PCOS Treatment Metformin and PCOS Health Benefits and Side Effects By Angela Grassi, MS, RDN, LDN Angela Grassi, MS, RDN, LDN Facebook LinkedIn Twitter Angela Grassi, MS, RDN, LDN, is the founder of the PCOS Nutrition Center. Learn about our editorial process Updated on September 28, 2021 Medically reviewed Verywell Health articles are reviewed by board-certified physicians and healthcare professionals. These medical reviewers confirm the content is thorough and accurate, reflecting the latest evidence-based research. Content is reviewed before publication and upon substantial updates. Learn more. by Alex Yampolsky, PharmD Medically reviewed by Alex Yampolsky, PharmD LinkedIn Alex Yampolsky, PharmD, is a clinical pharmacist at Elizabeth Seton Children’s Center, a pediatric long-term care facility in Yonkers, New York. Learn about our Medical Expert Board Print fluxfoto / E+ / Getty Images Table of Contents View All Table of Contents How It Works Health Benefits Possible Side Effects Natural Alternatives Frequently Asked Questions The majority of people who have polycystic ovary syndrome (PCOS) have insulin resistance. Insulin resistance is associated with: Type 2 diabetes Obesity High cholesterol and triglycerides (dyslipidemia) Non-alcoholic fatty liver disease Insulin resistance is believed to play a role in the pathogenesis of PCOS. The mechanism by which insulin resistance gives rise to oligomenorrhea and hyperandrogenemia, however, is unclear. Metformin is not approved by the Food and Drug Administration (FDA) for treating PCOS, but since many people with PCOS also have insulin resistance, your doctor might monitor you for insulin resistance and prescribe Metrofim for you if you have early signs. 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 healthcare provider 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: GlucophageGlucophage XRGlumetzaFortametRiomet Although usually used to treat type 2 diabetes, metformin can also help relieve insulin resistance in PCOS. It works by improving insulin sensitivity, which decreases glucose production in your body and increases peripheral glucose uptake and utilization. This enables the cells of the body to absorb and use the glucose that's already available in your body. Metformin has been studied in children as young as 8 years old who are diagnosed with PCOS or who have symptoms of the condition. 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: 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. What to Know About Metformin Health Benefits In addition to controlling blood glucose levels, metformin may provide many other health benefits for people who have PCOS. Metformin can help lower LDL cholesterol and blood fat levels and reduce the risk of cardiovascular disease. 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. PCOS comes with an elevated risk of miscarriage, and metformin may lower that risk. It can also prevent and help treat diabetes that develops during pregnancy (gestational diabetes), which is common with PCOS. This medication may also delay or prevent full-blown diabetes from developing in people with PCOS who are overweight. Possible Side Effects Overall, most people can tolerate metformin. Although metformin can cause side effects, many are mild and occur when first starting to take it. Gastrointestinal Issues Some of the most common side effects of metformin include: NauseaStomach painGasBloatingDiarrhea Slowly increasing your metformin dose over several weeks can help you avoid these issues. If you have ongoing digestive issues, your healthcare provider 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. 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 damage to the nervous system. While taking this drug, 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: Diamox (acetazolamide) Keveyis (dichlorphenamide) Methazolamide Topamax, Qsymia (topiramate) Zonegran (zonisamide) Symptoms of lactic acidosis include: NauseaVomitingWeakness You can prevent lactic acidosis by: Letting your healthcare provider and pharmacist know about all drugs you're taking so they can watch for potential interactionsAvoiding alcohol while taking metforminTaking only the amount prescribed by your healthcare provider If you develop symptoms of lactic acidosis, get medical attention right away. Natural Alternatives There is no natural substitute for metformin. However, there are natural ways 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. 