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Treatment with Metformin for PCOS and Infertility

What Is Metformin, Possible Side Effects, and Why It's Used for Infertility

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Updated May 30, 2014

Written or reviewed by a board-certified physician. See About.com's Medical Review Board.

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Metformin is sometimes used to treat women with PCOS who want to get pregnant. While metformin may be used for the treatment of infertility, it is not a fertility drug.

In fact, using metformin to treat infertility in women with PCOS is considered an off-label use. (In other words, pregnancy achievement is not the original intended purpose of this drug.)

What Is Metformin?

Metformin is an insulin-sensitizing drug. To understand what metformin does, you first need to understand what insulin resistance is.

Many women with PCOS have insulin resistance. Insulin resistance is when the body's cells stop reacting to normal levels of insulin. They become less sensitive, or resistant. As a result, the body thinks that there is not enough insulin in the system, which triggers the production of more insulin than it really needs.

There seems to be a connection between insulin and the reproductive hormones. While no one is quite sure exactly how the two connect, it seems that increased insulin levels lead to increased levels of androgens, also known as the male hormones. High androgen levels lead to PCOS symptoms and problems with ovulation.

Metformin, and other insulin-sensitizing medications, help to lower the excess levels of insulin in the body. Besides metformin, rosiglitazone and pioglitazone are other insulin-sensitizing medications that may be used to treat PCOS.

Why Is Metformin Used to Treat PCOS?

There are several reasons why your doctor may prescribe metformin when treating your PCOS:

Insulin Resistance: As stated above, insulin resistance is common in women with PCOS. Metformin may be prescribed to treat insulin resistance, which may then help regulate the reproductive hormones and restart ovulation.

Ovulation Induction and Metformin: Some research on metformin and PCOS shows that menstrual cycles become more regular and ovulation returns with the treatment of metformin, without needing fertility drugs like clomid.

However, some recent, larger research studies did not find a benefit to taking metformin. For this reason, some doctors are recommending that metformin be used to only treat women who are insulin-resistant, and not all women with PCOS regardless of whether or not they are insulin-resistant.

Metformin for Clomid Resistance: While clomid will help many women with PCOS ovulate, some women are clomid-resistant. (This is a fancy way of saying that it doesn't work for them.)

Some research studies have found that taking metformin for 4 to 6 months prior to starting clomid treatment may improve success for women who are clomid-resistant.

Metformin for Repeated Miscarriage: Women with PCOS may be more likely to experience miscarriage than the general population. Some research studies have found that metformin treatment may help reduce the risk of miscarriage in women with PCOS.

A few studies have found that continued metformin treatment during the first trimester of pregnancy may also help prevent miscarriage in women with PCOS. However, the safety of metformin during pregnancy is not well-documented. Deciding to take metformin during pregnancy is a risk that should be carefully discussed with your doctor.

Metformin for Weight Loss: PCOS is linked with obesity, and to the frustration of many women, losing weight with PCOS may be more difficult. Some studies have shown that metformin can help women with PCOS lose weight.

Since losing weight has been shown to help restart ovulation and achieve pregnancy, your doctor may prescribe metformin, along with a diet plan and exercise routine, to help improve your fertility.

What Are the Side Effects of Metformin?

Metformin's most common side effect is stomach upset, usually diarrhea, but sometimes also vomiting and nausea. Taking metformin in the middle of a meal may help lessen this side effect.

This side effect may also lessen over time, and some women find that particular foods trigger more stomach upset than others.

More serious side effects associated with metformin are liver dysfunction and a rare, but extremely serious side effect, lactic acidosis.

While taking metformin, your doctor should monitor your kidney and liver functions. People with heart, liver, kidney, or lung disease should not take metformin. Be sure to provide your doctor with a thorough medical history.

The use of metformin to treat infertility related to PCOS is still being researched, and different doctors have opposing views on if, when, and how to use metformin to treat infertility. Don't be afraid to voice your concerns and questions to your care provider, so that together, you can decide if this treatment is for you.

Take a PCOS Symptoms Quiz here!

More on fertility drugs and treatment:

Sources:

Creanga AA, Bradley HM, McCormick C, Witkop CT. "Use of metformin in polycystic ovary syndrome: a meta-analysis." Obstetrics and Gynecology. 2008 Apr;111(4):959-68.

John E. Nestler, M.D. "Metformin in the Treatment of Infertility in PCOS: An Alternative Perspective." Fertility and Sterility. 2008 July; 90(1): 14-16.

Medications for Inducing Ovulation: A Guide for Patients. American Society of Reproductive Medicine. Accessed September 20, 2010. http://asrm.org/uploadedFiles/ASRM_Content/Resources/Patient_Resources/Fact_Sheets_and_Info_Booklets/ovulation_drugs.pdf

Nawaz FH, Rizvi J. "Continuation of metformin reduces early pregnancy loss in obese Pakistani women with polycystic ovarian syndrome." Gynecologic and Obstetric Investigation. 2010; 69(3):184-9. Epub 2009 Dec 21.

Roy KK, Baruah J, Sharma A, Sharma JB, Kumar S, Kachava G, Karmakar D. "A prospective randomized trial comparing the clinical and endocrinological outcome with rosiglitazone versus laparoscopic ovarian drilling in patients with polycystic ovarian disease resistant to ovulation induction with clomiphene citrate." Archives of Gynecology and Obstetrics. 2010 May; 281(5):939-44. Epub 2009 Dec 3.

Tang T, Glanville J, Hayden CJ, White D, Barth JH, Balen AH. "Combined lifestyle modification and metformin in obese patients with polycystic ovary syndrome. A randomized, placebo-controlled, double-blind multicentre study." Human Reproduction. 2006 Jan; 21(1):80-9. Epub 2005 Sep 30.

Tso LO, Costello MF, Albuquerque LE, Andriolo RB, Freitas V. "Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome." Cochrane Database Systematic Reviews. 2009 Apr 15; (2):CD006105.

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