Metformin: Does It Induce Ovulation in Women With PCOS?

How does metformin induce ovulation in women with polycystic ovary syndrome?

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Insulin-lowering agents and PCOS

Polycystic ovary syndrome (PCOS) is often associated with a degree of insulin resistance. In the most severe cases of PCOS, insulin resistance is one of the classic findings and results in a skin abnormality called acanthosis nigricans (HAIR-AN). A small percentage of PCOS women have measureable insulin resistance and the correction of this metabolic abnormality may improve attempts at ovulation induction or even spontaneous ovulation. One of the most recent developments in the treatment of polycystic ovary syndrome (PCO) is the use of insulin lowering agents to induce ovulation and/or to assist in ovulation induction when used in conjunction with other drugs like clomiphene citrate. The most commonly utilized insulin-lowering agent at present is metformin hydrochloride.

Metformin hydrochloride

Metformin improves insulin sensitivity (increases peripheral glucose uptake and utilization), decreases the production of glucose by the liver, and decreases the absorption of glucose in the gut. Its use is contraindicated in patients with kidney disease or abnormalities, acidosis (disorders resulting in the production of lactic acid like diabetic ketoacidosis), and heart failure.

This drug causes gastrointestinal side effects especially when it is started. These gastrointestinal side effects include: diarrhea, nausea, vomiting and flatulence (gas). These nuisance side effects usually resolve over a few weeks. Metformin is mainly cleared from the body through the kidneys therefore kidney function must be normal. If a radiologic study (CT scan, intravenous pyelogram [IVP], intravenous cholangiogram [gallbladder evaluation] ) was planned which included intravascular injection of iodinated contrast material the drug should be stopped. This avoids potential problems caused by renal dysfunction caused by the iodinated contrast (very rare). If a patient using metformin developed malaise (not feeling good) , myalgias (nonspecific aches and pains in the muscles), respiratory distress (difficulty breathing), significant abdominal pain and distress, or sleepiness, the drug should be stopped. These may be signs of lactic acidosis, which could be life threatening.

Type I or insulin-dependent diabetics do not use this type of medication. Type II or non-insulin dependent diabetics are often prescribed this medication to help control blood sugars. A small percentage of young PCOS women have actually been diagnosed as Type II diabetics.

Long term effects and potential effects on the developing child are not fully defined but preliminary evidence suggests it is safe to use until a pregnancy is achieved.

Efficacy

Recent small studies document over 80% of obese PCOS women treated with metformin either ovulated spontaneously or in response to clomiphene citrate compared to only 12% treated with placebo or placebo plus clomiphene. Further studies will help define the patients for whom metformin is most appropriate.

Recommendations

Your reproductive endocrinologist can evaluate your case and determine if a trial of metformin may be indicated. The duration of therapy will be determined by your responsiveness and other factors particular to your case. Many doctors document insulin resistance prior to initiating these medications.

 

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