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Insulin Sensitizing Agents and PCOS
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About PCOS |
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Polycystic Ovarian Syndrome (PCOS) is a common cause of infertility, menstrual irregularity, and hirsutism (excessive hair growth) affecting women. In addition to reproductive problems, women with PCOS have a higher chance of developing medical problems such as Type 2 (non-insulin dependent) diabetes, high blood pressure, and heart disease. By the age of 40, up to 40% of PCOS patients develop impaired glucose tolerance or clinical diabetes. |
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Role of Insulin in PCOS |
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Insulin resistance is an intrinsic feature of the Polycystic Ovarian Syndrome (PCOS). Almost all obese PCOS women and more than half of those of normal weight are insulin resistant. Many women with PCOS have a decreased sensitivity to insulin for which their bodies compensate by overproducing insulin (compensatory hyperinsulinemia). High insulin levels may lead to excessive production of androgens (male hormones, like testosterone), which in turn contributes to ovulation disorders. |
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Controlling Insulin to treat PCOS |
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Because no exact cause for PCOS is known, a comprehensive cure for PCOS is currently not available. Instead, women with PCOS must rely upon long-term management of their symptoms. However, there is increasing evidence to suggest a connection between insulin resistance and PCOS. Reducing the circulating levels of insulin may help restore normal reproductive function. Insulin levels can be controlled through behavioural changes and insulin sensitizing agents. |
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Behavioural Changes |
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Regular exercise, a healthy diet, and weight control are key treatments for PCOS. These behavioural changes should be the first lines of therapy for an overweight woman with PCOS. |
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Insulin Sensitizing Agents |
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Insulin sensitizing agents have been shown to improve the body’s response to insulin, thereby reducing the need for excess insulin and restoring the levels to normal. Initially approved by the FDA to treat Type 2 diabetes, these new drugs have shown promise in PCOS treatment as well. Some drugs which are effective insulin sensitizing agents include:
 Metformin
Rosiglitazone
Pioglitazone
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Metformin |
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Metformin is the most popular anti-diabetic drug in the United States and one of the most prescribed drugs in the country. It is also the best studied insulin sensitizing agent available for women with PCOS. Metformin is a a biguanide, which reduces circulating insulin and androgen levels and restores normal ovulation in some women with PCOS. Though it may not restore ovulation all by itself, it may improve a woman’s response to fertility drugs. The most common side effect of metformin is gastrointestinal irritation, including diarrhea, cramps, nausea and vomiting. These symptoms usually improve after a few weeks. Lactic acidosis is a rare but serious adverse effect of metformin. Metformin is not recommended for patients with kidney, lung, liver, or heart disease. Metformin should be temporarily stopped prior to surgery or X-ray procedures that use intravenous contrast. |
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Rosiglitazone and Pioglitazone |
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Rosiglitazone and pioglitazone belong to the thiazolidinedione group of antidiabetic agents, are also prescribed for PCOS treatment. Thiazolidinediones have been shown to reduce hyperandrogenism and restore ovulation in some PCOS patients. Liver toxicity is the most serious potential side effect associated with these agents. Liver tests should be performed every two months for the first year and periodically thereafter. These medications should avoided by women with any evidence of liver disease. In general, thiazolidinediones may be considered if metformin is ineffective or not tolerated by the patient. |
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Though there is no evidence to link these new insulin sensitizing agents to birth defects in animals or humans so far, they are not recommended for use during pregnancy. Unlike ovulation induction drugs, insulin sensitizing agents have little or no risk of multiple pregnancies. More clinical studies are needed to determine the outcomes, risks, and complications when these medications are used to treat PCOS (though the results so far have been encouraging).
Clinical data gathered so far favours the use of insulin sensitizing agents for ovulation induction in PCOS patients who want to conceive. These medicines correct the underlying metabolic abnormalities associated with PCOS, and it is plausible that their long-term use may delay the emergence or reduce the likelihood of developing Type 2 diabetes and cardiovascular diseases. For lack of clinching data, the long-term use of insulin sensitizing agents for this purpose cannot be recommended at present. |
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