PCOS

Question 1

Definition of PCOS

Answer 1

A common disorder often complicated by chronic anovulatory infertility and hyperandrogenism with the clinical manifestations of oligomenorrhoea, hirsutism and acne. Many women with PCOS are obese and have a higher prevalence of impaired glucose tolerance, T2DM and sleep apnoea than the general population.

Question 2

What is the prevalence of PCOS

Answer 2

One of the most common endocrine disorders in women of reproductive age, however due to differences in diagnostic criteria, prevalence ranges from 2.2-22% (prevalence higher according to the Rotterdam criteria)

Question 3

How can PCOS be diagnosed

Answer 3

According to the Rotterdam criteria (with two out of three of the following criteria being met):
* Polycystic ovaries (12 or more follicles or increased ovarian volume >10cm3)
* Oligo-ovulation or anovulation
* Clinical and/or biochemical signs of hyperandrogenism
* Hirsutism characterised by excess fascial and body hair and midline hair growth.
* Free androgen index (free and total androgen levels >5 nmol/l can also be used)
* Signs of virilisation (deep voice, reduced breast size, increased muscle bulk)

Question 4

What needs to be ruled out before diagnosis

Answer 4

alternative causes of irregular cycles (thyroid dysfunction, acromegaly, hyperprolactinaemia) and hyperandrogenism (CAH, androgen secreting tumours)

Question 5

Most common age of presentation of PCOS

Answer 5

15-35 years old

Question 6

What is the pathophysiology of PCOS

Answer 6

• Cause is incompletely understood, may be due to early androgen exposure
• In PCOS the pituitary secretes too much LH, with increased pulsatility (at least double the amount of FSH)
• Increased levels of LH causes theca cells to produce excess androstenedione (too much for granulosa cells to convert)
• Due to the lack of LH surge (high pulsatility), there is anovulation, and the dominant follicle forms a cyst or degenerates.
• PCOS also involves insulin resistance which leads to compensatory insulin hypersecretion
• Insulin promotes the release of androgens from the ovaries and adrenal glands. Therefore, higher levels of insulin result in higher levels of androgens (such as testosterone).
• Insulin also suppresses sex hormone-binding globulin (SHBG) production by the liver. SHBG normally binds to androgens and suppresses their function.
• Reduced SHBG further promotes hyperandrogenism in women with PCOS.
• The high insulin levels contribute to halting the development of the follicles in the ovaries, leading to anovulation and multiple partially developed follicles (seen as polycystic ovaries on the scan).
• Diet, exercise and weight loss help reduce insulin resistance.

Question 7

What is the common presentation of PCOS

Answer 7

• Oligomenorrhoea/ amenorrhoea due to chronic anovulation in 70%
• Infertility
• Obesity (presents in 70% of patients)
• Clinical hyperandrogenism: hirsutism, acne, male pattern baldness
• Acanthosis nigricans (dark, velvety patches in creases of neck, groin and underarms (due to insulin resistance)

Question 8

What are some complications of PCOS and how can we screen for them

Answer 8

2x increased risk of developing gestational diabetes compared to the general populations- women with PCOS should be offered screening with OGTT at 24-28 weeks gestation

Insulin resistance (present in around 65-80% of women with PCOS, independent of obesity but exacerbated by weight gain)
* Women presenting with PCOS who are overweight (BMI ≥ 25 kg/m2 ) and women with PCOS who are not overweight (BMI < 25 kg/m2 ), but who have additional risk factors such as advanced age (> 40 years), personal history of GDM or family history of T2DM, should have a 2-hour post 75 g OGTT
* In women with impaired fasting glucose (fasting plasma glucose level from 6.1 to 6.9 mmol/l) or impaired glucose tolerance (plasma glucose of 7.8 or more but less than 11.1 mmol/l after a 2-hour OGTT), OGTT should be performed annually

Sleep apnoea- prevalence is further increased with obesity
* Women or partners of women with PCOS should be asked about snoring and daytime fatigue (CPAP therapy improves insulin therapy in affected women)

CVD- lifetime risk is higher in women with PCOS and is mostly preventable
* Should be assessed for CVD by assessing individual CVD risk factors (obesity, lack of physical activity, cigarette smoking, family history of type II diabetes, dyslipidaemia, hypertension, impaired glucose tolerance, type II diabetes)
* BP should be measured at the time of diagnosis and during oral contraceptive therapy

Mental health issues:
* Psychological issues should be considered in all women with PCOS. Depression and/or anxiety should be routinely screened for and, if present, assessed
* Screen for depression and anxiety

