Endocrine regulation of female fertility

Question 1

What is primary amenorrhoea?

Answer 1

Never had a period

Question 2

What is secondary amenorrhoea?

Answer 2

No periods for 6 months

Question 3

What are the causes of primary amenorrhoea?

Answer 3

•Genitourinary abnormalities
 - absence of uterus, cervix or vagina
 - Rokitansky syndrome 
 - Androgen insensitivity syndrome 
•Chromosomal abnormalities 
 - turners syndrome 
•Secondary hypogonadism (pituitary/hypothalamic cause) 
 - Kallmann syndrome
 - pituitary disease 
 - hypothalamic amenorrhoea (low BMI, stress, illness)

Question 4

What are the causes of secondary amenorrhoea relating to the axis?

Answer 4

• Hypothalamic: weight loss, stress, drugs e.g. opiates
• Pituitary: prolactinoma, pituitary tumour
• Ovarian: PCOS, premature ovarian failure
• Uterine: ashermans syndrome

Question 5

Explain the Hormonal axis

Answer 5

• Hypothalamus releases GNRH
• GNRH stimulates the pituitary to release LH and FSH
• LH and FSH act on the ovary and the ovary releases oestrogen and progesterone which acts on the uterus

Question 6

What are the physiological causes of amenorrhoea?

Answer 6

• Pregnancy

* Lactation

Question 7

What are the iatrogenic causes of amenorrhoea?

Answer 7

• OCP

* Other hormonal contraceptives

Question 8

What are the other causes of amenorrhoea?

Answer 8

•Thyroid dysfunction 
•Hyperandrogenism 
 - Cushing's 
 - Congenital adrenal hyperplasia 
 - Adrenal or ovarian tumour

Question 9

What is hirsutism?

Answer 9

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

Question 10

What is the leading cause of hirsutism?

Answer 10

PCOS

Question 11

What is the presentation of PCOS?

Answer 11

• Anovulation- amenorrhoea, oligomenorrhoea (infrequent), irregular cycles
• Symptoms of hyperandrogegism: hirsutism, acne, alopecia
• Typically presents during polycystic ovaries

Question 12

What are the typical endocrine features of PCOS?

Answer 12

• Raised testosterone

* Raised LH

Question 13

What metabolic abnormalities are PCOS associated with?

Answer 13

• Hypertension

* hyperglycaemia due to insulin sensitivity -> T2DM

Question 14

Explain the gonadotrophin component of the pathophysiology of PCOS

Answer 14

• Increased LH concentration, there are increased LH receptors in PCOS ovaries
• LH supports the ovarian theca cells which are responsible for ovarian androgen production
• Decreased FSH- constant low level resulting in continuous stimulation of follicles without ovulation
• Low FSH means there is a decreased conversion of androgens to oestrogen in granulosa cells

Question 15

Explain the androgen component of the pathology of PCOS

Answer 15

• Increased androgen production from theca cells under the influence of LH
• May also be due to disordered enzyme action
• Decreased Sex hormone binding globulin (SHBG) which is produced in the liver and binds to testosterone. Only free testosterone is biologically active -> hyperandrogegism and hyperinsulinaemia

Question 16

Explain the insulin component of the pathophysiology of PCOS

Answer 16

• Increased insulin in response to glucose load
• Increased insulin resistance
• Insulin stimulates the theca cells of the ovaries, reduces hepatic production of SHBG resulting in increased circulating androgens

Question 17

What are the investigations for PCOS?

Answer 17

•Confirm the profile of PCOS:
 - testosterone 
 - androstenedione 
 - DHEAS 
 - SHBG 
 - FSH/LH 
•Assess for other features: type 2 diabetes and abnormal lipids 
•Exclude other pathologies e.g. cushings

Question 18

Explain reversal of PCOS by weight loss

Answer 18

• Losing weight decreases amount of insulin
• This increases the amount of SHBG produced and decreases the androgens produced
• This results in lowered free testosterone and therefore increased ovulation and decreased hirsutism

Question 19

Explain the use of metformin in PCOS

Answer 19

• Improves insulin sensitivity
• Leads to decreased LH and increased SHBG
• not useful for treatment of infertility
• Not very effective for treatment of hirsutism
• useful for those at risk of developing type 2 DM and allowing for more frequent cycles

Question 20

What is the mechanism of the oral contraceptive?

Answer 20

Ovarian androgen suppression

Question 21

What is the mechanism of corticosteroids?

Answer 21

Adrenal androgen suppression

Question 22

What is the mechanism of action of spironolactone?

Answer 22

Androgen receptor antagonist

Question 23

What is the mechanism of action of finasteride?

Answer 23

5 alpha reductase inhibition

Question 24

What is the effect of calorie restriction on insulin and fertility in obese women with PCOS?

Answer 24

improves ovulation and fertility