Polycystic Ovarian Syndrome

Question 1

Definition

Answer 1

A heterogenous genetic clinical syndrome characterosed by hyperandrogenism (both ovarian and adrenal), ovulatory dysfunction, and hyperinsulinaemia in which other causes of androgen excess have been excluded

Question 2

Symptoms

Answer 2

Irregular or absence of menses 
Hirsutism 
Acnw
Acanthosis Nigricans 
Weight Gain 
Alopecia

Question 3

Signs

Answer 3

Hyperandrogenism 
Hyperinsulinaemia 
Hypercholesterolemia 
Type 2 DM 
Impaired glucose tolerance 
High LH levels 
Polycystic Ovaries

Question 4

Diangosis (Rotterdam)

Answer 4

Exclusion of other disease

At least 2 out of 3 of the following:

• Oligo/ammenorrhoea
• hyperandrogenism (clinical or biochemical)
• Polycystic ovaries on US

Question 5

Pathophysiology

Answer 5

Gonadotrophins

1)Gonadotrophin releasing hormone (GnRH) is released from the hypothalamus in a pulsatile manner
2)This pulsatile manner is extremely important to prevent desensitisation of the pituitary to GnRH, which would occur if GnRH were released continuously.
3) In PCOS there is either a rapid release rate of GnRH, causing the hypersecretion of Luteinising Hormone (LH) and ultimately the LH:FSH (Follicle stimulating hormone) hormone imbalance seen in PCOS. Or
there is increased LH receptors which supports the ovarian theca cells to produce more ovarian androgen production
4) As there is decreased FSH
- low constant levels result in continuous stimulation of follicles without ovulation
- decreased conversion of androgens to oestrogen in granulosa cells

Androgen

1) In PCOS there could be a disordered enzyme action which prevents peripheral conversion of testosterone to oestrogen
2) As a result of hyperandrogenism there is decreased SHBH produced from the liver (binds testosterone and makes in inactive)

Insulin resistance

• Insulin resistance is exacerbated by increase in androgens. Insulin resistance then causes compensatory hyperinsuiinaemia which acts to increase androgen by two methods:
  a. lowers circulating levels of SHBG
  b. Acts on both insulin and IGF-1 receptors on the ovaries

This increases the pulse frequency of GnRH leading to an increase in LH:FSH ratio

Normally the levels of the ovarian steroids would negatively feedback to the hypothalamus, which in turn would reduce the pulsatile release of GnRH. But in PCOS the hypothalamus becomes increasingly insensitive to ovarian steroids and ultimately there is no negative feedback.

Question 6

Investigations

Answer 6

EXCLUDE other causes of oligomenorrhoea and hirsutism

Confirm profile of PCOS

• androgen levels (testosterone, andrestenedione, DHEAS, SHBG, FSH/LH
• assess for other features (type 2 DM, abnormal lipids)

transvaginal ultrasound to examine ovaries for cysts

Question 7

Treatment

Answer 7

1st line - lifestyle changes
-losing weight has significant advantages on improving features, and regular exercise

Pharmacological

• Metformin - reduces insulin resistance and hyperinsulinaemia by increasing the bodys response to insulin and therefore reducing circulating insulin ~ NOT USEFUL IN FERTILITY OR HIRSUITISM
• OCP (ovarian androgen suppresion) - regulates menstruation and promotes complete uteriene shedding which decreases the risk of endometrial cancer.
• Anti-androgens e.g spironolactone - inhibits evelctions of androgens by either blocking androgen production or androgens receptors

Question 8

Long term complications

Answer 8

• higher risk of diabetes
• 2-4 increase in pregnancy related complications including (GDM, preterm labour, pregnancy induced hypertension)
• Disylidiaemia
• Cardiovascular disease (early atherosclerosis)
• Endometrial hyperplasia/cancer