Letrozole for Treating Infertility in Women With PCOS

Research has been showing that the breast cancer drug Femara (letrozole) may be a better option than Clomid (clomiphene) to improve pregnancy rates in women with polycystic ovary syndrome (PCOS). PCOS is the leading cause of ovulatory infertility in the United States.

Pregnant Woman With Cat
Buena Vista Images / Getty Images

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 Clomid.

Follow-up studies have confirmed that Letrozole is more effective than Clomid for treating infertility in PCOS.

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

What Is Letrozole?

Letrozole is an aromatase inhibitor that prevents the conversion of androgen to estrogen. It is commonly used to treat estrogen-dependent tumors, particularly breast cancer, in peri-menopausal or post-menopausal women.

This medication is approved for treating hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.

Uses

While not approved by the FDA for this use, letrozole has been shown to induce ovulation in women who do not ovulate. This is a common cause of infertility in PCOS, described as anovulatory infertility.

For this reason, some infertility specialists have been using the drug in women who cannot tolerate or who do not respond well to Clomid. Over the past years, it has emerged as the first-line treatment for anovulatory infertility in PCOS.

It works by improving endometrial thickness and encouraging healthy ovarian follicular development.

Dosing

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 the 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, taking this drug before you become pregnant 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
5 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. Khakwani M, Parveen R, Yousaf S, Tareen AU. Efficacy of letrozole versus clomiphene citrate on ovulation induction in patients with polycystic ovarian syndrome. Pak J Med Sci. 2022 May-Jun;38(5):1155-1158. doi:10.12669/pjms.38.5.5565

  4. Bahri Khomami M, Teede HJ, Joham AE, Moran LJ, Piltonen TT, Boyle JA. Clinical management of pregnancy in women with polycystic ovary syndrome: An expert opinion. Clin Endocrinol (Oxf). 2022 Aug;97(2):227-236. doi:10.1111/cen.14723

  5. 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.