Letrozole is an oral medication which has been FDA approved and marketed in order to lower blood levels of estrogen in certain medical conditions such as breast cancer. It acts by preventing formation of estrogen. There is a large body of medical research showing that letrozole, when taken briefly early in the menstrual cycle, increases the production of the hormone FSH and can promote ovulation in patients who are not ovulating. Letrozole is not FDA approved for treatment of infertility and ovulation. Like many drugs, after FDA approval for a different reason, physicians have conducted clinical research studies showing usefulness of the drug for a different form of therapy. It is now a commonly used medication internationally for infertility.
At this point, the medical literature contains increasingly positive information about the effectiveness of letrozole in the treatment of ovulatory problems. Most studies suggest that it is similar in effectiveness to clomiphene citrate (FDA approved for many years for treatment of ovulation). One recent study suggests that Letrozole is more effective than Clomid for ovulation treatment in women with Polycystic Ovary Syndrome. Because the mechanism by which letrozole acts is somewhat different than clomiphene citrate, it may reduce the incidence of several undesirable clomiphene citrate side effects: reduced endometrial thickness, reduced cervical mucus, and emotional mood swings. The side effects of brief use (5 days) of letrozole tend to be minimal: headache, nausea, hot flashes, bone pain and reduced energy level (longer therapy related to other applications has other side effects). Similar to clomiphene citrate, letrozole may result in development of more than one egg and therefore there is a somewhat higher risk of multiple pregnancy. The precise risk with this drug has not been defined. It is probably similar to clomiphene citrate with twins at approximately 8% and higher order multiple pregnancy (triplets) less than 1%.
The studies related to the use of letrozole for ovulation treatment and risk of fetal anomalies are all very reassuring and those large studies do not show an increased risk of birth defects when letrozole is used to induce ovulation. Based on these multiple, very large studies, there does not appear to be any reason for concern about birth defects from letrozole. Nevertheless, the manufacturer has warned against using this drug for the purpose of ovulation/fertility treatment, clearly to avoid liability issues. We believe this medication is safe for your use but we consider it a “second-line” agent because the FDA has not officially approved its use compared to clomiphene or FSH.