Robert MacDermott - Consultant Gynaecologist
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  KIMS Hospital
  Kent, ME14 5FT
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Metformin for the treatment of Polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a disorder of body metabolism that affects 5-10% of women and can cause infrequent periods, weight gain, acne, unwanted hair growth and infertility. PCOS should not be confused with the incidental finding of polycystic ovaries on an ultrasound scan which occur in about 20% of the female population and usually do not cause any symptoms. The cause of PCOS is not fully understood but is thought to have a genetic component. The small cysts seen in the ovaries do not cause PCOS but are the result of the underlying disturbance of metabolism.

Most women with PCOS do not have every symptom and the treatment that a doctor recommends is usually chosen to treat the symptoms that bother the woman. In recent years there has been a lot of interest in the use of Metformin to treat the symptoms of PCOS. This information sheet aims to answer many of the questions that women have about this treatment.

 What is Metformin?

Metformin is a medicine that is taken by mouth. It is from a family of drugs known as biguanides and was developed to treat type 2 (late onset) diabetes.

 Why is it used to treat PCOS?

There are a number of similarities between PCOS and adult-onset diabetes. In both conditions, people have a resistance to the effects of insulin with resulting high levels of insulin in their blood stream. These high insulin levels cause an increased production of androgens (male-type hormones that can cause acne and unwanted hair growth) in the ovaries and adrenal glands. This in turn affects the pituitary hormones (LH and FSH) that normally stimulate the ovaries to produce eggs. The result is often irregular infertile periods. Metformin increases the effectiveness of insulin, resulting in a lowering of blood insulin levels which in turn lowers the androgen levels and returns the pituitary hormones back to normal.

 Does it work for all the symptoms of PCOS?

Although Metformin has been used to treat diabetes for many years, it has only been used to treat PCOS for a few years. There are therefore only a few trials that have looked at the effects on the various symptoms of PCOS. There is good evidence of benefit in women who want to get pregnant and are not ovulating or have irregular periods. After 6 months of treatment, up to 90% of women with infrequent periods will start having regular periods and most will start to ovulate. Metformin enhances the effect of Clomifene, another drug that is often used to stimulate ovulation.

There is reasonable evidence that Metformin reduces the levels of androgens in the blood stream. This would be expected to cause an improvement in excess hair growth and acne, but there is insufficient evidence to be sure of this.

There is limited evidence that Metformin will result in weight loss. It is likely that, without alterations in lifestyle with diet and exercise, it has no effect on weight. When combined with such lifestyle changes, it probably helps weight loss.

 Does it work in all women with PCOS?

No. There is no clear way of predicting which women will benefit from Metformin.

 What dose should be used?

The best dose of Metformin is not known. It comes in 2 different tablet strengths - 500mg and 850mg. Women are commonly advised to start at a lower dose (eg one tablet, once or twice daily) for 1-2 weeks before increasing the dose. A dose of 500mg three times per day or 850mg twice daily is then often used. Side-effects are more likely with higher doses. It is better to reduce the dose to one that can be tolerated than stop the medicine because of side-effects, unless they are severe (see below).

 What are the side-effects of Metformin?

Metformin is a well tolerated medicine. It may cause gastro-intestinal side-effects such as diarrhoea, nausea, vomiting and flatulence. These side-effects usually resolve after a few weeks and can be reduced by taking the tablets with food.

Lactic acidosis is an extremely rare side-effect of Metformin and is virtually unheard of in women with PCOS (because these women are usually young and in good health). The symptoms are lethargy, drowsiness, breathing difficulty, muscle pains and abdominal pains. Women who develop these symptoms whilst taking Metformin should stop taking it and seek urgent medical attention.

 Who should not take Metformin?

Metformin should be used with great caution (if at all) in women with poor kidney or liver function. Women who drink alcohol excessively should tell their doctor as they have an increased risk of developing lactic acidosis.

 Does Metformin interact with other medicines?

Metformin should be stopped before special x-rays (eg. CT scan or intravenous urogram ) which involve the injection of an iodine-based material. Use with Cimetidine may increase the effect of Metformin. Use with Warfarin can increase the effect of the Warfarin, the dose of which may need to be adjusted.

 Will Metformin affect my blood sugar levels?

No. Metformin has no effect on blood sugar levels in non-diabetic people.

 How long can I take Metformin for?

The optimum duration of treatment is not known. There is some evidence that it can improve the levels of lipids (fat) in the blood stream and this may possibly reduce the long term risk of heart attack and stroke. Women with PCOS have an increased risk of developing diabetes in later life. It is not known whether Metformin can reduce this risk.

 Should I stop Metformin if I get pregnant?

Most doctors suggest that Metformin is stopped when a woman has a positive pregnancy test. There is insufficient information at present to know whether continuing Metformin during a pregnancy is beneficial or not. There is no evidence that it is harmful to the developing baby and there is no evidence of harm from animal studies. Women with PCOS have an increased risk of miscarriage (around 30%) and there is some evidence that Metformin might reduce this risk. If you have had a previous miscarriage, you should discuss these issues with your gynaecologist.

 Is there anything that I can do myself to help my PCOS?

Weight loss of between 1 and 2 stones can have a dramatic effect on the symptoms of PCOS, including fertility. This is best achieved by a combination of exercise and diet. Exercise needs to be regular and moderately strenuous eg. aerobic gym work (jogging, cycling, steps).

 What other medicines can be used to treat the symptoms of PCOS?

Women who do not want to become pregnant can use the contraceptive pill to treat irregular periods, acne and unwanted hair growth. However, the Pill cannot be used by very overweight or older women, and some women put on weight when they take the Pill. Women who are not ovulating and want to get pregnant may be prescribed Clomifene, a drug which stimulates the ovaries to produce eggs.

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