Medical Oncologist
Medicines
Letrozole vs anastrozole vs exemestane: does it matter which?
Letrozole, anastrozole and exemestane are the three aromatase inhibitors used for hormone-receptor-positive breast cancer after menopause. Trials comparing them show similar benefit and broadly similar side effects. This page explains how they differ, why switching between them can help if side effects are hard, and how choices change in advanced cancer.
NG
Medically reviewed by Dr. Naresh GunduConsultant Medical Oncologist · MBBS, DNB (Internal Medicine), DM (Medical Oncology, AIIMS) · last reviewed September 2026, next review due September 2027
On this page
- Does it matter whether you take letrozole, anastrozole or exemestane?
- A quick profile of each aromatase inhibitor
- How the three compare, in general terms
- The vocabulary, in plain language
- What the evidence can and cannot tell you
- When and how women switch between them
- Choosing between them when cancer has spread
- Practical points that may shape the choice
- What people assume about the three tablets
- Common questions about letrozole, anastrozole and exemestane
The short answer
Does it matter whether you take letrozole, anastrozole or exemestane?
Letrozole, anastrozole and exemestane are all aromatase inhibitors. They lower oestrogen in women after menopause by blocking the aromatase enzyme, which turns other hormones into oestrogen in fat, muscle and other tissues. For most women with hormone-receptor-positive breast cancer, the choice between them matters less than taking one of them steadily for the planned years. Large trials comparing them head to head have not shown a clear difference in how well they prevent the cancer returning. One trial compared letrozole with anastrozole in women with cancer in the lymph nodes and found similar results, and another compared exemestane with anastrozole and again found similar outcomes. The main difference is in how they work. Letrozole and anastrozole are non-steroidal and block the enzyme reversibly, while exemestane is steroidal and switches the enzyme off permanently. Their side effects are broadly similar: hot flushes, joint pain and stiffness, tiredness, bone thinning and vaginal dryness. However, individual women sometimes find one easier to tolerate than another, so switching is a useful option when side effects make it hard to continue. Practical points can also shape the choice, such as the tablet your oncologist is most familiar with, which one was used in a trial for a combination treatment, whether you need to take it with food, and cost. In advanced breast cancer, changing from one type to another is sometimes used when the cancer starts to grow.
Similar benefit
Head-to-head trials suggest the three work about equally well for early breast cancer.
Similar side effects
All three share the effects of low oestrogen, though individual experience varies.
Switching can help
If one tablet is hard to tolerate, another may suit you better.
This page gives general information only. Your oncologist will recommend the tablet that suits you.The three tablets
A quick profile of each aromatase inhibitor
They share a purpose but differ in small practical ways.
Letrozole
A non-steroidal tablet taken once a day, with or without food. It is widely used alone and with CDK4/6 inhibitors in advanced cancer.
Anastrozole
A non-steroidal tablet taken once a day, with or without food. It has long-term trial data for early breast cancer and prevention.
Brand name Arimidex.Exemestane
A steroidal tablet taken once a day, ideally after food, which helps it be absorbed. It switches off the enzyme permanently.
What they share
All three need the ovaries to be inactive, through natural menopause or ovarian suppression.
Common shared side effects
- Joint pain and stiffness
- Hot flushes and tiredness
- Bone thinning and vaginal dryness
Side by side
How the three compare, in general terms
Question
General answer
Which prevents recurrence best?
Trials show no clear winner for early breast cancer
Which has fewest side effects?
Broadly similar; individuals differ
Food needed?
Exemestane after food; the other two either way
Steroidal structure?
Only exemestane
Can you switch between them?
Yes, often done for side effects
Words you will hear
The vocabulary, in plain language
- Aromatase
- An enzyme that turns other hormones into oestrogen, mainly in fat and muscle after menopause.
- Aromatase inhibitor
- A medicine that blocks aromatase to lower oestrogen levels.
- Non-steroidal
- Letrozole and anastrozole, which attach to the enzyme and block it while present.
- Steroidal
- Exemestane, which is shaped like a natural hormone and disables the enzyme permanently.
- Head-to-head trial
- A study comparing two treatments directly with each other.
- Cross-intolerance
- When a side effect from one medicine also happens with a similar one.
Being straight with you
What the evidence can and cannot tell you
The trials are reassuring, but they compare large groups, not individuals.
Small differences may exist
Letrozole lowers measured oestrogen slightly more than anastrozole in laboratory studies, but this has not translated into clearly better results in trials.
