PCOS Treatment Metformin and PCOS Health Benefits and Side Effects By Angela Grassi, MS, RDN, LDN facebook twitter linkedin Angela Grassi, MS, RDN, LDN, is the founder of the PCOS Nutrition Center. Learn about our editorial process Angela Grassi, MS, RDN, LDN Medically reviewed by Medically reviewed by Lindsey Waldman, MD, RD on November 12, 2019 linkedin Lindsey Waldman, MD, RD, is a board-certified pediatrician and pediatric endocrinologist. Learn about our Medical Review Board Lindsey Waldman, MD, RD Updated on June 29, 2020 Print fluxfoto / E+ / Getty Images Table of Contents View All Table of Contents How Metformin Works Health Benefits Possible Side Effects Natural Alternatives 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. What to Know About Metformin 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. 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 Article 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 Ibáñez L, López-Bermejo A, Díaz M, Marcos MV, de Zegher F. Early metformin therapy (age 8-12 years) in girls with precocious pubarche to reduce hirsutism, androgen excess, and oligomenorrhea in adolescence. J Clin Endocrinol Metab. 2011;96(8):E1262-E1267. doi:10.1210/jc.2011-0555 Lashen H. Role of metformin in the management of polycystic ovary syndrome. Ther Adv Endocrinol Metab. 2010;1(3):117-128. doi:10.1177/2042018810380215 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. Corcoran C, Jacobs TF. Metformin. [Updated 2020 Feb 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK518983/ 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 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 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. Published 2017 Nov 29. 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. Published 2019 Oct 11. doi:10.3389/fphar.2019.01172 Additional Reading Bailey CJ, Turner RC. Metformin. N Engl J Med. 1996;334(9):574-579. doi:10.1056/NEJM199602293340906 Costantino D, Minozzi G, Minozzi E, Guaraldi C. Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double-blind trial. Eur Rev Med Pharmacol Sci. 2009;13(2):105-110. Galazis N, Galazi M, Atiomo W. D-Chiro-inositol and its significance in polycystic ovary syndrome: a systematic review. Gynecol Endocrinol. 2011;27(4):256-262. doi:10.3109/09513590.2010.538099 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 Gerli S, Papaleo E, Ferrari A, Di Renzo GC. Randomized, double blind placebo-controlled trial: effects of myo-inositol on ovarian function and metabolic factors in women with PCOS. Eur Rev Med Pharmacol Sci. 2007;11(5):347-354. 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. Oner G, Muderris II. Clinical, endocrine and metabolic effects of metformin vs N-acetyl-cysteine in women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2011;159(1):127-131. doi:10.1016/j.ejogrb.2011.07.005 Papaleo E, Unfer V, Baillargeon J-P, et al. Myo-inositol in patients with polycystic ovary syndrome: a novel method for ovulation induction. Gynecol Endocrinol. 2007;23(12):700-703. doi:10.1080/09513590701672405 Raffone E, Rizzo P, Benedetto V. Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women. Gynecol Endocrinol. 2010;26(4):275-280. doi:10.3109/09513590903366996 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