Testosterone Therapy: Latest Evidence and Clinical Applications with Dr. Doreen Saltiel

Hormone therapy is still a highly controversial topic, fraught with lots of emotion, fear, and misleading information. And let me tell you: am I glad to be having a deep dive into the literature with my colleague and friend, the very brilliant Dr. Doreen Saltiel from Precision Analytical. She’s been practicing medicine for 40 years and preventative cardiology for more than 25 years. With advanced training in endocrinology as well as metabolic, anti-aging, and nutritional medicine, Dr. Saltiel is a leading expert on male and female hormone health. In this episode of New Frontiers, she brings her talent of dissecting the scientific evidence on testosterone deficiency and shares excellent clinical pearls to guide both physicians and patients in making decisions around hormone therapy. Folks, you’ll want to bookmark this one and save the show notes. Thanks for listening, sharing, and commenting! ~DrKF

Which patients are most likely to benefit from testosterone therapy? How do we determine the most appropriate hormone delivery method? And what are the best screening and monitoring labs? In this episode of New Frontiers, we’re joined by Dr. Doreen Saltiel, leading hormone health expert, clinician and research author from Precision Analytical. Dr. Saltiel has practiced medicine for almost 40 years, with advanced certifications in cardiology, endocrinology and functional medicine. In this interview, she provides an in-depth and clinically relevant review of testosterone therapy, including how to screen for testosterone deficiency effectively, optimal hormone levels in men, therapy and lab testing considerations, including the importance of monitoring with advanced labs such as the Dutch test. And just like in her recent blog post, Dr. Saltiel gives us a critical overview of the scientific literature on testosterone therapy, prostate cancer, and cardiovascular diseases risks.

In this episode of New Frontiers, learn about:

Doreen Saltiel, MD, JD, has practiced medicine for almost 40 years. She completed a cardiology fellowship and board certification and practiced interventional cardiology for more than 25 years. She currently practices functional medicine with an emphasis on hormone health in both men and women as well as preventive cardiology. Dr. Saltiel completed advanced fellowship training in Metabolic and Nutritional Medicine from MMI and is a Diplomate of the American Board of Anti-Aging and Regenerative Medicine. She also completed MMI’s advanced certification in Endocrinology and Cardiovascular Health. Dr. Saltiel has co-authored multiple peer-reviewed papers and recently joined the Founder of Precision Analytical, Mark Newman, to present hormone testing research at the North American Menopause Society’s Annual Meeting.

• Dr. Saltiel’s Recommendations
• New Frontiers podcast: In Pursuit of Best Practice for Menopausal Hormone Therapy (MHT)
• Article: Testosterone Therapy in Males with Testosterone Deficiency (TD): Debunking the Myths
• Article: In Pursuit of Best Practice: Menopausal Hormone Therapy (MHT)
• ADAM questionnaire
• GELDING theory
• Morgentaler paper
• Huggins and Hodges landmark paper
• Vigen study
• Finkle study
• Traverse trial
• TOM trial
• Testosterone therapy and cardiovascular risk: advances and controversies
• The state of testosterone therapy since the FDA’s 2015 labelling changes: Indications and cardiovascular risk
• TLANDO study
• Younger You
• DrKF Study

• DrKF FxMed Clinic: Patient consults with DrKF physicians
• DrKF FxMed Nutritional Residency Program

Dr. Kara Fitzgerald: Hi, everybody. Welcome to New Frontiers in Functional Medicine, where we are interviewing the best minds in functional medicine. And of course, today is no exception. I am here with my colleague and friend, the very brilliant Dr. Doreen Saltiel. Let me give you her background, you know her, she’s been on New Frontiers before, she’s blogged on our site. She’s created some of the most brilliant content we have, but let me just tell you about her first.

She’s practiced medicine for almost 40 years. She completed a cardiology fellowship and board certification and practiced interventional cardiology for more than 25 years. She currently practices functional medicine with an emphasis on hormone health in both men and women, as well as preventative cardiology. Dr. Saltiel completed advanced fellowship training in metabolic and nutritional medicine from MMI and is a diplomat of the American Board of Anti-Aging and Regenerative Medicine. She also completed MMI’s advanced certification in endocrinology and cardiovascular health. She’s co-authored multiple peer-reviewed papers, and recently joined the founder of Precision Analytical Mark Newman to present hormone testing research at the north American Menopause Society’s annual meeting. Dr. Saltiel, welcome, welcome, welcome back to New Frontiers. It’s great to have you.

