Ep 34: Understanding Estrogen: Facts vs. Myths

In this episode of Reset Recharge, Dr. Komal Patil-Sisodia, a triple board certified endocrinologist and women's health expert, explores the complexities of estrogen therapy. She breaks down bioidentical and synthetic estrogen, compares their safety and effectiveness, and provides evidence-based insights into cardiovascular and cancer risks. This informative session aims to empower women with the knowledge to make informed decisions about hormone therapy. Dr. Patil-Sisodia emphasizes the importance of understanding individual risk factors and the critical distinctions between FDA-approved and compounded hormone products. Tune in for a deep dive into estrogen therapy, and learn practical questions to bring to your next healthcare appointment.

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Audio Stamps:

00:00 Introduction to Reset Recharge

00:54 Understanding Estrogen: Bioidentical vs. Synthetic

02:02 Bioidentical Estrogen Explained

03:38 Synthetic Estrogen: What You Need to Know

05:21 Safety and Efficacy: Bioidentical vs. Synthetic

06:43 Compounded Hormones: Risks and Considerations

08:56 Cardiovascular Health and Estrogen

11:20 Cancer Risks: Breast and Endometrial

14:05 Key Takeaways and Practical Questions

17:12 Conclusion and Next Steps

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Transcript

Dr. Komal Patil-Sisodia 0:02

Welcome to Reset Recharge, the podcast where women's health takes center stage. I'm your host, Dr. Komal Patil-Sisodia, a triple board certified endocrinologist and women's health expert. This show is all about empowering you with the knowledge to understand your metabolic health, navigate hormonal changes, and feel confident in the conversations you're having with your healthcare provider. Whether you're managing symptoms, exploring treatment options, or just want to feel more in tune with your body, you're in the right place. As a physician, my goal is to educate on this podcast. The content shared here is for informational purposes only and should not replace personalized medical advice. If something we discuss resonates with you, please talk to your healthcare provider at your next visit. Now let's dive in and help you reset, recharge, and take control of your health. Welcome back to Reset Recharge. Today we are going to pull back the curtain on something that causes a lot of confusion and a lot of fear. Estrogen more specifically, bioidentical, estrogen, synthetic estrogen, and everything you've been heard or sold about which one is better or safer. If you've ever felt overwhelmed by conflicting claims, if you've heard that bioidentical hormones are natural or synthetic hormones cause cancer, or that estrogen is both your best friend and your biggest risk, you are not alone. This episode is about demystifying estrogen, what it is, how it works, and what the science actually says about. Bioidentical versus synthetic estrogen, FDA, approved estradiol versus compounded products, cardiovascular risks, breast and endometrial cancer risks, blood clot risks, and why. How you take your estrogen may matter more than which type you choose. My goal today is to help you understand estrogen without fear, without a marketing spin, and without outdated myths, slinging from the early two thousands. Just clear evidence-based information you can use to make confident decisions about your own health. Let's start with the basics, because a lot of fear and confusion around hormone therapy comes from not really knowing what these words mean. You'll hear people say things like bioidentical hormones are natural and safe. Synthetic hormones are dangerous and artificial, but the truth is a lot more nuanced. What is bioidentical estrogen? Bioidentical estrogen is estrogen that is chemically and structurally identical to the estrogen your body makes, specifically the hormone estradiol, and sometimes estriol your body has its own native estrogen. That's what the ovaries are doing. They're making your estrogen and bioidentical. Estrogen is designed to match that exact molecular shape. Common bioidentical estrogens, are estradiol and estriol. Fun fact, these hormones are often derived from plant sources, so yams or soy, but they are chemically modified in a lab so that their final structure matches human estrogen. So while they come from a natural source, they are still processed, purified, and manufactured. Bioidentical is a marketing term. It does not mean that they came directly from a raw source. So yes, they may start from plants, but they're still processed, purified, and manufactured. You'll see FDA approved bioidentical, estrogen in prescription estradiol patches, estradiol pills, estradiol gels or sprays, and then vaginal estradiol, tablets, creams, or rings. These products have gone through rigorous testing for safety, purity, dose consistency, and effectiveness. So what is synthetic estrogen? Synthetic estrogen refers to estrogen-like compounds whose structure is not identical to human estrogen. Two of the biggest examples are ethinyl estradiol, which is often used in birth control pills and conjugated equine estrogens or CEE, a mixture of estrogens that were originally derived from. The urine of pregnant horses and used in some traditional menopause hormone therapy, these molecules are similar to human estrogen, but not identical, and those small structural differences can change. Number one, how long they last in your body. Number two, how strongly they bind to the estrogen receptors. And number three, their overall effects on things like cholesterol, clotting, and tissue. For example, ethinyl estradiol is designed to be a lot more stable and have a longer half life, meaning that it sticks around in your system longer than natural estradiol, and that's one of the reasons that it works so well in birth control. You want estrogen around that is stable and has a longer half life because that's what helps suppress ovulation. Now, CEE or conjugated? Equine estrogen is a mix of different estrogen types and many are not naturally found in humans. So if we zoom out, bioidentical estrogen means the same molecular structure as your own estrogen and synthetic estrogen means