Is Testosterone Right For Me Now? Case Study of a 35-year-old Male

Full Transcript and Time Stamps

0:00 Dr. Doreen Begins

1:15 Case Study Begins

5:54 What Tests Do We Do?

12:41 Kevin’s Hormone Labs

17:12 Making the Diagnosis

24:52 Root Cause Analysis

32:27 Kevin’s DUTCH Plus

43:37 Testosterone metabolism and testosterone excretion?

57:59 Testosterone Options and Raising T Levels

1:00:47 Kevin’s Treatment Plan

1:04:09 My Approach to Males with Suspected TD

1:07:08 Final Thoughts

1:09:12 Q&A

0:00 Dr. Doreen Begins
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All right. So, let's get started.

0:03

This is the case of a 35-year-old male asking, “Is testosterone therapy right for me?”

0:14

So, this lecture and the cited literature, when referring to men or males, is referring to individuals' born biological males.

0:21

So, I thought today, we’d use this real-life case study to guide our discussion on what is testosterone deficiency, what laboratory tests do we need when we're thinking a male has testosterone deficiency, and what else needs to be considered when making a diagnosis, and when determining the need for treatment?

0:44

And, in addition, we'll also discuss treatment options. But first, before I start, there are lots and lots of myths out there about testosterone therapy.

0:55

Two of them that are absolutely not true, testosterone therapy does not cause prostate cancer, and testosterone therapy does not increase cardiovascular disease risk. There are some citations there and in 2022, we will dive deeper into each of these topics.

1:15 Case Study Begins

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So, Kevin comes to the office, and asks, “Is testosterone therapy right for me?” So, let’s meet Kevin.

1:21

He's a 35-year-old male who presents with decreased energy vitality fatigue, he's got some brain fog, he's anxious, he has difficulty sleeping. His wife tells me he doesn't snore, but he can't lose belly fat. He complains of decreased libido, states that he recently has developed, probably over the past 6 or 8 months, erectile dysfunction manifested by difficulty achieving and maintaining an erection as well as an orgasm. His erections and not as strong as previously.

1:54

In addition, he has lost muscle mass, and despite aggressive training, he has been unsuccessful in increasing muscle mass and losing body fat.

2:05

Further, he states his work performance is slipping, he denies a history of snoring.

2:10

And he comes and says, “I want solutions.” His past medical history is remarkable for using anabolic steroids as a teenager for approximately nine months, he wanted to play baseball, and he's not that big of a guy, and so, one of his friend said, “Why don't you take anabolic steroids?” And of course, they're not legal, so he got them off-market, and he developed a varicocele, which is fairly common, which are scrotal varicose veins, that typically require surgical removal. And varicoceles, just as an aside, are associated with decreased testosterone, as well as decreased fertility.

2:48

In his late twenties, he received pellets for, quote, unquote, low T and in 2019, which is very interesting, he did a weight loss challenge, lost weight and his total testosterone increased.

3:01

In 2020, he received HCG for a bit and a testosterone troche.

3:06

Again, an aside, never do testosterone troches orally. There is an FDA approved oral testosterone that is safe for the liver. Oral testosterone has been shown to increase liver damage, and in some settings, liver cancers, he currently is not taking any testosterone supplementation.

3:29

His family history, despite having taken anabolic steroids, and his testosterone being low, he’s had three children, naturally, not on testosterone therapy.

3:39

Otherwise, his family history is unremarkable. He's happily married, works in sales in a high stress industry, he exercises regularly, doesn't smoke or drink, and his diet is OK when he pays attention.

3:52

He has gut issues that necessitated an extensive GI workup, which is when he was diagnosed with irritable bowel syndrome. Interestingly, he is HLA DQ2.

4:05

He's got one allele, not both, and DQ2 is more common, and DQ8 he has negative, he's negative for both alleles, he is not gluten or dairy free. Which is probably adding two his amino acids.

4:18

He's 5”10, is 170 pounds. His BMI is on that borderline. His waist to hip ratio is greater than one, meaning he's got some, you know, central obesity, his blood pressure is borderline, and his resting heart rate is 80. So, he's being driven by catecholamines, and it may be because he's in the office and asking questions about testosterone, testosterone deficiency, and the symptoms he’s having around that.

4:47

We get additional testing; he had a testicular ultrasound to assess testicular volume. And it was 8cc’s, less than 10cc's is indicative of HPG-axis dysregulation. So, this is something that you should consider doing in males who you are considering, have testosterone deficiency. I also asked each male to fill out an ADAM questionnaire. Now, it's only been validated in males greater than or equal to 40 years old. That doesn't mean it's not valuable. And it doesn't mean it doesn't work, because sometimes guys forget things. And sometimes, they're just not comfortable talking about it.

5:32

And, so, Kevin checked boxes one, and seven, as well as boxes 2, 3, 5, 6, 8, and 10.

5:43

And so, if you check one, or seven, or any of the three, which he has, basically, he should be tested for testosterone deficiency.

5:54 What Tests Do We Do?

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So, what tests do we do?

5:57

Serum is the gold standard for testosterone testing and monitoring. The evidence is clear if you give a male testosterone,

6:06

not only will his symptoms abate, but his testosterone levels will increase proportionately to symptomatic relief and improvement in clinical outcomes. And so, the evidence told us that serum works, regardless of whether you're using a gel, a cream, a shot, a pellet.

6:28

So, people who say that you can't monitor creams in serum are incorrect.

6:35

The evidence is you can.

6:38

All right. So, what lab tests should we do?

6:41

Well, we should do a CBC, CMP, serum hormone binding globulin total testosterone.

6:41

And we shouldn't get a measure of free testosterone. It's not accurate. You should calculate free testosterone. In order to do that, you need an albumin and a serum hormone binding globulin.

7:01

Of course, you should measure estradiol in all males. It is important for bone mineral density, and sexual function, and similar to post-menopausal women. You need to use an LC-MS/MS

7:14

assay because at lower levels where men live, as well as post-menopausal women, testing using an immunoassay, I don't care if it's serum. I don't care if it's saliva. It's not accurate.

7:29

You want to get an FSH and LH, you want to get prolactin.

7:33

Prolactin, if it's elevated, if somebody has a prolactinoma, will decrease FSH LH signaling and will decrease testosterone.

7:45

You want to get FSH, you know, I only get an initially unless somebody's on Clomid, then I may get it more regularly, because what is Clomid?

7:53

Clomid is a selective estrogen receptor modulator. It binds to the receptor in the hypothalamus and the pituitary and sends the signal that it needs to increase FSH and LH. So, Clomid, in addition to increasing testosterone will also increase estradiol, and you really want to monitor those things.

8:14

And, of course, you're going to get the other labs you typically get, thyroid, Vitamin D, pregnanolone, if you get that, progesterone, and really have a high index of suspicion for metabolic diseases and obstructive sleep apnea, because 80% almost, give or take, of testosterone deficiency, secondary testosterone deficiency, meaning normal to low LH with low testosterone, is due to an underlying cause. So, you don't need to jump at giving people testosterone or even Clomid, need to look at underlying ideologies, correct those, and then retest. You want to do a PSA. You want to do a digital rectal exam, and you want to do a testicular volume. Now, let me go back, when do I order these tests? I get them at baseline. I get them at one month.

9:11

Typically, after three treatment months, which is four months, the eight months, give or take, maybe not.

9:21

But, definitely at 12 months, and then, as long as things are stable, I literally do with 2 to 3 times a year. And that's the same thing for all of these.

9:33

I don't repeat prolactin, you know, I typically don't repeat FSH, I do repeat LH it, just figure out where I'm going to land, and I do repeat these as deemed appropriate.

9:48

And, again, I do a… and don't except just a PSA, you need to do a digital rectal exam.

9:57

It's the standard of care. You do it a baseline. I typically do it at four months, and then at 12 months, and then probably yearly.