Dr. Doreen Saltiel: Oh, thank you, Kara. And please call me Doreen.

Dr. Kara Fitzgerald: Okay, I will. I look forward to this deep dive. I love it when you decide that you’re really going to tussle carefully with a subject and you blaze through all of the literature and you create an exquisite sort of work of scientific art that will guide both physicians and patients in making decisions around hormone therapy. Of course, hormone therapy is always fraught with lots of emotion, lots of fear and you just cut through the emotion, you cut through the BS, you look at the science, you pull it out, you write it really clearly. And so you did that with us for menopausal hormone therapy and folks, we will link to Doreen’s blog as well as her New Frontier’s podcast so you can get those two pieces. And now you’ve done it with testosterone therapy. And so I just want to thank you for that work. It’s extremely helpful to physicians as well as patients, really providers as well as patients.

Dr. Doreen Saltiel: Oh, it’s my pleasure.

Dr. Kara Fitzgerald: All right. So you’ve turned your attention towards male hormones, and I know I’ve just given a huge introduction, but tell me why you decided to go in this direction to apply that same brain, that same laser focus to testosterone hormone replacement, as you did with menopausal hormone replacement therapy.

Dr. Doreen Saltiel: Well, in addition to a good percentage of my patients being male, over the years, I’ve been an expert witness, reviewing medical records, testifying, teaching, and mentoring. And I saw the same knowledge gap that I did with menopausal hormone therapy. And most people think treating males is easy, that they can just go to the corner to a testosterone clinic, get testosterone, and all the issues are resolved. That’s not the case. Is it as complicated as females? No, but it is complicated.

Dr. Kara Fitzgerald: Why is that?

Dr. Doreen Saltiel: Well, because you have to consider not only testosterone, you have to consider estradiol, you have to consider prostate health, you have to consider serum hormone binding globulin. And all of these factors, similar to women, it’s like a symphony. They all have to be in harmony or else you’ll increase your risk of not only, really osteopenia and osteoporosis, but then you’ll increase your risk of adverse cardiovascular outcomes if they’re not all balanced.

Dr. Kara Fitzgerald: Okay, okay. We’re going to go in that direction, but I want to kind of move through actually the structure that you laid out for our conversation, just so we make sure we get every kind of tidbit and nuance of the work that you’ve done in this area.

Dr. Kara Fitzgerald: All right. So let’s just start with defining testosterone deficiency, and how do we test for that?

Dr. Doreen Saltiel: Well, first of all, it’s two pronged. It’s symptoms and laboratory data. And really you have to look at the symptoms that are specific to testosterone deficiency. Similar to vasomotor symptoms in women, you want to look at decreased libido, erectile dysfunction, which is sort of complicated, decreased muscle mass, increased fat mass, as opposed to the nonspecific symptoms of brain fog, fatigue. Look for those specific symptoms. And in essence, what a physician should do is download the ADAM questionnaire. It’s easily downloadable, ask the patients to fill it out and you’ll have a good sense of whether patients have symptoms of testosterone deficiency. In addition, look for anemia, unexplained anemia, think about decreased bone mineral density. If a guy tells you he’s had a fracture, young males shouldn’t have fractures, or even guys who are 50 shouldn’t have fractures.

And then testing, serum will always be the gold standard. And interestingly, the guidelines are all over the place. Every society has a different definition, but you can be really comfortable with a total testosterone of less than 300 and a free testosterone of less than 100 or 65 to 100. And really Morgentaler, who everybody should read the references in this blog, one of them by Morgentaler to says 300 to 350 for total testosterone, less than, and really a free testosterone of less than 65 to a 100. And really that 300 to 350 is because of serum hormone binding globulin. Okay. It’s that wide variability, and you want to test males on two separate mornings. One is not enough, even though-

Dr. Kara Fitzgerald: Are you altering their prep? I mean maybe no intense exercise the day before, or, I mean, are you doing anything prior to testing to prepare them?

Dr. Doreen Saltiel: No. Basically tell people do your regular activities. Let’s not do anything artificial. I test them on two separate mornings and before I will initiate hormone therapy in anybody, they get a digital rectal exam in addition to a CBC, a CMP, serum hormone binding globulin, of course, LH and FSH, estradiol, you want to use an LC-MS/MS assay because males fall at that lower end of the reference range.

