Letrozole for PCOS

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By CNY Fertility Updated on
Letrozole for PCOS

Letrozole is a fertility medication that is growing in popularity as a treatment option for patients with Polycystic Ovarian Syndrome (PCOS).

Letrozole has proven so beneficial to those with PCOS that many fertility specialists, including those at CNY, have left Clomid (arguably the most famous fertility medication for PCOS) in the wayside for the near-exclusive use of Letrozole as the go-to, first-line medication in helping those with PCOS get pregnant.  

Research has shown that Letrozole can help to significantly increase pregnancy and live birth rates for individuals with PCOS.  

Those with PCOS commonly use Letrozole to induce ovulation in combination with different fertility treatments (like IUI) to increase their chances of getting pregnant.   But how does Letrozole work for PCOS?

Keep reading below to learn all about what Letrozole is, how it helps those with PCOS, success rates, and more!

Fast Facts About Letrozole for PCOS

  • Polycystic Ovarian Syndrome (PCOS) is the most common cause of anovulatory infertility (infertility caused by lack of ovulation).    90–95% of anovulatory women seeking treatment for infertility have PCOS.
  • Letrozole is also known by its brand name Femara.  It is classified as an aromatase inhibitor (lowers estrogen production).  
  • When Letrozole blocks estrogen production, it encourages the body to produce more follicle-stimulating hormone (FSH).  The additional FSH stimulates egg development and increases the likelihood of ovulation.
  • Research shows that Letrozole is effective at inducing ovulation in women with PCOS.
  • Due to similar success rates and lower chance of side effects, letrozole is now the preferred first-line medication for PCOS replacing the famous fertility medication, Clomid.

What is Letrozole?

Technically speaking, letrozole is an aromatase inhibitor (lowers estrogen production).  Letrozole (Femara) was developed for and approved by the Food and Drug Administration to treat specific types of estrogen-sensitive breast cancers.  Letrozole works to decrease the amount of estrogen in the body, which can slow or stop the growth of these types of cancers.

In the early 2000s, fertility specialists took note of this estrogen-lowering mechanism and began exploring its ability to treat infertility.    Today, fertility doctors prescribe Letrozole off-label to increase egg development and ovulation in female patients, including those with PCOS.

How Does Letrozole Work for PCOS?

PCOS accounts for 90% of infertility cases caused by anovulation (lack or absence of ovulation).   For women with PCOS, anovulation is usually caused by an imbalance of the hormones that cause a woman to ovulate, specifically estrogen and FSH.   

Letrozole works for PCOS through its primary mechanism of action, that is, it inhibits estrogen production by repressing the enzyme aromatase.   Research shows that Letrozole can inhibit estrogen levels by at least 97% to 99%. When estrogen production is restricted, the body releases additional amounts of FSH.  

The additional levels of FSH stimulate ovarian follicle(s) to develop and mature in the ovary and help to correct hormonal imbalances which prevent women from ovulating.

In addition to stimulating egg development and ovulation, research has shown that Letrozole can help to significantly improve women’s endometrial thickness, endometrial receptivity, blood flow, and other indicators of endometrium health which helps support implantation and pregnancy rates even further.

Letrozole and Inducing Ovulation

As described above, Letrozole has been shown to reduce estrogen production, increase FSH production, and induce ovulation.  But how effective is Letrozole at inducing ovulation? 

In one study, researchers measured the efficacy of Letrozole for inducing ovulation in patients with infertility and PCOS.  After Letrozole treatment 59 of the 68 women ovulated (86.8%).

Percentage of Those with PCOS That Ovulated with Letrozole Treatment

Clomid (clomiphene) is another medication that is used to induce ovulation in infertility patients, especially those with PCOS.  Research has shown that Letrozole can improve ovulation rates and live birth rates for women who have failed to ovulate with Clomid

Percentage of Those with PCOS That Ovulated with Letrozole v Clomid

Letrozole and Timed Intercourse for PCOS

Timed intercourse is the simplest and least invasive “fertility treatment,” that is paired with Letrozole. Timed intercourse is essentially, just like it sounds; a couple engages in intercourse a few days before ovulation which allows the sperm just enough time to swim through the uterus and into the fallopian tube where it hopefully meets an egg that was ovulated approximately 6-24 hours earlier.

In order to properly time the intercourse, ultrasound and blood work monitoring (or even a home ovulation predictor kit) are used to monitor follicular development, egg growth, and hormone levels. 

