Clomid vs. Femara: Why Two Similar Fertility Pills Work So Differently

Not all fertility pills are created equal. In this episode of Taco Bout Fertility Tuesday, Dr. Mark Amols breaks down the real differences between Clomid (clomiphene citrate) and Femara (letrozole)—two medications that may look the same but work in totally different ways.

Learn how each medication triggers ovulation, why increasing your dose doesn’t always improve your chances, and when doctors decide to switch from oral pills to injectable gonadotropins. Dr. Amols also shares the surprising origins of both drugs (spoiler: one started as birth control and the other as a cancer treatment!) and explains why “doing more” isn’t always the right move in fertility treatment.

Whether you’re trying to understand your options, navigating PCOS, or wondering why your doctor didn’t bump your dose, this episode will help you make sense of your fertility journey—one taco at a time. 🌮

Thanks for tuning in to another episode of 'Taco Bout Fertility Tuesday' with Dr. Mark Amols. If you found this episode insightful, please share it with friends and family who might benefit from our discussion. Remember, your feedback is invaluable to us – leave us a review on Apple Podcasts, Spotify, or your preferred listening platform.

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Join us next Tuesday for more discussions on fertility, where we blend medical expertise with a touch of humor to make complex topics accessible and engaging. Until then, keep the conversation going and remember: understanding your fertility is a journey we're on together.

