The use of metformin in the polycystic ovary syndrome
The Use of Metformin in the Polycystic Ovary Syndrome
There is increasing interest in the use of Metformin in womenwith PCOS. This information sheet outlines the current state of
Serious side effects to Metformin treatment are very rare. In
knowlegdge regarding its use in this condition.
particular, Metformin does not cause hypoglycaemia. In the firstweek of taking Metformin, an upset stomach or diarrhoea is
common and this side effect can be reduced by taking it afterfood and by starting with a very low dose (250 mg) and to
The polycystic ovary syndrome (PCOS) is one of the most
increase slowly by 250 mg per week until the full dose of 1700
common disorders affecting women. It has been estimated that
mg is achieved (850 mg twice per day). Women who have
20% of women have polycystic ovaries as detected by
kidney damage are at an increased risk of a very rare side effect
ultrasonography and that 10% of all women experience a
of Metformin therapy called lactic acidosis. The drug should be
symptom of PCOS. The most common symptoms associated
given cautiously, if at all, in this instance. While safety during
with PCOS are unwanted hair growth, irregular periods and a
pregnancy has not yet been established, many women over the
failure to ovulate. About half of women with this syndrome are
years have inadvertently taken Metformin when pregnant and no
overweight and one third become diabetic at some time in their
adverse effects have been reported. Indeed, one group has
lives. In general, as a women with PCOS gains weight so the
reported the intentional use of Metformin to treat diabetes
symptoms get worse and the risk of diabetes rises.
The most typical hormone changes associated with PCOS are
Criteria for the use of Metformin
raised concentrations in the blood of testosterone, luteinisinghormone (LH) and insulin. One third of women, however, will
1. Established diagnosis of PCOS. 2. Body mass index over 30
show no hormone abnormality. The simplest picture that
km/m2 or BMI < 30 and gaining weight.
explains the syndrome is that the ovary makes an excess oftestosterone by one of two mechanisms. The ovary might be
Metformin comes in two sizes of tablet 500 and 850 mg. Take
over active in its testosterone production spontaneously with no
tablets after food - if side effects are encountered then stop the
external drive, or the ovary might be driven to produce excess
increase in dosage at the last acceptable level. Metformin works
testosterone by the action of either LH or insulin.
much better if combined with a strict regime of diet and exercise. Diet should be at least three light meals per day which are low in
Conventional treatment for PCOS aims to suppress ovarian
sugar and fat and high in fruit, fresh vegetables and salad. Light
testosterone production using the combined oral contraceptive
sustained exercise such as walking, cycling or swimming for at
pill. In some women 'the pill' is not appropriate treatment. For
least an hour at a time several times per week.
instance, one of the side effects of the pill is to increase the riskof a blood clot - a thrombosis - and this risk exaggerated in obese
Daily dose – slow route to avoid side effects
women. Also, in some women the use of the pill coincides with
weight gain and this might make the symptoms of PCOS worse
in the long run. For these reasons alternative treatments are
increasingly being tested to good effect. The focus of these newapproaches to treatment is the insulin axis.
Daily dose – fast route if stomach can take itweek 1 500 mg twice
The main role of insulin in the body is in regulating the level ofglucose in the blood. In some individuals, high concentrations
Monitoring the use of Metformin
of insulin are required in order to maintain normal glucose levels- insulin resistance. When insulin fails in this effort, glucose
Tests at the start of Metformin and every 2 months thereafter
levels rise and diabetes ensues. Raised insulin concentrations
Menstrual cycle diary for 6 months (recall), Weight, Urinalysis
have a side effect in the body of stimulating the ovary to produce
LH, FSH, Testosterone, Glucose, HbA1c, U&E, Cholesterol,
more testosterone. Reducing insulin by diet, weight loss or
triglycerides, HDL, LDL – fasting insulin is optional.
drugs results in a lowering of testosterone and improvedsymptoms of PCOS. All women with PCOS who are over
Stop taking Metformin if pregnancy occurs.
weight would benefit from a regime of diet reform and exercise.
There is no particular time limit for the use of Metformin - if no
The only drug currently available in the UK which reliably
effect is seen in six months then there is no point in continuing.
reduces insulin concentrations is Metformin. Metformin has
After one year the goals of future treatment should be reviewed.
been used for over 30 years to treat maturity onset diabetesmellitus. It acts by making the body more sensitive to insulin.
The long term place of Metformin in PCOS is not clear. It isstrongly recommended that the use of Metformin is monitored
The use of Metformin in women with PCOS
either in an official trail or as a formal audit in a specialist unit inorder that the effectiveness of this treatment can be clearly
Several studies have recorded the use of Metformin in women
with PCOS. Metformin is effective in reducing testosteronelevels and in making the menstrual cycle more regular. While
Metformin starts to improve the prospects for fertility in fewweeks, a reduction in unwanted hair growth would be expected
For those women who do not wish to get pregnant but for whom
to take some months and be slower than conventional treatment.
unwanted hair growth is the main concern then the addition of
Women can find weight loss easier when taking Metformin even
Spironolactone 50 mg twice daily is suitable.
though it is not a traditional weight reducing agent. Oneplacebo-controlled trail has shown that Metformin is better than
placebo in inducing ovulation in women with PCOS. The
effectiveness of Metformin has been best demonstrated in obese
women and it is likely that women of normal weight would
Alcohol & Alcoholism Vol. 42, No. 5, p. 506, 2007 doi:10.1093/alcalc/agm058 Advance Access publication 1 August 2007 GAMMA-HYDROXYBUTYRATE (GHB)-DEFICIENCY IN ALCOHOL-DEPENDENCE? 23 rue du Depart—BP 37—7 5014 Paris, France (Received 10 January 2007; first review notified 17 January 2007; in revised form 3 March 2007; accepted 28 March 2007; advance access publication 1 August 2007) J
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