Predisposition to endometrial hyperplasia and cancer- good practice to recommend treatment with progestogens to induce a withdrawal bleed at least every 3 to 4 months
* TVUSS should be considered in the absence of withdrawal bleeds or abnormal uterine bleeding
* In PCOS, an endometrial thickness of less than 7 mm is unlikely to be hyperplasia. A thickened endometrium or an endometrial polyp should prompt consideration of endometrial biopsy and/or hysteroscopy.
* There does not appear to be an association with breast or ovarian cancer and no additional surveillance is required

Question 9

Investigations of PCOS

Answer 9

History and relevant screening (as above)

Bloods for diagnosis and exclusion of alternative pathology:
* Testosterone, SHBG, DHEAS, Free-androgen index, LH, FSH (raised LH:FSH ratio), Prolactin (may be normal or mildly elevated), TSH

OGTT

Imaging- PELVIC USS:
* Polycystic ovaries present in 75% of women with PCOS but also seen in up to 25% of normal women
* TVUSS gives higher resolution images than transabdominal
* Will see 12 or more follicles or increased ovarian volume >10cm3
* Can also assess endometrial thickness (should be done after first withdrawal bleed in women starting progestogens)
* Follicles may be arranged around the periphery of the ovary, giving a string of pearls appearance

Question 10

What lifestyle advice can be given to women with PCOS

Answer 10

Initial management involves diet, exercise and weight loss (lifestyle change) , which should precede and/ or accompany any pharmacological treatment
* In the general population, motivational interviewing and established behaviour techniques appear more effective than traditional advice giving for changes in weight, diet and/or exercise
* Women should have regular monitoring for weight change and excess weight (minimum 6-12 monthly)- should also have BP monitoring at this time.

Question 11

How can metabolic dysfunction be treated in PCOS

Answer 11

• Orlistat may be used to help weight loss in women with a BMI above 30. Orlistat is a lipase inhibitor that stops the absorption of fat in the intestines.
• There is no current conclusive evidence indicating the use of metformin in women with PCOS in the absence of insulin resistance
• Statins should be initiated in women at risk of CVD (QRISK>10%)
• Bariatric surgery may be an option for morbidly obese women with PCOS (BMI of 40 kg/m2 or more or 35 kg/m2 or more with a high-risk obesity-related condition) if standard weight loss strategies have failed

Question 12

Treatment of oligomenorrhoea/amenorrhoea in PCOS

Answer 12

COCP or Cyclical oral progesterone (such as medroxyprogesterone) – if amenorrhoea/dysfunctional uterine bleeding. This increases sex hormone-binding globulin which helps relieve androgenic symptoms. Regulates the withdrawal bleed (should take place at least every 3-4months)

Question 13

How can the risk of endometrial cancer be reduced in women with PCOS

Answer 13

To reduce the risk of endometrial cancer (women with PCOS are predisposed due to obesity, T2DM, IR and amenorrheoa)
* Mirena coil for continuous endometrial protection
* Inducing a withdrawal bleed every 3-4 months with cyclical progestogens or COCP
* oVUSS should be conducted after this first withdrawal bleed

Question 14

Treatment of anovulation in PCOS

Answer 14

• Weight loss is the initial step for improving fertility- can restore regular ovulation
• Clomiphene citrate- 1st line treatment in women with a normal BMI (selective oestrogen receptor modulator)- used for up to 6 months, but increased risk of multiple pregnancy
• Ovarian electrocautery/ laparoscopic ovarian drilling surgery- should be considered for selected anovulatory patients, especially those with a normal BMI, as an alternative to ovulation induction
• IVF

Question 15

Treatment of hyperandrogenism in PCOS

Answer 15

• Co-cyprindiol (Dianette) is a COCP licenced for the treatment of hirsutism and acne. It has anti-androgenic effects and works as a contraceptive. However, it confers increased risk of VTE and therefore should not be used for longer than 3 months
• Topical eflornithine can be used to treat fascial hirsutism. It usually takes 6-8 weeks to see a significant improvement. Hirsutism will return within 2 months of stopping eflornithine
• Other options include: electrolysis, laser hair removal, spironolactone (mineralocorticoid with anti-androgenic effects), finasteride, flutamide, cyproterone acetate

Question 16

Pathophysiology of endometrial cancer in PCOS

Answer 16

Under normal circumstances, the corpus luteum releases progesterone after ovulation. Women with PCOS do not ovulate (or ovulate infrequently), and therefore do not produce sufficient progesterone. Consequently, the endometrial lining continues to proliferate under the influence of oestrogen, without regular shedding during menstruation. This is similar to giving unopposed oestrogen in women on hormone replacement therapy. It results in endometrial hyperplasia and a significant risk of endometrial cancer