similar, but structurally different. Ironically, both are made in a lab. And that's the chemistry. But what you really need to know, probably what you really want to know is does bioidentical automatically mean safer? So let's go there next. You've probably seen marketing that says things like bioidentical hormones are safer and more natural, or synthetic hormones cause cancer and heart disease. But here's the evidence-based bottom line. There is no strong high quality clinical evidence that bioidentical estrogens are universally safer or more effective than all synthetic estrogens, and that might surprise you because the marketing is really loud. Perimenopause and menopause are having their moment. We're hearing a lot of stuff online, and there is a lot of misinformation too. But when researchers zoom in on outcomes like heart attacks and strokes, breast cancer and endometrial cancer and blood clot risk, the differences between bioidentical estradiol and synthetic estrogens like CE, are often modest, sometimes uncertain, and highly influenced by the dose, the route in which you take it, meaning oral versus topical, and the type of progesterone or progestin that it's paired with. If you have a uterus. This is the first of three episodes looking at hormone therapy. The next two will focus on progestins and testosterone. Here's another key point, FDA approved bioidentical. Estradiol products have strong safety and quality data. Compounded bioidentical hormone blends. Do not. Let's talk about that for a second. When people say bioidentical hormones, they might mean two very different things. Number one, FD, a, approved estradiol products like your standard prescriptions that your regular pharmacy will dispense. Number two, compounded bioidentical hormones. These are custom mixtures made in a compounding pharmacy and come in, creams, troches pellets, and so on. These are not the same in terms of regulation. FDA approved bioidentical. Estrogen has dosing that is standardized. The product is tested for purity, potency, and stability, and there's clinical trial data behind it. Risks and benefits are documented and monitored, and this is bioidentical estrogen with a known track. With compounded hormones, they are often a custom mixed formulation that are marketed as natural or safer. They are not FDA approved as finished products and they are not held to the same rigorous batch by batch quality control as FDA approved medications. So it really comes down to the quality of the compounding pharmacy you use. I do use compounded hormones in some of my patients, but a lot of times it comes down to the fact that they were not able to tolerate an FDA approved medication. I have a pharmacy that I trust that has a high regulation standard within its own practices. This means doses may vary from what's on the label. Purity and potency can be inconsistent, and there's very limited safety or outcomes data over the long term professional groups like acog, which is the American College of Obstetrics and Gynecology, and the North American Menopause Society, generally recommend using FDA approved hormone therapies whenever possible and avoiding compounded hormones unless there's. Specific medical reason. You cannot use standard products like an ingredient allergy or a very specific dosing need that can't be met otherwise. When people say quote, I want bioidentical, a helpful clarification is, do you mean FDA approved estradiol or compounded bioidentical estrodiol or compounded bioidentical creams or pellets? Because those are very different in terms of what we know about long-term safety. Now let's talk about the big stuff, cardiovascular health, meaning your heart and your blood vessels. When we discuss cardiovascular risk, we're mainly looking at heart disease, stroke, and the risk of blood clots, otherwise known as venous thromboembolism or VTE. And here's what the current evidence suggests. Number one, the route matters, especially transdermal versus oral. One of the clearest patterns in the research is that the way the estrogen gets into your body really matters oral estrogen is a pill you swallow that goes through your liver first before it gets to your bloodstream, and that can increase certain clotting factors and affect triglycerides and other metabolic markers with transdermal estradiol, a patch, a gel, or a spray. These are absorbed through the skin and they bypass that first pass effect of the liver. Because of that, many studies and reviews find that transdermal estradiol is associated with a lower risk of blood clots and possibly stroke compared to oral estrogen. Oral estrogen, especially oral CE E is more consistently linked with an increased blood clot risk. So if someone has a history of blood clots, genetic clotting, tendency, major cardiovascular risk factors or obesity, I often favor transdermal estradiol rather than an oral pill. Just as a side note, for people who struggle with overweight or obesity, they are at an increased risk of blood clots, which is why I added that in there. Number two, bioidentical estradiol versus CEE, which is the synthetic mix. When we compare bioidentical estradiol to synthetic CEE, some observational data suggests that oral CEE may carry a higher risk of blood clots than oral estradiol, transdermal estradiol generally. The safest one compared to the other two. However, this is key. Randomized control trials haven't consistently shown a big difference in heart attack or stroke rates between estradiol and CEE. So what we can say is that the strongest and clearest difference is the blood clot risk, particularly with oral estradiol. And transdermal estradiol often comes out looking better, especially for women who have a higher risk of blood clots. Like we talked about, differences in actual heart attack and stroke events are a lot more subtle and not definitively settled, meaning we need more research. The other huge set of questions is around cancer, especially breast cancer and endometrial or uterine cancer. So let's break this down. Number one, what did the Women's Health Initiative show? The Women's Health Initiative or WHI is the big landmark trial that shaped a lot of the public fear around hormone therapy, and