Metformin and PCOS Health Benefits and Side Effects

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Updated on June 29, 2020

The majority of women with polycystic ovary syndrome (PCOS) have insulin resistance or high insulin levels. Too much insulin generates inflammation, which in turn can lead to the development of type 2 diabetes, obesity, dyslipidemia, and non-alcoholic fatty-liver disease. Insulin resistance is also one of the root causes of PCOS.

Given the important role insulin resistance plays in the pathophysiology of PCOS, common treatments involve insulin and the diabetic drug metformin, which improves insulin sensitivity. Although metformin is not approved by the FDA for treating PCOS, many doctors prescribe it to address some of the most common symptoms of the condition.

May 28, 2020: The Food and Drug Administration (FDA) has requested that manufacturers of certain formulations of metformin voluntarily withdraw the product from the market after the agency identified unacceptable levels of N-Nitrosodimethylamine (NDMA). Patients should continue taking their metformin as prescribed until their health professional is able to prescribe an alternative treatment, if applicable. Stopping metformin without a replacement can pose serious health risks to patients with type 2 diabetes.

How Metformin Works

Metformin is one of the oldest and most-studied drugs available in the United States. It is also known by brand names Glucophage, Glucophae XR, Glumetza, Fortamet, and Riomet.

Although usually used to treat type 2 diabetes, metformin can also help relieve insulin resistance in women with PCOS. It works by improving insulin sensitivity which in turn decreases insulin resistance and glucose production in your body.

Metformin has been studied in girls as young as 8 years of age, with some researchers recommending it to prevent the onset of PCOS. The drug can be safely administered at a dosage ranging from 500 mg to 2550 mg daily.

Metformin lowers blood glucose and insulin levels in three ways:

It suppresses the liver's production of glucose.
It increases the sensitivity of your liver, muscle, fat, and cells to the insulin your body makes.
It decreases the absorption of carbohydrates you consume.

Health Benefits

In addition to controlling blood glucose levels, metformin may provide other health benefits to women with PCOS. Although primarily used to treat type 2 diabetes, metformin can help lower LDL cholesterol and blood fat levels and reduce the risk of cardiovascular disease.

Metformin can also be used to treat infertility and pregnancy complications associated with PCOS. Women with PCOS often have low ovulation rates and irregular menstrual cycles, making it difficult to conceive. Metformin can stimulate ovulation and regulate menstruation, increasing your chances of getting pregnant.

It can also treat diabetes that develops during pregnancy (gestational diabetes) and delay or prevent full-blown diabetes from developing in women who are overweight.

Possible Side Effects

Overall, most people can tolerate metformin just fine. Although metformin can cause side effects in some people, many are mild and are associated with taking the medicine for the first time.

Gastrointestinal Issues

Nausea and gastrointestinal issues such as stomach pain, gas, bloating, and diarrhea are some of the most common side effects. Slowly increasing the dose of metformin over several weeks is recommended for the best results. Some people also find that the extended-release version of metformin is gentler on the digestive system and better tolerated.

Drinking alcohol while on metformin is not recommended. Metformin should be taken with food to minimize side effects, however, you should avoid eating sugary and processed foods, as they can worsen the digestive side effects of the medication.

You may find working with a registered dietitian/nutritionist who specializes in PCOS helpful for establishing an eating plan that works best for your unique needs.

Vitamin B12 Deficiency

Long-term use and high doses of metformin increase the likelihood of vitamin B12 deficiency. A lack of vitamin B12 can cause mood changes, memory loss, and can cause permanent damage to the brain and nervous system.

You should supplement your diet with vitamin B12 and have your levels checked annually. Optimal ranges of vitamin B12 should be >450 pg/mL. Elevated serum homocysteine and urinary methylmalonic acid (MMA) levels, the gold standard in assessing B12, also indicate a B12 deficiency.

Lactic Acidosis

The most serious side effect of metformin is lactic acidosis, a condition caused by the buildup of lactic acid in the blood. This can occur if too much metformin accumulates in the blood due to chronic or acute kidney problems.

Natural Alternatives

There is no natural substitute for metformin. But for those individuals who can’t tolerate it or don’t want to take prescribed medication, there are other ways to improve insulin sensitivity if you have PCOS without the side effects. The most important are following a healthy diet and engaging in regular physical activity.

N-acetyl cysteine is an antioxidant that was shown in one randomized controlled trial to work as well as metformin for reducing insulin and cholesterol in women with PCOS. Myo-inositol was found to restore ovulation resulting in more pregnancies than metformin. Myo-inositol has also been shown to improve insulin and other metabolic aspects of PCOS.