Dr. Kara Fitzgerald: For the high sensitivity assay.

Dr. Doreen Saltiel: Yes.

Dr. Kara Fitzgerald: Yep, yep. I just want to assure people that we’re going to gather what Doreen’s kind of laying out here and we’ll make sure we have it in the show notes, we’ll link to the blog. We’ll get the ADAM questionnaire linked, et cetera, et cetera. So we’re going to get those resources, but keep going.

Dr. Doreen Saltiel: You want to check prolactin because high prolactin will inhibit LH. And then if you inhibit LH testosterone gets inhibited. You want to check thyroid. All of those things. And if somebody falls into that borderline zone, you should consider a testicular ultrasound because if testicular volume is less than 10 ml, boom, you have it, because that’s not normal. So these other tests will help you if you fall into that border zone. But most guys, when their testosterone gets about 300, they have symptoms. They have decreased libido, they will have erectile dysfunction, they will lose their morning erections. All of the things that are signals that they have hypogonadism. They’ll lose muscle mass, they’ll tell you that no matter how much strength training they do, they can’t gain muscle.

Dr. Kara Fitzgerald: Let me just ask you out of curiosity, what if somebody is presenting with the clinical findings, but laboratory evidence is not compelling?

Dr. Doreen Saltiel: Well, that’s very interesting because then I would do something called CAG repeats. And what that looks at is androgen receptor sensitivity. And the higher the number of CAG repeats, the less sensitive the androgen receptor is. And that’s both in men and women and so that will give you a signal that even with normal testosterone levels they may need testosterone. And the other side of that is if you give somebody testosterone, they may need higher doses.

Dr. Kara Fitzgerald: Yep, because of that-

Dr. Doreen Saltiel: And a higher serum level to improve their symptoms and clinical outcomes.

Dr. Kara Fitzgerald: Now, can you look at CAG repeats? I mean, can you measure those through a standard?

Dr. Doreen Saltiel: Yeah. You can. There’s a company called GeneDx and they have the ability to measure CAG repeats.

Dr. Kara Fitzgerald: How often do you need to do that dive or are you sufficiently satisfied with standard lab evidence?

Dr. Doreen Saltiel: If I have a guy who’s symptomatic and their total testosterone is normal, 400, 450 and their free testosterone is normal, I will give them a trial of testosterone therapy if they have classic symptoms. However, if they don’t respond to the average doses, I then will go do CAG repeats because it’s like genomics, they’re expensive. And then document it in the medical record that they have these, it’s in the literature that these require higher doses. So you’ve dotted your I’s and crossed your T’s, such that you are not viewed as giving testosterone to people with normal testosterone levels.

Dr. Kara Fitzgerald: Well, I’ve got one more question and then we’ll get back on task. Is there a way to improve sensitivity? Is there a way to sort of functionally address this?

Dr. Doreen Saltiel: No. No.

Dr. Kara Fitzgerald: Okay. So if they have it, they just need a supraphysiologic amount?

Dr. Doreen Saltiel: Yes.

Dr. Kara Fitzgerald: To move through that. Okay, that’s extremely helpful. This is great. All right. So they’ve met your criteria or they meet the testosterone deficiency criteria, what are you looking for to achieve in serum levels and how often do you monitor and what battery of testing? So you just gave us a pretty involved laboratory workup for baseline, and then how do you track it?

Dr. Doreen Saltiel: Well, first, and it depends on the delivery, but in general, I shoot for a serum testosterone greater than 500, clearly less than a thousand with the goal being greater than 500 to 800 or 900, if somebody is in that range and they’re not getting better, look at the HPA axis, look at the gut. Don’t leave your clinical acumen at the door, don’t forget about the rest of functional medicine. I mean, because you can’t do it. You can give people all the hormones you want and if you don’t address the HPA axis and the gut and all the other things, they’re not going to get better, they’re just not going to get better.

And then once I give somebody hormones, how do I follow them? Well, everybody gets a CBC at a month automatically because you’re looking for erythrocytosis. Less so with gels and creams, more so with injections and pellets are somewhere in the middle. I do a PSA in the beginning and then I check it at three months and at a minimum 12 months, that’s what the guidelines say. A lot of times I’ll do it three, six and 12 the first year. The same thing with a digital rectal exam. I do it at three months and I do it at 12 months. Unless somebody complains, then I’ll do it at six months. And then after that, it’s twice a year.