10:07

Do I repeat testicular volumes? Maybe once, not always, if I'm going to give actual testosterone therapy, you need to tell your guys that it’s going to reduce testicular size. Some guys don't care. Some guys care a lot. And it's important that you set expectations.

10:28

And then I do DUTCH testing.

10:30

Let me just pause here and tell you about 3 or 4 years ago, I was a saliva tester.

10:36

I then dug into the literature and realized, number one:

10:40

there were no outcome studies using saliva, and number two: there are no validated, salivary tests out there.

10:48

And most saliva tests use immunoassays, which are not reliable.

10:54

And when you are using testosterone therapy, this is primarily for testosterone therapy. Baseline, you can probably use any test you want.

11:03

But when you're giving somebody testosterone therapy, what happens is, salivary testing overestimates testosterone levels. So, in other words, you'll think you're getting a ton of testosterone, lower the dose. And you'll lower the dose to a point where you're not going to affect clinical outcomes, it’s documented in the literature.

11:28

That, we’ll do it another time, or Mark will touch on that at some point.

11:28

But I do DUTCH testing for a couple of reasons.

11:37

Now, all the time, I do it at baseline, I do it after three treatment months, and then I do it at 12 months, and I typically do it twice a year.

11:46

Why? I want to know about somebody's HPA-axis, whether I do a DUTCH Plus and get saliva. If I'm interested in the cortisol awakening response, which you can only get in saliva, or I want metabolites and urinary cortisol, then I'm looking at urine. Now, urine gets some metabolites with a DUTCH Plus. And really hormones, when you're looking at androgens, you want to evaluate hormone metabolism initially, and then on testosterone therapy.

12:18

You want to evaluate total androgen production and activity, and you want to optimize detoxification pathways, very important, not just for women,

12:32

but for men, you need to look at estrogen metabolism. You want to look at androgen metabolism and we're going to get into this in a little bit.

12:41 Kevin’s Hormone Labs

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So, let's look at Kevin's labs from 3/2021, his hemoglobin hematocrit were normal.

12:55

Now, if these were high, I would then send him for an obstructive sleep apnea test because that's one of the most common causes of an elevated hematocrit. 47, 48. If it's above 50, I would never give him testosterone or any other guy.

13:06

OK, until I figured out why, and I evaluated and treated, his fasting blood sugar is 90, his hemoglobin A17 is 5.7, so he has some degree of insulin resistance.

13:21

And then, you know, it's not much change six months later, and then when you look at his total testosterone or his androgen, you see there are about the same, his total testosterone is low.

13:33

290/300, depending on what you consider low, his free testosterone calculated is on the borderline here. It's lower here.

13:43

His estrogen is, you know, on the lowish normal side. Do you want a guy’s estrogen to be between 20 and 40? PICO grams per mill for optimum bone mineral density, sexual function below 20, as you'll see in a little bit and, certainly, below 15, you increase the risk of osteopenia or osteoporosis. And your goal should be about 30 to 35.

14:12

His serum hormone binding globulin is 16. You know, that’s on the lower side, his FSH is OK, his prolactin is normal, so it doesn't have a prolactinoma, and his LH is OK, and his PSA was low, so now you have a guy who's got low testosterone,

14:38

his testicular volume is low when his PSAs low because what stimulates PSA? Testosterone, So, you're thinking along with his symptoms, yeah,

14:45

he has symptoms, he has signs of testosterone deficiency. Clinical Pearl: in men with testosterone deficiency and some degree of central adiposity, add a low serum hormone binding globulin.

15:00

Think metabolic disease, OK, a low serum hormone binding globulin, think

15:05

central obesity, metabolic disease, and in a third of these men, as opposed to an elevated estradiol, which you would expec,t secondary to up regulation of the aromatase enzyme due to the central adiposity and chronic inflammation, E2 will be unexpectedly normal.

15:27

These guys have what's called hypogonadotropic hypogonadism, so just be aware of that, that that exists. So, if we look back at Kevin, his serum hormone binding globulin on the low side, his estradiol is not high.

15:44

You'd expect it would be higher due to his central adiposity.

15:50

It's really not, you know, it's probably not that significant, but you have to start thinking that he's got low testosterone. And he has insulin resistance.

15:59

So, these are signals to you, that he may have an underlying etiology, a metabolic etiology, for his testosterone deficiency. Clinical Pearl: All right, in a male with borderline criteria,

16:15

testicular volume and PSA may be helpful in deciding whether a male has, especially a young male, has testosterone deficiency.

16:29

All right.

16:34

So, now, we have to ask the question. I think we've kind of answered this. Does Kevin meet the diagnosis?

17:02

If he meets the diagnostic criteria, what, in addition to alter HPG axis signaling, he took anabolic steroids, needs to be considered, what additional tests will be helpful, either with the diagnosis or with treatment, and what treatment option should we consider? So, number one, let's talk about making the diagnosis, well, what does the guidelines tell us? Well, they're all over the place.

17:12 Making the Diagnosis

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The American Urological Society says less than 300, the British Society says 230, Canada says, “We're not going to have any kind of cut off.” The International Society says 230. The Endocrine Society says 300.

17:38

The European Menopause and Andropause Society says, less than 350, and when you read what key opinion leaders talk about with men with testosterone deficiency, in a commentary in 2014, and I have the reference for you at the end, Morgentaler, Khera, Maggi, Zitzmann, all talk about a total testosterone of less than 350. They look at PSA, they look at testicular volume and Mohit Khera, who is a World Authority. And actually, I am honored to say a friend, will tell you that in a young guy with a low testicular volume and low PSA, if his testosterone’s less than 400 and he has symptoms that are consistent with testosterone deficiency, like, decrease libido, etcetera, etcetera, he will consider testosterone therapy.

18:12

He will definitely do things to increase his testosterone and a lot of it will depend on whether the young man has an interest in becoming fertile or maintaining fertility, because once you give a guy testosterone, it's going to suppress his intrinsic HPG axis.

18:34

And he may not be able to conceive. And then if you stop at that, people, say, well, stop it. If you stop, the testosterone, his testosterone may not come up again. And so, that didn't help at all. But, anyway, in healthy males, unfortunately, testosterone decreases by about 1 to 2% per year. Sorry, guys.

18:55

And the most common and reliable symptoms are sexual.

18:59

Decreased libido is a number one symptom, and then you have a guy over 50 and he has decreased libido, test his testosterone, and again, other symptoms difficulty achieving or maintaining an orgasm or an erection.

19:16

All of those kinds of things and non-sexual symptoms are a lot of the general symptoms that you will see: fatigue, decreased energy, decreased vitality, etcetera.

19:29

Signs: loss of muscle mass, an inability to increase muscle mass, and guys, with low testosterone and low estradiol,

19:39

check bone mineral density and, again, decreased testicular volume. Now, what about testosterone levels?

19:47

So, if you look at a total testosterone of less than 300 to 350. And so, you say, “Doreen, how do I know whether you use 300 to 350?”

20:00

Use all the other things we've already talked about, it's a reasonable threshold, but it's not absolute. Remember, look at serum hormone binding globulin and I'm going to introduce another term called Androgen Receptor Sensitivity as measured by what's called DNA CAG repeats, and they're on the X chromosome, and yes, if you look at this genediagnosis.com, it's for Huntington's Disease and a lot of others.

20:26

But for the androgen receptor specifically, if you have CAG repeats greater than 24 to triplet, then you have decreased androgen receptor sensitivity, and these guys may have testosterone deficiency at higher testosterone levels and they may need with treatment higher testosterone levels. And here's just average for African Americans, it's about 18 to 24, Caucasians 21 to 23, and East Asians 22 to 23. Now, there is some data out there, not well delineated that low CAG repeats may increase the risk of prostate cancer, more to...

21:11

And then when you look at a calculated three T, I tend to use less than 100.

21:18

Because what I found is that less than 300, it's going to be less than 65.

21:26

And, again, you need a serum hormone binding globulin and albumin, but remember, a total testosterone of less than 200 to 250 is associated with lots of adverse health outcomes.

