Definition

Polycystic Ovarian Syndrome (PCOS) is a common condition affecting between 5-10% of women of reproductive age and almost 400,000 women in Australia. It is an endocrine (hormonal) abnormality with widespread manifestations including metabolic, reproductive and psychological features and long-term complications.

The appearance of the ovaries in the majority of women with the disorder (large and studded with numerous follicles), gives the disorder its name.

Causes

PCOS is a condition of unknown cause. However, it is believed that the condition stems from a disruption in the monthly menstrual cycle. In the past, it was thought that PCOS was caused solely by the over-production of androgens (male hormones).

More recent studies indicate that the cause is multifactorial with genetic, lifestyle and environmental traits playing a role. Current theories suggest that elevated insulin levels and insulin resistance by the body increase the secretion of androgens and collectively disrupt the ovarian cycle. This in turn both leads to weight gain, missed ovulation. Added weight gain then further increases insulin levels and resistance whilst simultaneously stimulating further androgen production. This is likewise with missed ovulation and multiple follicle/ cystic formation of the ovaries. A vicious cycle develops, where each factor compounds stimulation of another factor.

It is important to note that in more than two-thirds of cases PCOS is associated with being overweight.

Symptoms

In Polycystic Ovarian Syndrom there is a wide spectrum of clinical features including:

Reproductive Feature

• Menstrual Problems- irregular or infrequent periods & episodic heavy bleeding
• Irregular or absent ovulation
• Difficulty falling pregnant
• Formation of multiple follicles in the ovaries

Metabolic Features

• Elevated insulin or insulin resistance
• Increased levels of cholesterol in the blood
• Elevated blood pressure

Cosmetic Features

• Increased central body fat
• Excess facial & body hair and acne
• Thinning of the scalp hair (male pattern balding)
• Uneven pigmentation
• Skin tags

Psychological Features

• Poor self-esteem
• Depression
• Anxiety

Differing symptoms may be present at any one time. Also, these symptoms are exacerbated by excess body weight.

In addition to these, women with PCOS have an increased risk of long-term complications including reduced fertility, impaired glucose tolerance and Type II Diabetes, high blood pressure, heart disease, fatty liver disease, sleep apnoea, and increased risk of endometrial cancer.

The combination of high blood pressure, elevated blood cholesterol and diabetes in women with PCOS is called the Metabolic Syndrome. These long-term complications can be prevented with early diagnosis and appropriate management.

Diagnosis

PCOS is usually highly suspected by a woman’s history and physical examination. Apart from a gynaecological examination being performed, a general physical examination is done to search for any signs of the Metabolic syndrome.

Tests used to confirm the diagnosis may include:

Ultrasound Scan

This visualises the ovaries, confirming the presence of numerous follicles and delineating the size and number. It will also measure the thickness of the lining of the uterus. It is important to remember that 25% of women with PCOS do not have the classical imaging features of the ovaries on Ultrasound.

Blood Tests

• Lipid profile -- checking for elevated cholesterol levels
• OGTT -- checking for glucose intolerance and Diabetes
• Hormonal Assays -- looking specifically at androgen levels, hormones that control the ovarian cycle (LH, FSH and progesterone), prolactin, and thyroid hormones. Thyroid hormones are tested as some women who have PCOS also have impaired thyroid function due to autoimmune thyroiditis. Impaired thyroid function can also lead to increased testosterone levels adding to and complicating the vicious cycle of impaired ovarian function and formation of more cycles.

The current agreed criteria (Rotherdam Consensus) for a positive diagnosis of PCOS includes ant two of the following features:

• Menstrual dysfunction - infrequent menstruation with anovulation
• Clinical or Laboratory evidence of Increased male hormones (for example increase body hair, acne, high blood levels of testosterone)
• Polycystic ovaries on ultrasound scan

Treatment of Polycystic Ovarian Syndrome

It is important that a broad approach is utilised in the management of PCOS to treat both the acute features of PCOS and to prevent long-term complications.

Treatment needs to be individualised and must take into account the presenting symptoms of the syndrom, fertility wishes, the presence of any long-term complications and the patient’s current psychological state.

Management of the majority of patients is directed at lifestyle changes with targeted medical therapy as required. However, as psychological well-being may suffer considerably, lasting lifestyle changes are improbable without first tackling the psychological problems. Counselling and patient education should fortify and form the basis of other multidisciplinary and medical treatments.

Weight-Loss and Exercise

Many women with PCOS are overweight and whether this is a cause or a result is unclear. However, it is well documented that the symptoms of PCOS may be lessened by weight loss, or increased by weight gain.

Even a minor weight loss has been shown to have remarkable clinical worth with improvements in psychological well-being, reproductive factors (menstrual regularity, ovulation & fertility) and metabolic sequelae (Insulin resistance reduces appreciably thereby diminishing the risk factors for heart disease and diabetes)

A regular dietician review is thus imperative.

