PCOS and Metformin (Glucophage)

Metformin (brand name "Glucophage" or "Glucophage XR") is a drug that your doctor may have prescribed for you if you have polycystic ovary syndrome (PCOS). This drug offers both benefits and risks, summarized below. We also offer some suggestions if you are now taking it.

What Is Metformin (Glucophage)?

Metformin is a drug that has been used to help control blood glucose levels in people with Type 2 Diabetes. Although Glucophage has been used in Europe for over 25 years, it was not available in the US until 1995. The FDA has approved metformin only for the treatment of Type 2 Diabetes. Consequently, some physicians don't have much clinical experience with Glucophage, or are reluctant to use it unless the patient has diabetes.(1)
Metformin appears to work in three ways. First, it decreases the absorption of dietary carbohydrates through the intestines.
Second, it reduces the production of glucose by the liver.(2) The liver uses the raw material in your food to create a reserve supply of blood sugar. When your body experiences stress, the liver releases the reserve glucose to supply your brain and muscles with an immediate source of energy to cope with the stress. Glucophage suppresses the production of this reserve fuel.
Third, and perhaps most importantly, metformin increases the sensitivity of muscle cells to insulin.(2) Insulin is the hormone that delivers glucose into your cells to be burned as fuel, or stored. Women with PCOS frequently have "insulin resistance", a condition where excessive amounts of insulin are required in order to get blood glucose moved into cells, where it belongs. Glucophage helps your body to transport glucose with relatively less insulin, thus lowering your insulin levels. Chronically high levels of either glucose or insulin in your blood contributes to obesity, heart disease, infertility, and certain cancers, as well as the development of diabetes.
Metformin is available in three different forms:

1. Generic Metformin Hcl
2. Glucophage (brand name)
3. Glucophage XR (brand name)

Glucophage is available in 500 mg, 850 mg, or 1,000 mg tablets. The usual dose is 850-1,000 mg twice daily. The maximum safe dose is thought to be 850 mg three times daily. To minimize GI upset or diarrhea, it's recommended that you start with a low dosage and work your way up to the recommended dose.
Glucophage XR, an extended-release version of Glucophage, allows you to take only one dose a day. The slower release of long-acting Glucophage XR may help to reduce stomach upset that may occur with the regular Glucophage or metformin.
Glucophage is chemically identical to generic metformin, so you can save money by using generic metformin.

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Benefits of Metformin (Glucophage)

LOWERING OF INSULIN, TESTOSTERONE, AND GLUCOSE LEVELS. Quite a number of studies indicate Glucophage reduces insulin, testosterone and glucose levels -- which reduces acne, hirsutism, abdominal obesity, amenorrhea and other symptoms. In one study conducted at Virginia Commonwealth University, 24 obese PCOS women were given metformin or placebo. The 11 women who received the metformin experienced a reduction in insulin levels, which slowed the activity of an enzyme in the ovaries that stimulates excess production of testosterone. As a result, testosterone levels also dropped.(3)
Glucophage appears to do the same for non-obese PCOS women, according to a study from the University of Medical Sciences in Poznan, Poland. Thirty nine PCOS women were given Glucophage for 12 weeks. They had improvements in insulin, testosterone, hirsutism and acne. (4)

PREVENTION OR DELAY OF ONSET OF DIABETES. Glucophage may help to prevent diabetes, according to a study at George Washington University.(5) In this study, 3,234 non-diabetics with elevated blood glucose were given metformin, placebo, or lifestyle recommendations. The incidence of diabetes in the metformin group was 31% less than in the placebo group.

RESTORATION OF NORMAL MENSTRUAL CYCLE. A number of studies have shown that menstruation can be restored in many women with PCOS. For example, in a study at Jewish Hospital in Cincinnati, 43 women who were not having periods took Glucophage, and 39 of them resumed normal menses.(6) In another study at Jewish Hospital, 11 teenage girls with PCOS were put on metformin and a high-protein, low-carbohydrate diet. Ten of the 11 girls resumed regular periods.(7)

IMPROVED CHANCE OF PREGNANCY. A study of 48 women with PCOS and infertility was conducted at the Baylor College of Medicine. They were first given metformin and 19 of them resumed menstruating and showed indications of ovulation. But 10 required clomiphene (a fertility drug) in addition to metformin in order to show evidence of ovulation. Twenty women of the 48 (42%) became pregnant. However, 7 of the 20 miscarried.(8)

REDUCED RISK OF MISCARRIAGE. Another aspect of PCOS-related infertility is the tendency for repeated miscarriages. A study from the Hospital de Clinicas Caracas in Venezuela looked at 65 women who received Glucophage during their pregnancies vs. 31 who did not. The early pregnancy (first trimester) loss rate in the metformin group was 8.8% as compared to a 41.9% loss in the untreated group. Of those women who previously had miscarried, 11.1% of the metformin group miscarried again, while 58.3% of the untreated group again miscarried. (9)

REDUCED RISK OF GESTATIONAL DIABETES. In another study at Jewish Hospital in Cincinatti, gestational diabetes risk was evaluated in two groups of PCOS women. The first group was 33 non-diabletic women who had conceived while taking metformin or took it during their pregnancy. This group was compared to a group of 39 PCOS women who did not take it. Only 3% of the metformin group developed gestational diabetes as compared to 31% in the non-metformin group.(10)

WEIGHT LOSS AND OTHER BENEFITS. Metformin may contribute to weight loss in some diabetics.(11) However, weight loss does not appear to be one of its primary benefits. Glucophage may also be of some value improving success with in vitro fertilization, lowering cholesterol, and improving energy.

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