Diagnosis and management of polycystic ovary syndrome continued

Management

Clinical management of a woman with PCOS should be focused on her individual problems

Obesity

• Obesity worsens both symptomatology and the endocrine profile and so obese women (BMI >30kg/m2) should therefore be encouraged to lose weight
• Weight loss improves the endocrine profile, the likelihood of ovulation and a healthy pregnancy
• The right diet for an individual is one that is practical, sustainable and compatible with her lifestyle. It is sensible to reduce glycaemic load by lowering sugar content in favour of more complex carbohydrates and to avoid fatty foods; it is often helpful to refer to a dietitian, if available
• An increase in physical activity is essential, preferably as part of the daily routine. 30 minutes per day of brisk exercise is encouraged to maintain health, but to lose weight, or sustain weight loss, 60 to 90 minutes per day is advised
• Concurrent behavioural therapy improves the chances of success of any method of weight loss
• Anti-obesity drugs may help with weight loss and both orlistat and sibutramine have been shown to be effective in PCOS in small studies:
  • orlistat is a pancreatic lipase inhibitor which prevents absorption of around 30% of dietary fat, whereas sibutramine is a centrally acting serotonin and noradrenaline reuptake inhibitor, which enhances satiety
  • both agents can also improve insulin sensitivity and are currently licensed for individuals with a BMI of 30 kg/m2 or lower if comorbidities such as type 2 diabetes are present
  • both agents have been shown to improve insulin resistance, lipid profile and glycaemic control and orlistat has been shown to reduce blood pressure and testosterone. Orlistat and sibutramine are increasingly being used in primary care as an adjunct to diet and lifestyle advice; both require monitoring for efficacy and sibutramine for possible increases in blood pressure and pulse rate
  • new agents in development for obesity and the metabolic syndrome may also have a role to play in PCOS, such as rimonabant, but data is lacking at present. Metformin can also improve insulin resistance and may aid some women with modest weight loss, though this has not been confirmed by randomised trials. The combination of metformin and an anti-obesity agent may be ideal and while metformin combined with orlistat is not contraindicated, their combination is still unproven and clinical trials to formally evaluate this approach are required

Menstrual irregularity

• The easiest way to control the menstrual cycle is the use of a low dose combined oral contraceptive preparation. This will result in an artificial cycle and regular shedding of the endometrium. An alternative is a progestogen (such as medroxyprogesterone acetate or dydrogesterone) for 12 days every 1–3 months to induce a withdrawal bleed
• It is also important once again to encourage weight loss, as women with PCOS are thought to be at increased risk of cardiovascular disease, a "lipid friendly" combined contraceptive pill should be used Metformin is an alternative agent, which could be tried if contraception is not required
• In women with anovulatory cycles, the action of oestradiol on the endometrium is unopposed because of the lack of cyclical progesterone secretion. This may result in episodes of irregular uterine bleeding, and in the long term, endometrial hyperplasia and even endometrial cancer. An ultrasound assessment of endometrial thickness provides a bioassay for oestradiol production by the ovaries and conversion of androgens in the peripheral fat. If the endometrium is thicker than 15 mm, a withdrawal bleed should be induced and if the endometrium fails to shed then endometrial sampling is required to exclude endometrial hyperplasia or malignancy
• The only young women to get endometrial carcinoma (<35 years), which otherwise has a mean age of occurrence of 61 years in the UK, are those with anovulation secondary to PCOS or oestrogen-secreting tumours

Infertility

• Ovulation can be induced with the antioestrogens, clomiphene citrate (50–100 mg) or tamoxifen (20–40mg), days 2–6 of a natural or artificially induced bleed. While clomiphene is successful in inducing ovulation in over 80% of women, pregnancy only occurs in about 40%. Clomiphene citrate should only be prescribed in a setting where ultrasound monitoring is available (and performed) in order to minimise the 10% risk of multiple pregnancy and to ensure that ovulation is taking place

A daily dose of more than 100 mg rarely confers any benefit. Once an ovulatory dose has been reached, the cumulative conception rate continues to increase for up to ten to twelve cycles. Clomiphene is only licensed for six months use in the UK, and so we would advise careful counselling of patients if clomiphene citrate therapy is continued beyond six months

Hyperandrogenism

• Hyperandrogenism is usually managed with ethinyloestradiol (35 μg) in combination with cyproterone (2 mg). Rospirenone (3 mg) and ethinylestradiol (0.030 mg) may also be of benefit
• Alternatives include spironolactone, flutamide and finasteride (all unlicenced) are not routinely prescribed because of potential adverse effects. Reliable contraception is required

Indications for referral

• Serum testosterone > 5 nmol/l (to exclude other causes of androgen excess, e.g. tumours, late onset congenital adrenal hyperplasia, Cushing's syndrome)
• Infertility
• Rapid onset hirsutism (to exclude androgen secreting tumours)
• Glucose intolerance / diabetes
• Amenorrhoea of more than 6 months – for pelvic ultrasound scan to exclude endometrial hyperplasia
• Refractory symptoms

full guidelines available from…
Address (Tel – 01234 567890)
http://www.pcos-uk.org.uk/

PCOS UK. The polycystic ovary syndrome: guidance for diagnosis and management. December 2006