Superhero Hormone: What Progesterone Is Really Doing Behind the Scenes

You’ve heard of estrogen, maybe even LH—but the real superhero in fertility? It’s progesterone.

In this episode of Taco Bout Fertility Tuesday, Dr. Mark Amols reveals how progesterone silently supports pregnancy, stabilizes the uterine lining, and prevents early contractions—all without the recognition it deserves.

We break down the science: how progesterone is made from cholesterol, how it converts into testosterone and estrogen, and how granulosa and theca cells work together to build a pregnancy-ready uterus.

Plus, Dr. Amols explains why blood levels may look “low” on vaginal progesterone, why that doesn’t mean treatment failure, and why route of delivery really matters—especially in frozen embryo transfers.

Whether you're trying naturally, doing IUI, or planning an FET, this episode will help you understand what progesterone is really doing behind the scenes—and why it might just be the most important hormone you never thought about.

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.

Stay connected with us for updates and fertility tips – follow us on Facebook. For more resources and information, visit our website at www.NewDirectionFertility.com.

Have a question or a topic you'd like us to cover? We'd love to hear from you! Reach out to us at TBFT@NewDirectionFertility.com.

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 the most powerful hormone in the world, maybe the universe. Stronger than Thanos, stronger than Superman, stronger than Captain America. excuse me, are you talking about superheroes? Okay, maybe I got a little carriry right there. It's the most powerful hormone infertility called progesterone. I'm Dr. Mark Amols, and this is Taco about fertility Tuesday. Back in 2020, I did a podcast on the two most important hormones in the female body. But reality, progesterone is really a super hormone. The reason I wanted to get back to this podcast was today I had a patient who was frustrated because she thought because her progesterone levels were low that we weren't treating luteal phase defects, which means low progesterone, even though we were given her vaginal progesterone. It was that point I realized it may not be obvious that when taking vaginal progesterone, it's helping things even when your progesterone levels are low in your blood. And so in today's episode, we're going to talk a little bit more about progesterone, give you a little science about it, but also help explain some of these confusing conundrums so you're not worried about if your progesterone levels are causing problems. So what is progesterone? Why do we care about it? Well, progesterone is the hormone that takes your uterine lining from under construction to move and ready. It stabilizes the lining, preventing it from shedding and making it receptive to an embryo. It's made after ovulation by a structure called the corpus luteum, which forms the follicle that release the egg if pregnancy happens. The EMY then sends out hcg, which tells the corpus lithium to keep making progesterone. If it doesn't, the corpus luunum breaks down, progesterone levels drop, and you get your period. So this is important. HCG from a pregnancy rescues the corpus lithhium. It's destined to die in 14 days and collapse. But pregnancy creates a hormone, HCG, which looks like LH and keeps the production of progesterone. So as you can see, it literally is a superhero. It saves the day. It rescues the corpus luteum. Let's go a little deeper. Where does progesterone come from? Well, all reproductive hormones come from cholesterol. Basically, the pathway is cholesterol becomes pregnantulolone, which then becomes progesterone. Then progesterone is converted to androgens like testosterone Then testosterone is converted to estrogen by an enzyme called aromatase. Interesting. Letrazole, also known as femaarra, blocks ratase, meaning it blocks the conversion of testosterone and estrogen. Now, this dance involves two types of cells in the theca cells which make testosterone from progesterone, and granulosa cells that take the testosterone and convert it into estrogen using aromatase. Now, before ovulation, the system is estrogen dominant and supposed to be. But after ovulation, the granulosa cells become leuteinized. They shift from making estrogen to producing progesterone. Basically, luteonization is a hormone career change for the granulosa cells. They stop helping build the lining and they start working to support it. This transformation is triggered by the LH surge right before ovulation. And those newly ludinized granioa cells become now progesterone producing powerhouse we call the corpus lithuteum. Think of it as estrogen, as the architect that builds the house, but it's progesterone that furnishes it. It adds the warmth, the food, the comfort. So the, embryo can then move in and feel right at home. The other great thing about progesterone, as it prevents contractions in pregnancy, the high