they studied. CEE, which is conjugated equine estrogen plus medroxyprogesterone acetate, a synthetic progestin in women with a uterus and CEE alone in women without a uterus who had undergone hysterectomy. Over time they found that CEE plus the synthetic progestin increased breast cancer risk, but decreased endometrial cancer risk. CEE alone over long-term follow-up may actually lower breast cancer risk when compared to placebo. This is important. The increased breast cancer risk was most clearly seen with a combination of CEE plus a particular synthetic progestin, and not just any estrogen or any hormone therapy. So we have to be really careful about that when we interpret that. And then number two, where does bioidentical estradiol fit into all of this? Studies that look at estradiol based regimens, especially when combined with micronized progesterone, which is the bioidentical form of progesterone. We'll talk more about that on the next episode. Studies that look at estradiol based regimens, especially when combined with micronized progesterone, a bioidentical form of progesterone suggest that breast cancer risk appears similar or possibly slightly lower than with CEE plus synthetic progestins, but we don't have big head-to-head randomized trials that can specifically compare breast cancer outcomes between these regimens. So for now, the fairest summary is that breast cancer risk seems to be influenced more by whether estrogen is combined with a progestogen, which progestogen is used, and the dose and duration of therapy rather than simply bioidentical versus synthetic. With endometrial cancer for women with a uterus, if you take estrogen by itself, otherwise known as unopposed estrogen, that in and of itself can increase the risk of endometrial hyperplasia and cancer. The good news is that both bioidentical and synthetic estrogens can be used safely as long as you add an adequate progestogen, progesterone, or progestin to protect the uterine lining. Without that progestogen. Both can increase the risk of endometrial cancer if you still have your uterus. So this is less about bioidentical versus synthetic, and again, more about using the right combination correctly. So let's zoom out and put this into practical language that you can use in a real appointment. Here are the key takeaways that I want you to walk away with. Number one, bioidentical estrogen is chemically identical to your body's estrogen, and synthetic estrogen is structurally different. This does not automatically mean good or bad, just different. Number two, FDA, approved bioidentical. Estradiol products are generally preferred over compounded bioidentical hormones because they have tested doses and regulated quality compounded products often lack strong safety and efficacy data and vary in potency depending on the type of pharmacy that you're using and what their standards are. Number three, there is no strong evidence that all bioidentical estrogens are dramatically safer than all synthetic estrogens. Marketing really oversimplifies this, and the real answer is very nuanced. Number four. The root matters a lot. Oral estrogen, especially oral CEE, is more clearly linked with higher blood clot risk and transdermal estradiol patch gel spray ring looks to be safer for blood clot risk and is often favored in women who have high risk factors for developing a blood clot or have high risk factors for cardiovascular disease. Number five, cancer risk is complex and not purely about bioidentical versus synthetic breast cancer risk is often influenced by type of estrogen, type of progesterone or progestin duration of therapy. How old you were when you started it? And additional individualized risk factors such as family history, prior biopsies, breast density. There's a lot that goes into it. And then with the appropriate progestogen, both bioidentical and synthetic estrogen can be used safely and for endometrial cancer risk, both bioidentical and synthetic estrogens can be used safely as long as they're paired with an appropriate progestogen to protect the uterine lining. And number six, evidence differences are modest, and we don't have big definitive head-to-head trials. They're very limited. A lot of what we know comes from what we call observational studies and indirect comparison, so we don't have perfect experiments that tie this all up in a nice bow. When we talk in terms of likely lower risk and modest advantages, these are not miracles or guarantees. So if you're listening to this and thinking, okay, so what do I actually ask my doctor? Here's some practical evidence informed questions that you can take to your next appointment. Number one, do you think transdermal estradiol would be better for me than an oral pill given my risk factors? Number two, can we use an FDA approved estradiol product rather than a compounded hormone? Number three, what are my personal risks for blood clots, heart disease, and breast cancer? And how does hormone therapy fit into that picture? And number four, if we use estrogen, what progesterone or progestin are we pairing it with and why? Remember, the goal of menopause hormone therapy is not perfection. It is to relieve symptoms, protect long-term health, where appropriate and match therapy to the individual woman not the marketing trend of the moment. That's all for today's deep dive into estrogen, bioidentical versus Synthetic, and what the evidence currently tells us about safety, cardiovascular risk, cancer risk, and blood clots. If this episode helped clear up some confusion for you, please follow or subscribe to the podcast, share this episode with a friend who is wrestling with perimenopause or menopause decisions and needs more information. And if you feel called to, please leave a quick rating or review. Some more women can find evidence-based grounded conversations like this. And if you're considering hormone therapy, please remember this podcast is education not medical advice. You need to take your questions, your family history, and your concerns to a clinician you trust and use what you learned today to have a more informed and empowered conversation. Thank you so much for tuning in today. I will see you all on the next episode.