Ovarian
   
   • Polycystic ovarian syndrome (PCOS) - 95% of cases
   • Androgen secreting tumour
2. Adrenal
   
   • Congenital adrenal hypertrophy
   • Androgen secreting tumour
3. Idiopathic

Question 8

What is the classic presentation of polycystic ovarian syndrome (PCOS) and what symptoms is it associated with? [8]

Answer 8

1. Classic presentation is with symptoms of anovulation
   
   • amenorrhoea,
   • oligomenorrhoea,
   • irregular cycles
2. Associated with symptoms of hyperandrogenism
   
   • hirsutism,
   • acne,
   • alopecia

Question 9

When does polycystic ovarian syndrome (PCOS) typically present (childhood/adolescence/adulthood?) [1]

Answer 9

typically presents during adolescence

Question 10

What are the typical endocrine features of polycystic ovarian syndrome and what other abnormalities is it associated with? [4]

Answer 10

1. Typical endocrine features:
   
   • raised testosterone
   • raised LH
2. Also associated with metabolic abnormalities and increased risk of type 2 diabetes

Question 11

The pathophysiology of polycystic ovarian syndrome involves gonadotrophins, androgens and insulin resistance. Describe the role gonadotrophins play in the pathophysiology [7]

Answer 11

1. Increased LH concentration
   
   • Increased LH receptors in PCOS ovaries
   • Support ovarian theca cells
   • Increased ovarian androgen production
2. Decreased FSH
   
   • Low constant levels result in continuous stimulation of follicles without ovulation
   • Decreased conversion of androgens to oestrogens in granulosa cells

Question 12

The pathophysiology of polycystic ovarian syndrome involves gonadotrophins, androgens and insulin resistance. Describe the role androgens play in the pathophysiology [7]

Answer 12

1. Increased androgen production from theca cells under the influence of LH
2. Disordered enzyme action:
   
   • Ovarian enzyme expression
   • Peripheral conversion
3. Decreased sex hormone-binding globulin (SHBG)
   
   • Produced in liver, binds to testosterone
   • Only free testosterone is biologically active
     
     • Hyperandrogenism
     • Hyperinsulinemia

Question 13

The pathophysiology of polycystic ovarian syndrome involves gonadotrophins, androgens and insulin resistance. Describe the role insulin resistance play in the pathophysiology [7]

Answer 13

1. Increased insulin in response to glucose load
2. Eventually there is increased insulin resistance
3. Cause vs. association?
   
   • Insulin stimulates theca cells of ovaries
   • Insulin reduces hepatic production of sex hormone-binding globulin (SHBG)
   • Increased circulating androgens

Question 14

What investigations are used to diagnose polycystic ovarian syndrome (PCOS)? [8]

Answer 14

1. Confirm profile of PCOS
   
   • Testosterone
   • Androstenedione
   • DHEAS
   • SHBG
   • FSH/LH
2. Assess for other features
   
   • Type 2 diabetes
   • Abnormal lipids
3. Exclude other pathologies

Question 15

What are the treatment options for hirsutism? [6]

Answer 15

1. Ovarian androgen suppression
   
   • COCP (Dianette ideal)
2. Adrenal androgen suppression
   
   • Corticosteroids
3. Androgen receptor antagonists
   
   • Spironolactone
   • Cyproterone acetate
4. 5-alpha reductase inhibition
   
   • Finasteride
5. Insulin sensitisers
   
   • Metformin
6. Topical inhibitors
   
   • Eflornithine