Infertility and Metformin
A common cause of ovulation problems and female infertility is Polycystic ovarian syndrome (PCOS). Women with PCOS do not ovulate regularly and have irregular menstrual cycles. Their ovaries contain multiple small cystic structures, usually about 2-9 mm in diameter. For those who suffer from PCOS-induced infertility, Metformin may be a viable option.
Metformin, traditionally a first-line treatment for type 2 diabetes, is also being used as a new treatment for ovulation problems in women with PCOS. Metformin can either be used alone or in combination with Clomiphene Citrate.
Effect of Metformin on Infertility
Metformin helps restore normal menses and reverse infertility by lowering insulin concentrations (which is why it is used to treat type 2 diabetes as well.) Metformin mainly affects insulin sensitivity. Women with insulin resistance-related PCOS produce insulin in excessive amounts. Ovaries seem to be sensitive to high blood levels of insulin, they respond by overproducing male hormones (androgens) like testosterone and this will cause PCOS symptoms such as infertility, excessive hair growth, male pattern baldness and acne. Metformin can cause a decrease in testosterone levels which allows the ovaries to work more efficiently.
Research Evidence on Metformin
During the past decade, scientists have conducted several clinical studies to determine ovarian responsiveness to Metformin. One of these studies (Velasquez et. al) showed that Metfomin use promoted menstrual cycle restoration in a large majority of the participants who had menstrual disorders. Metformin was given to 22 women for 6 months. In addition to restoration of menstrual cycles in about 96% of the participants, Metformin also showed its ability to promote ovulation and pregnancy. Ovulation occurred in about 87% of the women who had menses, whereas pregnancy rate was 18%.
Many other studies suggested that Metformin improves ovarian function, helps in menstrual cycle restoration and promotes fertility. Among these was the extensive 2- year study on 43 women who had amennorrhea and hyperinsulinic PCOS. This study showed that Metformin use restored menstrual cycle in more than 90% of the participants.
How to Use Metformin
Metformin is available in 500 mg, 850 mg, and 1000 mg immediate release tablets. It is also available in 500 and 750 mg slow-release forms.
The usual starting dose of Metformin is 500 mg, once a day for 1 week. Patients need to be advised about the need for regular intercourse (about every 2-3 days) in order to maximize chances for pregnancy. The daily dosage will then be increased by 500mg each week until the maximum daily dose (1200- 1500 mg) is reached. Ovulation may occur within 6 to 8 weeks.
Metformin may also be prescribed in combination with Clomiphene for patients with Clomiphene-resistant PCOS in a dosage determined by a fertility specialist.
Side Effects and Warnings
#What are the precautions when taking this medicine?
• Wear disease medical alert identification.
• You should stop this medicine for 2 days after an x-ray with dye.
• Use caution if you are having surgery, if you have a heart attack, severe infection, or stroke, or if you are 80 years of age or older and have not had your kidney function tested.
• If you have lung disease, talk with healthcare provider.
• If you have a weakened heart, talk with healthcare provider.
• Do not drive if blood sugar has been low. There is a greater risk of an accident.
• Check medicines with healthcare provider. This medicine may not mix well with other medicines.
• Avoid alcohol (includes wine, beer, and liquor).
• Tell healthcare provider if you are pregnant or plan on getting pregnant.
• Tell healthcare provider if you are breast-feeding.
#What are some possible side effects of this medicine?
• Low blood sugar. Signs include anger, shaking, fast heartbeat, confusion, or sweating. Keep hard candies, glucose tablets, liquid glucose, or juice on hand for low blood sugar.
• Belly pain.
• Nausea or vomiting. Small frequent meals, frequent mouth care, sucking hard, sugar-free candy, or chewing sugar-free gum may help.
• Not hungry.
• Abnormal taste. This is usually reversible.
• Blood acidity (lactic acidosis) may rarely occur.
#Reasons to call healthcare provider immediately
• If you suspect an overdose, call your local poison control center or emergency department immediately.
• Signs of a life-threatening reaction. These include wheezing; chest tightness; fever; itching; bad cough; blue skin color; fits; or swelling of face, lips, tongue, or throat.
• Very low blood sugar or very high blood sugar.
• Severe dizziness.
• Difficulty breathing.
• Feeling cold.
• Severe belly pain.
• Severe nausea or vomiting.
• Severe diarrhea.
• Severe muscle pain or weakness.
• Feeling extremely tired or weak.
• Any rash.
• No improvement in condition or feeling worse.
- Balen H., et al. Polycystic ovary syndrome: a guide to clinical management. Informa UK. 2006