Letrozole and Clomid are both fertility medications used for stimulating ovulation. Clomid or Clomiphene citrate is more common among them. It has been prescribed for over 50 years, while Letrozole was initially used as a breast cancer drug. And since 2001, it has been prescribed off-label for infertility treatment.

And from then, the Letrozole VS Clomid debate has started. Many researchers compare the efficiency of these two drugs. In this article, you will see a comparative discussion of these two drugs based on the latest information.

At first, let’s see what Letrozole and Clomid are in detail.

What is Letrozole?

Letrozole is an oral medication that has been used to treat various breast cancers. It mainly blocks the aromatase enzyme that converts testosterone into estrogen in the ovaries and some other tissues.

Anyway, when the aromatase enzyme stops working, the estrogen level in the blood drops, which makes the pituitary gland produce more FSH (Follicle Stimulating Hormone). And the FSH is responsible for developing mature follicles in the ovary and later ovulation of an egg.

What is Clomid?

Clomid is also an oral-taking drug that belongs to a class called Selective Estrogen Receptor Modulators. This drug stimulates the production of FSH and LH (Luteinizing Hormone). And as we said earlier, FSH produces one or multiple egg follicles that develop and release during ovulation. Along with it, high levels of LH also help to stimulate ovulation.

This medication is often prescribed to a couple at a primary stage before seeing a fertility specialist for more specialized care.

How Do Letrozole And Clomid Work?

As you have seen, Letrozole and Clomid both help the ovaries to develop and ovulate eggs by lowering the estrogen in the body.

They triggered the Hypothalamus part in the brain to think that the body needs more FSH and LH since the estrogen level is very low. And a higher level of FSH is the main thing that achieves the desired output.

Although the result is the same, these two drugs work differently. Now, we will see that elaborately.

Mechanism of Letrozole

Letrozole blocks estrogen synthesis from androgen precursors. This aromatase inhibitor really stops the production of estrogen. Then the brain senses it and increases the production of FSH and LH because of less estrogen in the body.

Letrozole is comparatively short-acting and doesn’t have direct anti-estrogenic effects on the cervical mucus or uterine lining. The recommended dose of this medicine is 2.5 mg daily.

Mechanism of Clomid

Unlike the Letrozole Clomid blocks estrogen receptors in the brain. The selective estrogen receptor modulator actually doesn’t lower the estrogen but tricks the brain into believing that the estrogen level in the body is low. Hence, the pituitary gland ramps up to produce more FSH and LH.

In some cases, Clomid might make the uterine lining thinner and cervical mucus thicker. It takes up to two weeks to be out of the body, which is longer than Letrozole.

The initial dose of this drug is 50 mg for 5 days. The dosage may increase to 100 if the body doesn’t respond. After 30 days of the previous treatment, the dosage may be repeated.

Which One is Better for Pregnancy?

According to various research, Letrozole is more efficient than Clomid for pregnancy. 30% – 40% of women suffer infertility due to ovulatory disorders. PCOS or Polycystic Ovarian Syndrome is the most common cause of infertility.

Clomid has been used to treat PCOS or other ovulatory issues for many years. Despite being a new addition in this field, Letrozole shows an amazing result.

The National Institute of Health researched in 2014 and found that the ovulation rate of Letrozole is 61.7%, and Clomid is 48.3%. Many other studies also show a similar result.

So, overall Letrozole is definitely a better alternative to Clomid. Moreover, it also lowers the chances of multiple pregnancies since it has higher instances of mono-follicular production.


Letrozole is Also a Better Option for Clomid Resistant Patients

Another benefit of Letrozole is it can be used for patients who are Clomid resistant. You know, some patients don’t ovulate with Clomid even after the highest dosage. A patient can be Clomid resistant due to many reasons. Such as-

  • Patient with over 25 BMI (Body Mass Index) tends to be Clomid resistant
  • Hyperprolactinemia (high levels of prolactin in the blood) patient has a low chance of working
  • Women with insulin resistance might experience Clomid resistant
  • Women with hyperandrogenic levels and PCOS also have a lower possibility of Clomid working

Which One is Better for Unexplained Infertility?

Both these drugs are good for unexplained infertility. Although there is no clear verdict on which one is more effective, many studies show that these two medications show a similar result in this case.

However, according to research conducted in 2015, Clomid shows the more effective output. 28% of the Letrozole group and 35% of the Clomid group had a positive pregnancy test during the study.

But despite the difference at that time, the birth rate was similar. So simply to say, Clomid is slightly better than Letrozole for helping patients with unexplained infertility.

Letrozole vs. Clomid Side Effects

In terms of side effects, Clomid tends to have more than Letrozole. And this is one of the main reasons doctors have started prescribing Letrozole instead of Clomid.

Anyway, we have listed some of the common side effects of these two medicines in the following section. So, take a look.

The side effects of Letrozole are as below.

  • Nausea
  • Vomiting
  • Diarrhea
  • Headaches
  • Muscle aches
  • Chest pain
  • Fatigue
  • Constipation
  • Increase cholesterol level
  • Decrease bone mineral density
  • Increase the risk of osteoporosis and fractures.

The side effects of Clomid are as follows.

  • Nausea
  • Vomiting
  • Flushes
  • Blurred vision
  • Ovarian enlargement
  • Breast discomfort
  • Stomach discomfort
  • Increase heartbeats
  • Provoke acne
  • Allergic reactions
  • Uterine bleeding
  • Back pain
  • Muscle pain

Endometrial thinning and multiple pregnancies

These two things have direct effects on fertility. So, let’s talk about them more elaborately.

Endometrial thinning

A thin uterine lining makes it more difficult to achieve pregnancy. Since Clomid blocks estrogen receptors in the brain, the uterine lining does not thicken as it should. Meanwhile, Letrozole cleared from the body more quickly. Thus, the uterine lining has enough time to be thicker.

Multiple pregnancies

Both of these drugs can cause multiple eggs to be ovulated. However, Letrozole produces more mono-follicular cycles. Because of this, the possibility of having twins or triplets becomes lower. You can say this is a positive side effect of Letrozole since it reduces the chances of a complicated birth.

Letrozole vs. Clomid: Which Treatment is More Costly?

Letrozole and Clomid are both inexpensive. Moreover, they are also covered by insurance at an equal rate. You can buy them from any pharmacy at almost the same price.

Which One is Better?

Well, after seeing the discussion, you must realize that Letrozole is certainly a better option. But since the human body is not the same, Clomid might work for you better. So, see what your doctor says and then take the final decision.

Anyways, are you wondering whether these drugs work on men’s fertility or not? Okay, before finishing the write-up, let’s know about it.

Letrozole Vs. Clomid for Men

These two drugs can also be used to treat men’s infertility. They increase the testosterone-oestradiol ratio as well as improve sperm concentration.

Sometimes, male athletes take Clomid for bodybuilding purposes too.

Final Words

Hopefully, this Letrozole Vs. Clomid discussion removes all your confusion by the time. Letrozole and Clomid are both safe and trusted medications. Although Clomid has been used in this field for many years, several research shows Letrozole is a more useful alternative.

However, the final decision is up to your doctor. According to your body, they will judge which one will be the most suitable for you.