METFORMIN USE IN POLYCYSTIC OVARIAN SYNDROME (PCOS)
As a Gynaecologist, Fertility and Melbourne IVF Specialist I’m often asked what role Metformin plays in PCOS.
Polycystic ovarian syndrome (PCOS) and insulin resistance
In some patients, PCOS results in insulin resistance and impaired glucose intolerance or diabetes. During the luteal phase, follicular recruitment is aided by a reduction in the LH pulse frequency. Insulin resistance and increased LH frequency results in increased ovarian androgen production which ultimately results in arrested follicular development. Metformin decreases insulin resistance by the following mechanisms: decrease hepatic glucose production; decrease intestinal absorption of glucose and increased peripheral insulin sensitivity.
Obviously diet and exercise alone can reduce weight, but in patients with PCOS and insulin resistance the addition of Metformin may facilitate this process. This seems to be independent of its gastrointestinal side effects and more related to a suppression of appetite.
Prevention of diabetes
Given the association of PCOS with impaired glucose intolerance (IGT) there is a role for treatment with Metformin in this setting. There is some evidence that Metformin can prevent or delay the onset of diabetes in patients with IGT.
The use of Metformin restores ovulation as measured by mid-luteal progesterone in 50 per cent of women. Whilst ovulation and pregnancy does occur a Cochrane review in 2012 showed no increase in live births compared to placebo and less birth rates compared to alternatives such as clomiphene.
In the PPCOS trial, 600 women were randomised to receive Metformin alone, clomiphene alone or the combination of both. The live birth rates are Metformin alone 7.2 per cent; clomiphene 22.5 per cent; and combination 26.8 per cent (though this is not statistically significant compared to clomiphene alone).
Metformin alone is less successful at achieving a baby compared to clomiphene; and that the combination provides no additional benefit. Furthermore the addition of Metformin exposes the patient to additional side effects.