Polycystic Ovary Syndrome

Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder affecting 5-15% of women in the reproductive age. It is characterised by chronic anovulation, hyperandrogenism and polycystic ovaries.

Polycystic Ovary Syndrome (PCOS) is a complex condition that may require management by a multidisciplinary team. Despite the fact that no cure is available for this condition, good control of the symptoms can be achieved with lifestyle and dietary modifications. PCOS should be diagnosed early to promote long-term health and prevent metabolic and cardiovascular complications.

Menstrual irregularities

Approximately 60-70 percent of women with Polycystic Ovary Syndrome (PCOS) exhibit menstrual dysfunction related to anovulation. The most common abnormalities are infrequent periods (oligomenorrhoea) and absence of period (amenorrhoea). Frequent and prolonged periods (polymenorrhoea) are very uncommon (less than two percent). One quarter of patients have regular periods.

Skin problems

They are either markers of hyperandrogenism (excessive production of male hormones) or insulin resistance.

1. Hirsutism
   It is the growth of terminal hairs on the face or body in a male pattern. It is the most important feature of Polycystic Ovary Syndrome (PCOS), affecting 65-75 percent of women and varies with ethnicity.
   
2. Acne
   Acne persisting beyond adolescence and oily skin can be clinical signs of hyperandrogenism. Its prevalence in Polycystic Ovary Syndrome (PCOS) is 12-14 percent.
   
3. Acanthosis Nigricans
   It is a marker of insulin resistance occurring in 1 to 3 percent of women and manifests as dark and thickened, pigmented areas of skin commonly affecting the underarm, neck, perineum or skin surfaces of the elbow and knuckles.

Infertility

The difficulty in conceiving is mainly due to chronic anovulation. Polycystic Ovary Syndrome (PCOS) accounts for approximately 75 percent of anovulatory subfertility.

Obesity

Obesity is often associated with PCOS (30-70 percent), but many patients with PCOS are of normal weight.

Causes of Polycystic Ovary Syndrome

The exact causes remain unclear but more than one can be involved. Genetic and environmental contributors combined with obesity, ovarian dysfunction and hormonal changes contribute to Polycystic Ovary Syndrome (PCOS).

Long-term risk

• Weight gain/obesity
• Insulin resistance and type 2 diabetes (T2DM)
  Adolescents and adult women with PCOS are at increased risk for Impaired Glucose Tolerance (IGT) and T2DM. A diagnosis of Polycystic Ovary Syndrome (PCOS) confers a 5- to10-fold increased risk of developing T2DM. The use of an Oral Glucose Tolerance Test - OGTT (consisting of a fasting and a 2-hour glucose level using a 75 g oral glucose load) is recommended to screen for IGT and T2DM.
• Cardiovascular disease
  Women with PCOS should be screened for the following cardiovascular disease risk factors: family history of early cardiovascular disease, cigarette smoking, IGT/ T2DM, hypertension, dyslipidaemia, obstructive sleep apnoea, and obesity (especially increased abdominal fatty tissue).
• Endometrial cancer
  Women with Polycystic Ovary Syndrome (PCOS) have a threefold increased risk of developing an endometrial cancer (cancer of the inner lining of the uterus). There is currently no data supporting routine endometrial biopsy of asymptomatic women or ultrasound screening of the endometrium. However, women should be counselled to report unexpected bleeding and spotting.
• Depression and mood swings
  Women with Polycystic Ovary Syndrome (PCOS) should be screened for depression and anxiety by history and, if identified, appropriate referral and/or treatment provided.

The diagnosis criteria follows the 2003 Rotterdam diagnosis consensus workshop:

The diagnosis of Polycystic Ovary Syndrome (PCOS) is present if any two out of the following three criteria are met and other hormonal conditions are excluded:

• Oligo- or Anovulation usually diagnosed when menstrual cycles are longer than 35 days and/or the progesterone level in the late luteal phase is low
  
• Clinical and/or biochemical signs of hyperandrogenism diagnosed when the clinical markers of hyperandrogenism mentioned above are present and/or total or free testosterone level is elevated
  
• Polycystic ovaries visualised on the pelvic ultrasound, defined by the presence of 12 or more follicles 2-9 mm in diameter and/or an increased ovarian volume >10 ml (without cyst or dominant follicle in either ovary)

And exclusion of other causes such as pregnancy, thyroid diseases, hyperprolactinemia, congenital adrenal hyperplasia, hypothalamic amenorrhoea, premature ovarian insufficiency, androgen secreting tumour, Cushing syndrome and acromegaly.