Transcript

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Today we talk about two things that may look the same but definitely aren't the same. Clomid and FEMAORA. I'm Dr. Mark Amols, and this is Taco about Fertility Tuesday. Clomid and femaa, also known as clomiphene citrate and Letrozole. Both are pills, both used for ovulation, but they're often mentioned in the same breath. And many people assume that they did the exact same thing. But the truth is they take very different routes to get your ovaries to do the same job. And just when you think you figured it out, I'm, going to throw in a third player then injectables, also known as ganaotropins. So by the end of this episode, you're going to know why your doctor picked one over the other, why higher doses don't always work better, and why sometimes doing more isn't really helping at all. Now, all three of these medications share the same goal, and that is to help your body release a, mature egg or sometimes multiple eggs. But as I mentioned before, they go about it in different ways. We've got Clomid andh femaa, which are oral medications that are going to trick the brain into releasing more hormones. And then you get the gonadotropins. These are the injectables that skip the brain entirely and go straight to the ovaries, mimicking the exact same hormones that come from the putuary. Now, I say mimicking, I'm saying theyre actually bioidentical, not the actual hormone. So Clomid andh femaara are the indirect way, and gonadotropins is the direct way to stimulate the ovaries. Now, Im sure its obvious that gonadotropins were made to stimulate the ovaries. Thats why they were made that way. And theres been different versions. Some are from humans, which are from menopausal women who release fsh by likeipur. And then some are made as bioidentical, where they actually go and generate the hormone. And that's what a lot of people take. But what about Clomid and femaa? Well, were those made for fertility? Well, Clomid was actually created in 1950 as a birth control pill. They thought that maybe the estrogen blocker would then stop ovulation. But to their surprise, it did the exact opposite. Women started ovulating. So by 1967, Clomid was officially approved to treat infertility. It was kind of the worlds first oops. But in A good way. Now, femaara, also known as Letrazole, came along much later, back in the 1990s, a long time ago, its original purpose was breast cancer treatment. It worked by lowering the estrogen levels, which helped slow estrogen sensitive tumor growth. Then fertility specialists started realizing that the short drop in estrogen could actually trick the brain into releasing more fsh, leading to ovulation. And because fe ours effects wear up so quickly, it doesnt mess with the uterine lining like Clomid does. So Clomid was an accident that helped women conceive and Fe mar was intentionally repurposed to become a fertility favorite. Now in the prior podcast I did talk about how Femara and Clomid work, but let's break them down next to each other. Clomid is what we call a selective estrogen receptor modularator, called a serirm. What this means is it binds to estrogen receptors. Now at some receptors it may activate them, in other receptors it may block the real estrogen from binding. And that's actually how it works when it comes to fertility. It binds to the receptors in the pituitary, in the hypothalamus, but then the estrogen in your body can't stimulate the receptor. So in some ways it's kind of blocking it. And by blocking it, it then makes the pituitary think that the estrogen level is low. And then it says, hey, I need to make more estrogen. So it releases more FSH and lh, which then cause your ovaries to grow and to eventually ovulate. But this is the interesting thing about Clomid, because it is not specific to just one receptor. It goes to all orogen receptors. Sometimes it will stimulate, sometimes it will not. And so it could be going to, let's say the breast, it can go to the uterus and it can even cause your uterine lining to be affected, even causing your cervical mucus to dry up. Whereas at the bone it's going to work as an agoonist and actually help build up bone. So it's not a pure blocker, even though it works that way for fertility. It's like a key that goes into the lock for many different things, but doesn't always unlock everything. Sometimes it's going to be antagonist, sometimes it's going to be an agonist. But Feara, also known as Letrosool, takes a completely different path. The outcomes are the same. Both of them are going to cause FSH and LH to rise, but because it's a aromatase inhibitor, it Means it does just one thing. It stops the enzyme aromatase from converting androgens into estrogen. All the estrogen that you have in your body comes from testosterone or some type of androgen. So if you stop the conversion of testosterone to estrogen, then you'going to temporarially lower the estrogen level. And when the brain sees that now instead of tricking the brain into thinking there's low estrogen, the estrogen level actually did drop. And that causes the pituitary to release more FSH and lh which then will stimulate your ovaries to make more follicles. Now once you stop taking fer, your estge action levels will return to normal, but the follicles are already growing. And because FMR only lowers estrogen for a short time, it doesn't have that lasting anti estrogen effect on the uterine lining like Clomid would. It's essentially cleaner, quicker and for many women much easier on their body. And we now know it actually benefits women with PCOS even more. So to help clear up this picture, lets take a step back and compare these side by side. Let's talk about mechanism. So for Clomid we are blocking the estron receptors in the brain because we're preventing the real estrogen from going to the receptors. Whereas Femaarra, also known as Letroole, actually blocks the estrogen production because it stops the enzyme. Now, what about the duration? Well, for Clomid it'very long. It usually stays active for about five to seven days whereas femaara is very short, about two to three days. Now it comes to the impact on the lining. As we talked about. Clomid can thin the uterine lining and it can also dry out the mucus of the cervix. Whereas Feara preserves the lining and it doesn't usually affect the cervical