Ok so, if you’ve been down the road of trying to conceive for a while you may have come across the names Clomid (or Clomiphene) and Letrozole. In the world of fertility they are used to bring on the very necessary step in the process: ovulation! Ovulatory disorders are the number one reason for infertility. Given that, we thought it would be helpful to give a quick crash course – in English so you feel educated about your own treatment. You have to be your own advocate and knowledge is power! 

So what do Clomid and Letrozole actually do? 

Clomid (aka Clomiphene) and Letrozole (brand name Femera) both impact estrogen in the body and both lead to (in theory) an increase in the all important hormone FSH which stimulates growth of our immature eggs. Plus LH which surges right before ovulation. Both drugs do this in slightly different ways….

How does Clomid work? 

In case you care about the nitty gritty details (if not skip forward!). Clomid works (this is in a nutshell) by blocking estrogen receptors. This block means that the body registeres a lower level of estrogen which has a knock on effect on another hormone (GnRH). Estrogen normally inhibits GnRH, so when there is less of it, you get more GnRH (and vice versa). More GnRH = more FSH – the hormone that stimulates follicles to grow. Hopefully grow big enough to cause ovulation – the intended end result! Hooray!

How about Letrozole? 

Letrozole is what is known as an Aromatase inhibitor. Sounds technical (once again skip forward if you don’t care on this part!) but in a nutshell it stops some of the key building blocks (androgens) being converted into estrogen. It does that by acting on the enzyme (Aromatase) which allows this process to happen. Once again, as with Clomid – when there is less estrogen registered, it means more GnRH and more FSH/LH. Which once again hopefully means more mature follicles and hopefully ovulation.

Why would I be prescribed either of these? 

There are several reasons a doctor might do this but principally it is because your doctor feels you are not ovulating which as above is one of the major reasons why people struggle to get pregnant.

Why would I not ovulate? 

As always there can be a few reasons for something like this. However, the major cause is PCOS which impacts as many as 20% of women (half of which don’t know they have it). Click here for more.  

Moreover it is estimated that between 55-75% of women with PCOS will struggle with ovulation. Correcting this can be a powerful positive. Hence the popularity of these drugs.

So should I be taking these if I’m not ovulating? 

First and foremost these are both prescription drugs and therefore can only be given by your doctor. Further, the first step most doctors will want to address if you’re not ovulating is lifestyle alterations. Which can be very effective particularly if you have a higher BMI. The results from even 5% weight loss can be powerful when it comes to ovulation. So, this is very individual and is a conversation to have with your doctor.

How are these drugs taken? 

Usually you start taking them between day 2-5 of your cycle for 5-6 days. This (plus the dose) will be decided by your doctor.

What is better? Clomid or Letrozole? 

There has been much debate of late on this topic with as many as 60 studies over the last decade or so. Clomid has been the first port of call for the last 40 years or so, however Letrozole is fast gaining attention. Here are a few points to flesh out the debate:

Clomid the pros and cons: 

• Pro: it has been around a long time. It is FDA approved for bringing on ovulation and we have good data on results (ovulation rates between 60-85% on average), side effects and safety profile. It is also cheap.
• The downside with Clomid is that because of it’s ‘anti estrogen’ effects and because of the length of time it stays in your system (called a half-life), it can have an effect on your endometrial lining (thinning). Which is not good for enabling implantation of a fertilised egg.
• This is why it is thought that there is a lower rate of live birth despite a high rate of ovulation success (around 20-40%).
• There has been a slightly higher rate of multiple pregnancy with Clomid (ie. twins) as on occasion more than one follicle (immature egg) matures and ovulates.
• It does not work for everyone. Some women are Clomid resistant (usually classed as this after 6 cycles).

Letrozole the pros and cons: 

• Pro: it has shown decent rates of success in ovulation particularly with women with higher BMI (+30). In some studies it has also been shown to have higher levels of live birth rate. Not all studies show this.
• Evidence suggests less incidence of multiple pregnancy with Letrozole as usually just one dominant follicle is released at ovulation.
• The downside: this is a drug that is FDA approved for breast cancer treatment. It is not approved for fertility and ovulation induction. That means doctors prescribe it ‘off label’.
• Because of this there are question marks about dosage/cycle of its use.
• Why does it not have approval? There was a study done back in 2015 which linked it to birth defects. However, the study has been discredited to an extent because of the design, the small number of patients on the trial and the fact that Letrozole does not linger in the body so long as Clomid (shorter half-life).

What about for Endometriosis? 

There have been some trials looking at the use of Letrozole specifically for Endometriosis. Click here for more on Endo. 

Endometriosis is known as an estrogen dependent disease. Some of the more recent research looking at why it happens argues that it may be because too many of the enzymes (that Letrozole effectively blocks) that turn our androgens into estrogen being produced. This would then theoretically cause these growths or lesions we see in Endometriosis.

So, if we use Letrozole to block this enzyme then it could stop the growth of these lesions and the associated pain. The clinical trials are showing some positive results although more needs to be done. Could be worth a chat with your doctor about however. N.b medication to protect the bones was given alongside this.

What’s the bottom line on all of this? 

One really smart starting point is to work out if you’re ovulating as a first port of call. It is surprising how many people do not know this (mainly because the information out there is so basic and outdated!) There are so many ways to do this which are pretty confusing. The most effective at home way is with Ovusense (no we are not sponsored by them it is just their mechanism is the most accurate based on science – click here for more). That has to be step one.

If you do think you may be having issues with ovulation or know you have PCOS then the first port of call is your doctor for a discussion about what is right for you as an individual. Weight/age etc and your reasons for not ovulating are all things that they will consider. The good news is that if one doesn’t work then there are other options. Hopefully this has given you a bit of food for thought for discussion with your doctor.

References: 

Clomiphene citrate or Letrozole for ovulation induction in women with polycyctsic ovarian syndrome: a prospective randomised trial: Fertility and Sterility: Sept 2009 

Ovulation induction with clomiphene citrate: Seki, Enre, Arici A: www.uptodate.com 

Letrozole or Clomiphene citrate as first line for a ovulatory infertility: a debate: Reproductive Biology and Endocrinology: 2011. 

Treatment of endometriosis and chronic pelvic pain with Letrozole and more thunder one acetate: a pilot study. Fertility and Sterility: Feb 2004 

An assessment of current clinical attitudes towards Letrozole use in reproductive endocrinology practises: Fertility and Sterility: Dec 2013

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