Hormone Testing Why Method Matters

Welcome back to the deep dive. Today we're tackling something that seems straightforward but is actually full of surprises: hormone testing.

Specifically, why do different hormone tests sometimes give you completely different results? Especially if you're using things like hormone creams or gels. It's a really common point of confusion.

It turns out the way you test can totally change the picture — maybe even leading to misunderstandings about your health.

If you've ever been puzzled by hormone results or you're dealing with hormone therapy, this deep dive is definitely for you.

Let's unpack this.

Getting hormone levels right is just so essential, especially for people on therapies or going through menopause. Accuracy is key.

And what often gets missed — and what we're really digging into today — is how the test method itself can drastically alter what those numbers tell you and therefore how your health gets managed.

The goal is to shine a light on those differences. So, you can be better informed, understand your results better, and ask better questions. Advocate for yourself.

Okay, so let's start with the basics.

Hormones like progesterone, estradiol, testosterone — they’re huge players in our bodies. Mood, energy, bone health.

They influence just about everything. So, if they’re that important, why isn’t measuring them easier, like checking your blood pressure?

That’s the million-dollar question. And a big part of the challenge comes down to how the hormone gets into your body in the first place.

You mean like a cream versus a pill?

Exactly. Cream, pill, injection, patch — even vaginal inserts. Each one delivers the hormone differently, and that method seriously impacts where the hormone ends up and how it spreads through the body.

Then the type of sample you collect — blood, saliva, or urine — interacts with that delivery method.

So it’s the combination. And that interaction can lead to results that seem totally contradictory.

Understanding this is vital if you’re managing your health with hormones. Misinterpreting results can lead down the wrong path.

Right? Got it. So, let's map this out.

First: how do we actually collect the samples? The studies talk about four main ways — four types of body fluids.

That’s correct:

• Serum – The standard blood test, usually taken from a vein in your arm.
• Saliva – Super easy, often collected at home. Very convenient.
• Urine – Often measures hormone metabolites, not just the hormones themselves, showing how your body is using and clearing them.
• Capillary blood – Collected via dried blood spot (DBS), a simple finger prick on special filter paper.

Each method has its uses — and its potential drawbacks.

And on the flip side, there are many ways to get hormone therapy now. It’s definitely not just about taking a pill anymore.

Options include:

• Oral pills
• Topical creams and gels (rubbed on the skin)
• Skin patches that deliver hormones steadily
• Pellets inserted under the skin
• Injections
• Troches – lozenges that dissolve in the mouth
• Vaginal creams or suppositories – for more localized effects

That’s a lot of different routes.

And what’s often missing from the conversation is how each route changes where the hormone shows up most in the body — and where it doesn’t show up enough to be accurately measured by certain tests.

That mismatch is the heart of it.

The body’s pathways for absorbing and distributing these hormones are varied, and if you don’t match the test to the delivery method, it creates real challenges for accuracy.

So, where does it all go wrong? What’s the big insight from the studies about how these methods interact — especially with something common like a topical cream?

The key finding: Topical hormones — creams and gels — are often very hard to track accurately with standard serum blood tests.

That mismatch can lead to misleading results, or results that don’t tell the full story.

Let’s break it down.

If you're using a topical cream and do a standard serum blood test, you might get back a surprisingly low hormone level.

That might make you think it’s not working, when in fact, if you used saliva or DBS (finger prick) testing, the levels might actually appear high.

Because those tests reflect what’s getting into the tissues — where you want the hormone to be active.

It’s like checking the main highway traffic when all the action is on the local roads. The serum test is the highway — not showing what’s really happening in the tissues.

What about other methods like pills?

Oral pills go through your digestive system and then directly to the liver. That’s called first-pass metabolism.

This can strain the liver and also affects how the hormone is processed. Urine tests might show high levels of metabolites, but that doesn’t always mean the hormone is being fully absorbed into other tissues.

High urine levels ≠ high tissue levels necessarily.

Then there are troches — lozenges that dissolve in your mouth. Big caution here: they can easily contaminate a saliva sample.

