PCOS

Question 1

What are the symptoms of PCOS?

Answer 1

1. oligomenorrhoea (defined as <9 per year)
2. infertility or subfertility
3. acne
4. hirsutism
5. alopecia
6. obesity/difficulty losing weight
7. psychological symptoms → mood swings, depression, anxiety, poor self-esteem
8. sleep apnoea

Question 2

What are the signs of PCOS?

Answer 2

1. presence of hirsutism → 60% of women with PCOS
2. male-pattern balding, alopecia
3. obesity
4. acanthosis nigricans → insulin resistance or gastric cancer
5. occasionally: clitoromegaly, increased muscle mass, deep voice (signs of more severe hyperandrogenism syndromes)

Question 3

Explain the pathogenesis of PCOS and its relationship with insulin resistance.

Answer 3

• excess androgens produced by the theca cells of the ovaries (due to either to hyperinsulinaemia or increased LH levels)
• insulin resistance (loss of sensitivity to insulin) resulting hyperinsulinaemia in many women with PCOS
• weight gain further increases insulin resistance
• increase in insulin results in:
  (i) increased androgen production
  (ii) reduced production of sex hormone-binding globulin in the liver (free testosterone may be raised as it usually binds to SHBG)
• raised LH levels due to increasd production from the anterior pituitaru
• raised oestrogen levels in some women, which may lead to a hyperplastic endometrium

Question 4

What is the Rotterdam criteria?

Answer 4

• criteria used for the diagnosis of PCOS
• need to fulfill at least 2 of 3 criteria to meet diagnosis of PCOS
• criteria:
  1. polycystic ovaries (either 12+ or more peripheral follicles or increased ovarian volume)
  2. oligo-ovulation or anolvulation
  3. clinical ± biochemical signs of hyperandrogenism

Question 5

What are the potential differential diagnoses of PCOS?

Answer 5

1. hypothyroidism
2. hyperprolactinaemia
3. cushing’s syndrome
4. acromegaly
5. side effects of medicatino (medication causing hirsutism, weight gain, or oligomenorrhoea)
6. late onset congenital adrenal hyperplasia (Ashkenazi Jews or family history)
7. androgen-secreting ovarian or adrenal tumours
8. ovarian hyperthecosis

Question 6

Describe the investigations carried out to diagnose PCOS.

Answer 6

1. Total testosterone: normal to slightly raised in PCOS
2. Free testosterone levels may be raised but if total testosterone is >5nmol/L, exclude androgen-secreting tumours and CAH
3. SHBG: normal or low in PCOS
4. LH: may be elevated, with the LH:FSH ratio increased (>2), with FSH normal
5. USS: characteristic ovaries (average volume 3x that of normal ovaries)
   - in adolescence s scan should be interpreted with caution as follicle counts are hgiher
6. Other blood tests might include:
   - TFTs
   - 17-hydroxyprogesterone
   - Prolactin
   - DHEA-S and free androgen index
   - 24h urinary cortisol
7. Fasting glucose and oral glucose tolerance tests are useful in assessing insulin resistance
8. Fasting lipid levels should be checked

Question 7

What is the pharmacological treatment for women who are not planning pregnancy?

Answer 7

1. Co-cyprindol:
   - license for hirsutism and acne, not specifically PCOS
   - used to induce regular endometrial bleeds
   - reduced risk of endometrial carcinoma
2. COCP:
   - used to control menstrual irregularity
3. Metformin:
   - increasingly used off-license for PCOS
   - less effective than COCP for menstrual irregularity, hirsutism and acne
4. Eflornithine:
   - may be used for hirsutism, if other cosmetic treatments are not appropriate
5. Orlistat:
   - can help with weight loss in obese women with PCOS
   - may improve insulin sensitivity

Question 8

What is the pharmacological treatment for women who are planning pregnancy?

Answer 8

1. Clomifene:
   - induces ovulation
   - should not be used for >6 months
   - associated with an 11% risk of multiple pregnancy
2. Metformin:
   - can be used instead or or together with clomifene to improve pregnancy rates
3. Laparoscopic ovarian drilling or gonadotropins:
   - 2nd line for those who are resistant to clomifene

Question 9

What are the complications of PCOS?

Answer 9

• infertility
• predisposition to endometrial hyperplasia and endometrial cancer
• high CV risk
• increased risk of T2DM
• higher risk of gestational diabetes (screena t 24-28 weeks gestation by OGTT)
• higher risks of preterm births and pre-eclampsia