Dr. Kara Fitzgerald: Okay.

Dr. Doreen Saltiel: Unless something changes.

Dr. Kara Fitzgerald: These labs and a DRE?

Dr. Doreen Saltiel: Yeah.

Dr. Kara Fitzgerald: Twice a year?

Dr. Doreen Saltiel: Twice a year. And I will tell you that a lot of clinicians negate a digital rectal exam. Don’t do it, it’s part of the workup. A woman gets a GYN exam and a mammogram or thermogram, whatever your choice is. This is the same thing. The other thing I do is I do a breast exam on males.

Dr. Kara Fitzgerald: Good. That’s so smart, it’s really smart. Let me ask you this, we’re actually going to start to talk about risks. And so maybe we’ll get there, or concerns. But for me, there’s pause in introducing testosterone into an individual who’s just very clearly inflamed and kind of following the standard American life. They’re sedentary, they’re overweight, they’re eating a profoundly pro-inflammatory diet. And that’s because I know that inflammation can drive aromatase production and an increased conversion of testosterone to estrogen. So you just outlined the functional medicine interventions, just the functional lens that you’re using concurrently to the hormone replacement therapy. Might you start somebody with addressing these underlying imbalances before you introduce testosterone to them? Is that something that you think about or can you do it concurrently or do you not worry about it?

Dr. Doreen Saltiel: I do it all the time first.

Dr. Kara Fitzgerald: Okay. Oh, you do? So you have a sort of a runway where you’re dialing them in functionally?

Dr. Doreen Saltiel: Yeah. Because I tell them if they’re that inflamed and there’s some literature, and the theory is called the GELDING theory, that gut endotoxemia can suppress testicular production of testosterone. And I address the HPA axis, I address the gut and I make sure all their micronutrients are okay. And I do functional medicine before I commit somebody to lifelong testosterone. And what I try and explain to people is they didn’t get this way overnight. So give me six months, sometimes a year. And if they do what I ask them to do, they’ll get better and their testosterone levels should come up. Sometimes it doesn’t come up to where it needs to be, but they’ll definitely need less testosterone.

Dr. Kara Fitzgerald: And a percentage may not need it at all?

Dr. Doreen Saltiel: Correct.

Dr. Kara Fitzgerald: They’ll need less and how they use it will be healthier. And they’re going to feel great moving through that six months of treatment.

Dr. Doreen Saltiel: And their mitochondria will be healthier, their detoxification pathways will be healthier, they will be healthier overall.

Dr. Kara Fitzgerald: How are you addressing HPA? What are you looking at? Are you using the cortisol awakening response? I mean, yeah.

Dr. Doreen Saltiel: Well, as you know, I use the Dutch test and everybody gets a baseline Dutch test for me, which I didn’t talk about.

Dr. Kara Fitzgerald: Yeah. And tell me what you’re looking at? I mean, you’re looking at CAR I’m sure. But talk to me about how you’re using the baseline Dutch test with these-

Dr. Doreen Saltiel: A couple of ways. One, I look at cortisol, I look at the CAR, I look at cortisol metabolites, I look at total production. And then I look at estrogen metabolism because a hormone’s ultimate effect is really dependent on how it’s metabolized. And the whole issue with prostate cancer and estradiol, which is really complicated, is that if a guy’s not healthy and a lot of his testosterone goes to estradiol systemically, you can assume that some of it is going infroprostatically to estradiol and then they have a barren aromatase activity in the prostate. That’s where the supraphysiologic testosterone levels come in and you can increase your risk of prostate cancer and even an inflamed individual who you give testosterone to, if they’re at risk for prostate cancer, they may abnormally increase aromatase and alter that testosterone to estradiol ratio.

Dr. Kara Fitzgerald: So part of that six months runway is correcting the imbalances on the Dutch?

Dr. Doreen Saltiel: Correct.

Dr. Kara Fitzgerald: And making sure they’re detoxifying their androgens and estrogens. Correct?

Dr. Doreen Saltiel: Correct.