21:39

To include metabolic disease, cardiovascular disease, as well as decreased bone mineral density, which is something people don't think about in men.

21:50

They think about it in women, and remember to measure two AM specimens, and in healthy young males, T has a diurnal pattern. And in men over 40, this diurnal pattern may be lost. Do I give two samples on every guy? Yes.

22:04

Are they both in the morning? One is definitely in the morning.

22:08

And then, a second one, maybe, you know, later in the morning, in a guy who's 50 or something. But I always give two, because, you know, key opinion leaders still say, get two.

22:20

And then, here are your optimum testosterone levels, 500 to less than a thousand. And here's your goal.

22:28

As I said, some guys do fine with 550, 500, other guys may need 8, 9, 8 or 900 for complete symptomatic relief and to improve clinical outcomes. And it depends on a lot of the other factors.

22:43

So, it's not a one size fits all, and, you know, since we're talking about looking at the whole patient, don't forget about risk factors.

22:55

Don't forget about the cardiovascular system, hormones, lifestyle, the HPA-axis, because those are going to affect testosterone levels.

23:06

So, here are some key points in a male, greater than 50, with signs and symptoms consistent with testosterone deficiency, I used the ADAM Questionnaire, low total testosterone and our free, calculated, evaluate, and treat any underlying etiology, and consider testosterone therapy.

23:24

In a male less than 50, with signs and symptoms consistent with testosterone deficiency, with primary testosterone deficiency, meaning, LH is elevated, testosterone is low, free T is low.

23:39

After ruling out other possible etiologies, testosterone therapies, the treatment of choice and in these guys, it's usually a genetic issue, in a male less than 50, with signs and symptoms consistent with testosterone deficiency. Now, we have secondary testosterone deficiency, evaluate and treat any and all underlying etiologies. And I would recommend against testosterone therapy as the first choice. Against. I'd use other options. I'd use nutraceuticals, I'd use HCG, I'd use Clomid, but, once you commit somebody to testosterone, they’re, in essence, going to be committed for life.

24:18

So, does Kevin meet diagnostic criteria? Yeah, his testosterone’s low. His free T is low.

24:24

He's got positive symptoms.

24:27

Sexual and nonsexual, he's got decreased muscle mass, his bone mineral density is normal. He doesn't have anemia. His PSA is low, and he's got low testicular volume, which I forgot to include, which I'll add before the slides go out.

24:42

So, since he meets criteria, what in addition to altered signaling needs to be considered? Let's talk about root cause.

24:52 Root Cause Analysis

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The HPA-axis is probably one of the more significant underlying etiologies.

24:58

Chronic stress increase is critical dropping releasing hormone suppresses gonadotropin releasing hormone, FSH and LH, elevated cortisol itself, inhibits FSH LH, leads to gonadal tissue receptor resistance, Decreasing T levels and T’s effectiveness.

25:17

We all know that chronic stress increases inflammation, which directly affects testicular function

25:25

decreasing LH and testosterone.

25:28

This depiction is from the Tsigos’ and Chrousos’ article, which I recommend if you haven't read. It is an excellent article and should be part of your library, as is the Pasquali article. And, as you see here, stress, the first thing it does is trigger catecholamines, which sends the signal you get the political trope in Corticotropin-releasing hormone, ACTH, cortisol.

25:56

And then, you get inhibition of LH testosterone, also estradiol, TSH T3.

26:04

You get increasing catecholamines, which increases inflammatory cytokines which will increase the HPG axis.

26:16

And what about the gut? Well, it mediates hormone metabolism and hormone related diseases. And we all know that there's no such thing as a, quote, unquote, normal gut, microbiome, it’s diverse, And it needs to be balanced. And what happens when individuals have dysbiosis, you get reduced diversity. You can have a decrease or increase in beta glucuronidase, and what happens if you have low beta glucuronidase? You're going to have low testosterone states, and, you know, beta glucuronidase is how you get recirculation of estrogens, and you get estrogen dominant syndromes.

26:47

And remember that the gut has five alpha and beta Reductase activity. Which will impact oral progesterone in women. I know we're talking about, guys, but I can't leave this out, oral progesterone metabolism in women.

27:06

All right.

27:07

So, this was the first study to assess the association between serum hormone levels, the gut microbiome, and the Bacterial toxin.

27:16

There were 50, it's a small study, 57 participants, and we're going to focus on the males, 31 males, and they looked at serum testosterone levels and divided them into three groups, low T, medium T, and high T. And what they found was that, in both men and women, but we're talking about guys, high serum hormone groups, there was a greater diversity than in the medium and low groups.

27:41

So, what they concluded is that sex hormones in the gut are going to have a bidirectional relationship. Sex hormone levels may impact gut health.

27:50

And gut health may impact, as we know, serum hormone levels. So, that's not surprising.

27:57

So, what do we know so far about Kevin? He meets diagnostic criteria.

28:03

He probably has HPA-axis dysfunction with increased inflammation, which is impacting his testosterone production. He's got central adiposity. You know, he's got anxiety, he's not sleeping well, signaling and tissue responsiveness.

28:19

And we know we have gut dysbiosis, he's got irritable bowel. He's got one allele for HLA DQ2, and he's still eating gluten and dairy. And he's got increased visceral fat, which leads to a permeable gut, some degree of metabolic endotoxemia, which will increase inflammation and decrease testosterone production.

28:40

Let's dig into this a little bit more.

28:43

Kelton Tremellen, who I also am honored to know, is an Australian researcher.

28:50

And he came up with a hypothesis about gut endotoxin leading to a declining in gonadal functioning called the GELDING theory and it’s for central adiposity related male hypogonadism.

29:05

And what used to be thought was that low testosterone, because it's an immune modulator and that cortisol kind of balance each other, low T, increased inflammation, and he posited that whatever is causing inflammation: Central obesity, a poor diet, you get increased gut permeability. You get this chronic low-grade inflammation, which will lead to impaired testicular function. How's that?

29:35

Well, when you have increased gut permeability, you get LPS.

29:40

LPS is the is part of the outer wall of gram-negative bacteria that translocate into the systemic circulation. It triggers pro inflammatory cytokines.

29:53

It will decrease test the testicular testosterone production directly by inhibiting Leydig cell steroidogenesis and indirectly by suppressing both LH and FSH.

30:07

Now, I'm going to give you a plausibility argument, and replace obesity with any trigger or any driver of chronic stress, will increase gut permeability and chronic low-grade inflammation, and that can lead to impaired testicular function. And it's the same mechanism as we just described.

30:30

And so, under normal conditions, testicular macrophages are necessary for Leydig cell development but with inflammation, from whatever cause, macrophages and Leydig cells both produce pro inflammatory cytokines.

30:45

In addition, Leydig cells have receptors for TLR4, which bind LPS, as we just talked about, directly inhibits testosterone production.

30:56

So gut dysbiosis, so let's step back.

31:00

Chronic inflammation from whatever cause can increase in gut permeability. And this increased gut permeability and low-grade inflammation will drive testosterone deficiency.

31:14

So, the bottom line is evaluate and treat the HPA-axis in the gut, in addition to testosterone deficiency.

31:22

So, what additional tests will be helpful?

31:25

We know he has testosterone deficiency with diagnosis and treatment. Now, before choosing a test, other than the gold standard, you must ask, “Has the test been validated against the gold standard, and/or, are there outcome studies documenting its clinical utility?”

31:44

Well, serum’s the gold standard for testosterone testing and monitoring, we've already established that.

31:52

So, why will I recommend you do urine?

31:56

Because urine adds comprehensiveness, it allows you to assess estrogen metabolism, which can be a driver in hormonally dwelling cancers in males, whether it be breast cancer or prostate cancer.

32:08

It'll tell you about androgen tissue exposure, it will tell you about estrogen metabolism and detoxification pathways, which are really, really important. In addition, it'll tell you about cortisol.

32:20

Right, so you get an organic acid, and it'll give you the biggest bang for your buck, so now let's talk about our DUTCH Plus.

