Fertility Drugs, Metformin (Glucophage)
Metformin for the Treatment of PCOS
Polycystic ovary syndrome (PCOS) is a common condition characterized by failure to ovulate (and irregular menstrual periods), a tendency toward excess body hair, acne and/or oily skin, and a tendency to be overweight. It is estimated that one in twenty reproductive age women have PCOS. While this is a common problem in the infertile population, the cause of this condition is still not completely understood. There is new information to suggest that the underlying cause in many women with PCOS is insulin resistance. Women with this condition are not diabetic-their blood sugar levels are normal-however, their insulin levels are frequently elevated. Lowering the insulin levels acts to decrease elevated levels of male-type hormones (such as testosterone) and, in many cases, restores ovulation and normal fertility.
Treatment of infertility for women with PCOS is ovulation induction with clomiphene citrate (Clomid, Serophene) and/or Metformin. For those who fail to ovulate in response to clomiphene citrate alone, treatment with Metformin may be added. Metformin does not have a F.D.A. indication for its use in PCOS but there is substantial research on the application of Metformin in this setting and Metformin is being used at reproductive endocrinology and infertility clinics around the world for this common problem.
Metformin has no effect on insulin production per se but facilitates insulin action in the body so that the body will naturally make less of it. It should not be used in women with insulin-dependent diabetes, liver dysfunction, kidney disease, or who are exposed to IVP dye (for X-ray testing of the kidneys).
It should not be used in times of acute physical stress such as severe illness (influenza), surgery or recovery from significant trauma. Dehydration should be avoided while taking Metformin. Alcohol should be avoided while taking Metformin (we recommend no alcohol intake while attempting to conceive but limiting consumption to one drink or less per day is sensible).
If surgery is anticipated, Metformin can be discontinued 2 days in advance. Metformin may interact with steroids, diuretics, nicotinic acid, oral contraceptives, and coumadin (warfarin sodium). Please let us know if you are taking or anticipate taking those medications.
The most common side effects are nausea, vomiting or diarrhea. Starting the medication slowly and increasing the dose gradually will help avoid these symptoms. Also, these side effects improve and usually resolve after a few weeks of taking Metformin as your body adjusts to the new treatment. If the medication causes vomiting it should be discontinued. If diarrhea or nausea is bothersome, reduce the dose for a week and then attempt to resume your previous dose. Metformin may cause a metallic taste in the mouth and decreased appetite. Many women lose weight while taking Metformin and this is encouraged as long as you are heavier than your “optimal” weight and you follow a sensible, nutritious diet.
Related medications, such as Troglitazone, have caused liver injury and even liver failure in a small number of women. Troglitazone was taken off the market in 2000 for these concerns. Persistent vomiting or pain in the upper abdomen should be brought to our attention.
Lactic acidosis is a dangerous condition that can be caused by Metformin. Lactic acidosis occurs most commonly in patients with impaired kidney or liver function, or who are dehydrated. It is recommended if you become dehydrated, such as during a bad case of the flu, or you develop any serious medical problem, you should discontinue Metformin until the dehydration or serious medical problem has resolved. The overall incidence of lactic acidosis in Metformin users is 1 in 33,000.
Metformin preparations come as 500 or 850mg pills and may be taken as three different dosing regimens: (Always take with food. If you have trouble tolerating an increased dose, drop back to the previous dose and try to increase again the following week. If it takes 4 or 5 weeks to get up to the correct dose that is okay. Increase the dose as slow or as fast as tolerated.) The cost of Metformin is approximately $75.00 per month.
Kidney and liver function blood testing will be performed as a baseline before you begin Metformin. Unless the initial test results are abnormal, repeating these tests is not necessary.