Because they dissolve right in the mouth, they can give you an artificially high saliva reading that doesn’t reflect systemic levels.

It’s like measuring the sugar in your coffee while you’re still stirring the spoonful in.

So avoid saliva tests right after using a troche.

Other methods like patches, pellets, and injections tend to give more consistent levels in both serum and DBS tests. They’re easier to track.

And finally, vaginal creams. These are mostly for local absorption — helpful for treating local symptoms, but harder to track systemically using blood tests.

Let’s go deeper with a real example. One study looked at a post-menopausal woman using 20mg of progesterone cream daily.

Same person, same dose — but different tests gave totally different results.

• Serum test (blood draw): Very low levels — almost undetectable.
• DBS (finger prick): Much higher — showing significant progesterone levels.
• Saliva test: Extremely high — orders of magnitude above the serum result.
• Urine test: “Normal range” of progesterone metabolites.

Same person. Same dose. Four totally different results.

This shows that depending on the test, you could be told your hormone level is very low, normal, or extremely high — all at once.

It challenges the idea that blood tests are always the gold standard.

Why? Because topical progesterone doesn’t travel well into the bloodstream. It often enters the lymphatic system or stays in nearby tissues instead of circulating widely in the blood.

So serum tests miss it, even though it’s active in the body.

Some studies show that hormone levels in tissues like breast tissue can be 100 times higher than what serum tests show.

That’s why people using creams may be overdosed if providers rely only on serum results and keep increasing the dose unnecessarily.

That’s a real risk — and a real reason to understand this mismatch.

So, if the standard blood draw isn’t always the best for topicals, what should people be looking at?

Saliva and DBS (finger stick blood tests) are often more accurate for tracking hormone levels with creams and gels.

Saliva reflects the free, unbound hormone — the part that’s readily available to enter cells. Levels spike quickly after using transdermal hormones, showing what’s active around the cells.

DBS tends to show more sustained levels over time. It captures hormones within red blood cells, not just in the fluid part of the blood like serum does.

This means DBS may provide a better reflection of tissue-level exposure, especially with topical applications.

Knowing this lets you have more informed conversations with your provider. You can ask: “I’m using a cream — is a serum test really the best way to track it?”

Let’s summarize the pros and cons of each method:

• Serum (blood draw): Good for pills, injections, patches, pellets. Weak for topicals, often underestimates tissue levels.
• Saliva: Great for tracking topicals and circadian hormone rhythms (like cortisol). Risk of contamination, especially after using troches or oral hormones.
• Urine: Useful for checking metabolites and how hormones are processed. Can be helpful for oral therapies. But risk of contamination from vaginal/topical hormones.
• DBS (finger prick): Strong for measuring true tissue absorption. Good for creams, patches, injections. But requires very clean technique to avoid contamination.

Bottom line: There’s no one-size-fits-all test.

The best test depends on your delivery method and what you're trying to measure.

This is why personalized healthcare matters.

You need a provider who understands how to match the test to the therapy and interpret it in the context of your treatment and how you’re feeling.

If you’re using creams or gels, talk with your provider about whether saliva or DBS testing might be more accurate than relying only on serum levels.

And remember: If doctors only look at low serum numbers for topicals, they may keep increasing the dose — even when tissues are already saturated.

This mismatch has real-world consequences. Understanding it is empowering.

Okay, we’ve definitely unpacked a lot today.

And here’s one final thought to leave you with:

How many other medical tests — things that seem simple — might have hidden complexities like this?

Where the method of testing profoundly changes the meaning of the result?

Thinking about this might shift how you approach healthcare.

Next time you get a test or start a treatment, ask:

“Are we sure we’re getting the full picture?”

It’s a powerful question. And a good reminder that informed patients can make better decisions.

So, if you’ve ever been confused by hormone levels, or your provider’s recommendations seemed off — now you know there might be more to the story.

Understanding why the testing method matters can help you advocate for yourself more confidently.

Thanks for joining us on this deep dive. Stay curious, and keep asking smart questions.