32:27 Kevin’s DUTCH Plus

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Alright, let's look at how we approach a DUTCH Plus.

32:35

First of all, here's your overview slide and what I use this slide for, let me orient you, this in-between star one and star two is your reference range, right?

32:49

It's like a clock, and your dial is where the patient lives.

32:56

And as you see, even though Kevin's dials are, in the green, they are low for me, his testosterone for a 26 to a 40-year-old should be 40 to 95. I'd like to see it in here.

33:13

I'd like to see his estradiol over here. But really, we're going to use serum as well as urine, I'm using urine mainly for estrogen metabolism.

33:24

What's striking, when you look at his initial page is look at this salivary cortisol curve.

33:31

If this is a true CAR, which we'll get into, he's lost resiliency.

33:38

Now, why do I say it?

33:40

Because I suspect that he did this when he was quote, unquote awake, as opposed to the sense of being awake, and if this is, this may actually be the second point. And his first point may actually be down here. And so, in essence, that would be a normal CAR. But, for argument’s sake, we're going to say he did the test, right and this is his CAR.

34:07

And then, when we look over, here, it is DHEA. That's on the lower side.

34:13

And what that tells me is, despite Kevin making a lot of cortisol,

34:22

he's lost resiliency. And he's a little further along on that HPA-axis continuum, whereby, if it's not addressed, he can wind up with a low cortisol state.

34:38

All right, so let's get into this now.

34:40

You can use urine.

34:42

You can use a DUTCH Complete.

34:45

And I say that because I said if you're going to choose an alternative than the standard of care and for saliva, for cortisol, it's saliva.

34:55

Has the test been validated? And the answer is yes.

34:59

Precision Analytical, Mark et al, actually looked at 68 individuals who did both saliva and urine on the same day and what they found is that, indeed, it is a good surrogate, but you have to be aware of certain things. Number one, here's your saliva.

35:19

This is a CAR.

35:20

Right.

35:21

Sense of awakening, and then 30 minutes later, this is not a CAR.

35:29

This is everything in your bladder from the night before, which is really important. So, you can see what the HPA-axis and how well you slept and whether your brain has been running like, a hamster on a wheel, and the CAR is somewhere in here, right. Because this point is two hours later, so please, if you want to know about resiliency, get a DUTCH Plus.

35:55

If you're just looking at the HPA-axis and metabolites, you can start with a DUTCH Complete.

36:05

All right, and when we talk about metabolism, it's really important to understand the enzymes involved. When we talk about cortisol and cortisone, 11 beta HSD1 is bidirectional.

36:22

In the liver, it can convert cortisol to cortisone, and cortisone to cortisol. In adipose tissue you're mainly activating cortisol.

36:35

Deactivation primarily occurs in the kidneys to protect the mineralocorticoid

36:41

receptor and here is the liver. In the liver, and remember, this is irreversible by beta metabolism. Primarily, tells you about liver metabolism, right? Five alpha metabolism is really peripheral and tissue metabolism, and really global metabolism, and most of the metabolites are beta metabolites. So, cortisol and cortisol are metabolized primarily in the liver remember, this is metabolism. It is converging two different things, right?

37:17

Now, I know this looks complicated and we'll go step by step.

37:22

As we talked about earlier, this is Kevin’s CAR and we're going to assume it's correct, zero point seven three.

37:30

So, we've lost resilience.

37:32

The rest of his cortisol curve, you know, was kind of at this point. Probably, normal. This point is a little on the low side and it's nice that it's low at night.

37:41

His DHEA is low.

37:44

So, again, DHEA is 100% produced in the adrenal glands. Again, you have to have the signal to produce DHEA and cortisol, so he's a little, now this is not an adrenal problem. This is a brain problem. This is a signaling issue, right?

38:05

And so, he's further along, and again, this is just explaining all of that.

38:11

And so, then when you look at his total cortisol production, you have to ask is visceral adiposity increasing 11 beta HSD1 activity, resulting in more cortisol, possibly?

38:28

Is the liver trying to deactivate cortisol, to cortisone?

38:34

Thereby, 11 beta HSD1 is working in the other direction.

38:42

Well, the liver is favoring five beta reductase activity with cortisone metabolites. That's possible.

39:08

And then when you look at cortisone and cortisol, is the kidney deactivating cortisol to cortisone? This is where you look at that, and you know the reality is maybe it's a little, you know, higher here, but it's pretty balanced.

39:22

But, so again, cortisol metabolites, the liver, this intro conversion is kidney, as well, and then here is your saliva curve. And if this were over here, and this were all the way down here, and your cortisol curve was more normal, and you have a really high cortisone curve, then maybe that could be happening.

39:39

This is complicated, and I recommend, if you're new, call our consultants and they will walk through this with you.

39:50

This is probably the most complicated portion of the DUTCH test but do it in a step-by-step fashion.

39:59

So, Kevin has HPA-axis dysfunction with loss of resiliency, increased cortisol production, probably secondary, the up regulation, liver metabolism, favoring cortisone, and kidney protecting, possibly protecting, the mineralocorticoid receptor.

40:18

Maybe, so it's not easy, this is not easy, But clearly, we know that he has HPA-axis dysfunction which needs to be addressed.

40:29

And he's got loss of resiliency.

40:32

So, some key points before we get on. Remember that estrogen metabolism in men is as important as it is in women.

40:41

And poor estrogen detoxification is associated with hormonally driven cancers similar to women.

40:50

All right, so now let's look at Kevin's estrogen metabolites.

40:54

Well, let's start up here. Again, there's your references.

40:59

And estrone, same thing, and estriol, you see that his estradiol is always less than what I would consider the 50th percentile, and is as shown is a little higher.

41:12

Now, let's look at his metabolites.

41:16

CYP3A4 is the most abundant

41:19

CYP enzyme, and his 16-hydroxy compared to his 4-Hydroxy. and his 2-hydroxy is on the lower side.

41:29

His 4-hydroxy is higher than I would like, the 1B1, and his 2-hydroxy is OK.

41:36

I'd like to try and shift this down to 2-hydroxy and decrease his 4-hydroxy, actually.

41:45

But, remember, one thing that's really, really important is that 2-hydroxy, even though it's supposed to be the least harmful,

41:55

if it is not methylated, will be a toxic intermediary, and could be as damaging as 4-hydroxy.

42:07

So, you need to make sure that phase two detoxification occurs normally.

42:14

Now, let's look at this, his methylation activity. Remember, we're not measuring methylation. You can only measure by looking at DNA.

42:28

But, as methylation connectivity is, you know, OK, and so, before I start pushing, I got to make sure that I increases methylation activity, so that I don't wind up with a whole bunch of 2-hydroxy, or, you know, 2-methoxy-E1, or 2-hydroxy-E1. We want to get it methylated.

42:50

Here, we don't want to wind up with a whole bunch of this. We want to get more of that methylated.

42:55

And again, just a couple of pointers, remember that estradiol is 100% metabolized from testosterone.

43:16

And we already talked about, it's important for sexual function and bone mineral density. And here are your optimum ranges for men.

43:22

And you want to use an LC- or GC-MS/MS assay, and this is very important. The literature has clearly documented that you need serum E2 levels. I would say, greater than 20, even though, you know, the literature says, greater than 15 to 17, you know, that they're all over the place. Greater than 20, will prevent significant and market bone loss.

43:37 Testosterone metabolism and testosterone excretion?

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So, what about testosterone metabolism and excretion?

43:41

It's much more complicated in both men and women.

43:46

Urine testing assumes normal phase 2 metabolism, and from in most cases, it occurs normally.

43:54

However, testosterone is subject to phase two SNPs that may limit urine clinical utility. Testosterone glucuronidation, which is what happens, doesn't always happen normally.

44:08

And so, you really have to understand the nuances that go along with this. All right, so let's look at the steroid pathway.