mucus. Now when it comes to side effects, if you'ever taken Clomid, you know it has a lot of side effects. Hot flashes, mood swings, visual spots actually require you then to stop the medication. Feara doesn't have as many side effects. Some people will get fatigue and some mild headaches because of the drop in the estrogen. But overall do very well on it. And as I mentioned, people with PCOS do very well on. So it comes to the best use case. Clomid can be used in people who maybe are just taking the medication on their own. Think of like timed intercourse cycles on your own. Whereas Letrazole anytime I'm doing iuis if I know someone had a Thin lining with Clomid or they have PCOS or even Clomid resistant cases. I'm going to put them on Fe Mara. Now the question is why one over the other with timed intercourse? Well, that's because Clomid is the only FDA labeled medication for fertility. For Mar is not. That is absolutely off label. It'being repurposed as a fertility drug and there is actually a terteratogenic effect. If you are taking femaora and you are pregnant and you have a female, it is possible that you could androgenize the female to develop a penis. Now this is more theoretical because first of all, you don't develop a penis or a vagina, until you're about 10 weeks in utero. So you would have to really not know youre pregnant while taking that FEMAORRA to be able to affect it. Plus you have to keep continuing taking the FEMAORRA to lower the estrogen levels, to then reduce the estrogen levels that are exposed to the baby. So in summary, Clomid is the OG fertility pill. Its powerful and effective, but not always as gentle. Femaara is the modern alternative. Its subtle, short acting and often a better fit for certain patients. So here's an interesting question. If Femar didn't work at 5mg, why not go up to 7.5 or 10? Or just keep going up until it finally works, Just like with Clomid. And that's a great idea, right? If some works, then more is going to work better. But if, remember, they work indirectly, not directly. Both Clombin and femaor depend on the pituitary gland to release FSH and lh. So there's a point where your pituitary says, hey, that's all the hormone I got. Once it's maxed out, it doesn't matter if you increase the dose of either of them. You can't make more eggs because the pituitary cannot make more hormone. You effectively bled it dry. So what we find is for clomid DOS over 150 milligrams, it, usually doesn't help much, partly because the higher doses can hurt your lining and affect the cervical mucus. But again, you pretty much burn out the pituitary. Theres not much more you can get. The same goes with femaara. Usually people dont go above 7.5 milligrams, but I see people go the 10. Ive done it myself and honestly, I dont see much of a difference either. Think of it like pushing the gas pedal on your car. If the engines already at full speed. Pressing harder wont make it go faster. That's the limit of that vehicle. And your pituitary also has a limit. Another common question will come is you take the Clomid, you take the femaarra and you don't get pregnant. So common sense would say well if you didn't get pregnant on 5mg of femaar100omomet then we should go higher. But not necessarily. If your follicles grew normally then that means you responded. Not getting pregnic doesn't mean the medication failed. Ovulation is only one step in the process. Remember you still have fertilization, a healthy embryo implantation. So increasing the doses is not going to fix anything. It'already working. And potentially as we talked about with Colomid, overstimulating can even cause issues such as drying out the cervical mucus. Now if you don't respond yes you should go up on the dosage or even switch the medication because at that point it not working. And that takes us into the next catery Gotropins. When Clomid and femaora don't work and the pituitary is out of hormones, the only way to get it then to work is giving goanotropins because that is actually injecting effsh directly to the ovaries. when I say directly, yes it's going through your skin, going through your blood supply to the ovaries but it's getting there. And we're not tricking the pituitary. They skip the brain entirely and go straight to the ovariary. And it gives us precise control where we can fine tune it, go up and down on the medication as we need to. Now there's a downside to this medication. You think well why don't we use it on everyone? Well because it's expensive and it carries a higher risk of things like twins and triplets. Now some clins we will combine them we call Minstemms where we actually use oral meds and injections together. Now keep in mind not all clins do that so don't be surprised if yours doesn't. Very few do. A matter of fact there is a big push against going away from godadotropins because of the multiple cycles. As a matter of fact if you have insurance, it's not uncommon nowadays to see insurances not even allow us to use inadropants because they're worried about the multiples. They would prefer you to go on the IVF and once youe just doing clomid or from marab by itself. So what are the key takeaways? Well first clombin and feomor both trick the brain into producing more hormones. They just do it differently. Two Gonadotropins bypass the brain and go directly to the ovaries. Its not indirect but direct has 3 higher doses dont always mean higher success. They can mean higher side effects which nobody wants. And number four the goal is quality ovulation, not quantity of medication. So next time you wonder why your doctor didnt bump your dose, remember it. Its not about doing more, its about doing whats right for your body. And if you ever want to dig deeper into some of these topics, join me on Sperm Meets Egg where you can come on live and ask your specific questions in real time. As always, I greatly appreciate everyone that listens to this podcast and if you love us, give us a five star review on your favorite medium. And if you know someone who hasn't heard us, tell them about us. If you have an idea for an episode, please send it to me atbftirectionfertility.com commt I'll be more than happy to do an episode on that. Until next time, keep learning, keep laughing and keep t talko about Fertility. I look forward to talking you again next week on Taco About Fertility Tuesday.