Letrozole CAS:112809-51-5

Description

Letrozole, also known by its brand name Femara, is an oral medication used to stimulate egg development and ovulation in female patients undergoing fertility treatment. It has been prescribed by fertility doctors since the early 2000s. Many clinics now prescribe Letrozole in place of Clomiphene Citrate (Clomid), which has been the standard first-line fertility drug for over 50 years.

Reproductive endocrinologists and fertility specialists have started prescribing Letrozole for fertility in place of Clomid because it has fewer side effects, a lower risk of multiple pregnancies and recent research suggests it may result in higher ovulation and pregnancy rates. Letrozole can also be used to improve fertility and induce ovulation for patients who don't respond to Clomid and are considered "Clomid resistant."

In this article, we will cover the basics of what Letrozole is, how it improves fertility, who should take it, how it's used in conjunction with treatments and different protocols.

Clinical Data

How does Letrozole Help Improve Fertility?

Letrozole (brand name Femara) is an aromatase inhibitor primarily used in fertility treatments to help women ovulate and increase egg production. Here's how it works and its benefits in the context of fertility:

1. Inducing Ovulation

How it works: Letrozole helps stimulate ovulation by lowering estrogen levels. When estrogen production is suppressed, the body compensates by producing higher levels of follicle-stimulating hormone (FSH), which helps stimulate the ovaries to develop and mature follicles (where eggs are stored).

Effectiveness for women with PCOS: For women who have Polycystic Ovary Syndrome (PCOS), Letrozole can help regulate ovulation. Women with PCOS often have elevated estrogen levels, which can interfere with ovulation. By reducing estrogen, Letrozole encourages ovulation, giving women a chance to conceive.

2. Increasing Egg Production

Multiple follicle development: In typical ovulatory cycles, one follicle develops and releases an egg. Letrozole can increase the number of developing follicles, leading to multiple eggs being released. This increases the chances of fertilization and conception.

Controlled ovarian stimulation: When used in combination with other treatments, Letrozole can help promote the development of several follicles, which is known as controlled ovarian stimulation. This is beneficial for women seeking to increase their chances of conceiving, especially in fertility treatments like intrauterine insemination (IUI) or in vitro fertilization (IVF).

3. Letrozole for Clomid-Resistant Women

When Clomid doesn't work: For women who do not respond to Clomid (another common ovulation-stimulating drug), Letrozole can be an effective alternative. Studies have shown that Letrozole can improve ovulation rates and live birth rates in women who were Clomid-resistant.

4. Mechanism of Action

Inhibition of aromatase: Letrozole works by inhibiting aromatase, an enzyme responsible for converting androgens into estrogen. This reduces estrogen levels in the body.

Increased FSH and LH: With lower estrogen levels, the pituitary gland releases more FSH and Luteinizing Hormone (LH). These hormones stimulate the ovaries to develop and release mature eggs.

Key Benefits of Letrozole in Fertility:

Helps women with ovulatory disorders, especially those with PCOS.

Increases the chances of ovulating multiple eggs, which can enhance the chances of conception.

May be a better option than Clomid for women who have not responded to other ovulation medications.

Overall, Letrozole is an effective fertility medication that helps women with ovulatory problems, especially PCOS, and can increase the chances of conception by inducing ovulation and promoting the development of multiple eggs in each cycle.

Who Should Take Letrozole

If you experience any of the following, you may be a candidate for Letrozole:

Your periods are very irregular, or you don't experience periods at all.

You have been diagnosed with PCOS.

If your periods are regular but your progesterone levels are low.

You are experiencing unexplained infertility.

You are undergoing fertility treatment.

If you are male with infertility due to low testosterone.

Letrozole for PCOS Patients

Polycystic Ovarian Syndrome (PCOS) is the most common cause of anovulatory infertility ^[5] . 90–95% of anovulatory women seeking treatment for infertility have PCOS ^[6] . As such, it makes sense that a large portion of Letrozole research is conducted on patients with Polycystic Ovarian Syndrome.