44:17

UGT2B17 is the most common deletion or SNP that we see in Phase two

44:27

conjugation. UGT2B17 conjugates testosterone by beta androstanediol

44:27

and five alpha DHT, whereas UGT2B7 conjugates epitestosterone and five alpha androstanediol

44:47

So, what do we do with this?

44:50

Firstly, let's look at the study that everybody's cites, which is the Jacobson study, where they looked at 122 Caucasian men and compared them to 74 Korean men.

45:01

They looked at serum, free testosterone, and they found that Caucasian men had statistically significantly higher testosterone levels, not dramatic, but higher.

45:13

And then when they looked at urine, it was also statistically significantly higher, but look at this, 16 times higher.

45:24

Whereas, epitestosterone in both groups were the same.

45:30

And so, what they concluded was that UGT2B17, occurs frequently in Korean or Asian males, where it occurs less than 10% of Caucasian men.

45:43

Now, I will tell you that since this article was published, there are many more articles that states that it occurs more frequently in Caucasian men and African American men. And that's why you need to be aware of this, also in women.

46:01

And this deletion actually explains the differences in urinary testosterone excretion but, you can still use metabolites. So, how do we translate this?

46:13

Well, you'll look at testosterone metabolism, if testosterone is low

46:18

five alpha DHT is low, and  five beta DHT is low, and epi testosterone, and five alpha androstanediol are normal,

46:30

then this individual, male or female has a UGT SNP.

46:35

And this is one of the reasons why we say that serum should be the primary tool because of the nuances, it does correlate without the UGT SNP.

46:48

So, what is epitestosterone?

46:50

Well, it's an epimer of testosterone. It's structurally identical, not a mirror, image entities, not encouraging.

46:57

And really, it's a useful marker for identifying the UGT2B17 SNPs.

47:04

In men, it also is an approximate measure of gonadal T suppression and gonadal T production.

47:12

If you're giving somebody, in this case, testosterone, in women, it's hard

47:17

because testosterone, it comes to 25% from the ovary, 25% from the adrenal, and the rest is via peripheral conversion. So, the literature is not as clear, but our data suggests that comes from the ovary. But, again, this needs to be further delineated.

47:35

And so, let's just look at how epi-T

47:38

can help you in somebody, you give testosterone therapy to, not Clomid, but testosterone therapy, OK.

47:47

Yeah. Yeah.

47:48

This is somebody who has, basically, a low testosterone.

47:53

I like to get my guys into, you know, this area, here, and let's see what happens.

48:02

Before you give them testosterone therapy, epi-T and testosterone, about the same, with testosterone, epi-T will decrease to the degree that LH and gonadal androgen production is suppressed, here are some normal ranges for you.

48:17

So, let me show you, give somebody 25 milligrams of a gel, this is aggregate data, and you get testosterone, creeps up a little bit. It's not that impressive, but epi-testosterone doesn't move that much. It moves 40 to 23, it's moving, so you see you're getting some gonadal and some LH suppression.

48:39

Now you give them 50 milligrams of a gel, testosterone comes up into that area. And look how nicely you can see that L H is decreasing, and you're seeing some degree of gonadal

48:52

of suppression, so you haven't fully suppressed his HPG axis.

49:00

Now, you give them 100 milligrams, and indeed, you have suppressed his HPG axis, look how low this is.

49:07

Usually when it's less than 10, you know, you're on the way, and his testosterone is, you know, 76, which is nice place to see it, so you can use epi-testosterone to gauge whether you're augmenting his testosterone, or whether you're suppressing his Intrinsic HPG axis, useful tool if you want to give testosterone to a younger guy. Now let's look at Kevin's androgen metabolism.

49:38

We saw his DHEA was already low.

49:41

His testosterone is on the lower side, let's look at testosterone, 40 to 95. I like to see it at about 75, 80, or 90, especially in a young guy.

49:56

His androsterone is on the lower side, he's etiocholanolone, which are, in addition to being DHEA metabolites are also testosterone metabolites.

50:09

His DHT is low. His five beta is low, everything's low, so let's look, and see if he's got a UGT SNP.

50:16

T is low, DHT is low.

50:19

Five beta is low.

50:20

But so, was five alpha. And I put this he or she can see his epi-testosterone is also low, so he has no evidence of a UGT SNP.

50:30

Everything is low.

50:31

He's favoring five beta reductase, the less androgenic pathway. So, his urine is consistent with his serum, and, indeed, his testosterone deficiency, here’s his serum. Interestingly, his calculate afraid he was 63, this is 50 not that far off, and again, you're looking at trends.

50:51

No, absolutely, you can look at serum, but no test is perfect.

50:57

All right. Let's look at Kevin’s organic acids.

51:01

His B6, and B12, may be deficient.

51:06

And this is not surprising has got HPA-axis dysfunction, drains B vitamins, pyroglutamate marker's OK.

51:16

But what I found interesting is his VMA marker is within range, but it's at the high end of the range. So, he's being driven a lot by catecholamines.

51:28

If Kevin HPA-axis, if his cortisol curve was low, I would make sure that if this were high, I would not try and tame this, because this is what he's living off of, he’s living off of catecholamines.

51:46

When you look at is melatonin is within range, but it's at the lower end of the range, I'd like to see this higher. And he doesn't look like he's got a lot of DNA damage, oxidative stress, but he's got some degree of oxidative stress. I can tell you because he's chronically inflamed.

52:04

What if I told you that this was Kevin’s androgen metabolites, you say holy Toledo? Look at his testosterone.

52:14

The first thing, when I see this, I think UGT SNP, his testosterone is low, his five alpha DHT is low.

52:24

His five beta DHT is low.

52:28

His five alpha androstanediol is OK and is epi-T was at the high end of normal.

52:37

So, it looks like he's got a UGT SNP.

52:42

You can still use metabolites, and I will tell you he is making adequate testosterone.

52:48

How do I know that? Well, estradiol is high, or high-ish, too high for me, and testosterone synthesizes estradiol 100% in males. Estradiol only comes from testosterone, so he’s got to have adequate testosterone.

53:09

And then when you look at his androsterone, that's also high.

53:14

So, you can use these metabolites to say, gee. He's got adequate testosterone.

53:22

His tissues are seeing adequate testosterone.

53:26

There's no reason to, you know, flip out or you get a serum testosterone and that’s why serum is the primary tool, and this adds comprehensiveness.

53:40

All right. So, what do we know?

53:41

He definitely meets diagnostic criteria. He's got HPA-axis dysfunction.

53:47

He has gut dysbiosis,  some degree of metabolic endotoxemia, he's got inflammation, and he's got decreased testosterone production.

53:56

His estrogen metabolism and detoxification are OK but may need to be addressed. I want to shift that a little bit more to the 2-hydroxy to get it methylated, but I have to address his methylation.

54:12

And Kevin’s androgen metabolism favors the less androgenic five beta reductase, his T and all its metabolites are low, and he does not, remember,

54:25

have a UGT SNP, so you can use this to monitor, as well as assess testosterone production. Now, what are we going to do about treatment? Ah.

54:36

This is complicated. Well, the first thing you got to talk about is age.

54:41

Think about LH, and think about prolactin, which we've looked at.

54:45

So, let's start with, he has low testosterone by all tests.

54:51

We look at is prolactin, first of all. Is it normal, yes?

54:54

If it were high, you want to work him off to make sure he should have a prolactinoma, which the treatment would be Capriglione, and it's typically zero point twenty-five milligrams twice a week for about six months. And then you decrease, then you stop it. And see whether he needs it. If you're located kidneys, your look and see if he's significantly hyperthyroid, I'm not talking about functional hypothyroidism.

55:19

And you look at his cortisol if it were elevated because cortisol will drive prolactin.

55:26

And now we look at his LH, if it's greater than the upper limit of normal, you start thinking about primary causes of hypogonadism, which are typically genetic colon syndrome, is one of them. And then secondary hypogonadism, which is where Kevin fits. You start thinking about, number one lifestyle.

