What’s the Difference Between Clomid and Letrozole (Femara)?

As a Reproductive Endocrinologist and Infertility specialist, I often encounter patients struggling with ovulatory dysfunction. One of the most common approaches to treating ovulatory dysfunction is through ovulation induction using medications like Clomid and Letrozole. These two medications are used to induce ovulation, but they work in different ways and have different benefits and side effects.

Clomid (clomiphene citrate) has been used for many years to induce ovulation. It is an oral medication taken for five days, usually starting on the third, fourth, or fifth day of the menstrual cycle. Clomid works by blocking estrogen’s action on the pituitary gland, stimulating the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which are essential for ovulation. Clomid is relatively inexpensive and easy to use, which makes it a popular choice for ovulation induction. If you want to read more about how Clomid works and specific side effects it might have, please check out my recently published post looking to all facets of Clomid.

Letrozole (Femara) is a newer medication used to induce ovulation. Like Clomid, Letrozole is also an oral medication taken for five days starting on the third, fourth, or fifth day of the menstrual cycle. However, Letrozole works differently than Clomid. It is an aromatase inhibitor, which means it blocks the conversion of androgens to estrogen. This lowers estrogen levels in the body, stimulating the release of FSH and LH, leading to ovulation. Letrozole has been found to be more effective than Clomid in inducing ovulation in women with polycystic ovary syndrome (PCOS).

The benefits of Letrozole over Clomid include having a lower incidence of side effects. While both medications can cause hot flashes, mood changes, and headaches, Letrozole is less likely to cause thinning of the endometrium (the lining of the uterus) and cervical mucus, which can make it harder for sperm to reach the egg. Additionally, Letrozole has been found to be more effective than Clomid in achieving pregnancy, particularly in women with PCOS. Studies have shown that Letrozole has a higher ovulation rate and pregnancy rate compared to Clomid in women with PCOS.

However, there are some downsides to Letrozole. Unlike Clomid, Letrozole is not FDA-approved for ovulation induction, meaning it is being used off-label. Ultimately, the choice between Clomid and Letrozole comes down to the patient’s individual needs and goals. Both medications can be effective in inducing ovulation, but Letrozole may be the better choice for some patients, particularly those with PCOS. As a reproductive endocrinologist and infertility specialist, I recommend discussing the options with your healthcare provider to determine the best medication for your individual situation.