This YouTube interview (Ben Greenfield with Cameron Sepah) examines how testosterone is diagnosed and measured. Sepah argues that standard lab reference ranges are flawed (broad, non-age-referenced samples have shifted 'normal' downward), explains the clinical relevance of free versus total testosterone (free more tied to symptoms), notes that accurate free-T requires LC-MS or validated calculations (Vermeulen equation using total T and SHBG), and introduces an FDA-approved at-home capillary whole-blood device (Tasso) that provides clinically validated measures comparable to venous draws. He criticizes dried blood spot and salivary tests for inaccuracy and describes tests/biomarkers measured and treatment options (clomiphene, oral testosterone), with indicative pricing.
Chapters
What are you looking for when it comes to deciding whether or not their testosterone is low or their free testosterone?
Yeah, so our advisors always say we treat people, not numbers. The treatment or the designation of hypogonadism based on testosterone values is highly problematic because the reference range, as I mentioned earlier, has actually shifted. Usually super physiological testosterone back in the day was considered a total testosterone over 1200. But because it keeps dropping over the last couple decades, some of the recent lab reference ranges, which is usually between the second and a half to 97.5 percentile, have dropped to almost 900. I think I saw one that was like 827 is considered high, which back in the day was almost like normal for an athletic male. And so what is considered low is honestly kind of arbitrary. And there's in fact there's public published research papers that prove that. Because what is low for, you know, a 20 something year old male, it's probably very different than low for an 80 something year old male. These are not even age referenced samples.
You mean they're not age reference. Like if I go to a Doctor and I'm 80 versus when I'm 20, they're looking at the same chart.
Exactly. The reference range for a lab is based on 18 to 80 something year old men. Also people who are really sick. As you know, 88% of people have some form of metabolic syndrome, 70% are overweight or obese. And they're comparing that their normal testosterone levels. Yours, which is a healthy young athletic male, should be totally different. So it's a bit of a joke to use standard reference ranges in the sick care system, as I call it, in order to be diagnosed with low testosterone or hypogonadism, as we discussed, typically you have to have a total testosterone under 300, which is right around the second and a half percentile. That's obviously a shitty way of doing a diagnosis because when you what if you're third percentile, you're at 301. Technically you don't have hypogonadism anymore. And then the other problem is we didn't talk about the difference between total and free testosterone. Total testosterone is the total amount of testosterone in your system, but it's not necessarily bioavailable in order to bind to the androgen receptor because it gets bound to these two different molecules, one being albumin, the other being SHBG or sex hormone binding globulin. Free testosterone is the unbound testosterone that's actually free, like a lock and key to bind to the androgen Receptor free testosterone is more associated with clinical symptoms like libido, energy, all the things that we're talking about. So most clinicians who are experts in testosterone actually pay attention to free testosterone. You can calculate it pretty easily. If you've measured total testosterone, you have albumin or shbg, you can calculate essentially what's your free testosterone. So that's essentially what we do.
Oh, really? How do you calculate that? For some reason, I thought you just measured the actual free T, but it's a ratio type of thing. With shbg, you can.
The problem is a lot of the measures of free testosterone are not accurate unless it's done by an LC Ms. Test, which is more expensive, takes longer to run, et cetera. There is something called the vermulin vermillion equation. So if you basically have. Even if you just have total testosterone, shbg, you can plug it into a little online calculator, it'll calculate your free testosterone and it's actually pretty accurate. There's a lot of clinical validation for that.
Kind of makes logical sense because sex hormone binding globulin would bind total testosterone. And if it's high, you're going to have less free testosterone. So I'm assuming this calculation is based on big data or something like that.
Yeah, it's large cohorts. And yeah, to your point, high SHBG means lower free testosterone. Low shbg, higher free testosterone. So what we do, and this is really the innovation is it's obviously kind of a pain in your arm to go to Equestrian LabCorp and get a huge needle stuck in your vein. Now it's great because you can measure 100 biomarkers, but it's inconvenient to do. And so what we've done is we've partnered with a medical device company that's actually gotten these FDA approved. This is what the device looks like.
It's holding it up. For those of you watching the video, check it out on YouTube or BenGreenfieldLife.com Maximus podcast.
Yeah, it basically looks a lot like a CGM. And it works in a similar way. You just stick it on your shoulder. There's a big red button, as you can see here. You press it and it actually uses micro needles, so they're very small. And it's virtually painless. Like I would say on a, on a one to ten pain scale, it's like a maybe a two. So I have friends, in fact, who are blood phobic. They'll pass out of the sight of blood. They can do this test, while they would have a lot trouble, a lot of trouble with a traditional blood test, you can literally do this in the comfort and convenience of your home in five minutes and it'll draw out. I'm showing this on the camera basically for those who are listening on audio. It's about half of your pinky worth of whole blood. This is whole blood that comes from capillary blood. And it's mailed off to a lab via next day air via FedEx and then it arrives in the lab and within two days they can analyze your total testosterone, your SHBG, calculate your free testosterone and then measure other key markers, including your estradiol, your lh, your fsh, your PSA that you mentioned, your hemoglobin, hematocrit, your, and your liver enzymes like ALT and ggt.