levels progesterone literally keep the uterus quiet until labor begins. This is why we use progesterone supplementation in the luteal phase to help prevent preventable issues that can occur from a luteal phase defect. So then why does the corpus luteum shut down after 14 days? Is it some type of, like California labor law that says it can only work 14 days at $50 per hour? No, it's because the corpus luteum has a built in expiration date, about 12 to 14 days. Unless it gets a very specific signal, LH from the form of HCG from the growing embryo. Without the HCG, the LH levels will drop. The lutinized granulosis cells stop receiving stimulation, which then causes the corpus luteum to undergo a process called apoptosis, which is just a fancy way of saying programmed cell death that causes your progesterone levels to drop and that leads to menstruation. Because remember, the estrogen was the architect. The progesterone is the support. And if you lose support, everything comes tumbling down, causing menstruation. And this timer, it's hardwired into the system. It ensures that your uterine lining only sticks around if there's an embryo to support it. What this means is if you have A very long cycle, let's say like 35 days. It's not that the middle of the cycle is in the middle, but Instead you ovulate 12 to 14 days before you get your next period, which means it's the follicular phase, the part where the focollicle is developing, the estrogen dominant portion that is being extended, and that the luteal phase after ovulation always stays the same because that is hard wired. Now, it's true if you have a luteal phase defect, it may be shorter, but it's not going to be longer. Now, is it possible? Could be longer, yes, but then that's pathological, meaning you might have a cyst, like a corpus luteial cyst, and that could be creating progesterone that's causing you not to get your period. But in general, like women who have polycystic ovarian syndrome, if you have a 45 day cycle, you're not actually ovulating in the middle, around the 20s. Instead you're ovulating around day 31 and then you're getting your menses on day 45. So then overall, why do we give progesterone supplementation? Well, there's a couple reasons. Sometimes we suppress ovulation and bypass it. So we have to get progesterone like in a frozen embryo transfer. But even when we do a retrieval, we disrupt those granulosa cells when we pull the eggs out, and that can lead to a disruption in progesterone production and that could potentially cause problems. So instead we supplement it. Now, when it comes to IUIs, we probably do overdo it. We probably don't need to getgesterone all the time. But in the end it's not harmful, it could only help. And so a little bit of prevention may go a long ways, and that's why we end up using it in IUIs. The question is, what's the best route? Well, this is what actually caused me to do this podcast, because of that person getting frustrated thinking that her lower progesterone level meant she wasn't getting enough progesterone. We'll get that in just a minute. There are essentially three ways to geterone vaginal, which can be through gels, suppositories or tablets, intramuscular, which means that painful muscle shot or oral. Now, in the US we don't really use the oral one because progesterone ends up undergoing a first pass effect in the liver, which then removes a lot of the progesterone and Less gets to the uterus. However, in other countries they have a different form of progesterone called digidrogesterone and that has better absorption and more progesterone gets to the uterus. Fortunately, that is not in the US yet. Now, the gold standard is going to be intramolcular progesterone. That's because it gives high consistent blood levels that absorbe into the entire body and that goes through the muscle which then absorbed by the blood vessels. Unfortunately, this does come with daily injections in the glute, which can be painful. It can sometimes even cause some irritation. If it wasn't so good, we wouldn't use it. We realized that those injections are painful and the only reason we use it is because it is the best option. Now, that doesn't mean there aren't other options. Like we talked about. Vaginal progesterone. Matter of fact, if you are dealing with a fresh transfer, there is literally zero difference between using injectable progesterone or vaginal progesterone suppository. However, it changes a little bit depending on the treatment. If you're doing a frozen embryo transfer, there is a difference between used in vaginal progesterone, the intramuscular, you do not want to use vaginal progesterone only. Now, it doesn't mean you can't use a combination. There are several studies out there looking at using combinations where you use injections and vaginal progesterone. But using just vaginal progesterone from the very beginning for the frozen embro transfer is not a good method. Now, what's unique about the vaginal progesterone, Instead of going