Bypassing the Barrier

Emily Clarke

Hello and welcome back to "Why Sublingual Hormone Dosing is Superior to Oral or Topical Dosing." I’m Emily Clarke, and as always, I’m joined by Dr. Richard Nkwenti. Today’s episode is called "Bypassing the Barrier," and, well, I think we’re about to get into why so many people feel let down by traditional hormone therapy. Richard, can we start with the basics—what’s actually going wrong when people take hormones by mouth?

RICHARD NKWENTI

Absolutely, Emily. You know, it’s almost counterintuitive—people assume swallowing a pill is the most direct way to get medicine into the body. But with hormones, it’s actually the opposite. When you take, say, oral progesterone or testosterone, up to 90% of that hormone is destroyed by the liver before it ever reaches your bloodstream. That’s what we call first-pass metabolism. So, you’re left with just a fraction of the active hormone, and the rest is turned into metabolites—some of which can cause side effects or, worse, confuse your lab results.

Emily Clarke

That’s wild. So, you could be taking your pills religiously, but your body’s only getting a tiny bit of what you actually need. And then, if your lab results look "normal," it might just be those metabolites showing up, not the real, active hormone?

RICHARD NKWENTI

Exactly. I’ve seen this so many times. I remember a patient—let’s call her Sarah—her oral progesterone dose kept going up and up because her symptoms just wouldn’t budge. Her labs looked fine, but she still felt exhausted, moody, couldn’t sleep. It wasn’t until we switched her to a different delivery method that we realized the problem wasn’t her body—it was the way the hormone was being delivered. The oral route was sabotaging her therapy from the start.

Emily Clarke

That’s so frustrating. And I guess, for a lot of people, the answer from their doctor is just to increase the dose, which only makes the side effects worse, right?

RICHARD NKWENTI

Right. It’s a vicious cycle. More pills, more metabolites, more side effects, but not necessarily more of the hormone you actually need. And, as we discussed in our last episode, this is why personalized, data-driven approaches are so important. The old "one-size-fits-all" model just doesn’t work here.

Emily Clarke

So, let’s talk about the alternative—sublingual dosing. What makes it so much better?

RICHARD NKWENTI

Sublingual delivery is a game-changer. Instead of sending the hormone through your digestive system and liver, you place it under your tongue, where it’s absorbed directly into the bloodstream. That means you get five to ten times higher bioavailability compared to swallowing a pill. The hormone keeps its structure, so you get more stable levels, faster symptom relief, and way fewer side effects.

Emily Clarke

I love that. And, you know, I always use this astronomy metaphor when I’m explaining it to people—maybe it’s a bit nerdy, but bear with me. Imagine oral dosing is like a planet trying to keep its atmosphere as it enters a star system. Most of it gets stripped away before it even reaches the surface. But with sublingual, it’s like the planet just appears right where it needs to be, atmosphere intact, ready to support life. Does that make sense?

RICHARD NKWENTI

That’s actually a brilliant analogy, Emily. The hormone doesn’t have to fight its way through all those destructive forces. And the results speak for themselves. I’ve had patients—Sarah, who I mentioned earlier, and another, Emily—who both saw dramatic improvements in mood, sleep, and energy after switching to sublingual. The difference can be night and day.

Emily Clarke

And it’s not just about feeling better, is it? The science backs it up. Clinical studies show more consistent hormone levels, fewer peaks and crashes, and, honestly, it’s just easier for a lot of people. No more worrying about food interactions or gut issues.

RICHARD NKWENTI

Exactly. Plus, the dosing is more precise, so you’re not playing catch-up with your symptoms all the time. It’s a much more predictable, patient-friendly approach.

Emily Clarke

So, this is where things get really exciting—personalized medicine. How does sublingual delivery fit into that future?

RICHARD NKWENTI

Sublingual delivery is almost tailor-made for personalized medicine. Because you’re getting more of the active hormone, you can fine-tune the dose to each person’s needs. And, with advanced diagnostics—like measuring free, bioactive hormone levels—you can actually see what’s happening in real time, not just guess based on metabolites.

Emily Clarke

And it’s not just the doctor, right? It’s a whole team—pharmacists, labs, sometimes even remote monitoring. I mean, telehealth is making it so much easier to keep tabs on patients and adjust things quickly.

RICHARD NKWENTI

Absolutely. I keep a notebook of patient stories, and one that stands out is Lisa. She was struggling for years on oral estrogen—her labs looked "normal," but she felt terrible. When we brought in a multidisciplinary team—her doctor, a compounding pharmacist, and a lab that could measure free estradiol—we switched her to sublingual, monitored her remotely, and adjusted her dose based on both her symptoms and her real hormone levels. Within weeks, her mood stabilized, her sleep improved, and she finally felt like herself again. That’s the future—collaborative, data-driven, and patient-centered.

