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Aug 17, 2021
5 min read

How metformin can be used for PCOS treatment

Metformin (brand name Glucophage) is a prescription medication commonly used to treat type 2 diabetes. Because people with polycystic ovary syndrome (PCOS) often have insulin resistance, healthcare providers may prescribe metformin to prevent diabetes. It is also used to regulate menstrual cycles in people unable to take hormonal birth control. The most common side effects of metformin include diarrhea and nausea. The FDA has issued a boxed warning for the risk of lactic acidosis, a rare but serious complication of metformin therapy.

Disclaimer

If you have any medical questions or concerns, please talk to your healthcare provider. The articles on Health Guide are underpinned by peer-reviewed research and information drawn from medical societies and governmental agencies. However, they are not a substitute for professional medical advice, diagnosis, or treatment.

If you’re struggling with the symptoms of polycystic ovary syndrome (PCOS), it may feel like you’re fighting an endless battle against your hormones. Luckily, effective treatment options, including metformin, are available. Here’s what you should know about metformin for PCOS treatment and if it could be an option for you. 

What is metformin?

Metformin (brand name Glucophage) is a prescription medication FDA-approved to treat type 2 diabetes mellitus. Metformin works by lowering blood glucose (sugar) levels and by improving insulin sensitivity (how well your body uses insulin to lower blood sugar) (Corcoran, 2021). 

Metformin can also be used “off-label” to treat other conditions, meaning the FDA didn’t explicitly approve it for those uses. Still, providers can choose to prescribe it for their patients if they believe the benefits outweigh any risks. These conditions include gestational diabetes (diabetes during pregnancy), prediabetes, and polycystic ovary syndrome (PCOS) (Corcoran, 2021). 

How can metformin help treat PCOS?

PCOS is a common hormonal disorder that can cause ovulation and fertility problems, irregular menstrual cycles, excess hair growth, acne, and obesity (Escobar-Morreale, 2018). 

People with PCOS often have insulin resistance, which means their body needs to make more insulin to lower blood glucose to healthy levels. High insulin levels increase androgens—sometimes called male sex hormones, though they’re present in both men and women—including testosterone. Excess androgen levels (hyperandrogenism) contribute to the symptoms of PCOS (Escobar-Morreale, 2018). 

Since metformin improves insulin sensitivity and lowers insulin levels, it can help decrease androgen levels. This fact led researchers to become interested in the role of metformin for PCOS treatment (Corcoran, 2021). 

Benefits of metformin for PCOS 

Healthcare providers used to prescribe metformin to target many symptoms of PCOS, including infertility and hirsutism (excess hair growth on the face, chest, and back). They believed that the effects of metformin on insulin levels and excess androgen could help treat these symptoms. However, further research found other treatment options to be more effective for these issues (Legro, 2013). Still, there are certain situations where metformin may be preferred: 

  • Menstrual dysfunction: Hormonal birth control is the preferred treatment for normalizing menstrual cycles. But some people have conditions that prevent them from safely taking birth control, such as uncontrolled high blood pressure or smoking 15 or more cigarettes per day if they’re over 35. If you’re unable to take birth control, metformin is an acceptable option to help regulate your period (Corcoran, 2021). 
  • Prevention of ovarian hyperstimulation syndrome: Ovarian hyperstimulation syndrome is a potentially serious condition that occurs when medications used for in vitro fertilization (IVF) overstimulate the ovaries. People with PCOS are at increased risk of developing this condition. Several clinical trials have shown that metformin therapy can help prevent this syndrome (ASRM-a, 2016). 
  • Diabetes prevention: Because insulin resistance is common in people with PCOS, your healthcare provider may periodically recommend an oral glucose tolerance test (OGTT). This test involves drinking a sugary liquid, then testing your glucose level several hours later. If your levels come back higher than expected (but not in the diabetes range), this is considered impaired glucose tolerance or prediabetes. In this situation, metformin can be used to prevent prediabetes from developing into type 2 diabetes. Lifestyle modifications, such as diet and exercise, are also important to reduce your risk of diabetes and cardiovascular disease (Escobar-Morreale, 2018). 

Metformin side effects 

Gastrointestinal complaints are the most common side effects associated with metformin treatment. Diarrhea and nausea occur most commonly, but upset stomach, gas, vomiting, and abdominal pain can also be bothersome (Bonnet, 2017). 

Taking metformin with food and slowly increasing the dose (when it needs to be increased) may help limit side effects. Your healthcare provider may also recommend switching to the extended-release form of metformin if your symptoms don’t go away (Bonnet, 2017). 

Metformin warnings and risks

Before starting metformin, be sure to review these warnings and discuss any concerns you have with your healthcare professional: 

Lactic acidosis 

Rarely, metformin can cause lactic acidosis—a serious condition involving low blood pressure, decreased body temperature, heart rhythm problems, and even death if not treated. The FDA has issued a boxed warning (its strongest warning) for this risk (BMS, 2017). 

