How The Diabetes Medication Metformin Works For PCOS

Polycystic ovary syndrome (or PCOS for short) is characterized as a hormonal disorder that affects women of reproductive age. Current estimates from the Centers for Disease Control and Prevention (CDC) suggest that up to 12% of reproductive-age women may have PCOS.

In people with PCOS, the ovaries may develop small cysts which contain immature eggs. These cysts may appear as a "string of pearls" on ultrasound imaging, explains PERLA Health. If you have PCOS, you might notice various symptoms, such as irregular periods, ovarian cysts, acne, excess hair growth, weight gain, and infertility, per the CDC.

To diagnose PCOS, your doctor might use the Rotterdam criteria, where at least two of three common symptoms must be present. According to a 2018 study published in the Australasian Journal of Ultrasound in Medicine, this includes oligo-anovulation, polycystic ovaries, or excess androgen.

Treatment for PCOS may include lifestyle and dietary changes, along with medications like Metformin. In order to understand how medications like Metformin work, it's important to first understand what causes PCOS.

What exactly causes PCOS?

Although PCOS is triggered by an imbalance of hormones, including elevated androgens (male hormones), the exact cause is not known, per Healthline

According to the Mayo Clinic, one of the primary factors contributing to PCOS is insulin resistance — a condition in which the body's cells become less responsive to the effects of insulin, a hormone that helps regulate blood sugar levels. When the body becomes insulin resistant, the pancreas produces more insulin in order to compensate. Too much insulin can elevate the body's androgen levels.

Genetic factors may also play a role in the development of PCOS. According to the Mayo Clinic, women with a family history of PCOS may be more likely to develop the condition themselves. 

Additionally, low-grade inflammation may contribute to the development by increasing the production of androgens in polycystic ovaries.

What is Metformin, and how does it work?

Metformin is used to treat type 2 diabetes and belongs to a class of drugs called "biguanides," which work by reducing the amount of glucose produced by the liver and improving the body's response to insulin, per MedlinePlus. This claim is reiterated in a 2006 study published in the American Journal of Physiology-Heart and Circulatory Physiology. According to this study, biguanides activate an enzyme called "AMP-activated protein kinase," which helps to regulate glucose metabolism in the body. Biguanides can also help reduce glucose production in the liver and increase glucose uptake in the muscles, leading to improved blood sugar control, according to another 2019 study published in the journal Scientific Reports.

Metformin is typically taken orally, in the form of either immediate- or extended-release tablets. The tablets are usually taken with meals, although the specific dosing instructions may vary depending on your doctor's orders and the specific brand or type of medication.

How Metformin works for PCOS

As mentioned, insulin resistance is a common underlying issue in many women with PCOS — around 60% of women with PCOS have insulin resistance, according to a 2020 study published in the European Review for Medical and Pharmacological Sciences. Metformin's success in treating the condition seems to be related to its ability to reverse insulin resistance. According to the study, this can, in turn, reduce androgen production. 

However, according to a 2014 study published in The Journal of Clinical Endocrinology & Metabolism, rather than improving insulin sensitivity, Metformin improves glucose effectiveness. The authors drew this conclusion after treating a number of women for 12 weeks with Metformin. The results showed clear changes in glucose, insulin, and androgen levels.

Another 2020 study published in the journal Endocrine Connections also adds that long-term use of Metformin can help women with PCOS lose weight

While Metformin is not a cure for PCOS, it can help improve overall health outcomes.

Potential side effects of Metformin

Metformin is generally considered a safe and effective medication for treating type 2 diabetes and PCOS. However, like any medication, it can cause side effects. Some people experience heartburn, nausea, and diarrhea. Other common side effects include loss of appetite, metallic taste in the mouth, headache, constipation, and weight loss. These symptoms tend to go away independently as the body adjusts to the medication. In some cases, taking Metformin with food or starting on a low dose can help reduce these symptoms, says Healthline.

A rare but serious side effect of Metformin is lactic acidosis. This can happen when there's a buildup of lactic acid in your bloodstream, which can be life-threatening. You might experience weakness, fatigue, muscle pain, difficulty breathing, abdominal pain, and vomiting.  However, Healthline says that this condition is more likely to occur in people with kidney or liver disease.

Other treatment options for PCOS

If you have PCOS, your doctor might recommend making lifestyle changes. These may include dietary changes, weight loss, and exercise, says the Mayo Clinic

In addition, you might be prescribed birth control pills which can help regulate menstrual cycles and reduce symptoms such as irregular periods and heavy bleeding. 

Your doctor might also recommend fertility treatments if you are having difficulty becoming pregnant. These may include ovulation induction with medications or in vitro fertilization (IVF).

Your doctor might also prescribe anti-androgen medications, which will help block the effects of androgens in your body and reduce symptoms such as excess hair growth, explains the Children's Hospital of Eastern Ontario. However, these medications can take a while to work. 

Surgery may be recommended to remove ovarian cysts or address other issues, such as endometriosis, per the Cleveland Clinic.