Letrozole vs Clomiphene for Fertility: Ovulation Induction in PCOS Explained

If you have polycystic ovary syndrome (PCOS) and are trying for a baby, you may be offered tablets to help you ovulate. The two best known are clomiphene (often sold as Clomid) and letrozole. Letrozole is mainly a breast cancer medicine, so many people are surprised to hear it suggested for fertility. This guide explains how the two compare and what current guidelines say.

A note on names: the NHS now calls PCOS polyendocrine metabolic ovarian syndrome (PMOS)⁶. We use PCOS here because it is still the name most people know.

Why ovulation tablets are used in PCOS

Many women with PCOS do not ovulate (release an egg) regularly, which makes it harder to get pregnant. Medicines that encourage the ovaries to release an egg each month are a common first step⁵. For the wider treatment of PCOS, including metformin and lifestyle changes, see our guide to PCOS treatments.

How the two medicines differ

• Clomiphene is licensed to treat women who do not ovulate properly and want to become pregnant³. It encourages the monthly release of an egg⁵.
• Letrozole is an aromatase inhibitor that lowers oestrogen levels. It is licensed for breast cancer, but the NHS notes it can occasionally be used as a fertility treatment for PCOS⁴. Its use for ovulation is off-label in many countries². For its use in cancer, see our guide to letrozole, anastrozole or tamoxifen.

What the guidelines say

The 2023 International Evidence-based Guideline for PCOS, developed with dozens of professional societies, recommends²:

• letrozole as the first-choice medicine to help ovulation in women with PCOS who do not ovulate and have no other fertility problems
• letrozole rather than clomiphene, to improve ovulation, pregnancy and live birth
• that where letrozole cannot be used, for example because it is not allowed off-label, other ovulation medicines can be used

This advice is based partly on a large US trial of 750 women with PCOS. Women given letrozole had more ovulations and more live births than those given clomiphene, with no significant differences in miscarriage, twins or birth defects overall¹. Your own chances depend on many things, including your age and your partner’s fertility, so ask your specialist what to expect.

How treatment works

• Before starting: pregnancy is ruled out, and a prenatal vitamin is started alongside treatment, as part of normal pre-pregnancy care².
• Clomiphene is usually started at 50 mg a day for 5 days, early in the menstrual cycle. The dose is only increased if you do not ovulate, and a lower dose is advised in PCOS because the ovaries can over-respond. Treatment is usually limited to around six cycles³.
• Letrozole is used off-label for fertility, so there is no licensed fertility dose. Your specialist will set the dose and timing².
• Monitoring: your team will check whether you are ovulating and how your ovaries are responding²³.

Side effects

In the large trial, clomiphene caused hot flushes more often, while letrozole caused tiredness and dizziness more often. Other side effects were similar¹. Fertility medicines in general can cause nausea, vomiting, headaches and hot flushes⁵.

Clomiphene has some specific warnings³:

• Vision changes such as blurring, spots or flashes. Tell your doctor straight away; these are usually reversible but can sometimes last.
• Multiple pregnancy (twins or more) is more likely.
• Over-stimulated ovaries (ovarian hyperstimulation). Report tummy pain, swelling or sudden weight gain.

Is letrozole safe for the baby?

Letrozole must not be taken if there is any chance you are already pregnant, which is why pregnancy is ruled out first². It is not recommended during pregnancy⁷. When it is used briefly to help ovulation, the 2023 guideline found no difference in birth defect rates between letrozole, clomiphene and natural conception².

Where to find these medicines

Both medicines need a prescription and should only be used under a fertility specialist’s care. See our letrozole and clomiphene pages.

We supply letrozole, including Fempro 2.5 mg, and clomiphene, including Clofi 50 mg.

Frequently asked questions

Is letrozole better than Clomid for PCOS?

The 2023 international PCOS guideline recommends letrozole as the first choice for women with PCOS who do not ovulate and have no other fertility problems, because it led to more ovulations and live births than clomiphene in trials.

Why is a breast cancer drug used for fertility?

Letrozole lowers oestrogen for a short time, which can help the ovaries release an egg. Using it for fertility is off-label in many countries, so your specialist should explain the evidence and side effects.

Does letrozole cause twins?

In the large trial comparing the two, twin pregnancies were not significantly different between letrozole and clomiphene. Clomiphene’s label warns that multiple pregnancy is more likely with it.

What are the side effects of letrozole for fertility?

Tiredness and dizziness were more common with letrozole than with clomiphene in the large trial. Hot flushes were more common with clomiphene.

Can I take letrozole if I might be pregnant?

No. Letrozole should not be taken if there is any chance of an existing pregnancy. Your specialist will rule out pregnancy before each course.

Sources & references

1. Legro RS, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014;371(2):119-129.
2. Teede HJ, et al. Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2023.
3. US National Library of Medicine, DailyMed. Clomiphene citrate tablets prescribing information.
4. NHS. About letrozole. Page last reviewed 24 November 2023.
5. NHS. Infertility: treatment. Page last reviewed 9 August 2023.
6. NHS. Polyendocrine metabolic ovarian syndrome (PMOS): treatment. Page last reviewed 30 June 2026.
7. NHS. Common questions about letrozole. Page last reviewed 24 November 2023.

Related reading

• Letrozole in breast cancer
• Can women take Viagra?
• PCOS treatments
• The combined pill: a guide

This content is for informational purposes only and is not medical advice. Fertility medicines should only be used under the care of a fertility specialist. Used as prescribed by a licensed medical professional.