What is PCOS?
Polycystic ovary syndrome (PCOS) is the commonest endocrine condition (15-20%) affecting women of reproductive age. The presence on ultrasound scan of multiple, small, fluid filled cysts in the ovaries is known as polycystic ovaries, which may exist per se independent of the complex syndrome. To make the diagnosis of PCOS, according to published recommendations there must be two out of three of the following criteria:
• Multiple small cysts on one or more ovary. One or more enlarged ovary may also be diagnostic
• Clinical symptoms or blood test evidence of raised levels of androgens (male hormones) such as testosterone
• Irregular periods or evidence that ovulation is not occurring
In PCOS, the cysts may be accompanied by an imbalance of sex hormones, specifically elevated androgens. Normally women have both oestrogens (female hormones) and androgens (male hormones). In PCOS the balance is tilted towards overproduction of androgens. This may lead to acne and/or excessive hair growth on the face and body. Blood test may sometimes show an elevated level of testosterone.
PCOS is associated with irregular, infrequent or even absent periods. If the periods are irregular, it is unlikely that ovulation is occurring. As a result, women may experience problems conceiving (subfertility). Further, women with PCOS may also suffer repeated early pregnancy losses (also known as recurrent miscarriage).
Women with PCOS may have difficulty controlling their weight. Being overweight makes the symptoms even worse. Conversely weight loss can lead to a dramatic improvement in the full spectrum of symptoms.
Women with PCOS are at increased risk of developing diabetes mellitus because their tissues are resistant to insulin. The prevalence of diabetes in obese PCOS subjects is about 11%. Other possible sequelae of PCOS include an increased risk of hypertension (high blood pressure), of fat-like molecules in the blood stream (dyslipidaemia) and of cardiovascular disease. These may all be linked to each other. If there are very long gaps between menstruations (periods), there is small increase in the risk of endometrial (lining of the womb) cancer.
Why have I got PCOS?
The exact mechanism is not fully understood yet but there is an underlying resistance to the hormone insulin. Insulin is a hormone produced by the pancreas, which circulates in the blood stream to enable the uptake of glucose by the cells. To compensate for the resistance, the pancreas produces large amounts of insulin (hyperinsulinaemia). High levels of insulin affect hormone production by the ovary, leading to an excess production of androgens.
These male hormones and the increased number of small follicles (cysts) that produce the anti-Müllerian hormone (AMH) disrupt the normal cyclical functioning of the ovaries. As a result, ovulation may be absent or irregular. It is thought that there may be a genetic reason why some women develop this syndrome. Women with PCOS report female family members with similar symptoms, while the male family members have frontal baldness.
Investigations for PCOS
The diagnosis of PCOS can be suspected based on symptoms and a general examination. To confirm the diagnosis the following investigations will be undertaken:
• ultrasound scan of the pelvis to look at the ovaries (and the womb)
• blood test to measure the levels of androgens (testosterone, sex hormone binding globulin), prolactin (PRL), anti-Müllerian hormone (AMH), luteinising hormone (LH) and follicle stimulating hormone (FSH)
• random glucose test (in some selected cases)
The following tests can also be done to rule out some other serious but less common conditions that may cause similar symptoms, such as:
• androgen secreting tumours in the adrenal gland or ovary
• congenital adrenal hyperplasia (CAH), a rare inherited condition resulting in abnormal production of androgens
• Thyroid gland problems
• Cushing's syndrome caused by overproduction of the steroid cortisol by the adrenal gland
Treatment of PCOS
An association between PCOS symptoms and a significant reduction in health-related quality of life (physical, psychological and social aspects) has been demonstrated. Therefore, treatment has to be tailored according to the main symptoms at presentation on an individual basis.
Weight loss and Diet
If overweight or obese weight loss must be the starting point as it helps to reduce the insulin levels and improve the overall hormone imbalance. Ideally the body mass index (BMI) should be 20-25 (BMI = W/H2, W is weight in Kg and H is height in metres). Symptoms will improve significantly and may even disappear with weight loss. In some cases this may be the only treatment needed to restore ovulation and regular periods.
The most appropriate diet for women with PCOS is one that promotes more stable levels of blood sugar and lower levels of insulin. The standard low fat, high carbohydrate weight loss diet is not ideal. High intakes of carbohydrates, especially refined carbohydrates - like sweets, white bread, white rice, etc. - will quickly turn to sugar and cause elevated levels of insulin. A low glycaemic index diet which will not cause a rapid rise in blood sugar is better for women with PCOS.