Oligomenorrhoea/Amenorrhoea/ Prevention of endometrial cancer

To prevent endometrial cancer, a woman should have at least four to six periods in a year. This can be achieved through the following methods:

1. Lifestyle changes
   Management of lifestyle habits should be the first-line therapy for all women with Polycystic Ovary Syndrome (PCOS) and the target should be a weight loss (5-10 percent) in women with a body mass index (BMI) ≥ 25 kg/m2 and a prevention of weight gain in women with a BMI 18.5-24.9 kg/m2. The program should include both reduced dietary energy intake and regular exercise.
2. Oral contraceptive pill (OCP)
   It would preferably be a 30 μg Ethinyl Estradiol containing pill for its impact on insulin resistance. OCP is used when hyperandrogenism is associated and/or contraception is needed. 
3. Cyclic progestogens
   They should be used when contraception is not required and there are no signs of hyperandrogenism. Dydrogesterone or Medroxy Progesterone Acetate is usually used for 10-14 days every two to three months.
4. Metformin and Thiazolidinedione (glitazones) but they are not as efficient as initially shown.

Hirsutism

Choice of options depends on the patient’s preferences, impact on wellbeing, and access and affordability:

1. Self-administered and professional cosmetic therapy are first-line (laser recommended).
2. Eflornithine cream can be added and may induce a more rapid response.
3. Pharmacological therapy can be considered if cosmetic therapy is not adequate/affordable. The therapy chosen should be maintained for at least six months before changing dose or medication and a combination of therapies can be used.

The following options are available:

• OCP as a first-line in absence of contraindications.
• Anti-androgen (Spironolactone or Cyproterone acetate) in combination with an adequate contraception related to their teratogenic effect.

Infertility

1. Lifestyle intervention would be the first line of treatment to optimise preconception health and fertility and reduce pregnancy and longterm complications.
2. Patients should be advised for folates supplementation, smoking cessation before conception.
3. Infertility therapies may include:

• Clomiphene Citrate (CC) as the first-line. Standard practice is to titrate clomiphene citrate doses up to 150 mg/day. If ovulation is not achieved at this point, clomiphene citrate resistance is reached. If a pregnancy is not achieved after six ovulatory cycles with clomiphene citrate, this is termed a state of clomiphene citrate failure.

Studies with clomiphene citrate show ovulation rates of 60–85 percent and pregnancy rates of 30-50 percent after six ovulatory cycles.

• Metformin should be combined with CC to improve fertility outcomes in women who are CC resistant, or immediately if BMI ≥ 30 kg/m2.
  
• As a second-line, the three following options should be discussed with the patient:
• Ovulation induction with Letrozole (Aromatase inhibitor which has shown its efficacy in ovulation induction but in an off-label fashion) or gonadotropins (daily subcutaneous injection),
• Laparoscopic ovarian drilling (procedure whereby a few holes, generally four are created at the surface of the ovary by a monopolar needle. Ovulation is achieved in 70-80 percent of cases) or
• Bariatric surgery for PCOS obese patients with a BMI ≥ 35 kg/m2, who are anovulatory, and who remain infertile despite undertaking a structured lifestyle management program for a minimum of six months.
• In-vitro fertilisation will be considered as the last resort.

Cardio-metabolic risk

1. Lifestyle changes: A weight loss of more than 5 percent, in overweight patients, reduces diabetes risk by approximately 50-60 percent in high-risk groups.
2. Optimise cardiovascular risk factors (Cholesterol and Glycemia)
3. Consider Metformin (reduces the risk of diabetes by approximately 50 percent in adherent high-risk groups)
4. Bariatric surgery for Polycystic Ovary Syndrome (PCOS) obese patients with a BMI ≥ 35 kg/m2, who have at least one metabolic or cardiovascular complication and who maintain their weight despite undertaking a structured lifestyle management program for a minimum of six months.