Dr. Kara Fitzgerald: Awesome. Good. Makes total sense. And yeah, then you’re introducing it just so much more smartly and safely. Well, what about the idea, you did such a elegant jive into the literature on prostate cancer and I know here we’re talking about how to make it safer, but does testosterone replacement therapy increase the risk of prostate cancer in general? I mean, what’s the-

Dr. Doreen Saltiel: No, no. Very interesting, as I wrote in the blog, since that Huggins and Hodges landmark paper that documented if you decrease testosterone into castrate levels in men with prostate cancer, prostate cancer regresses. And if you give men with prostate cancer testosterone, prostate cancer grows. That got extrapolated to all men who get testosterone have an increased risk of prostate cancer. That was negated in the literature. I mean, there are some very good articles and studies that basically have documented that testosterone does not increase prostate cancer. And in fact, testosterone has a saturation point in the prostate and it’s about 250 nanograms per deciliter. Below that level, PSA will increase. Above that level, it hardly increases at all. So that’s that threshold saturation point where the prostate is saturated. The issue with prostate cancer and testosterone, it’s the conversion to estradiol. It’s the estradiol issue that more than anything will drive prostate cancer in an inflammatory environment.

Dr. Kara Fitzgerald: Right. Are you using an aromatase inhibitor then in some individuals?

Dr. Doreen Saltiel: I really try to keep their estradiol in that 30 to 35 range and I really try to keep testosterone in around that 600 to 900 and then I don’t have to use an aromatase inhibitor.

Dr. Kara Fitzgerald: Okay. I’m sure the lifestyle interventions, if they’re adhering to them, they’re natural aromatase inhibitors.

Dr. Doreen Saltiel: Yes, yes.

Dr. Kara Fitzgerald: Okay, awesome. This is really helpful. So testosterone replacement in an individual with prostate cancer would be contraindicated?

Dr. Doreen Saltiel: Yes.

Dr. Kara Fitzgerald: For the obvious reasons.

Dr. Doreen Saltiel: Yes, yes.

Dr. Kara Fitzgerald: Okay. Just out of curiosity, I mean, where are we now with using it? I mean, well, on one arm, I think it’s been overprescribed. I mean, it hit television, it hit commercials, low T and it just sort of became this aggressive sales pitch, which I don’t know that has been wildly helpful. I don’t know. I’m sure you have some thoughts on that. I guess the question would be since we’ve gone into prescribing it so much, have, I don’t know that we’ve seen an uptick in prostate cancer as it’s been used more?

Dr. Doreen Saltiel: No, there’s not.

Dr. Kara Fitzgerald: Yeah, and that’s interesting because most physicians aren’t thinking through a functional lens, so that’s kind of an interesting, so they’re giving it to plenty of really inflamed guys and we’re not seeing an increase.

Dr. Doreen Saltiel: Correct, correct. The really interesting thing to me was that I find this discussion similar to the estradiol and breast cancer discussion. I think it’s a real knowledge gap. And I think testosterone was done a disservice by all these corner T clinics that just give testosterone or people who prescribe supraphysiologic testosterone because more is better when actually it’s not.

Dr. Kara Fitzgerald: Right. So it hit the media, I think it’s probably been overprescribed. And as you say, supraphysiological amounts and in a pro-inflammatory milieu. But even with this misuse of it, we’re not seeing uptick in prostate cancer, which I think is-

Dr. Doreen Saltiel: Correct.

Dr. Kara Fitzgerald: That’s important. That’s extraordinarily important. We need to let go of this fear.

Dr. Doreen Saltiel: Yes.

Dr. Kara Fitzgerald: That’s great. That’s great. And yeah, folks again, the discussion that Doreen had with me on New Frontiers on estradiol, we’ll make sure we link to it. And again, do check out her blog. It’s a blog that I refer other physicians and providers as well as my patients to download, to take to their providers because it’s so well referenced just like the testosterone blog and what we’re talking about here today. All right. So then let’s talk about cardiovascular disease. I mean, cardiovascular disease, uptick in various studies have prompted the halting of those studies. I mean, there’s been again, this terror-based association with heart disease and testosterone. So walk us through your look on the literature on that.