Also, research shows that exercise, even in the absence of reducing weight, can help improve circulation, reduce blood pressure and increase HDL cholesterol (the “good” cholesterol).

The role of weight-loss and exercise cannot be emphasized enough.

Medical Therapy

A. Regulating the Menstrual Cycle

If becoming pregnant is not an issue, then a low dose oral contraceptive pill (OCP) can be taken. This decreases androgen production and breaks the cycle of continuous oestrogen thereby correcting abnormal bleeding and decreasing the risk of Endometrial cancer. Progestogens may also be used to achieve the same.

Metformin, a drug used to treat insulin resistance in Type II Diabetes, has been shown to improve ovulation and decrease androgen levels. However, this provides no contraceptive protection.

B. Improving Symptoms of Androgen (Testosterone) Excess

Medications specifically targeted at countering the effects of excess androgens may be taken. These are called Anti-androgens. Spironolactone (a special Diuretic) is one such drug and works by both blocking the effects of androgens and reduces new androgen production. Because of this complete block of androgens, it is not recommended if you’re pregnant or planning to become pregnant as it may cause feminisation of a male foetus.

Other anti-androgens are available, such as Cyproterone Acetate, but again are not recommended if planning to become pregnant or are currently pregnant.

The oral contraceptive pill combined with anti-androgens is the first line approach in treatment to excess androgens (if not caused by the adrenal gland). The oral contraceptive pill alone has limited effect in treatment excess androgens, however, they help in the treatment of acne, reduce the risk of endometrial cancer and provide contraception.

Topical Eflornithine (Vaniqa) may be used to slow facial hair growth in women. This prescription medication cream, is however, only effective for one-third of women who use it. Also, the effect rapidly reverses when treatment is stopped, and again, it is not recommended in pregnancy.

C. Ovulation Induction

Many women with PCOS have no trouble getting pregnant, while others do. Having polycystic ovarian syndrom may also increase the risk of miscarriage. In most patients with PCOS, the reduced fertility is due to anovulatory cycles (failure of the ovary to release an egg each cycle). Treatment is therefore directed at inducing regular ovulation.

Drugs used to induce ovulation include:

1. Clomid

Clomid is commonly used for ovulation induction in women with PCOS. It is a SERM drug (Selective Estrogen Receptor Modulator) that tricks the brain into releasing a hormone called GnRH, which stimulates release of Follicle Stimulating Hormone (FSH). This hormone in turn, then stimulates development of a mature follicle in the ovary.

In anovulatory women, the average day that ovulation occurs on is about 8-10 days after completing a course of Clomid. However, there is significant variation in how long it takes to ovulate on Clomid. Clomid is generally started early in the menstrual cycle and is usually taken for 5 days from day 2 through to day 6. Day 1 is counted as the first day of menstrual bleeding.

Clomid works best when the lowest dose that results in ovulation is used.

About three-quarters of anovulatory women in PCOS will ovulate on Clomid at some dosing level (increments are used). However, not all of these women will fall pregnant. If pregnancy has not occurred despite ovulation, there is no benefit of increasing the dose of Clomid if trying another cycle.

Whilst on Clomid, the development of follicles will be monitored by hormonal assays +/- ultrasound scans.

Clomid treatment has some potential for adverse effects and varies in each woman. Side-effects reported include mood swings and emotional lability, hot flashes, abdominal discomfort with an increased abdominal girth, nausea & vomiting, visual disturbance, ovarian cyst formation and thinning of the uterine endometrial lining. Sometimes a Hyper-stimulation syndrome ensues. Multiple pregnancy is also a documented side effect.

2. Metformin

Traditionally, the next step in attempting ovulation induction in those who failed on Clomid would be to use Injectable Gonadotropins. However, these medications are not only expensive and carry the risks of Ovarian Hyper-stimulation & multiple pregnancy, but the daily injections and trips to the office for monitoring make this a less user-friendly treatment.

Metformin treatment is the relatively new treatment method for inducing ovulation and has largely superseded use of Injectable Gonadotropins.

Metformin, an oral medication, is an agent used to help control Diabetes. In addition it has been found to facilitate ovulation in some women with PCOS. It is usually prescribed in combination with Clomid.

The most effective dose of Metformin is built up to, over a couple of weeks so as to avoid the side effects that are associated with starting with a high dose.

In about 25% of women, Metformin causes side effects that may include abdominal discomfort, cramping, diarrhoea and nausea. However, no serious complications have been reported with the use of Metformin.

Surgical Therapy

Surgical therapy for PCOS is not considered a first-line treatment. It may be attempted if medical treatment cannot be tolerated

Ovarian Drilling is a Laparoscopic procedure done as a day-case. This procedure has superseded the previously popular Ovarian Wedge Resection, which involved major abdominal surgery. The procedure involves making 4 punctures in the ovary using a small needle.