Polycystic Ovarian Syndrome

Polycystic ovarian syndrome (PCOS) is a common condition causing metabolic and reproductive problems in women. There are characteristic features of multiple ovarian cysts, infertility, oligomenorrhea, hyperandrogenism and insulin resistance.

There are some essential definitions to be aware of with polycystic ovarian syndrome:

  • Anovulation refers to the absence of ovulation
  • Oligoovulation refers to irregular, infrequent ovulation
  • Amenorrhoea refers to the absence of menstrual periods
  • Oligomenorrhoea refers to irregular, infrequent menstrual periods
  • Androgens are male sex hormones, such as testosterone
  • Hyperandrogenism refers to the effects of high levels of androgens
  • Hirsutism refers to the growth of thick dark hair, often in a male pattern, for example, male pattern facial hair
  • Insulin resistance refers to a lack of response to the hormone insulin, resulting in high blood sugar levels

 

Rotterdam Criteria

The Rotterdam criteria are used for making a diagnosis of polycystic ovarian syndrome. A diagnosis requires at least two of the three key features:

  • Oligoovulation or anovulation, presenting with irregular or absent menstrual periods
  • Hyperandrogenism, characterised by hirsutism and acne
  • Polycystic ovaries on ultrasound (or ovarian volume of more than 10cm3)

TOM TIP: If you are going to remember one thing about polycystic ovarian syndrome, remember the triad of anovulation, hyperandrogenism and polycystic ovaries on ultrasound. The Rotterdam criteria are commonly tested in MCQs and asked by examiners in OSCEs. It is important to remember that only having one of these three features does not meet the criteria for a diagnosis. As many as 20% of reproductive age women have multiple small cysts on their ovaries. Unless they also have anovulation or hyperandrogenism, they do not have polycystic ovarian syndrome.

 

Presentation

Women with polycystic ovarian syndrome present with some key features:

  • Oligomenorrhoea or amenorrhoea
  • Infertility
  • Obesity (in about 70% of patients with PCOS)
  • Hirsutism 
  • Acne
  • Hair loss in a male pattern

 

Other Features and Complications

In addition to the presenting features, women may also experience:

  • Insulin resistance and diabetes
  • Acanthosis nigricans
  • Cardiovascular disease
  • Hypercholesterolaemia
  • Endometrial hyperplasia and cancer 
  • Obstructive sleep apnoea
  • Depression and anxiety
  • Sexual problems

Acanthosis nigricans describes thickened, rough skin, typically found in the axilla and on the elbows. It has a velvety texture. It occurs with insulin resistance. 

 

Differential Diagnosis of Hirsutism

An important feature of polycystic ovarian syndrome is hirsutism. Hirsutism can also be caused by:

  • Medications, such as phenytoin, ciclosporin, corticosteroids, testosterone and anabolic steroids 
  • Ovarian or adrenal tumours that secrete androgens
  • Cushing’s syndrome
  • Congenital adrenal hyperplasia

 

Insulin Resistance

Insulin resistance is a crucial part of PCOS. When someone is resistant to insulin, their pancreas has to produce more insulin to get a response from the cells of the body. 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.

 

Investigations

The NICE clinical knowledge summaries recommend the following blood tests to diagnose PCOS and exclude other pathology that may have a similar presentation:

  • Testosterone
  • Sex hormone-binding globulin
  • Luteinizing hormone
  • Follicle-stimulating hormone
  • Prolactin (may be mildly elevated in PCOS)
  • Thyroid-stimulating hormone

 

Hormonal blood tests typically show:

  • Raised luteinising hormone
  • Raised LH to FSH ratio (high LH compared with FSH)
  • Raised testosterone
  • Raised insulin
  • Normal or raised oestrogen levels

TOM TIP: The key thing to remember for your exams is the raised LH, and the raised LH:FSH ratio.

 

Pelvic ultrasound is required when suspecting PCOS. A transvaginal ultrasound is the gold standard for visualising the ovaries. The follicles may be arranged around the periphery of the ovary, giving a “string of pearls” appearance. The diagnostic criteria are either:

  • 12 or more developing follicles in one ovary
  • Ovarian volume of more than 10cm3

Pelvic ultrasound is not reliable in adolescents for the diagnosis of PCOS.

TOM TIP: It is worth remembering the “string of pearls” description for your exams. It may come up in MCQs. It is also worth remembering that an ovarian volume of more than 10cm3 can indicate polycystic ovarian syndrome, even without the presence of cysts.