Dr. Doreen Saltiel: Prior 2013, there was a lot of data, most of it, clinical trials, observational studies that documented testosterone in men with low testosterone decreased cardiovascular events and cardiovascular mortality. However, two studies came out, the Vigen study and the Finkle study, which were both bad studies, which we can talk about. They got a ton of publicity. The FDA said, “Okay, we need to look into this.” Found two other studies, one was a meta-analysis and one was a randomized controlled trial. And based on those four studies, even though the FDA, when they looked at all of these studies individually said, “Eh, not really good data,” mandated a black box warning on all testosterone prescriptions. That really sent the community or the hormone community into a tailspin, and basically said, “We shouldn’t prescribe testosterone.”

And the four studies have been critiqued by experts all over the world saying these four studies are meaningless, which is how the Traverse trial, which is a large randomized control trial, which is ongoing, it hasn’t been stopped. And a friend of mine is a principal investigator and he says the data looks good. The data should come out in the next few years. And there’s no evidence that it increases adverse cardiovascular events. So that’s the good news.

But these four studies starting with the Basaria trial, which was the TOM trial, which was not a cardiovascular study, it looked at muscle strength in frail old men. And it was stopped early because of presumed cardiovascular events and most of them were palpitations and lower extremity edema. Those were the cardiovascular events. However, there were four real cardiovascular events in men who received testosterone. When they looked at the data further, all of these men had total testosterone levels greater than a thousand, and they all were given supraphysiologic doses. So that’s the first study.

The Vigen study was the 2013 study where they used a statistical analysis that had never been validated and they included 10% of females in that.

Dr. Kara Fitzgerald: Oh, is that right?

Dr. Doreen Saltiel: Yeah, there were 10% of them were women. And then the analysis was incorrect in that where they said the men who received testosterone had a higher incidence of cardiovascular events, actually it was a lower incidence. It was about 10.1% in the men who received testosterone and it was 21% in the men who didn’t receive testosterone.

Dr. Kara Fitzgerald: And was that a statistically significant difference?

Dr. Doreen Saltiel: Yes.

Dr. Kara Fitzgerald: So they just misreported it?

Dr. Doreen Saltiel: Yeah. And they tried to correct it. They tried to correct it and everyone said, “This study needs to be pulled from the literature.” Nobody pulled it. It still exists.

And then we get to the Finkle study, which also had flawed data analysis. And they compared pre-treatment testosterone with post-treatment MI rates, which makes no sense. They’re measuring two different things. They never attempted to validate the events, they just looked at ICD, at that time [ICD] 9 codes, there was no control group and they never looked at key data points like testosterone levels.

And then the last, this is actually the most mind boggling, was a meta-analysis where 35% of the studies were two. One was that TOM study, with the supraphysiologic testosterone, and the other was the Copenhagen trial where they gave men with liver cirrhosis oral methyl testosterone, 600 milligrams. And their testosterone levels reached as high as 21,000.

Dr. Kara Fitzgerald: Wow. Because they had cirrhosis?

Dr. Doreen Saltiel: Right. And when they pulled those two studies out of the meta-analysis, there was no difference between cardiovascular event rates in the treated and non-treated men. And since that time, there have been a ton of studies documenting that indeed it decreases cardiovascular events, it decreases mortality. And the longer you treat guys, the less the event rate. But none of them are randomized control trials. And you know as well as I do Kara in our traditional world, that’s all they looked at. And that’s why the Traverse trial is basically-

Dr. Kara Fitzgerald: So important.

Dr. Doreen Saltiel: Yeah, everybody’s waiting for.

Dr. Kara Fitzgerald: But the reality is that you’re comfortable using it, the evidence that you have.

Dr. Doreen Saltiel: Without a doubt.

Dr. Kara Fitzgerald: And the decision-making studies are horrible, horrible. Oh my God. It’s kind like the women’s health initiative, yeah.

Dr. Doreen Saltiel: There’s been a lot of data, and it’s in the blog itself, the citations really talking about how the studies were terrible. Those four studies and nobody thinks-

Dr. Kara Fitzgerald: Where did you read that the FDA said these are garbage but we’re going to black box it anyway? I mean, how did you dig that up?

Dr. Doreen Saltiel: The Morgentaler paper on cardiovascular disease since the FDA mandate and then Marty Miner’s paper on it. Yeah, they all wrote about it.

Dr. Kara Fitzgerald: Oh my God. Thank you for doing this work for us. It’s just incredibly helpful.

Dr. Doreen Saltiel: Yes.