Switching does not always solve side effects
Some women feel better on a different tablet, while others find the same problems return, because the cause is low oestrogen itself.
Brand loyalty is not evidence
A friend doing well on one tablet does not mean it will suit you best.
What this page cannot tell you
It cannot choose your tablet. Your oncologist can, based on your whole situation.
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Changing tablets
When and how women switch between them
Switching is one of the most practical ways to stay on hormone therapy when side effects are difficult.
For joint pain
Joint pain is the most common reason. Some women find it eases after changing from a non-steroidal tablet to exemestane, or the other way round.
For other side effects
Rashes, stomach upset or feeling generally unwell on one tablet may improve on another.
How it is done
Usually you stop one tablet and start the other the next day, without a gap. Your oncologist will confirm the plan.
If switching does not help
Tamoxifen may be an option, or treatment for the side effect itself.
Advanced cancer
Choosing between them when cancer has spread
In advanced hormone-receptor-positive breast cancer, the choice is shaped by combination treatments and earlier therapy.
With CDK4/6 inhibitors
Ribociclib, palbociclib and abemaciclib were studied mainly with letrozole or anastrozole, so these are often chosen as partners.
After a non-steroidal tablet stops working
Exemestane, sometimes combined with a targeted medicine such as everolimus, may be used as a later option.
Everyday factors
Practical points that may shape the choice
When the evidence shows similar results, everyday factors often decide which aromatase inhibitor you are prescribed.
Availability and cost
All three are available in India as generics, but prices and stock differ between pharmacies and brands. A tablet you can buy reliably every month is a sensible choice.
Your daily routine
Letrozole and anastrozole can be taken at any time with or without food. Exemestane is best taken after a meal, which suits some routines better than others.
Past experience
If you have already had side effects on one tablet, your oncologist may start or switch you to another.
Other treatment
Combination treatments in advanced cancer may favour a particular partner tablet.
Commonly believed
What people assume about the three tablets
The newest or most expensive tablet works best.
Trials show similar results for all three in early breast cancer.
Exemestane is a steroid like prednisolone.
It has a steroid-like shape but is not a corticosteroid.
If one causes side effects, they all will.
Some women tolerate a second tablet better, so switching is worth trying.
Changing tablets means starting the count again.
Time on any aromatase inhibitor usually counts towards the planned total.
Questions we are asked
Common questions about letrozole, anastrozole and exemestane
My doctor chose letrozole. Should I ask for anastrozole?
There is usually no need. The evidence suggests they work similarly, so doctors often choose based on experience, availability and cost. If you have a particular concern, such as side effects on one tablet before, do raise it.
Is one gentler on the bones?
All three can thin bones. Some studies hinted exemestane might affect bone slightly less, but the difference is not clear enough to guide the choice for most women. Bone checks and protection matter whichever tablet you take.
Can I switch if joint pain is bad?
Yes, this is common. Many oncologists suggest trying another aromatase inhibitor before considering tamoxifen. Exercise, weight management and pain relief can also help, and some women find joint pain settles with time.
Will switching reduce the benefit of treatment?
Switching between aromatase inhibitors is not thought to reduce benefit. Stopping hormone therapy altogether would, so a switch that helps you continue is usually the better choice. Your oncologist will guide the change.
Do I need a gap between tablets when switching?
Usually not. Most women stop one tablet and start the next the following day. Your doctor may advise otherwise in particular situations, such as waiting for a rash to settle, so follow the plan you are given.
Are they all suitable for younger women?
Only with ovarian suppression. On their own, none of them work well if the ovaries are active. Younger women who are not having ovarian suppression usually take tamoxifen instead.
Are the side effect timelines different?
Broadly no. Hot flushes and joint symptoms often appear within the first few months on any of them, and bone thinning builds gradually. Individual experiences vary more than differences between the tablets.
Do men with breast cancer take these tablets?
Tamoxifen is usually the main hormone tablet for men. If an aromatase inhibitor is used, it is generally combined with a medicine that lowers testosterone production, because the testes can otherwise overcome it.
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Sources
- National Cancer Institute — Hormone therapy for breast cancer
- Breast Cancer Now — Aromatase inhibitors
- American Cancer Society — Hormone therapy for breast cancer
This page is general information, not a prescription. Do not change or stop any treatment based on what you read here. If anything is worrying you, contact your own treating team — or call our helpline and we will help you reach the right specialist.