55:48

He needs to have eight hours of restful sleep, he needs to have, needs to move and exercise. He needs a higher protein diet. He needs Mediterranean eating. And then you look at nutraceuticals, Eurycoma, Tribulus, Testofen, Thai ginseng. And of course, meant you want to replace minerals.

56:05

And you want to make sure his vitamins and minerals are all within the optimal range. Now, I will tell you myself, I have not had success with this, really driving or increasing testosterone. Maybe I don't use enough, but, typically, I address all the underlying etiologies, and then my first choice is typically, Clomid. You can do 5 to 15, 3 times a week. You can do 25, 3 times a week, you may need higher doses

56:39

if you're talking about fertility, 50 milligrams, three times a week is what you may need to increase fertility, as opposed to 25, A lot of the studies suggest.

56:52

I don't use a lot of HCG. It's expensive.

56:55

And I find that my guys, at least, are not that reliable at giving themselves shots. And they don't want to pay the money when Clomid is so much cheaper.

57:04

Clomid HCG is an LH analog where Clomid, as we talked about, will increase FSH, LH, and estradiol.

57:13

This requires more diligence, and then if you're comfortable using peptide, you can use Kisspeptin. Kisspeptin is a naturally occurring peptide that occurs in the brain that actually sends the signal to trigger the gonadal releasing hormone.

57:28

You can give 10 milligrams at five days a week.

57:32

Times six months, it's a step two shot.

57:35

And in, guys greater than 55, you know, who are not interested in fertility, consider testosterone therapy, and remember in young guys,

57:45

don't forget to check for heavy metals, biotoxins illness, you know, don't ignore those things, and as you all know what somebody has TPO antibodies, try and avoid glandulars.

57:59 Testosterone Options and Raising T Levels

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Well, what about testosterone options, nobody really uses a patch. But I put it in here, topical testosterone, androgel, 50 milligrams is what most of the studies say that optimally improve clinical outcomes. If you're using a compounding cream, you may need a higher dose.

58:16

The studies have shown us that when you use a cream as opposed to a gel, an alcoholic gel, you need a higher dose to achieve the same results and remember, keep it above the belt and rotate it.

58:29

And again, I do labs in one month. You know, literally after three treatment months.

58:40

Sometimes I do six months, but I typically do a year and then twice a year, injectables. You can use IM or Sub-Q, propionate is the shortest acting, and actually Testopel, which is the FDA approved pellet, recommends using aPropionate for every 25 milligrams, you place two 75 milligram pellet. So, if you wind up giving a guy 25 milligrams 2 times a week, and his testosterone is above 500, and he’s symptom free, and he wants pellets that would be four pellets.

59:10

And Enanthate is not commonly used. Cypionate is the most common, and 25 to 50 milligrams biweekly. So, you don't get that rise in that drop off, and estradiol levels don't go up so high. And then serum hormone binding globulin doesn't go up so high. And of course, pellets are a viable option.

59:28

They are costly, patients don't really need as much as you think, and remember, PSA before and after. And if your PSA increases, that's worrisome for prostate cancer.

59:43

Now, testosterone doesn't cause prostate cancer. But in a guy who's got low grade undiagnosed prostate cancer, it may cause it to grow.

59:54

All right. And remember that, regardless of delivery, a serum level of greater than 500, improve sexual function, body composition, and bone mineral density.

1:00:03

You know, whether you're using Androgel, whether you use testosterone pellets, there are your doses, the average is 750 to 1000, or testosterone Undecanoate is a once every 10 to 12 week shot that they need to come to the office for, I tend use pellets guys love them.

1:00:21

And remember, serum estradiol should be maintained between 20 to 40 using an LCMS/MS. Your goal should be 30 to 35.

1:00:30

And, young guys, you have on Clomid or HCG after a year of treatment, and make sure lifestyle changes.

1:00:37

There'll be a percentage who no longer will require therapy, which is very nice. So, you stop treatment for three months, and after three months, re-assess the patient.

1:00:47 Kevin’s Treatment Plan

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And so, what was Kevin’s treatment? Well, I dressed as HPA-axis. Sleep hygiene, gentle exercise. I told him, he is not going to gain muscle mass, until we get a handle on everything else.

1:00:59

I gave him holy basil because of his elevated heart rate, and his blood pressure, and you can increase that to 100 BID. Now, there are lots of adaptogens out there. Get comfortable with some and use them. I gave him magnesium, 10 milligrams per kilogram of elemental magnesium, at HS that will also help his insulin resistance. Probiotic, he needs a plant based Mediterranean style eating that is definitely gluten and dairy free. We instituted some intermittent fasting, which will help weight loss, it will also help his gut dysbiosis, it will also help his insulin resistance, and this is, I didn't give them this. This is, I just put this down here. So, you know, you could also use Chromium. Make sure his Vitamin D is normal. But I try and do a lot of this with food and lifestyle.

1:01:53

Because if we don't do that, I tell people, I can give you all the testosterone everything in the world, and you're going to be on a ton of supplements.

1:02:02

Until we get lifestyle and everything else under check, you're not going to really feel better. For testosterone deficiency, I did all of this first.

1:02:13

And I did give him some Clomid, and I started 25 milligrams, Monday, Wednesday, and Friday, and I checked his labs in four weeks to make sure that his testosterone was going up, his estradiol wasn't rising too quickly.

1:02:29

And I gave him DIM to shift that down. In addition, he got a complex methylated B Vitamin, right? For his, low B vitamins are methylated them. He got methylated folate in his multivitamin, and I always try and talk people into IV hydration. So, they don't have to take so many supplements and people just feel so much better.

1:02:53

Amino acids, I gave him some glutathione phosphatidyl choline, which is important for cell walls and will help his dysbiosis.

1:03:02

And so, here's Kevin at four months.

1:03:05

This is, you remember, I'm sorry this is a little blurry, this is Kevin, initially, and here he is, at four months, his testosterone came up nicely, I may consider decreasing his

1:03:19

Clomid, his epi-testosterone came up nicely. His five alpha DHT is OK, and everything looks, looks good.

1:03:27

Uh, and let's look at his labs. His CBC is really unchanged. His CMP, his fasting blood sugar came down, his hemoglobin A1C is much better. His total testosterone is 700, he's happy where he is.

1:03:43

His free T is 188, which is very nice. His estradiol is 30. So, that's in a nice spot.

1:03:52

His serum hormone binding globulin came up to 23. His FSH didn't change, his LH went down, not surprisingly, his PSA came up. He got some testosterone, his testicular volume increased. So, all in all, Kevin is very happy.

1:04:09 My Approach to Males with Suspected TD

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So, I put this together, or my approach, to males to try and summarize, my art, and don't make fun of my artwork, to males with suspected testosterone deficiency.

1:04:22

Do a complete history with an ADAM questionnaire and a physical exam, including a testicular examine, and a direct rectal exam. A direct rectal exam is part of the standard of care.

1:04:35

I do a testicular exam. So, I get an idea of the size of his testicles, as well as I do with testicular ultrasound at times.

1:04:44

I do a complete laboratory panel. I do a DUTCH test, I evaluate and treat all the underlying etiologies, and then, I repeat selected labs.

1:04:54

If the total testosterone is less than, say, 300, it is less than 300. That's easier. If it's around 350, and his PSA is low, and its testicular volume is low, then we're talking about treatment or is free testosterone calculated, is in here.

1:05:12

I asked the question, is he older than 50 or younger than 50?

1:05:23

If he's younger than 50, is his LH elevated, and is a primary testosterone deficiency, he's not going to get better with our testosterone therapy, is it secondary?

1:05:28

Then, I tend to use Clomid and if I need to I’ll add an estradiol

1:05:32

And an aromatase inhibitor, if he's older than 50, now, I will tell you that Clomid, which we'll talk about here in a second, doesn't work as well in older men, but it's worth giving it a try and he wants to maintain fertility, Clomid.

1:05:46

And if his estrogens are high, the same thing, if he's not interested in fertility, most guys want testosterone therapy, now you could add HCG if you are giving testosterone therapy, which will help maintain testicular size.

