Letrozole For PCOS: How Does It Work?

Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects metabolic and reproductive health in people assigned female at birth. It is characterized by elevated androgens (male hormones) and multiple cysts on the ovaries.

PCOS explained

Polycystic ovary syndrome, also called polycystic ovarian syndrome, is a condition in which male hormones are elevated above normal female levels (but not as high as male levels or levels caused by some other conditions).

This results in the eggs not fully developing or being released from the ovaries, producing multiple small cysts and significantly reducing fertility.

PCOS may have symptoms that can include hirsutism, male pattern baldness, acne, and weight gain. However, some people do not discover they have PCOS until they attempt to become pregnant. Standard treatment for PCOS includes birth control pills, but treatment is different if you are trying to get pregnant. Thankfully, many people with PCOS are able to successfully conceive with the right treatment.

What is letrozole (Femara) and how does it help PCOS?

Letrozole is an aromatase inhibitor (lowers estrogen production) that is used to treat infertility in people with PCOS. It is also used to treat certain forms of breast cancer and to improve fertility in people with other issues with ovulation.

The use is currently considered off-label because letrozole is not specifically approved to treat PCOS-caused infertility.

However, studies show that it compares reasonably favorably with the older first-line treatment, clomiphene. It works by temporarily blocking the production of estrogen, which induces ovulation.¹

A clinical trial tested the combination of letrozole and clomiphene. While small, this trial showed that combining the two drugs can work better. Your doctor may thus prescribe you either or both drugs, and the results can vary from person to person.²

Benefits of letrozole for PCOS patients

Letrozole does not help with the general symptoms of PCOS and is prescribed solely to improve fertility. 

Taking letrozole significantly increases the chances of pregnancy and birth as long as it is used correctly and intercourse is timed afterward. Better results can sometimes be obtained by using intrauterine insemination (placing sperm directly into the uterus), which can reduce the time it takes to get pregnant and the related stress.

Letrozole also has a lower risk of multiple births compared to clomiphene.

Who should avoid taking letrozole?

You should make sure you are not already pregnant before taking letrozole. The drug can potentially harm the fetus, which is why it is typically not used to treat breast cancer before menopause. Letrozole is taken for a short period at a time and discontinued before the fetus starts developing.

You should avoid letrozole and seek alternatives if:

• You are taking ethinylestradiol, tamoxifen, or any other medication that impacts estrogen levels. These drugs can have serious interactions.

• You are breastfeeding, especially if your infant is male, as exposure to lactating rats was associated with impaired fertility in male offspring. While no studies have been done on humans, it is better to wait until you are no longer breastfeeding before using letrozole again.

Letrozole dosage for PCOS treatment

Letrozole comes in one dose: 2.5-milligram oral tablets.

For fertility, you will be told to take 2.5 to 7.5mg daily (one to three tablets) starting between the third and seventh day of your menstrual cycle. You should count your menstrual cycle from the first day of your period to the day before your next period to establish this. You will take it for five days — it's important not to take it any longer.

Five days after the last treatment, you should have intercourse every other day or intrauterine insemination.

The dosage is lower if you have a kidney or liver condition, as this can result in the drug staying in your system longer.

If you do not become pregnant, you may repeat the treatment or try something else.

Side effects of letrozole for PCOS

Letrozole can have several side effects, including:

• Hot flashes

• Joint pain

• Muscle pain

• Abdominal bloating

• Weight change

• Nausea. Taking the drug with food can help.

• Night sweats

• Fatigue

• Dizziness

• Headache

Because of the short period of time for which letrozole is taken, you are less likely to experience significant weight gain. Joint pain is a common reason why cancer patients stop taking letrozole, but they are usually taking it over a longer period.

How to further improve your fertility when taking letrozole

If you are trying to conceive with PCOS, then you should not rely entirely on letrozole or any other drug. Here are some other things you can do that can help improve your fertility:

• Quit smoking. Smoking lowers fertility and increases the risk of miscarriage.

• Reduce or eliminate alcohol. It is generally best not to drink at all if you are seriously trying to get pregnant. If you do drink, keep it below two drinks a day.

• Eat a healthy diet.

• Ask your partner not to smoke marijuana. Marijuana decreases sperm quality, which can aggravate fertility problems.

Alternatives to letrozole

Like all drugs, letrozole is not right for everyone. If it does not work for you or is contraindicated, there are a number of other alternatives you can use. They include:

1. Clomiphene. This is an older drug that was the go-to for fertility challenges with PCOS before letrozole. It simulates the action of estrogen to induce ovulation. It is also sometimes used to treat menstrual abnormalities. Clomiphene is not suitable for people with ovarian cysts except for PCOS, uterine fibroids, abnormal vaginal bleeding, thyroid problems, or adrenal disease. It can cause blurred vision. Clomiphene should not be taken if you are already pregnant. One issue with clomiphene is that it can cause both ovaries to release an egg at the same time, increasing the risk of twins.

2. Metformin. Although typically associated with treating diabetes, metformin also helps balance blood sugar levels in people with PCOS. While technically not a fertility drug, metformin can increase the chance of a woman with PCOS conceiving. Metformin is often prescribed alongside letrozole.

3. Gonadotropins. These are purified versions of the hormones FSH and LH, which are necessary for normal ovarian function. They are given by injection. These are not first-line treatments due to higher costs and a much higher risk of multiple pregnancies. However, your doctor may suggest them if other treatments are not working.

People with PCOS are also recommended to pursue lifestyle changes as listed above. Eating a healthy diet, exercising, losing weight, and quitting smoking can all help people with PCOS have a successful pregnancy.

The lowdown

Letrozole has become a first-line treatment for people with PCOS who wish to become pregnant. It is generally more successful than clomiphene and carries less risk of conceiving twins (or more). However, it is not recommended for all patients, does not work for everyone, and should be avoided if breastfeeding.

There are other treatments for PCOS-related infertility that may or may not work better for you. In many cases, your doctor will prescribe more than one drug, typically both letrozole and clomiphene or letrozole and metformin.

With treatment, most people with PCOS can successfully conceive and give birth to a healthy baby, and letrozole is one of the tools that can allow them to do so.