Dr. Kara Fitzgerald: So what do I want to say? We’ve covered a lot and yeah, very useful, useful, useful for all of us. What else? Anything else that you-

Dr. Doreen Saltiel: The last thing is delivery methods and the risk of erythrocytosis.

Dr. Kara Fitzgerald: Okay, good.

Dr. Doreen Saltiel: Because injections cause the highest incidence of erythrocytosis, gels and creams cause the least, pellets are somewhere in the middle. And if you have a male patient whose hematocrit is 48 or greater, don’t give them testosterone until you work them up, which includes a sleep study. Don’t just send them to donate blood. That’s not how you work people up. What you want to do if you are using injections, you want to give them subq [subcutaneously] and people of course start too high. Start with 25 or 30 milligrams twice a week. Check before the next dose about two or three weeks later and if their testosterone is less than 400 increase the dose a little. If it’s greater than 700, decrease the dose a little because you want to keep them in that greater 500 to about 800 or 900.

If you are using standard gels like AndroGel, start at 50 milligrams a day. If you are using creams, put the cream in an Atrevis base in a male. That base absorbs better through a guy’s thicker skin. Start at 50 milligrams, but be aware the one study that compared a gel with a cream, the cream required twice the dose. So you may need a higher dose of a cream than you will a gel, similar to women if you compound creams. Start at 0.5 with a woman and then work your way up based on serum levels.

And just a word about pellets and oral, the oral JATENZO or TLANDO. Pellets get a bad rap because people give too much. It’s not the pellet, it’s the pelleter. And for every 75 nanograms you want to increase testosterone so say you’re at 300 and you want to go to 900, give them 600 milligrams. They don’t need 800 milligrams, they don’t need 1000 milligrams of pellets. 750 is the average dose. And when you look at the pharmacokinetic studies, it’s based really on BMI. Guys who have a BMI of less than 25, they do best with about 750 milligrams. Guys who have a higher BMI, they may need a little more, but guess what? I still start at 750.

And the pellets are gone, the pharmacokinetics, they’re gone in 100 to 120 days. So I test them at the end of three months. And if their levels are still good, I gave them too much the first time. I’ll wait a little longer, I’ll lower the dose. If they’re back at baseline after three months, then I gave them the right dose. And the new JATENZO or TLANDO, the oral testosterone, be careful with older males, it tends to raise blood pressure and the concern is if you raise blood pressure, you may increase cardiovascular events. And so it may cause more lower extremity edema. And what I have found using them guys forget to take them. They’re twice a day.

Dr. Kara Fitzgerald: Oh, are they really? Oh yeah. That’s really-

Dr. Doreen Saltiel: Yeah, they’re all twice a day.

Dr. Kara Fitzgerald: So why are they going oral? Just out of curiosity.

Dr. Doreen Saltiel: Partially because they’re trying to get away from injections and the ability with erythrocytosis so they’re trying to do an oral. Similar, they think guys will do better. And a lot of guys don’t want to rub gels and creams on themselves either. So a lot of guys would rather have pellets and some guys don’t want pellets, or some docs are not comfortable using pellets. And that’s fine. And so this is another alternative for guys. And actually the TLANDO study, there was a study recently published by Mohit Khera and some of his other colleagues that documented that 225 milligrams twice a day doesn’t even need regular monitoring. Testosterone levels stay at about 750, 800. I wouldn’t do that. I’d still monitor guys but you got to monitor prolactin because it can raise prolactin levels. There’s a lot of monitoring you have to do with the oral medicine. So it may not be the best thing for everybody.

It’s kind of like, I don’t use a lot of digoxin, the reason, the therapeutic window is so narrow and testing doesn’t matter, but it makes me nervous. And so I’d rather worry less. And so for me, I get guys to do gels or creams or in some guys pellets. I don’t use a lot of injections because guys think more is better and I can’t control what they’re doing.

Dr. Kara Fitzgerald: Okay. Okay, good. I was going to ask you what you’re using primarily. Why a cream versus a gel out of curiosity?

Dr. Doreen Saltiel: Oh, I typically use a gel.

Dr. Kara Fitzgerald: You use a gel?

Dr. Doreen Saltiel: Yeah. I typically start with the standard AndroGel and it’s bioidentical. In case a guy says, “I don’t like the gel. I don’t like the alcohol,” then I may go to a cream. The problem with a cream is you got to put chrysin in the cream sometimes and it makes the skin yellow, it makes clothes yellow. So I typically use a gel-

Dr. Kara Fitzgerald: Or why do you need chrysin in it out of curiosity?