1:05:59

And, let's say, his testosterone is greater than 300, or his free T is greater than 65 and close to 100, and he has symptoms that are suggestive of testosterone deficiency. I then ask, does he have androgen receptor insensitivity?

1:06:18

I do CAG repeats.

1:06:20

If they are greater than 24, I consider treatments to increase testosterone. So, my arrow's come here.

1:06:27

I asked the question, is he greater than 50 or younger than 50? If they're less than 24, I aggressively treat other underlying causes, and typically don't give testosterone until all of those are optimized.

1:06:42

Now, many of you have seen this.

1:06:46

We're just going to look at here and as you see, that we have a question mark here, and it is because of the UGT SNPs.

1:07:00

Now, when we're looking at serum, as we know it’s the treatment of choice, and as we talked about, the saliva shouldn't be used.

1:07:08 Final Thoughts

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And so here are my final thoughts in males who meet diagnostic criteria. Don't stop there.

1:07:15

Address the HPA-axis, the gut, look at the toxins, assess his cardiovascular system.

1:07:19

Assess the whole person, whatever therapy you choose, start low, go slow, and set expectations, and if you're using Clomid, and it's not unreasonable, do 12.5 milligrams five days a week.

1:07:33

That's OK.

1:07:34

Unless you're interested in fertility.

1:07:37

Laboratory monitoring is key.

1:07:39

Don't just treat, test.

1:07:42

Don't guess.

1:07:44

Learn and understand hormone metabolomics, it is essential to a successful hormone practice, and ask yourselves, are your decisions evidenced based?

1:07:56

And are you questioning when people tell you the absolutes, and are you asking show me the data?

1:08:04

Where is the evidence?

1:08:06

And men, similar to women, may spend a third of their lives hormone insufficient or deficient. So, it's equally important we get it right. You know, what's very interesting in most of the studies out there on cardiovascular disease, women are underrepresented.

1:08:22

When you talk about hormones, we're always talking about postmenopausal women. We're always talking about perimenopausal women.

1:08:31

Men don't get enough attention, and I will tell you that 60% of my practice is guys, just like Kevin or older, who come in and say Doreen, do I need testosterone therapy?

1:08:43

And so, this is a great opportunity to learn about testosterone deficiency in men, to learn how to use the DUTCH test.

1:08:54

And complex problems require comprehensive testing, and that's what the DUTCH test is, and so, if you have any questions, I'm more than happy to answer them, and I will leave this slide up and Tim, back to you.

1:09:12 Q&A

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Doreen, thank you so much.

1:09:15

We just want to thank you for all the time you put into doing the research and putting this presentation together. You’ve done a fantastic job.

1:09:23

Actually, you got some kudos from a fan that said, Doreen you are awesome, thank you for sharing your expertise and experience, and what a great compliment, you know, during this holiday season, right? As we move into Thanksgiving.

1:09:39

That’s just really, really cool for someone to show their gratitude, because we are super grateful for you and just helping us understand, you know, how guys bodies work and what they need, based upon where they're at and what's happening.

1:09:54

So, we're going to dive into some questions.

1:09:57

I didn't ask permission of that provider to say their name, but maybe I can share that with you. I'm just going to say, thank you so much, whoever that is, I am pounding my heart, I'm forever grateful.

1:10:19

I had the opportunity for people to pay it forward to me and I just am so honored to be able to pay it forward to all those who want to learn this and I'm grateful for PA to giving me the opportunity to do that.

1:10:32

Absolutely, well, we have some great questions here, so people can stick around. We're going to answer some questions.

1:10:40

We also have our offer for new providers, for 50% off up to five testing kits, so you can get started.

1:10:46

If you haven't used the DUTCH test yet, we'd love to, you know, have you get started and check it out, and, and we can help walk you through everything. So, OK, here's our questions.

1:10:59

Let's just start off with, there's a question about with younger men

1:11:04

considering any type of therapy, hormone replacement therapy or increasing testosterone levels,

1:11:12

can you reboot the system, Dr. Saltiel, and get things running, again, and up to speed? Or how does that…

1:11:23

How do you think about that? Do you think about what the younger guy this is going to be

1:11:28

kind of a lifelong thing?

1:11:29

I know you kind of touched base on that, but did you unpack that a little bit more for us? You can reset the HPG axis.

1:11:37

Because a lot of the underlying etiologies when they are addressed, as you saw with Kevin, when he lost weight and decreased adiposity, his testosterone went up.

1:11:47

So, if you address the HPA-axis, you address that the gut. You look at toxins, all of those things that impact the HPG axis. The answer is, yes. You can reset.

1:11:58

You may not need Clomid. If you use Clomid, use it, or HCG for a period of time and after six months or a year, stop it and then re-assess in four months. A lot of guys won't need it anymore.

1:12:13

Oh, that's fantastic.

1:12:15

So, how does that impact fertility, because that's the big, probably decision maker for a lot of patients.

1:12:20

A lot of providers that are thinking about this as a possible solution for their patient.

1:12:27

Does fertility come back after therapy?

1:12:32

Or how do you address that with your patients as you talk to doctors? Well, if you're using Clomid or HCG, fertility is not affected, and Clomid has been shown to improve sperm count.

1:12:44

So, it improves fertility, spermatogenesis, I should say. Whereas, once you give an adequate dose of testosterone to shut that system off, all bets are off.

1:12:56

Some people say, you can stop it in six months, and they get better, and it'll improve.

1:13:02

And Kevin's case, he took anabolic steroids for nine months, and he was able to conceive children, so it's not 100%, in some guys

1:13:11

they will get fertility back, in others, they may not.

1:13:18

And it's a matter of what the risk is, and if it happens to you, it's 100%.

1:13:24

Thank you.

1:13:25

How about testosterone volume? There's a question about how testosterone volume’s tested.

1:13:31

Oh, it's an ultrasound. You send the patient to the hospital if you don't have, or a urologist, to get a testicular ultrasound. Now, you can measure the testicles, but it's, you know, using the tape measure, but it's not as reliable.

1:13:45

But I recommend everybody do a testicular exam.

1:13:49

You know, I like, in somebody like Kevin, I sent him, he had HPA-axis dysfunction. He had gut dysbiosis, his PSA was low, his testosterone, if you go by 300, was, you know, 290 is borderline. So, I was trying to use all the evidence that I could to determine if indeed he had testosterone deficiency, and indeed he did.

1:14:16

Interesting.

1:14:17

Then, how does A1C impact testosterone? How do you see those two correlate, what do you look for?

1:14:24

Insulin resistance is a driver of inflammation, right?

1:14:28

Insulin resistance will increase the aromatase enzyme, which increases estradiol, decreases testosterone.

1:14:39

And as we saw from the slides on inflammation, it could be any driver of inflammation that can potentially increase gut permeability, and then you'll have that added to it.

1:14:47

Diet, insulin resistance, bad diet.

1:14:52

And then, you get testosterone, decreased testosterone production, OK.

1:14:58

Thank you for clarifying that. And Tim, metabolic disease,

1:15:03

like insulin resistance, metabolic syndrome, is one of the more common causes of secondary testosterone deficiency, OK.

1:15:12 So, as a patient, improve some of those areas, they can see an improved, hopefully, maybe, an improvement and testosterone levels, that they drop their A1C, the information that they lower, their visceral fat, those, kind of things.

1:15:30

I do all of those things first, and, in Kevin, I did that, but I did give him testosterone due to how low everything was, OK.

1:15:42

And, so, and we just kind of touched base on that.

1:15:45

But, you know, what is the long term, a question came through, what is the long term management for low T in someone in the age range of 35 years old?

1:16:00

Yeah.

1:16:00

You do lifestyle, very, very important. They have to do lifestyle. They're not going to get better.

1:16:05

Then, I do Clomid, because HCG is expensive, and guys don't like to give himself shots or they don't do it right. They miss a shot and, you know, all of that sort of stuff.