through the whole body in a systemic way, it delivers the hormone directly to the uterus through a phenomenon called the first uterine pass effect. The uterus absorbs most of the progesterone locally, spilling very little into the bloodstream. That's why blood levels often look low on your labs, even though the uterine lining is getting everything it needs. So in the case this morning, when she was told her progesterone was low, she assumed that now the progesterone was too low in her body and that's why the pregnancy didn't continue. But the reason the progesterone levels were low in her body is because unfortunately the pregnancy wasn't working. And so the levels told us the corpus luteum was crashing. But it doesn't tell us the progesterone in the vagina wasn't getting to the uterus it was, but I can appreciate the concern there. And so don't be worried when you see those lower progestero levels when you're taking suppositories. But on the other hand, if you're pregnant, those levels should still be high because you should be getting in the blood from the corpus luteum. Unless you did a frozen embryo transfer, which, again, you shouldn't be using only vaginal progesterone as well, but then you wouldn't have a corpus lututeum, so your only progesteroion would be coming from the vaginal suppositories. Now, as I mentioned, in the U.S. really, no one uses oral progesterone, and that's because it gets broken down the liver, and so it's not as efficient. But as I mentioned, there's that synthetic oral form, and that one in another country shows some promising results and potentially may come to the US at some point. So overall, the route matters in different situations. If you created a corpus luteum M, you should never be worried about using vaginal progesterone because you are only supplementing in that situation. However, if it's a situation where you did not make a corpus luteum, you do need to use either injectable progesterone or some type of combination of IM and vaginal progesterone for better support. So here's where the conundrum comes. Why is it, if you're taking vaginal progesterone and you don't get pregnant, you'll get your period, but if you're takingramuscular progesterone and you don't get pregnant, you don't bleed until you stop the medication. Based on everything I've told you, that would make you think that the progesterone levels weren't good enough, and that's what caused the bleed, because the progesterone supports the endometrium. And although that sounds logical, that is not correct. And this is because when you use IM progesterone, the systemic levels are high enough to suppress menstruation longer. Basically, progesterone going everywhere to the brain and the pituitary and telling everyone, hey, we're still pregnant. But when you take vaginal progesterone, the uterine levels are high, but the blood levels are low. So the body sometimes starts the menstrual clock because it doesn't sense pregnancy. And this can be actually quite traumatic because you may think you're pregnant because you haven't got your period when you're using IM shot, in reality, you're just not getting your period because of the progesterone. Additionally, if one of you are taking vaginal progesterone and other ones taking IM and the first person ends up getting their period, they may feel like, wow, I didn't get pregnant. But they did. When in reality, maybe both didn't get pregnant. But just because of the way you're using progesterone via the route is why you had different experiences. So overall, is progesterone a superhero? Well, if you're the corpus luteum, I would think you would say yes. But overall, the important thing here is when it comes to progesterone, how we give it matters, where it goes matters, and what it does matters more than what a lab number says. If you're taking IM progesterone, you can follow the lab numbers and they're going to be very accurate. If you're using vaginal progesterone, you can't follow the lab numbers. It's only telling you what the corpus luteum is doing in a little bit of what the vaginal progesterone is doing. But it doesn't give you the full picture because you can have low blood levels and still have a very receptive uterus when taking vaginal progesterone. So we salute you progesterone. Thank you for protecting our babies. Maybe you've had this question before where you thought, isn't that weird? I'm getting my period but I'm on progesterone. Maybe have a friend going through this. Either way, if you liked this episode or know someone who it may benefit, please tell about it. And as I always say, if you like this podcast, give us a five star review on your favorite medium. But most of all, keep coming back. I do this because of you, so please let me know topics you'd like to do. Send an email to tbft newirectionfertility.com or you can even just tag me in a Facebook post. Until our next super hormone adventure, I look forward to talking to you again next week on Taco Bel Fertility Tuesday Avengers.