Polycystic Ovarian Syndrome (PCOS)
Polycystic Ovarian Syndrome (PCOS) occurs in 5-10% of women of reproductive age. The condition is characterized by abnormal ovarian function (irregular or absent periods, abnormal or absent ovulation and infertility), androgenicity (increased body hair or hirsutism, acne) and increased body weight/body mass index (BMI). The morphology (structure shape and size) of the ovaries is characterized by multiple micro-cysts under the ovarian capsule and an overgrowth of ovarian connective tissue (stromal hyperplasia). PCOS is also often associated with insulin resistance, high blood insulin levels (hyperinsulinemia) and non-insulin dependent diabetes mellitus, which could play a key pathogenic role in its development, contributing to the development of obesity, an abnormal lipid profile, and cardiovascular disease. Women with PCOS are also at a slightly increased risk of developing uterine, ovarian and possibly also breast cancer, and accordingly should be evaluated carefully on an annual or more frequent basis.
There has in recent years been a flurry of interest in the possible benefits of using Metformin derivatives such as Glucophage to treat women with PCOS in the hope of improving ovulation function, restoring menstrual cyclicity, reducing androgenicity and improving fertility potential. It has also been speculated that Metformin, by lowering blood insulin levels and regulating cellular metabolism, might reduce the long term risks of heart disease, stroke and diabetes mellitus in women in women with PCOS.
what is really known about the potential benefits of Metformin (500 mg TID for 3-6 months at least) with regard to treating PCOS in general, and enhancing fertility in specific? What follows is an attempt to put this in some perspective:
- 50% of women with irregular periods and about 25% of women with absent periods will experience a restoration of normal menstrual cycles.
- In about 25% of cases, ovulation is restored with 10% of women conceiving spontaneously within a 6 month period of treatment.
- In most cases where the blood testosterone level is raised, there will be about a 30% reduction in serum testosterone levels within 3-4 months, with levels plateauing thereafter. It is believed that this feature of Metformin activity could play an important role in improving ovulation function and/or response to fertility drugs (such as clomiphene citrate and/or gonadotropins) as well as accounting for a modest reduction in androgenicity (5-8%).
Metformin’s mode of action probably relates to a reduction in blood insulin level by decreasing bowel absorption of glucose, improving glucose uptake into the cells, and increasing the number of insulin receptors on the surface of cells. A significant contribution to fertility treatment might stem from an added advantage, namely that it lowers ovarian testosterone production and thereby may enhance egg development and quality. This has potential benefit in PCOS women whose condition is often characterized by excessive LH-induced ovarian testosterone production.
PCOS women who have the following features represent the ones that are most likely to benefit from Metformin therapy:
- Raised serum insulin levels (hyperinsulinemia) or insulin resistance
- Irregular rather than absent menstrual periods
- Raised serum testosterone levels
- An LH/FSH ratio greater than 1:1
Metformin therapy can be used safely in conjunction with IVF in women with insulin resistance. There is no evidence that it is harmful if taken during pregnancy.