1:16:16

And they can stay on Clomid as long as you monitor their estradiol, it's not dangerous, their estradiol and their testosterone until they reach the age where they say I've had enough.

1:16:30

I'm not having kids, give me pellets, which happens, literally, what happens. I start with guys who are younger, and a lot of it is cheerleading.

1:16:41

I tend to be their cheerleader. Come on, you can do it. You can change your diet. Come on, let's exercise. Blah, blah, blah. And they start seeing an increase in muscle mass.

1:16:50

They start getting better, and then they stay on Clomid, and then they hit about 50 or 55, and or they, usually, it's about 48 to 50, please. Please, I want testosterone. They begged me and I say, wait, you can take pills for two more years, and they're cheap.

1:17:10

Pellets are expensive. I tell them, then they hit 50, and they are making an appointment on the 50th birthday.

1:17:19

Sounds like a good thing to do.

1:17:22

In Kevin's case, why not use low dose aromatase to block conversion of E2 to TD? His E2 is already low, right, his E2 was 20 something.

1:17:39

So, when we started, if I would have used an aromatase inhibitor,

1:17:45

I would have driven his estradiol down.

1:17:49

And I would have increased his risk of osteoporosis, worsening a sexual dysfunction, because erectile dysfunction is impacted by estradiol, and he wouldn't have gotten better.

1:18:05

It makes sense.

1:18:06

And what about any kind of supplementation,

1:18:09

I know you touched base on that, but it if you could kind of review, would you do any with a younger patient, any, kind of, helpful alternatives to help? You can try.

1:18:26

There's nothing wrong with trying, but people really need to be meticulous with lifestyle and if their testosterone is a little low, yeah, it may come up to enough where they are asymptomatic and feel better.

1:18:42

My experience is guys aren't, you know, happy, supplements are a lot of money.

1:18:49

Clomid is cheaper and guys want results.

1:18:52

I guess that's why my practice is so big.

1:18:56

I try those, but, you know, I always give Zinc, you know, right, because you want to, I always optimize nutrients and vitamins and vitamin D, magnesium, you know, all of those things, but, whether you're using Eurycoma or Testofen,

1:19:16

you know, in my experience, people may have different experiences, in my population, I see guys who are sicker.

1:19:26

Sure. It’s not been successful. I'm not seeing the 50-year-old, who's testosterone is 400.

1:19:36

I'm seeing guys like Kevin, or guys in their fifties, or 55, who’s got risk factors for cardiovascular disease. Their insulin resistance, the testosterone is 270, you know, and so, again, it depends on the patient.

1:19:53

That makes sense.

1:19:55

Thank you, Dr. Saltiel, so a couple of gut health questions here.

1:20:00

Can a monocyte level, and in a CVC, indicate gut permeability?

1:20:08

Yes. Or something else?

1:20:09

Yeah.

1:20:10

You know, there's, there's clinical experience, I don't know if it's documented in the literature, but if you look at the percentage of

1:20:28

Monocytes and eosinophils, if you add them up, they should be less than 10, if they're elevated then that's a poor man's test of gut permeability.

1:20:34

But I'll tell you, everybody in this country has some degree of gut permeability.

1:20:39

The question is whether you recover or not.

1:20:41

For example, if you don't have gluten sensitivity and you eat gluten, you are going to have gut permeability transiently 15 to 30 minutes, but you should be able to recover.

1:20:54

The question is, will you or won’t you recover and have long lasting increased gut permeability? And so that, then you have to unravel and peel back the onion and say, what's driving the gut permeability, and most of the time it's low-grade chronic inflammation,

1:21:13

dysbiosis, you know, HPA-axis dysfunction and diets in this country.

1:21:22

Jumping back up here to questions about improving testosterone levels.

1:21:28

And this was actually, you helped me with this,

1:21:31

Because when I met with a naturopath awhile back, this is a question that I had, but does DHEA increase testosterone levels, how do you think about that on the steroid pathway as a provider?

1:21:48

And then, how do you talk to your patients about DHEA?

1:21:53

Well, DHEA is an anti-inflammatory, it's an immune modulator.

1:21:57

You need it.

1:21:58

In men, I have not found it to successfully increase testosterone.

1:22:06

Guy’s levels are just too high, in women, it’s more likely to help.

1:22:11

But then, women complain of increased facial hair growth, and side effects that they don't want.

1:22:19

I use DHEA. I use it to increase DHEA, because it's an immune modulator and it's helpful for, you know, HPA-axis function.

1:22:29

But I don't use it as a primary modality to increase testosterone in men, OK.

1:22:38

And then, when you check PSA level due to total PSA check or free PSA check, or what are you looking at? Both, and then I look at the, oh, I forgot what it's called.

1:22:54

I'll think of it. But, yeah, look at free PSA and a total PSA. OK, fantastic.

1:23:00

And then we had someone share a DUTCH tidbit.

1:23:06

So, I thought I would bounce this off you, when you talked about cortisol, their comment was, high waking cortisol equals LSA until proven otherwise, then low night, equals stress.

1:23:21

Say that all again?

1:23:26

So, they said that high waking cortisol equals OSA until proven otherwise, equal what? Oh, obstructive sleep apnea.

1:23:39

And then at night, O2 equals stress.

1:23:45

Yeah, I don't know. I'd like to, I'd like to see the data on that.

1:23:50

I've not seen any literature that says, if you have a high waking cortisol, you have obstructive sleep apnea.

1:23:57

Now, is it part of the differential diagnosis?

1:24:02

Yes, but it's not a center point on, that you should evaluate. Why does somebody have a high waking…

1:24:09

I'm talking about salivary cortisol.

1:24:12

A high waking salivary cortisol. One, they don't sleep well. They could be startled.

1:24:19

And yes, there's some literature that says a nighttime low free cortisol, nighttime point of cortisol is consistent with low free cortisol.

1:24:31

Yes, there's some data, but patients don't read textbooks.

1:24:36

And so, you really have to deal with everybody individually and decide, does this individual meet, in your mind, the need to evaluate for obstructive sleep apnea?

1:24:51

I have a very low threshold to send people for that.

1:24:57

But, you know, in Kevin, he probably did the test wrong, because his CAR being that low,

1:25:06

I wouldn't expect. I think he probably was awake when he did it as opposed to the sense of awakening, and then his CAR may be more normal.

1:25:15

And really, when you're looking at a cortisol awakening response, how you do the test is the most important thing.

1:25:22

And I like to, you know, I like to use urine for cortisol as my first test. Why?

1:25:28

Because that first morning point tells me a lot about what's going on overnight.

1:25:35

So, I don't have to guess. Interesting

1:25:39

Now, if that’s high, you know, really high, then I'm thinking to myself, OK, why is this patient intermittently up all night?

1:25:48

Why are they not sleeping well?

1:25:51

Well, yes. In that case, I look at obstructive sleep apnea first, second, and third.

1:25:58

Well, thank you so much, Dr. Saltiel, you know, all the males out there that are thinking about testosterone levels and staying healthy. And doctors that are trying to help them, you are a wonderful, wonderful asset to helping people understand how their body works, what they need to do, what they can do, what type of diagnostics to use.

1:26:26

So, your time today, we just really appreciate all that you've put into this webinar, the slides will be available. We'll be sending those out to everybody that's registered. There's a bunch of other questions that came in. I'd love to be able to get to all of them, but we spend an extra half hour tackling questions. So, I just want to encourage everybody that attended today, I just want to thank you for being here. Thank you for all the questions you submitted. And, you know, if you'd like to learn more about DUTCH, if you have questions that you need help with, but you can schedule a clinical consult, and we would love to spend time with you, answering your questions, and helping you to better understand hormones, and how to use that test.

1:27:08

So, thanks, again, everybody, for your time, thank you, Dr. Saltiel.

1:27:12

And we wish everybody the happiest of holidays and have a wonderful Thanksgiving.

1:27:19

This is Tim signing out.

Bye. Bye, Doreen.

1:27:26

Thank you.

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