Clomid has historically been used as the first-line fertility treatment for PCOS patients with ovulatory issues. However, recent research suggests that Letrozole may produce similar, if not better, results for inducing ovulation and producing live births for PCOS patients.

The National Institute of Health published a study in 2014 that measured the effectiveness of both Letrozole and Clomid to treat infertility for PCOS patients. During the study, 374 women received Letrozole treatment, and 376 women received Clomiphene treatment for five days starting on day three of their cycle for up to 5 cycles. Of the 374 women treated with Letrozole, 103 (27.5%) had a live birth. Of the 376 women treated with Clomiphene, only 72 (19.1%) of the women had a live birth ^[7] .

Researchers from the study above also measured how Letrozole and Clomid affect ovulation rates for PCOS patients. Not only was the live birth rate higher for the Letrozole group, but so was their cumulative ovulation rate. The women in the Letrozole group had a cumulative ovulation rate of 61.7% (834 times in 1352 cycles). The women in the clomiphene group ovulated 48.3% of the time (688 times in 1425 cycles).

Although Letrozole can cause women to produce multiple eggs, the result is not as common in women with PCOS or other ovulatory disorders. For patients with PCOS, Letrozole can provide a slightly different benefit, mono-ovulation. Patients with PCOS are commonly hyper-responsive to gonadotropin drugs. Ovarian hyperstimulation occurs when a woman's ovaries swell and leak fluid into the body. Research published by the American Society for Reproductive Medicine (ASRM) indicates that Letrozole is more likely to produce single ovulation than Gonadtropin drugs or Clomid ^[8] . Letrozole can cause PCOS patients to develop and ovulate an egg while keeping them at a lower risk for hyper-stimulation, which could be caused by other fertility medications.

Letrozole for Unexplained Infertility

Recent studies have shown that Letrozole can be beneficial in treating unexplained infertility ^[9] . In one study, researchers measured the effects of Clomiphene and Letrozole treatment on improving pregnancy rate, miscarriage rate, incidence rate of adverse events, and the number of dominant follicles for patients with unexplained infertility. The results of the study showed that women treated with Letrozole displayed a significantly higher rate of clinical pregnancy as compared to those treated with Clomiphene. There was no statistical difference between the groups for the other fertility outcomes. Researchers concluded that Letrozole is at least as effective as Clomiphene for treating women with unexplained infertility ^[10] .

Researchers compared the efficacy of Letrozole and Clomiphene treatment on 271 women with unexplained infertility in a randomized control trial. More than double the percentage of women treated with Letrozole achieved pregnancy (23.07%) compared to the group treated with Clomiphene (10.7%) ^[11] .

In addition to the higher pregnancy rate, the group treated with Letrozole also saw a statistically significant improvement in endometrial receptivity when measured by endometrial thickness and other indicators. Researchers concluded that Letrozole has a beneficial effect on the endometrium, which may improve implantation and pregnancy rates in women with unexplained infertility ^[12] .

How And When To Take Letrozole

Femara and the generic Letrozole come in 2.5 mg dosages. When treating infertility, the dosage will likely be higher.

A doctor will prescribe a patient 2.5mg, 5, or 7.5mg daily for five days. The course of Letrozole will typically fall between the second and sixth day of your menstrual cycle. Your physician will probably recommend intercourse during the five-day regimen.

How Many Cycles Of Letrozole To Get Pregnant

The response time to fertility drugs varies from woman to woman and is dependent on many factors.

On average, Letrozole induces ovulation and increases fertility after 90 days, which is three cycles.

After one five-day letrozole cycle, ovulation happens in approximately 60% of women, resulting in 24% to 30% of live births.

Foods To Avoid While Taking Letrozole

Most people can eat and drink what they want while taking letrozole. Some patients may experience a loss of appetite.

If this occurs, try eating frequent small meals. In other cases, some women get hungrier when taking Letrozole for infertility, which may require a change in diet.

Discuss with your doctor if you're concerned about a decrease or increase in appetite. Your physician may refer you to a dietitian.

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