Metformin and PCOS Health Benefits and Side Effects

A doctor handing his patient a prescription

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The majority of people who have 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:

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 Food and Drug Administration (FDA) for treating PCOS, many doctors prescribe it to address some of the most common symptoms of the condition.

Warning: Products Pulled From Market

May 28, 2020: The FDA asked manufacturers of certain formulations of metformin to voluntarily withdraw the product from the market after the agency identified unacceptable levels of N-Nitrosodimethylamine (NDMA), a substance that may cause cancer. Continue taking your metformin as prescribed until your doctor is able to prescribe an alternative treatment.

How Metformin Works

Metformin is one of the oldest and most-studied drugs available in the United States. It is also known by the following brand names:

  • Glucophage
  • Glucophage XR
  • Glumetza
  • Fortamet
  • Riomet

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

Metformin has been studied in children as young as 8 years of age, with some researchers recommending it for children diagnosed with PCOS and those with symptoms who are not yet diagnosed. The drug can be safely administered at a dosage ranging from 500 milligrams (mg) to 2550 mg daily.

Metformin lowers blood glucose and insulin levels in three ways:

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

Health Benefits 

In addition to controlling blood glucose levels, metformin may provide many other health benefits to those with PCOS. 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. PCOS often causes problems with ovulation and irregular menstrual cycles, making it difficult to conceive. Metformin can stimulate ovulation and regulate menstruation, increasing your chances of getting pregnant.

Studies show pregnancy rates in PCOS are significantly higher in those taking metformin than in those who aren't. However, research is mixed on whether it's as effective for this purpose as the similar drug clomiphene.

PCOS comes with an elevated risk of miscarriage, but metformin may lower that risk. It can also prevent and help treat diabetes that develops during pregnancy (gestational diabetes), which is especially common in those with PCOS.

Outside of pregnancy, it may delay or prevent full-blown diabetes from developing in people with PCOS who are overweight.

In addition, studies have suggested that metformin is an antioxidant and may have widespread beneficial effects on the body, including:

  • Anti-tumor activity: Research has associated metformin with lower cancer rates and deaths, especially from liver, colorectal, and pancreatic cancers.
  • Anti-aging properties: Metformin use may extend the lifespan, especially when it's started earlier in life.
  • Neuroprotective effects: While results are inconsistent, some research has suggested metformin may improve cognitive function and lower rates of dementia and neurodegenerative disease.

Possible Side Effects

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

Gastrointestinal Issues

Some of the most common side effects of metformin include:

  • Nausea
  • Stomach pain
  • Gas
  • Bloating
  • Diarrhea

Slowly increasing the dose of metformin over several weeks can help you avoid these issues. If you have ongoing digestive issues, your doctor may switch you to the extended-release version of metformin, which is gentler on the digestive system and better tolerated.

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 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 picograms/milliliter. Elevated serum homocysteine and urinary methylmalonic acid (MMA) levels, the gold standard in assessing B12 status, also indicate a B12 deficiency.

Lactic Acidosis

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

If you have serious kidney problems, you shouldn't take metformin. Drinking alcohol while on metformin, and especially binge drinking, can increase your risk of lactic acidosis. Some medications can also increase the risk, including:

Symptoms of lactic acidosis include:

  • Nausea
  • Vomiting
  • Weakness

You can prevent lactic acidosis by:

  • Letting your doctor and pharmacist know about all drugs you're taking so they can watch for potential interactions
  • Avoiding alcohol while taking metformin
  • Taking only the amount prescribed by your doctor

If you develop symptoms of lactic acidosis, get medical attention right away.

Natural Alternatives

There is no natural substitute for metformin. However, if you can’t tolerate metformin, you may be able to improve your insulin sensitivity in other ways. The most important things are eating a healthy diet and getting 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 resistance and cholesterol in people 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.

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