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Clomid or Femara: Which One Is Better?

Clomiphene citrate (Clomid, Serophene) is an oral medication that has been used for induction of ovulation for almost 40 years. Over the last 20 – 25 years it also has been used for superovulation to increase the chance of conceiving in women who are ovulatory. Commonly, intrauterine insemination (IUI) is combined with this medication.

Clomiphene is a very weak estrogen that attaches to the estrogen receptor in the hypothalamic-pituitary area. The medication acts like an “anti-estrogen”. The brain interprets this as the quantity of estrogen circulating in the body is low and, therefore, sends a signal to the pituitary to stimulate the ovary to work harder. For most women who do not ovulate, this medication commonly will make them ovulate. For women who are already ovulating, the medication will stimulate the ovary to increase the production of the female hormones and stimulate ovulation. Occasionally, a woman will become pregnant with twins. Unfortunately, this anti-estrogen action can affect the cervical mucus and the endometrium. The result is that there is less cervical mucus produced and the sperm may have a harder time penetrating the mucous. Also, the endometrial liming may not develop as well and this could interfere with an embryo implanting. In general, the positive effects of clomiphene outweigh the negative effects.

Letrozole (Femara) was developed to be used primarily to treat certain kinds of breast cancer in postmenopausal women. Letrozole is an aromatase inhibitor. Aromatase is an enzyme that converts estrogen precursors (androgens) into estrogen. The medication works by reducing the production of the total amount of estrogen in the body. It is very helpful for treating patients who have breast cancers that are fed by estrogen. Letrozole helps to starve those cancer cells by depriving them of estrogen. Letrozole was found to induce ovulation in the same manner as clomiphene. When letrozole inhibits the conversion of androgens to estrogens, the estrogen level in the body drops and the hypothalamus sends a signal to the pituitary to stimulate the ovary to work harder. Commonly, intrauterine insemination (IUI) is combined with this medication. In contrast to clomiphene, this medication does not have the anti-estrogen effect and has been found to be associated with better endometrial development. Theoretically, letrozole would be better for patients who have used clomiphene and experienced poor endometrial development. Experience with this medication reveals the pregnancy rates are very comparable to clomiphene. Also, the multiple birth rate with letrozole is lower.

Unfortunately there was a report of a concern about birth defects with the use of letrozole for induction of ovulation. This information led the manufacturer, Novartis, to add a black box warning in the package insert stating that the use of letrozole for induction of ovulation is contraindicated. However, there have been many follow up studies failing to demonstrate any adverse effects of the medication. Consequently, the medication is frequently used by many physicians. Also, letrozole is more expensive than clomiphene. Clomiphene is quite inexpensive.

When considering which if these oral medications to use, please ask your physician which one is better for you.

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