Drugs Q & AMedicines

Letrozole Vs. Clomid: Which is Better For Fertility

What is Letrozole?

Letrozole, more commonly known by the brand name Femara, is an aromatase inhibitor originally used to treat early breast cancer in women who have experienced menopause (change of life; end of monthly menstrual periods) and who have had other treatments, such as radiation or surgery to remove the tumor. It is also used to treat early breast cancer in women who have experienced menopause and who have already been treated with a medication called tamoxifen (Nolvadex) for 5 years.

Letrozole (Femara) is also used in women who have experienced menopause as a first treatment of breast cancer that has spread within the breast or to other areas of the body or in women whose breast cancer has worsened while they were taking tamoxifen.

Letrozole (Femara) is used off-label for fertility treatment and can be an effective fertility treatment for women with ovulation problems, or for those with unexplained infertility.

How Letrozole (Femara) works for fertility

Letrozole is in a class of medications called nonsteroidal aromatase inhibitors. Letrozole (Femara) works by decreasing the amount of estrogen produced by the body. Letrozole is typically taken once a day for five days. When you take the drug, it stops androgens in your body from converting into estrogen. When estrogen is blocked, the pituitary gland gets a message that it needs to produce follicle-stimulating hormone (FSH), which stimulates the ovary to produce an egg.

If the course of letrozole is successful (results in ovulation), then ovulation should occur along the normal time course of your menstrual cycle: approximately 12 to 16 days after the first day of your menstrual bleeding.

What is Clomid?

Clomid (clomiphene) is a non-steroidal fertility medicine. It causes the pituitary gland to release hormones needed to stimulate ovulation (the release of an egg from the ovary). Clomid is used to cause ovulation in women with certain medical conditions (such as polycystic ovary syndrome) that prevent naturally occurring ovulation.

How Clomid works for fertility

Clomid works by making the body think that your estrogen levels are lower than they are, which causes the pituitary gland to increase secretion of follicle-stimulating hormone, or FSH, and luteinizing hormone, or LH. Higher levels of FSH stimulate the ovary to produce an egg follicle, or multiple follicles, that will develop and be released during ovulation. High levels of LH stimulate ovulation.                                                                        

How long does it take to get pregnant on letrozole?

The average time to become pregnant in the group taking letrozole was 90 days or about 3 cycles. About 28% of women taking letrozole resulted in a live birth in the study. Letrozole is a drug in the class of medications called aromatase inhibitors.

How long does it take to get pregnant on Clomid 50mg?

Eighty percent of women taking Clomid will successfully ovulate and 10 to 12 percent will conceive per cycle. Which means it typically requires repeat cycles to achieve pregnancy. Ovulation typically occurs 5 – 10 days after taking the last Clomid pill. So if you took Clomid on days 3 to 7 of your cycle, you are most likely to ovulate between days 10 and 16.

What are the side effects of Clomid?

Common side effects of Clomid include:

·         flushing (feeling of warmth)

·         upset stomach 

·         vomiting 

·         breast discomfort 

·         headache 

·         abnormal vaginal bleeding 

Serious side effects

·         blurred vision 

·         visual spots or flashes 

·         double vision 

·         stomach or lower stomach pain 

·         stomach swelling 

·         weight gain 

·         shortness of breath 

Long-term use of Clomid may increase the risk of ovarian cancer.

What are the side effects of Letrozole?

Common side effects of Letrozole include:

·         hot flushes 

·         night sweats 

·         nausea 

·         vomiting 

·         loss of appetite 

·         constipation 

·         diarrhea 

·         heartburn 

·         stomach pain 

·         changes in weight 

·         muscle, joint, or bone pain 

·         excessive tiredness 

·         headache 

·         dizziness 

·         weakness 

·         swelling of the hands, feet, ankles, or lower legs 

·         difficulty falling asleep or staying asleep 

·         vaginal bleeding or irritation 

·         breast pain 

·         hair loss 

·         blurry vision 

Serious side effects

·         chest pain 

·         rash 

·         hives 

·         itching 

·         difficulty breathing 

·         unusual bleeding or bruising 

·         pain in the upper right part of the stomach 

·         yellowing of the skin or eyes 

·         flu-like symptoms 

·         pain, warmth, or heaviness in the back of the lower leg 

·         severe headache 

·         sudden speech problems 

·         sudden weakness or numbness of an arm or leg 

Letrozole may cause or worsen osteoporosis. It can decrease the density of your bones and increase the chance of broken bones and fractures.

Letrozole (Femara) vs. Clomiphene (Clomid)

Which is better?

Studies that compared letrozole vs Clomid reveal that Letrozole was more effective in achieving live births in patients with ovulatory disorders than clomiphene (Clomid) and is equally effective at resulting in births in patients with unexplained fertility.

According to a study on a group taking Letrozole, the average time to get pregnant was 90 days. That is about three cycles. Within that time, 28% of the women in the letrozole study gave birth. The risk of adverse outcomes including miscarriage, ovarian hyperstimulation syndrome, and multiple pregnancies is not also increased.

Why was letrozole banned in some countries?

Letrozole was banned in some countries because of potential risks to infants. The study suggested that letrozole could cause serious fetal anomalies when used off-label for ovulation induction. Researchers reported a malformation rate of 4.7% among 150 babies born after the use of letrozole, compared with a rate of just 1.8% in a database of 36,050 normal conceptions.


Dr. Oche Otorkpa PG Cert, MPH, PhD

Dr. Oche is a seasoned Public Health specialist who holds a post graduate certificate in Pharmacology and Therapeutics, an MPH, and a PhD both from Texila American University. He is a member of the International Society of Substance Use Professionals and a Fellow of the Royal Society for Public Health in the UK. He authored two books: "The Unseen Terrorist," published by AuthorHouse UK, and "The Night Before I Killed Addiction."
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