 

The screening test of choice for diabetes in patients with PCOS is a 2-hour 75g oral glucose tolerance test (OGTT). An OGTT is performed in the morning prior to having breakfast. It involves taking a baseline fasting plasma glucose, giving a 75g glucose drink and then measuring plasma glucose 2 hours later. It tests the ability of the body to cope with a carbohydrate meal. The results are:

  • Impaired fasting glucose – fasting glucose of 6.1 – 6.9 mmol/l (before the glucose drink)
  • Impaired glucose tolerance – plasma glucose at 2 hours of 7.8 – 11.1 mmol/l
  • Diabetes – plasma glucose at 2 hours above 11.1 mmol/l

 

General Management

It is crucial to reduce the risks associated with obesity, type 2 diabetes, hypercholesterolaemia and cardiovascular disease. These risks can be reduced by:

  • Weight loss
  • Low glycaemic index, calorie-controlled diet
  • Exercise
  • Smoking cessation
  • Antihypertensive medications where required
  • Statins where indicated (QRISK >10%)

 

Patients should be assessed and managed for the associated features and complications, such as:

  • Endometrial hyperplasia and cancer
  • Infertility
  • Hirsutism
  • Acne
  • Obstructive sleep apnoea
  • Depression and anxiety

 

Weight loss is a significant part of the management of PCOS. Weight loss alone can result in ovulation and restore fertility and regular menstruation, improve insulin resistance, reduce hirsutism and reduce the risks of associated conditions. 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. 

 

Managing the Risk of Endometrial Cancer

Women with polycystic ovarian syndrome have several risk factors for endometrial cancer:

  • Obesity
  • Diabetes
  • Insulin resistance
  • Amenorrhoea

 

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. They continue to produce oestrogen and do not experience regular menstruation. 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. 

Women with extended gaps between periods (more than three months) or abnormal bleeding need to be investigated with a pelvic ultrasound to assess the endometrial thickness. Cyclical progestogens should be used to induce a period prior to the ultrasound scan. If the endometrial thickness is more than 10mm, they need to be referred for a biopsy to exclude endometrial hyperplasia or cancer.

Options for reducing the risk of endometrial hyperplasia and endometrial cancer are:

  • Mirena coil for continuous endometrial protection
  • Inducing a withdrawal bleed at least every 3 – 4 months with either:
    • Cyclical progestogens (e.g. medroxyprogesterone acetate 10mg once a day for 14 days)
    • Combined oral contraceptive pill

 

Managing Infertility

Weight loss is the initial step for improving fertility. Losing weight can restore regular ovulation. 

A specialist may initiate other options where weight loss fails. These include:

  • Clomifene
  • Laparoscopic ovarian drilling
  • In vitro fertilisation (IVF) 

 

Metformin and letrozole may also help restore ovulation under the guidance of a specialist; however, the evidence to support their use is not clear.

Ovarian drilling involves laparoscopic surgery. The surgeon punctures multiple holes in the ovaries using diathermy or laser therapy. This can improve the woman’s hormonal profile and result in regular ovulation and fertility.

Women that become pregnant require screening for gestational diabetes. Screening involves an oral glucose tolerance test, performed before pregnancy and at 24 – 28 weeks gestation. 

 

Managing Hirsutism

Weight loss may improve the symptoms of hirsutism. Women are likely to have already explored options for hair removal, such as waxing, shaving and plucking.

Co-cyprindiol (Dianette) is a combined oral contraceptive pill licensed for the treatment of hirsutism and acne. It has an anti-androgenic effect, works as a contraceptive and will also regulate periods. The downside is a significantly increased risk of venous thromboembolism. For this reason, co-cyprindiol is usually stopped after three months of use.

Topical eflornithine can be used to treat facial hirsutism. It usually takes 6 – 8 weeks to see a significant improvement. The hirsutism will return within two months of stopping eflornithine. 

Other options that may be considered by a specialist experienced in treating hirsutism include:

  • Electrolysis
  • Laser hair removal
  • Spironolactone (mineralocorticoid antagonist with anti-androgen effects)
  • Finasteride (5α-reductase inhibitor that decreases testosterone production)
  • Flutamide (non-steroidal anti-androgen)
  • Cyproterone acetate (anti-androgen and progestin)

 

Management of Acne

The combined oral contraceptive pill is first-line for acne in PCOS. Co-cyprindiol may be the best option as it has anti-androgen effects; however, there is a significantly increased risk of venous thromboembolism. 

Other standard treatments for acne include:

  • Topical adapalene (a retinoid)
  • Topical antibiotics (e.g. clindamycin 1% with benzoyl peroxide 5%)
  • Topical azelaic acid 20%
  • Oral tetracycline antibiotics (e.g. lymecycline)

 

Last updated June 2020