Question

What are the differences between Clomiphene (Clomid) and Letrozole (Femara)?

Answer
By Kelly Park | Published: March 9, 2022

Clomiphene (Clomid) and letrozole (Femara) are both medications that help induce ovulation. Clomiphene has been around longer and has been developed specifically for fertility treatment. Clomiphene works by blocking the estrogen receptor (where estrogen sends its signals to) in the master hormonal gland called the pituitary. This works by making the gland think there is not enough estrogen in the system thus signaling the body to release more of the reproductive hormones called luteinizing hormone (LH) and follicle-stimulating hormone (FSH). As a result, a surge in these hormones stimulates egg release. Clomiphene has some anti-estrogen properties that may create unwanted effects such as thinning the uterine lining which may not allow for proper embryo implantation. In addition, the quantity of cervical mucus might also be reduced. Low cervical mucus can prevent sperm from traveling to the egg for fertilization.

Letrozole was originally developed for breast cancer treatment. It works by stopping the enzyme responsible for changing estrogen precursors into estrogen, which has the effect of reducing the overall amount of estrogen in the body. When used for fertility treatment, this is beneficial in sending a message to the pituitary to work harder to produce more estrogen. Like clomiphene, it stimulates more LH and FSH to be released. This creates more estrogen and stimulates ovulation. Unlike clomiphene, it does not negatively inhibit the uterine or cervical lining.

In comparison:

  • Pregnancy rates are very similar with both clomiphene and letrozole.
  • Clomiphene may negatively impact both the uterine lining and cervical mucus production.
  • Clomiphene may have more occurances of multiple births than letrozole.
  • Letrozole has had reports of birth defects associated with its use. These reports have not been backed by follow-up studies.
  • Letrozole can be more expensive than clomiphene.
  • Letrozole may be more beneficial for women with polycystic ovarian syndrome (PCOS) regarding pregnancy success rates, ovulation rates, and live birth rates in obese women.

As with all treatments, patients must discuss the best treatment options for them with their doctor.

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Written by Kelly Park | Contributor

Kelly Park

Kelly Park is the founder and editor-in-chief of FertilitySmarts. She is passionate about fertility education and shining light on the many ways people can become parents. Kelly holds a Bachelor of Arts degree in English Literature and a Master of Education degree in Educational Policy from the University of Alberta. She is a firm believer in the FertilitySmarts mission to help people get smart about their fertility.

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