Letrozole with Timed Intercourse Success Rates

As mentioned above, in addition to improving ovulation rates for women with PCOS, Letrozole can also increase live birth rates.  In a study published by the National Institute for Health, 374 women were given letrozole for five days starting on day three of their menstrual cycle.  Of the 374 women who received Letrozole treatment, 103 (27.5%) had a live birth.  For comparison, 376 other women were also enrolled in the study, but they received Clomiphene treatment.  Only 72 of the patients treated with Clomiphene achieved a live birth (19.1%.)

Pregnancy Rates - PCOS Clomid v. Letrozole

As a side note, this study further supported the notion that letrozole may induce higher rates of ovulation (61.7% compared to the Clomid treatment group at 48.3%).  

Letrozole with Intrauterine Insemnination (IUI) for PCOS 

The goal of IUI is to maximize the number of sperm that reach the egg so that successful fertilization can occur.  Letrozole is used to ensure the sperm have a healthy egg to shoot for (sometimes more than one). The IUI process consists of three main parts:

  • egg development (with letrozole)
  • determining ovulation
  • sperm collection, preparation, and insemination.  

Most women or couples switch to IUI treatment (aka artificial insemination) after trying multiple timed intercourse cycles.  Other times, like when a patient is using donor sperm, the male partner has sperm motility issues, or the woman is of more advanced age, IUI is used as a first-line treatment alongside Letrozole.

IUI has been shown to increase the chances of achieving pregnancy for women with PCOS compared to timed intercourse cycles.

Pregnancy Rates IUI vs Timed Intercourse in those with PCOS

While this study actually used Clomid, we can see that IUI is generally much more effective than timed intercourse. Since Clomid and Letrozole are fairly similar, we can assume that similar results would have been obtained had letrozole been used.

Success Rates of Letrozole and PCOS

In one study, researchers measured the effects of Letrozole treatment on women with and without PCOS.  The clinical pregnancy rate was 22.5% for both groups, demonstrating that Letrozole with IUI is as effective in treating PCOS as other types of infertility requiring IUI and letrozole.

In another study, researchers compared the effectiveness of Letrozole, Clomiphene, and Gonadotropin drugs in combination with IUI on treating infertility for women with PCOS.  The live birth rates for all three groups were very similar with live birth rates of those with PCOS treated with Letrozole and IUI coming in at 13.5%.

IUI and Letrozole for PCOS Treatment Live Birth and Multiple Gestation Rate

However, the multiple pregnancy rates did show some variance.  The Letrozole treatment group had half the multiples gestation pregnancies (ie twins, triplets, etc) compared to the Clomiphene treatment group, 4.1% vs 8.3%.

As a result of the study, they concluded that since Letrozole had the highest mono-follicular growth rate, it should be recommended as the first choice for women with PCOS undergoing IUI treatment.

Side Effects of Letrozole for PCOS

Like any medication, Letrozole treatment can result in some potential side effects, including:

  • headaches
  • fatigue
  • dizziness
  • hot flashes
  • bone, muscle, or joint pain
  • increased cholesterol in the blood

If you experience any of these symptoms while using Letrozole, please consult with your doctor immediately.

Unlike clomiphene, Letrozole hasn’t been shown to affect the endometrial lining or cervical mucus negatively (which can harm fertility.)

Other Helpful Tips When Considering Letrozole for PCOS

Go Keto

PCOS is caused or at least largely driven by excess an excess consumption of carbohydrate-based foods. Carbohydrates fuel high levels of insulin, which in turn disturb normal hormonal balances and thus PCOS.

A ketogenic diet is a high-fat low-carb diet that is helpful for PCOS and other fertility issues due in part to its hormone-balancing effects.

Consider Supplements

Even if you’re considering or have been prescribed letrozole to help improve or manage your PCOS symptoms, our experts at CNY always recommend those with PCOS take supplements specific to PCOS including inositol

Track Ovulation 

Because the most notable obstacle to getting pregnant with PCOS is a lack of ovulation and letrozole, along with supplements like inositol help those with PCOS ovulate, it’s a good idea to track your ovulation to monitor your progress and know when to have intercource.

In Conclusion

Letrozole is a wonderful treatment option for women experiencing infertility, especially those with PCOS.  Letrozole can help to increase the number of eggs produced, stimulate the ovaries and cause ovulation to occur.  Letrozole treatment is just one of many ways you can increase your chances of getting pregnant with PCOS.  If you are struggling to get pregnant and believe you may have PCOS, consider scheduling a consultation with a fertility specialist, but first, check out our article on fertility consultations with PCOS.

We hope this article was informative, and we look forward to helping you on your fertility journey!

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