While rare, certain risk factors increase your chance of developing lactic acidosis. They include (BMS, 2017):

  • Kidney or liver problems
  • Drug interactions that increase levels of metformin, such as ranolazine (brand name Ranexa), cimetidine, and dolutegravir (brand name Tivicay) 
  • Excessive alcohol consumption 
  • Being 65 or older 
  • Radiologic scans that require IV contrast or dye 
  • Surgery or other procedures that require you not to eat or drink beforehand 
  • Conditions that decrease the amount of oxygen in your body, such as uncontrolled heart failure or severe infections

Early signs of lactic acidosis include muscle pain, difficulty breathing, abdominal pain, tiredness, and generally feeling unwell. Let your healthcare provider know if you experience any of these symptoms while taking metformin (BMS, 2017). 

Vitamin B12 deficiency 

Long-term use of metformin can decrease levels of vitamin B12, but they rarely become low enough to cause problems. Your healthcare provider may recommend routine monitoring to check for any abnormalities, especially if you have anemia (low red blood cells) or peripheral neuropathy (nerve pain). Some people require a vitamin B12 supplement to keep their levels in the normal range (BMS, 2017). 

Alternatives to metformin for PCOS 

Metformin used to be a popular treatment choice for PCOS, but depending on your symptoms, other therapies are more effective. Here are some options your healthcare provider may recommend: 

Weight loss 

Losing weight can improve many symptoms of PCOS and is essential for decreasing your risk of other metabolic conditions, including high blood pressure and high cholesterol (dyslipidemia). Studies have found that losing just 5–10% of your body weight can improve ovulation and pregnancy rates (Sirmans, 2013). 

Unfortunately, diet and exercise alone may not be enough to lose enough weight to affect symptoms of PCOS. Weight loss surgery is an attractive option for some people with PCOS. It may be recommended if you have severe obesity—defined as a BMI (body mass index) over 40. Studies have shown that people who receive weight-loss surgery have significant improvements in hirsutism, menstrual dysfunction, ovulation, and pregnancy rates (Escobar-Morreale, 2018). 

Hormonal birth control 

Hormonal birth control is the preferred method for treating menstrual irregularities, hirsutism, and acne. Oral contraceptives (birth control pills), patches applied to the skin, and vaginal rings are all effective options (Rasquin Leon, 2021). 

Ovulation induction medications 

Clomiphene citrate and letrozole (brand name Femara) are the first-line treatments to induce ovulation. Ovulation is when your ovaries release an egg, a necessary process for pregnancy. Not ovulating (anovulation) or ovulating infrequently (oligoovulation) can cause fertility problems. Compared to metformin, clomiphene citrate and letrozole are more effective at inducing ovulation and improving the chances of becoming pregnant (ASRM-b, 2017). 

PCOS is a common condition that affects many women in their reproductive years. Fortunately, effective treatment options, including metformin, are available. Discuss your symptoms with your healthcare provider and let them know what your reproductive plans are, along with how your symptoms are affecting your day-to-day life. Together, you can develop a treatment plan that’s best for you. 

References

  1. Bonnet, F., & Scheen, A. (2017). Understanding and overcoming metformin gastrointestinal intolerance. Diabetes, Obesity & Metabolism, 19(4), 473–481. doi: 10.1111/dom.1285. Retrieved from https://pubmed.ncbi.nlm.nih.gov/27987248/
  2. Bristol-Myers Squibb Company (BMS). (2017). Glucophage (metformin hydrochloride) tablets. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020357s037s039,021202s021s023lbl.pdf
  3. Corcoran, C., & Jacobs, T. F. (2021). Metformin. In StatPearls. Retrieved from https://pubmed.ncbi.nlm.nih.gov/30085525/
  4. Escobar-Morreale H. F. (2018). Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nature reviews. Endocrinology, 14(5), 270–284. doi: 10.1038/nrendo.2018.24. Retrieved from https://pubmed.ncbi.nlm.nih.gov/29569621/
  5. Legro, R. S., Arslanian, S. A., Ehrmann, D. A., Hoeger, K. M., Murad, M. H., Pasquali, R., et al. (2013). Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. The Journal of Clinical Endocrinology and Metabolism, 98(12), 4565–4592. doi: 10.1210/jc.2013-2350. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399492/
  6. Practice Committee of the American Society for Reproductive Medicine (ASRM)-a (2016). Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. Fertility and Sterility, 106(7), 1634–1647. doi: 10.1016/j.fertnstert.2016.08.048. Retrieved from https://pubmed.ncbi.nlm.nih.gov/27678032/
  7. Practice Committee of the American Society for Reproductive Medicine (ASRM)-b. (2017). Role of metformin for ovulation induction in infertile patients with polycystic ovary syndrome (PCOS): a guideline. Fertility and Sterility, 108(3), 426–441. doi: 10.1016/j.fertnstert.2017.06.026. Retrieved from https://pubmed.ncbi.nlm.nih.gov/28865539/
  8. Rasquin Leon, L. I., Anastasopoulou, C., & Mayrin, J. V. (2021). Polycystic ovarian disease. In StatPearls. Retrieved from https://pubmed.ncbi.nlm.nih.gov/29083730/
  9. Sirmans, S. M., & Pate, K. A. (2013). Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clinical Epidemiology, 6, 1–13. doi: 10.2147/CLEP.S37559. Retrieved from https://pubmed.ncbi.nlm.nih.gov/24379699/