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. Frequently Asked Questions How long does it take for metformin to regulate menstruation in women with PCOS? Regular menstrual cycles usually return within about six months in women with PCOS taking metformin. Can metformin improve fertility in women without PCOS? Some studies have shown that women without PCOS may benefit from using metformin for infertility. Two studies showed a significantly improved pregnancy rate in women without PCOS who underwent IVF repeatedly and used metformin. Was this page helpful? Thanks for your feedback! Sign up for our Health Tip of the Day newsletter, and receive daily tips that will help you live your healthiest life. Sign Up You're in! Thank you, {{form.email}}, for signing up. There was an error. Please try again. What are your concerns? Other Inaccurate Hard to Understand Submit 16 Sources Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy. Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E. American Association of Clinical Endocrinologists, American College of Endocrinology, and Androgen Excess and PCOS Society disease state clinical review: Guide to the best practices in the evaluation and treatment of polycystic ovary syndrome - part 2. Endocr Pract. 2015;21(12):1415-1426. doi:10.4158/EP15748.DSCPT2 Vitek W, Alur S, Hoeger KM. Off-label drug use in the treatment of polycystic ovary syndrome. Fertil Steril. 2015;103(3):605-611. doi:10.1016/j.fertnstert.2015.01.019 Salber GJ, Wang YB, Lynch JT, et al. Metformin use in practice: compliance with guidelines for patients with diabetes and preserved renal function. Clin Diabetes. 2017;35(3):154-161. doi:10.2337/cd15-0045 Soliman A, De Sanctis V, Alaaraj N, Hamed N. The clinical application of metformin in children and adolescents: A short update. Acta Biomed. 2020;91(3):e2020086. doi:10.23750/abm.v91i3.10127 Prescribers' Digital Reference. Metformin hydrochloride - Drug summary. Wang YW, He SJ, Feng X, et al. Metformin: a review of its potential indications. Drug Des Devel Ther. 2017;11:2421-2429. doi:10.2147/DDDT.S141675 Wang YW, He SJ, Feng X, et al. Metformin: a review of its potential indications. Drug Des Devel Ther. 2017;11:2421-2429. doi:10.2147/DDDT.S141675 Priya G, Kalra S. Metformin in the management of diabetes during pregnancy and lactation. Drugs Context. 2018;7:212523. doi:10.7573/dic.212523 Nasri H, Rafieian-Kopaei M. Metformin: Current knowledge. J Res Med Sci. 2014;19(7):658–664. Aroda VR, Edelstein SL, Goldberg RB, et al. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101(4):1754-1761. doi:10.1210/jc.2015-3754 National Institutes of Health, U.S. National Library of Medicine: MedlinePlus. Lactic acidosis. National Institutes of Health, U.S. National Library of Medicine: MedlinePlus. Metformin. Choudhury H, Pandey M, Hua CK, et al. An update on natural compounds in the remedy of diabetes mellitus: A systematic review. J Tradit Complement Med. 2017;8(3):361–376. doi:10.1016/j.jtcme.2017.08.012 Chhetri DR. Myo-Inositol and its derivatives: Their emerging role in the treatment of human diseases. Front Pharmacol. 2019;10:1172. doi:10.3389/fphar.2019.01172 UpToDate. Patient education: Polycystic ovary syndrome (PCOS) (Beyond the Basics). Jinno M, Kondou K, Teruya K. Low-dose metformin improves pregnancy rate in in vitro fertilization repeaters without polycystic ovary syndrome: Prediction of effectiveness by multiple parameters related to insulin resistance. Hormones (Athens). 2010;9(2):161-170. doi:10.14310/horm.2002.1266 Additional Reading Genazzani AD, Prati A, Santagni S, et al. Differential insulin response to myo-inositol administration in obese polycystic ovary syndrome patients. Gynecol Endocrinol. 2012;28(12):969-973. doi:10.3109/09513590.2012.685205 Le Donne M, Alibrandi A, Giarrusso R, Lo Monaco I, Muraca U. [Diet, metformin and inositol in overweight and obese women with polycystic ovary syndrome: effects on body composition]. Minerva Ginecol. 2012;64(1):23-29. Venturella R, Mocciaro R, De Trana E, D’Alessandro P, Morelli M, Zullo F. [Assessment of the modification of the clinical, endocrinal and metabolical profile of patients with PCOS syndrome treated with myo-inositol]. Minerva Ginecol. 2012;64(3):239-243. Zhuo Z, Wang A, Yu H. Effect of metformin intervention during pregnancy on the gestational diabetes mellitus in women with polycystic ovary syndrome: a systematic review and meta-analysis. J Diabetes Res. 2014;2014:381231. doi:10.1155/2014/381231