Can You Take Letrozole for Fertility?
Key takeaways:
Letrozole (Femara) is an oral medication that lowers estrogen levels by blocking the enzyme (protein) aromatase. This can result in ovulation.
Letrozole appears to work as well, if not better, for improving fertility compared to other oral options.
Although not FDA approved as a fertility medication, letrozole is one of the first choices for fertility treatment in people with infertility related to polycystic ovary syndrome (PCOS).
Having difficulties getting pregnant can be frustrating, confusing, and emotionally draining, to say the least. Infertility is defined as not becoming pregnant after a year of trying (or after 6 months of trying if you’re over 35). Fertility struggles are common, affecting as many as 1 in 8 couples.
There are many possible causes of infertility, and medications are available to help treat certain types of infertility. Some infertility medications require an injection, while others can be taken by mouth. Some people have to try a few different options before having success.
In recent years, letrozole (Femara) has been gaining popularity as an oral pill for treating certain types of infertility. However, this medication isn’t FDA approved for this use. Still, it’s a common choice and recommended by experts.
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Below, we’ll discuss what letrozole is, what types of infertility it can be used for, and how it compares to another common oral fertility treatment.
What is letrozole typically used for?
Letrozole is FDA approved for the treatment of estrogen-sensitive breast cancer in postmenopausal people. More recently, letrozole has gained momentum as an off-label treatment to help improve fertility. This is because it can stimulate (trigger) ovulation in some cases.
Ovulation stimulation is when you use medications to help your body release an egg. Fertilization of an egg by sperm could then lead to a pregnancy. Ovulation stimulation medications are used in certain conditions affecting fertility, such as polycystic ovary syndrome (PCOS).
PCOS is a health condition caused by hormone imbalances. It can lead to problems with metabolism and reproductive health. Infertility is one possible complication of PCOS.
How does letrozole work?
Letrozole blocks an enzyme (protein) known as aromatase. Aromatase helps make the hormone estrogen from androgens, such as testosterone. After menopause, this is one of the primary ways the body creates estrogen. So, taking letrozole after menopause can help lower the amount of estrogen in the body.
This can be helpful in treating estrogen-sensitive cancers. However, it works a bit differently for fertility.
Why does letrozole work for fertility?
Fertility is based on a complex relationship between different hormones released at specific times during the menstrual cycle. Many things may cause infertility, including hormone imbalances.
In certain types of infertility, hormones may be released at the wrong time or in amounts too low to release an egg. Without an egg, pregnancy doesn’t happen.
By lowering estrogen levels in a premenopausal person’s body, letrozole causes the brain to release other hormones needed for fertility, including follicle stimulating hormone (FSH). FSH causes immature eggs — known as follicles — to grow and mature. Ovulation occurs when one dominant follicle matures and releases an egg.
Letrozole may be particularly useful in PCOS-related infertility. For people with PCOS, ovulation may not happen regularly or — in some cases — at all. People with PCOS may also have higher levels of testosterone compared to people without PCOS.
PCOS is the most common cause of infertility in people assigned female at birth. As we’ll discuss next, letrozole appears to be about as effective as other fertility medications in PCOS-related infertility.
How effective is letrozole for fertility?
For many years, clomiphene (Clomid) was the only available oral option for ovulation stimulation. Clomiphene blocks estrogen’s activity throughout the body, which can lead to ovulation. But since clomiphene affects many areas of the body, it can have many side effects as well.
Common side effects experienced with clomiphene include:
Enlarged ovaries
Hot flashes
Stomach pain or bloating
Nausea or vomiting
Breast tenderness
Visual problems (e.g., blurry vision, floaters, flashes, light sensitivity)
Headaches
Unusual vaginal bleeding and spotting
Some amount of clomiphene can stick around in the body for about a month, meaning these side effects can continue even after you’ve stopped taking it. Because of these disadvantages, researchers began looking into using letrozole for fertility.
In early studies, letrozole was compared to clomiphene in people with PCOS-related infertility. In these studies, letrozole and clomiphene generally showed similar rates of ovulation and pregnancy. But these early studies also hinted that letrozole may have a slight edge over clomiphene for ovulation in certain people.
There were also no differences between those who used letrozole and those who used clomiphene for:
Multiple births (such as twins)
When discussing fertility medications, it’s important to look at the number of live births. This is because even if ovulation happens, pregnancy and birth may not. These early results were promising because it demonstrated that letrozole works at least as well as clomiphene.
In more recent studies, letrozole has shown higher rates of live birth compared to clomiphene. Close to 28% of people with PCOS taking letrozole in one study successfully got pregnant and had a baby, compared to about 19% of those taking clomiphene. This study further supports letrozole as an option for PCOS-related infertility.
It’s important to remember that many factors go into treating infertility. Success rates can vary based on a person’s age, how well their fallopian tubes (the tubes connecting the ovaries to the uterus) work, and many other overall health factors.
Other medications that may be prescribed for PCOS-related infertility include metformin and gonadotropins. Gonadotropins are a group of medications that help stimulate ovulation. Evidence about how these treatments compare to letrozole is lacking. Typically, they are recommended after both letrozole and clomiphene have been tried.
What common side effects are associated with letrozole?
Common letrozole side effects can include:
Hot flashes
Joint pain
Flushing
Tiredness
Headache
Dizziness
It’s important to keep in mind that available letrozole side-effect information is what’s known for people with breast cancer. Side-effect research surrounding fertility is lacking.
When might a healthcare provider prescribe letrozole for fertility?
Based on the available evidence, your healthcare provider may choose to prescribe letrozole for PCOS-related infertility as a first-choice option. It may also be considered with other fertility problems related to ovulation.
What risks should you consider before taking letrozole off-label?
An unapproved use of a medication is considered “off-label.” This doesn’t mean a medication can’t be safely or effectively used in these situations. But more caution is needed when a healthcare provider prescribes a medication for an off-label use.
By comparison, if you’re taking a medication for an FDA-approved use, you can be sure:
The FDA reviewed the risks and benefits of the medication for that condition.
The approval is supported by strong scientific evidence.
There is standard information available about how to safely and effectively use the medication.
If you take a medication off-label, there may be less guidance surrounding these points. It’s important to thoroughly discuss what is known about an off-label medication with your healthcare provider before taking it. You may want to also ask them for reliable resources you can refer to after your appointment is over. This can help you feel more comfortable taking your medication.
The bottom line
While not FDA approved as a fertility treatment, letrozole is considered a first-choice option for improving fertility in people with PCOS. Letrozole has been shown to work as well, if not better, than clomiphene at stimulating ovulation, as well as leading to successful pregnancies and live births. If you have PCOS and have been having trouble getting pregnant, be sure to discuss your fertility concerns with your healthcare provider at your next visit.
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