Letrozole for Treating Infertility in Women With PCOS

New research is showing that the breast cancer drug known as letrozole (Femara) may be a better option than Clomid to improve pregnancy rates in women with PCOS. This is great news for the millions of women who suffer from PCOS, the leading cause of ovulatory infertility in the United States.

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Dr. Richard Legro, a reproductive endocrinologist at Penn State Hershey Medical Center presented results from his recent NIH-sponsored trial at the 2012 American Association of Reproductive Medicine (ASRM) conference that showed 25% of women treated with letrozole had a live birth compared to 16.8% of women who took cloned.

Traditionally, Clomid has been the first-line drug of choice to stimulate ovulation in women with PCOS but has a higher rate of multiple pregnancies and increases exposure to estrogen. In comparison, letrozole doesn't raise estrogen-like Clomid, has a lower risk of cardiac abnormalities and has a lower multiple pregnancy rate.

What Is Letrozole?

Letrozole is an aromatase inhibitor which prevents the conversion of androgen to estrogen. It also improves endometrial thickness and encourages healthy ovarian follicular development. While not approved by the FDA for this use, it has been shown to induce ovulation in women who do not ovulate. For this reason, some infertility specialists are using the drug in women who cannot tolerate or who do not respond well to Clomid.

Letrozole is a drug that is commonly used to treat estrogen-dependent tumors, particularly breast cancer in older, post-menopausal women.


Letrozole comes in 2.5 mg tablets and is taken once a day for five days, usually beginning on day three or day five of your menstrual cycle. You may need monitoring through blood tests and/or ultrasounds to determine when you are approaching ovulation.

Letrozole should be stopped as soon as pregnancy is achieved.

This medication is incompatible with pregnancy and breastfeeding. However, please understand that you are taking this drug before you become pregnant, so it does not increase your risk of having a child with birth defects.

Side Effects

Overall, letrozole is well tolerated. Side effects may include:

  • Fatigue
  • Weight gain
  • Headache
  • Bone or muscle pain
  • Hot flashes
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3 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Kar S. Current evidence supporting "letrozole" for ovulation induction. J Hum Reprod Sci. 2013;6(2):93-8. doi:10.4103/0974-1208.117166

  2. Legro RS, Kunselman AR, Brzyski RG, et al. The Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial: rationale and design of a double-blind randomized trial of clomiphene citrate and letrozole for the treatment of infertility in women with polycystic ovary syndrome. Contemp Clin Trials. 2012;33(3):470-81. doi:10.1016/j.cct.2011.12.005

  3. Monnier A. Long-term efficacy and safety of letrozole for the adjuvant treatment of early breast cancer in postmenopausal women: a review. Ther Clin Risk Manag. 2009;5(5):725-38. doi:10.2147/tcrm.s3858

Additional Reading
  • Nayereh Ghomian, M.D., Ashraf Khosravi, M.D., and Nezhat Mousavifar, M.D. A Randomized Clinical Trial on Comparing The Cycle Characteristics of Two Different Initiation Days of Letrozole Treatment in Clomiphene Citrate Resistant PCOS Patients in IUI Cycles. Int J Fertil Steril. 2015 Apr-Jun; 9(1): 17–26.