Carbohydrates should be spaced throughout the day to avoid peaks in blood sugar and insulin production. Importantly, carbohydrates should be combined with proteins and/or fat rather than be eaten alone. It is also best to avoid carbohydrates that trigger more hunger or cravings.
Drugs may be used to aid weight loss. These act by either reducing gastro-intestinal absorption of fats (Orlistat) or by suppressing appetite in the brain (Sibutramine). In severe cases of obesity, the gastric bypass and other similar approaches should be considered.
Hormone preparations for irregular periods
The combined oral contraceptive pill (COC) is given to regulate the menstrual cycle and to reduce the risk of endometrial cancer (cancer of the lining of the womb). The COC pill causes elevated circulating levels of sex hormone binding globulin (SHBG) in the blood which works 'mopping' up the androgens, resulting in improvements in the symptoms of acne and unwanted excessive hair.
Dianette is a hormone preparation containing the anti-androgen cyproterone acetate (CPA). Dianette is not licensed as a contraceptive but solely for treatment of acne and/or hirsutism. There is a small risk of deep venous thrombosis (DVT) and it is advisable to consider changing treatment 6 months after symptoms have improved. An individual risk assessment needs to be made taking into account all the important factors. Some women may choose to take Dianette long term if other options are not suitable. CPA may take 6-12 months to improve symptoms. In some severe cases, additional CPA can be added on day 5-15 of the menstrual cycle.
Yasmin is another hormonal contraception that contains ethinylestradiol (synthetic form of oestrogen) and drospirenone (synthetic form of progesterone). This preparation is taken exactly the same as the pill.
Metformin
Metformin is a type of drug known as insulin-sensitising agent which increases the sensitivity of the tissues to insulin, reduces insulin levels in the blood stream and indirectly reduces excess androgen levels. It may therefore restore ovulation, regular menstruation and improve symptoms such as acne and hirsutism in some cases. Metformin should only be prescribed to women with a BMI less than 30 kg/m2. A small number of patients taking Metformin, will discontinue treatment complaining of abdominal cramps, nausea and other gastrointestinal side effects. To avoid this it is recommended to take Metformin always at the time of the main meals.
Other anti-androgen treatments
The diuretic drug Spironolactone has anti-androgen properties. It is useful in women unable to take the COC or Metformin but it should not be taken if trying to conceive. Side effects may include gastro-intestinal disturbance and frequent periods. Finesteride is a powerful anti-androgen usually used to treat male-pattern baldness and overgrowth of the prostate in men. Although the manufacturer does not license it for use in PCOS, it is used in specialist clinics. It is particularly useful in resistant cases with good results and has few side effects. Finesteride should not be taken if trying to conceive.
Topical preparations
Eflornithine HCl Cream (Vaniqa®) is an effective non-hormonal approach to helping women with increased facial hair. It works directly to slow hair growth by inhibiting the enzyme ornithine decarboxylase (ODC). When this enzyme is blocked metabolic activity in the hair follicle decreases and hair growth is slowed down. Vaniqa® does not remove hair therefore it needs to be used in combination with a removal method. The studies so far have looked at facial and neck hair only, so Vaniqa® is not indicated for body use.
Cosmetic treatment
Cosmetic treatment can be used in addition to or as an alternative to medical drug treatments for excessive hair growth. Alternatives include plucking, shaving, waxing, electrolysis and laser treatments. All improve symptoms.
Treatments to improve fertility
Lack of ovulation is treated initially with up to six cycles of clomiphene citrate (Clomid®). This acts by blocking the oestrogen receptors, which in turn increases the levels of follicle stimulating hormone (FSH). FSH promotes follicle recruitment and development within the ovary. The first cycle of treatment with clomiphene should be monitored with ultrasound scan to confirm follicular response to treatment and to reduce the risk of multiple pregnancy (10%). If there is an over response to the treatment and more than 2 follicles are produced the treatment cycle should be abandoned. Clomiphene should not normally be used for more than 9-12 cycles because of the very limited benefits which have to be balanced against the small risk of ovarian cancer with prolonged exposure. Clomiphene should also not be used in women who have normal regular ovulatory periods as it does improve outcomes.
Some women with PCOS are resistant to treatment with clomiphene. In these cases alternatives include: ovarian drilling which involves making four small holes in the ovary using a needle that carries electricity (diathermy) performed at the time of laparoscopy (keyhole surgery), gonadotrophins (FSH/LH) injections alone or in an assisted conception programme (intrauterine insemination -- IUI or in vitro fertilisation -- IVF).
Ovulation induction with gonadotrophins should be carried out in a specialist fertility centre. Investigations on behalf of both partners to exclude other co-existing causes of infertility should be considered before starting treatment.