PCOS

Question 1

Describe the hormonal pathophysiology behind polycystic ovarian syndrome?

Answer 1

Chronically high LH and chronically suppressed FSH.

LH causes stimulation and hyperplasia of the theca and stroma cells.
The suppressed FSH levels cause follicles to partially mature but not to the point where ovulation is possible.

Hyperplasia of the theca and stroma cells causes there to be an increased production of androgens. (hyperandrogegism)

There is peripheral conversion of androgens into oestrogens in peripheral adipose tissue, resulting higher circulating volumes of oestrogens.

High level of oestrogens inhibit FSH secretion.

Women with PCOS also have increased pulses of GNRH which can further perpetuate the LH:FSH ratio.

Question 2

What are the clinical features of PCOS?

Answer 2

Oligo/amenorrhoea (80%)
Sub fertility (75%)
Hirsutism (70%)  (hyperandrogenism)
Obesity (50%)
Hyperinsulinaemia causing acanothis nigricans
Acne (hyperandrogenism)
Alopecia (hyperandrogenism)

HAIR-AN syndrome:
HyperAndrogenism
Insulin Resistance
Acanothis Nigricans

Question 3

What are the Rotterdam diagnostic criteria for PCOS?

Answer 3

2 out of the following 3 + exclusion of other disorders:

Irregular or absent ovulation (greater than 42 days)

Clinical or biochemical signs of hyperandrogenism:

• acne
• hirsutism
• alopecia

Polycystic ovaries on pelvic USS/ 12 or more astral follicles on one ovary/ ovarian volume greater than 10ml

Question 4

What are the risk factors for developing PCOS?

Answer 4

Genetic (FH)
Insulin resistance
Hyperandogenism
Obesity (particularly central)

Question 5

How should you investigate a women with symptoms of PCOS?

Answer 5

Any amenorrhoea always do a pregnancy test.

Basal (day 2-5)

• LH and FSH (LH likely raised and FSH normal/low in PCOS)
• TFT’s
• Prolactin (exclude prolactinoma)
• Testosterone (may be raised in PCOS will be very raised in androgen secreting tumour or congenital adrenal hyperplasia)

Progesterone:
Low levels

If hyperandrogenism:
-DHEAS (specific androgen produced from the adrenal glands)

TVUSS: To visualise ovaries and assess size and whether cystic or not.

Question 6

What would a raised FSH result in the context of amenorrhoea be suggestive of?

Answer 6

Ovarian failure

Question 7

What would a low FSH result in the context of amenorrhoea be suggestive of?

Answer 7

Hypothalamic disease

Question 8

How is PCOS managed?

Think of the separate issues associated aka obesity, irregular bleeding etc.

Answer 8

Lifestyle measures:
-Weight loss and exercise (reduce fat = reduced androgen conversion into oestrogen)

Irregular periods:
-COCP/Mirena

Hyperandrogenism:
-Anti androgens (face creams, finasteride, spironolactone)

Subfertility:

• Clomifene (oestrogen receptor modulator) used to help ovulation
• Metformin (2nd line after clomifene)
• Ovarian drilling (thought to help restart ovaries aetiology of why not known)
• Gonadotrophins
• IVF

Insulin resistance:
-Metformin

Question 9

What are then long term complications associated with PCOS?

Answer 9

Obesity and insulin resistance are risk factors for diabetes and IHD.

Long periods of amenorrhoea with resultant unopposed oestrogen (progesterone produced by corpus luteum)
increases risk of endometrial hyperplasia and Ca.

Question 10

How long can clomifene be used for and when should it be taken?

Answer 10

Can be used for 6 months (not used more than this as there is a slight increased risk of ovarian Ca)

Should be taken on days 2-6 of the cycle to stimulate follicular maturation.

This is a type of ovarian stimulation therefore there is an increased risk of multiple pregnancies and Ovarian Hyperstimulation Syndrome (note this is rare)