Oh, so you're getting it all from that once. Like it's like the staples easy button, that red button, you know, that begs the question though, because a lot of these companies that do the at home lab testing, they got the little cards and you prick your finger and sometimes it bleeds and sometimes it doesn't. You gotta milk it like a cow and wait and get X number of drops and sometimes, you know, relance at your finger to get it to start bleeding again. But is there a reason everybody doesn't just use the little slap it on your arm thing you just showed us?
Because there's a lot of unethical and pseudoscientific companies basically that are out there. It's much cheaper to do the dried blood spot test. We actually looked into it.
Oh, it's cheaper. Okay.
It's cheaper. Yeah. There's some companies out there that for 45 bucks you can do this little milk your finger dry blood spot test, which by the way, 20% of men can't even do it because their fingers are so callous.
Yeah, no, I got super callous. I gotta get in the sauna to do it. I gotta heat my body up in the sauna and then I can't even. This is gonna sound super unhygienic, but I can't even use the lancet. It's not deep enough. I literally have to use an insulin syringe and plunge it into my hand to get the blood to come out. Now I realize I've got very thick, my whole family, all the men in my family, these big sausage finger. But yeah, it is a little annoying.
Yeah. And so, yeah, it has a 1 in 5 failure rate. So it's just a terrible user experience. You have to do this multiple times. So it's hard to even get the blot out in the first place. And the problem is when it gets on the card, it's prone to heat issues. Cause it's going off.
It'S mailed, regular mail. And so if it's hot where you are or the postal carriers, the temperature's off, it can mess with the reading. And, and so dried blood spot testosterone tests are not very accurate.
That's what you call the cards, dried blood spot.
Yeah. If there's any company that's out there, if you're, if you're researching companies, salivary testosterone and dried blood spot testosterone, even though there's big companies that are selling them online, are just not accurate. And we know this because we tried it, because obviously it's convenient to just spit into a tube. And these tests are. The dried blood spot tests are cheaper, but they're just not accurate. And if you're obviously trying to, you know, have an accurate assessment of your health and whether these treatments are working, you need, you need an accurate blood test. And so this is best in class technology. Like I said, it's whole real blood. It's just like. And it's clinically validated. It's just as reliable and valid as essentially going to a Quest or a LabCorp. And so if people are not using this, I would not trust that company, basically.
Yeah. I mean, there is that Dutch test that does all the different metabolites and does melatonin and a whole bunch of other stuff via dried urine, but that was pretty expensive.
Yeah, I think that's, I've heard of that. It's not a lot of, like, more naturopathic doctors are using that. I wouldn't say it's super accepted in sort of traditional clinical.
It's not. I think you can get a ton of data out of it. I think you can get more data out of it than saliva or blood. But again, it is spendy. So that's a downside. But I think it is a good test.
So, yeah, what we do with the tasso, just to wrap this up, that's.
Called the tasso, the blood one you held up. T, A S, S O. Yeah.
That we use. So we measured obviously at baseline, and then the doctor will look at your numbers, but also your symptoms. And so you can technically be what's called eugenadal, meaning your normal testosterone. But like I said, that could be third percentile, it could be 50th percentile. And so that's less important as your symptoms. If you're saying I used to have great energy, I was happy, had great libido, but now I'm falling asleep in the afternoon or after dinner. I don't have the PEP that I used to have. And I'm having symptoms of low testosterone. And your numbers are maybe not optimal. You still can be a good candidate for especially the type of treatment that we provide with in Clomiphene, oral testosterone or the combination thereof because it's maintaining your natural production and your fertility. So it's not that, oh my God. This is a drastic treatment of last resort where I got to be on this for the rest of my life and shut off my own production. With this, you can really do more optimization or performance enhancement because it's a lot safer essentially than the old school, just injectable approach.
Right. And I can still meet with a doctor and get lab tests and everything. The only downside is, of course, insurance wouldn't cover it because I'm not hypogonadal. Right.
Yeah. I mean, I think insurance is a scam in this country because like I said, they're in the business of denying care, not providing care, and they only provide it to people who are really drastic, below the second and a half percentile. We're a cash pay, basically private practice.
It's another good reason to have an FSA hsa.
Yeah. Which we do accept. So we, you know, obviously you can get at least the tax savings from doing so and you know, the plans that we have, if you're committing for a year or more, so typically $100 to $200 a month. Clomiphene is 100, 100, 100amonth. Oral testosterone with Clomine is 200amonth. So it's actually pretty reasonable.
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