PCOS

Question 1

What is PCOS?

Answer 1

Polycystic ovary syndrome is a heterogeneous endocrine disorder that appears to emerge at puberty. The clinical features may include hyperandrogenism, ovulation disorders, and polycystic ovarian morphology on ultrasound. The features vary widely between individuals and over time.

Question 2

Features of PCOS (6)

Answer 2

Subfertility
Oligomenorrhea/amenorrhoea
Hirsutism
Acne
Obesity
Acanthosis nigricans

Question 3

Imaging for PCOS

Answer 3

Pelvic ultrasound - multiple cysts on ovaries

Question 4

General management of PCOS

Answer 4

Weight reduction if appropriate
Screen for diabetes and CVD risk (and OSA if symptoms)
Ask about mood/emotional wellbeing

Question 5

Management of hirsutism (3)

Answer 5

Healthy lifestyle, hair reduction/removal PLUS

COC pill e.g. a third gen one that has fewer androgenic effects or co-cyprindiol which has an anti-androgen action
OR
Topical eflornithine
OR
Spironolactone, flutamide and finasteride (under specialist supervision)

Question 6

Management of infertility

Answer 6

Healthy lifestyle
Refer to specialist

Supervised by specialist:
Metformin, clomifene or a combination 
Gonadotrophins
IVF 
Laparoscopic ovarian drilling

Question 7

What is the risk of clomifene for fertility?

Answer 7

Multiple pregnancies

Question 8

Cause of PCOS

Answer 8

Unknown - genetic and environmental factors involved

Question 9

Pathogenesis of PCOS

- insulin resistance

Answer 9

Insulin resistance and compensatory hyperinsulinaemia are key factors in the pathogenesis

• -> causes reduced production of sex hormone-binding globulin in liver and as SHBG binds testosterone, means there is more testosterone in the blood
• -> increased androgen production which stops follicular developement and causes anovulation
• -> weight gain, causing body to produce even more insulin

Question 10

Pathogenesis of PCOS - hormonal imbalance

Answer 10

1) Serum luteinizing hormone (LH) levels are elevated due to increased production from the anterior pituitary.

2) The theca cells of the ovary produce excess androgens due to hyperinsulinaemia or increased serum levels of LH compared to FSH.
In PCOS, theca cells in are more efficient at converting androgen precursors to testosterone than normal.

3) Women with PCOS may have increased serum oestrogen levels.
There is continued exposure to unopposed oestrogen, so endometrium may become hyperplastic. Also testosterone is converted to oestrogen in peripheral fat.

Question 11

Complications of PCOS

Answer 11

Metabolic syndrome
CVD risk higher
Infertility
Pregnancy complications
Endometrial cancer
OSA
Psychological disorders

Question 12

Diagnostic criteria in adults

Answer 12

Need two of three of the following (following exclusion of other causes)

• Infrequent or no ovulation
• Clinical and/or biochemical signs of hyperandrogenism (such as hirsutism, acne, or elevated levels of total or free testosterone).
• Polycystic ovaries on ultrasound scan, defined as the presence of 12 or more follicles (measuring 2–9 mm in diameter) in one or both ovaries and/or increased ovarian volume (greater than 10 cm3).

Question 13

What bloods to arrange?

Answer 13

• Total testosterone — normal to moderately elevated
• Sex hormone-binding globulin — normal to low (provides a surrogate measurement of hyperinsulinaemia)
• Free androgen index = (total testosterone/SHBG) x 100 (normal or elevated)
• LH and FSH (LH raised)
• Prolactin - mildly elevated
• TSH

Question 14

Other causes of hyperandrogenism? (3)

Answer 14

Late-onset congenital adrenal hyperplasia
Cushing’s syndrome,
Androgen-secreting tumour

Question 15

Differentials for PCOS - primary hypothyroidism bloods

Answer 15

Normal or mildly raised androgen levels, elevated TSH, subnormal thyroxine, may have raised prolactin

Question 16

Differentials for PCOS - premature ovarian failure bloods

Answer 16

Normal androgen levels
Elevated FSH
Normal or subnormal estradiol

Question 17

Differentials for PCOS - prolactinoma bloods

Answer 17

Normal or mildly raised androgen levels

Elevated prolactin

Question 18

Differentials for PCOS -non-classic congenital adrenal hyperplasia due to deficiency of 21-hydroxylase bloods

Answer 18

Raised androgen levels

Elevated basal 17-hydroxyprogesterone levels in the morning or on stimulation

Question 19

Differentials for PCOS - Cushing’s syndrome bloods

Answer 19

Raised androgen levels

Elevated 24-hour urinary free cortisol levels

Question 20

Differentials for PCOS - androgen-secreting tumour bloods

Answer 20

Extremely elevated plasma androgen levels

Question 21

Differentials for PCOS - acromegaly bloods

Answer 21

Normal or mildly raised androgen levels

Increased plasma insulin-like growth factor levels

Question 22

Differentials for PCOS - hypogonadotropic hypogonadism bloods

Answer 22

Decreased FSH and LH

Question 23

Other differentials?

Answer 23

Simple obesity, pregnancy, lactation, menopause, hypothalamic dysfunction e.g. weight loss/excessive exercise/chronic illness, drug-related causes, hyperandrogenic-insulin resistant-acanthosis nigrans syndrome

Question 24

How does clomifene work?

Answer 24

Non-steroidal anti-oestrogen that inhibits oestrogen negative feedback on the hypothalamus/pituitary, which in turn leads to an increase in FSH secretion that may allow follicular maturation and ovulation

Question 25

Managing acne

Answer 25

Healthy lifestyle
COC first-line
Topical retoinoids, topical antibiotics, and/or oral antibiotics

Question 26

Managing oligomenorrhoea or amenorrhoea

Answer 26

Prescribe a cyclical progestogen for 2 weeks to induce a withdrawal bleed then refer to transvaginal USS to assess endometrial thickness (may need to exclude cancer)

Options if normal endometrium:

• Cyclical progestogen
• Low dose COC
• IUS
• Refer if doesn’t want any of these options

Question 27

How to start metformin?

Answer 27

Do not initiate in primary care - refer to a specialist if being considered
e.g. if severe oligomenorrhoea/amenorrhoea, IGT or IFG, low SHBG