Emily Clarke

It’s so much more empowering for patients, too. You’re not just a number on a chart—you’re an active part of your own care. And, honestly, that’s what medicine should be about.

RICHARD NKWENTI

Exactly. The more we can personalize and adapt, the better the outcomes. And with technology, it’s only going to get easier to do this at scale.

Emily Clarke

Before we wrap up, I want to touch on something that confuses a lot of people—the controversy around hormone testing. Why do oral progesterone levels look higher in blood tests than sublingual, even though sublingual works better?

RICHARD NKWENTI

Oh man, this is such a critical—and honestly, kinda frustrating—thing that so many people (and even doctors!) miss with progesterone. Let me break it down in a way that makes sense, because once you get this, it’s like a lightbulb moment for why some people feel amazing on progesterone and others feel like it does nothing, even when their labs look ‘good.’""Okay, so first: most standard progesterone blood tests? They’re kinda like a bad translator. You ask for ‘progesterone,’ but instead of showing you the actual, active hormone your body can use, they mostly show you the broken-down leftovers—metabolites—from what your liver chewed up. It’s like ordering a steak and getting a receipt that says ‘meat’ but doesn’t tell you if it’s a filet mignon or ground beef scraps.""Here’s why that’s a problem. When you take progesterone ORALLY, it goes straight to your liver, which goes, ‘Ooh, snacks!’ and metabolizes like 90% of it into other stuff—pregnanediol, all these byproducts. Those byproducts still show up on standard blood tests as ‘progesterone,’ so your levels look high. But the real, usable progesterone? Only a tiny fraction actually gets through to your brain, your uterus, your mood, your sleep—all the places you actually want it. So you could have ‘perfect’ lab numbers but still feel like garbage because your body isn’t getting the active hormone it needs.""Now, compare that to sublingual progesterone. You let it dissolve under your tongue, and boom—it skips the liver party and goes straight into your blood. Way more of the actual, active progesterone gets where it needs to go. But here’s the kicker: because there are fewer of those metabolites floating around, your blood test might come back looking ‘low’—even though you’re getting way more of the good stuff where it matters. It’s like the test is lying to you!"*"And this is why dosing gets wild. Because oral progesterone gets destroyed by the liver, you might need 300, 400, even 500 mg orally to get the same effect as 100 mg sublingually. That’s a massive difference! So if someone’s on oral progesterone and their doctor says, ‘Your levels are great, why are you still tired/anxious/not sleeping?’, it’s not that progesterone isn’t working—it’s that the test is measuring the wrong thing, and the delivery method is wasting most of it."*"So what’s the fix? First, if you’re using progesterone and not feeling it, consider switching to sublingual, transdermal, or even injections—anything that bypasses the liver. Second, if you’re testing, ask for an LC-MS/MS progesterone test (that’s mass spectrometry—it’s way more accurate) or saliva testing, which measures the free, active hormone. Otherwise, you’re just guessing.""Bottom line? Progesterone isn’t tricky—but the way we test and dose it sure is. And once you understand this metabolite mess, suddenly a ton of ‘failed’ hormone therapy stories start making sense. "Honestly, we could do a whole episode just on how many hormone tests are basically fancy lies. Cortisol, estrogen—so many of them have these same pitfalls. But that’s a rant for another day!"

Emily Clarke

So, if you’re just chasing numbers on a lab report, you might think oral is better, but in reality, patients feel better on sublingual because it’s the active hormone that counts, not the leftovers from liver metabolism.

RICHARD NKWENTI

Exactly. That’s why it’s so important to look at both the science and the patient’s experience. Lab numbers can be misleading if you don’t understand what they’re actually measuring. It’s about how you feel, not just what’s on paper.

Emily Clarke

That’s such a good point. And I think it’s a perfect place to end for today. We’ve covered a lot—from the hidden pitfalls of oral dosing to the promise of sublingual and the future of personalized hormone therapy. Richard, thanks for sharing your stories and expertise as always.

RICHARD NKWENTI

Thank you, Emily. Always a pleasure. And thanks to everyone listening—remember, your experience matters just as much as your lab results. We’ll be back soon with more on optimizing your hormone health.

Emily Clarke

Take care, everyone, and see you next time on "Why Sublingual Hormone Dosing is Superior to Oral or Topical Dosing." Bye, Richard!

RICHARD NKWENTI

Goodbye, Emily. Goodbye, everyone.