Metformin Use in Polycystic Ovary Syndrome (PCOS)

PCOS and hormones PCOS was initially thought to be primarily a reproductive disorder, with major features related to reduced ovulation (egg release from the ovary) and high levels of androgens (male type hormones). It is now clear that PCOS is associated with other hormonal disturbances and the body is resistant to insulin with increased insulin levels. Insulin is a hormone or messenger that controls sugar levels and has many other actions including in the ovaries. First line therapy to reduce insulin resistance is a healthy lifestyle; however, medical therapy can also assist. Metformin in PCOS Metformin has been used for glucose lowering in diabetes for over 60 years and acts by improving the bodys sensitivity to insulin. The use of Metformin in PCOS is evidence based with many studies showing improved cholesterol and androgen levels, ovulation rates, menstrual cycle regulation, fertility and decreased diabetes in pregnancy. Metformin also appears to reduce the risk of developing diabetes but is not as effective as lifestyle change. How does it work? By improving insulin sensitivity, Metformin reduces the bodys resistance to insulin and therefore our body produces less insulin. This allows the ovaries to work more effectively and to restore themselves to more normal ovulation patterns. It does not work for every woman, yet for most Metformin improves ovulation and for some may improve fertility. Metformin can also reduce excess hair growth, but is not as effective as the oral contraceptive pill. Metformin is most effective in women who are not overweight and Metformin is never a substitute for a healthy lifestyle. Side effects The most common side effects are nausea and diarrhoea, which are limited if doses are started low and increased slowly. Severe side effects are extremely rare in healthy young women. Metformin has been used safely long term in patients with diabetes. The slow release (XR) Metformin tablets are generally used as they have less side effects. Metformin XR (500mg tablet) is often started at 1 tablet at night for 2 weeks, then 2 tablets at night for 2 weeks, then 3 tablets at night ongoing. You should then be reviewed by your doctor. Generally the maximum dose is 3-4 tablets per day. When used in conjunction with other diabetes medications, Metformin can cause low blood sugars; however, Metformin alone does not. Metformin and weight Metformin does not decrease weight but may help prevent weight gain. Metformin also reduces serum insulin and androgen levels in women who are not overweight with PCOS.

Approval The use of Metformin in PCOS is recommended by the Endocrine Society of Australia (ESA), by a large and increasing body of evidence and by National Australian evidence based guidelines. It has few side effects and may be considered as part of the management of PCOS in women with menstrual period irregularities, poor ovulation and in those with high risk of diabetes or existing pre-diabetes or diabetes. Financially, Metformin is readily available and is funded through the PBS system. Although approved by the Therapeutic Goods Association (the medicines regulation body in Australia) for use in Diabetes, no application has been lodged for approval for Metformin use in PCOS. As a result, your Doctor may explain this to you and may even ask you for your consent when prescribing Metformin for treatment of PCOS. Do not hesitate to speak with your Doctor to clarify this further should Metformin be recommended for your management.

References
www.jeanhailes.org.au Velazquez E, Mendosa S, Hamer T, Sosa F, Glueck C. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism 1994; 43:647-654. Velazquez E, Acosta A, Mendosa S. Menstrual cyclicity after metformin therapy in polycystic ovarian syndrome. Obstet Gynecol 1997; 90:392-395. Diamanti-Kandarakis E, Kouli C, Tsianateli T, Bergiele A. Therapeutic effects of metformin on insulin resistance and hyperandrogenism in polycystic ovary syndrome. Eur J Endocrinol 1998; 138:269-74. Fleming R, Hopkinson ZE, Wallace AM, Greer IA, Sattar N. Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial. J Clin Endocrinol Metab 2002; 87:569-74. Teede HJ, Zoungas S, Hutchison S.The Management of Insulin Resistance in PCOS. Trends in Endocrinology and Metabolism 2007, 18 (7): 273-279

Updated November 2010