Dr. Doreen Saltiel: Well, just in general, if their estradiol goes up, it’s the easiest way to-

Dr. Kara Fitzgerald: To turn it down?

Dr. Doreen Saltiel: Yeah.

Dr. Kara Fitzgerald: Interesting. Wow. That’s cool.

Dr. Doreen Saltiel: But it makes people’s clothes yellow which is pretty annoying.

Dr. Kara Fitzgerald: Yeah, for sure. I’m sure it is. Well, this has just been extremely useful. Let me ask you, as far as these various forms, so I mean, you would consider oral in a guy who’s otherwise healthy and liver function is fine, you’re not worried about high blood pressure if that’s the only way he’s going to use it? I mean, all these forms are fair game for you as long as they’re used in the correct context?

Dr. Doreen Saltiel: Yeah. I actually start with gels, even in guys who I’m going to ultimately pellet. I’ve been pelleting for 14 years. And I do that so I can see number one how they detoxify their hormones. It’s easier to stop a gel or back off on a gel than it is to me go fishing pellets.

Dr. Kara Fitzgerald: Yes, yes, yes, yes, absolutely. A hundred percent. That makes so much sense. And then you can get your dose for pellets based on how they respond, what you do with the gel.

Dr. Doreen Saltiel: Correct, correct. I make sure that detoxification pathways are optimized because I may optimize them before, but you know as well as I do you give somebody a hormone, things change. And so I keep things simple. I don’t like to put myself with a patient in a predicament where I have no out. I always learned in cardiology when I taught fellows, it’s easy to get in trouble, very easy. You have to know how to get yourself out of trouble. And pellets are a hard way to get out of trouble.

Dr. Kara Fitzgerald: Right, so you got make sure you go in there-

Dr. Doreen Saltiel: So I start with gels… Yes, yes. Even in a guy who begs me, start with gels and then we convert.

Dr. Kara Fitzgerald: Yeah. Makes absolute sense. Okay. This has been fabulously useful. And then again-

Dr. Doreen Saltiel: And I do metabalomics, just so you know, I do metabalomics after four months.

Dr. Kara Fitzgerald: Oh, thank you. I was going to ask you about that. And in erythrocytosis, you said you’re doing the CBC every three months?

Dr. Doreen Saltiel: 1, 3, 6.

Dr. Kara Fitzgerald: 6 and 12?

Dr. Doreen Saltiel: And 12. And if that prick goes up, I stop it until… most of the time, if I think somebody has sleep apnea me, I work them up in advance. But if I didn’t think so and their prick goes up, I stop it, I work them up and then I lower the dose when everything is worked up and I have an answer.

Dr. Kara Fitzgerald: Do you look at iron in some folks?

Dr. Doreen Saltiel: Yes, of course. At iron too. I do all of that in the beginning. And other thing is after I check metabalomics initially or the Dutch test after four months I do it twice a year.

Dr. Kara Fitzgerald: Okay. Oh, you’ll do a Dutch? So when you say metabolomics, you’re referring to the Dutch?

Dr. Doreen Saltiel: Correct.

Dr. Kara Fitzgerald: Okay. And then you’ll do that twice every six months?

Dr. Doreen Saltiel: Yes. Unless something changes and then I have to do it more.

Dr. Kara Fitzgerald: And if you’re curious about detoxing, I’m actually saying this to the audience that if you’re wondering how she’s actually working with the findings on the Dutch i.e. higher estrogen, metabolites, and so forth, you’re probably using the interventions that they list. I mean, it’s a really nice panel in that treatment and dosing, et cetera, are there. But do you want to just say some of your favorite supplements that you might use? Yeah, go ahead.

Dr. Doreen Saltiel: Sure. So first thing when I’m looking at estrogen metabolism, I have to make sure they have adequate methylation activity. And as you know, it doesn’t measure methylation. This is not a DNA test that’s measuring actual CpG islands and methylation. It’s really looking at the ratio of 2-hydroxy to 2-methoxy. And before I start addressing Phase I detoxification heavily, I make sure at the same time they have adequate methylation activity because those intermediates, whether it’s 4-hydroxy or 2-hydroxy can become toxic intermediaries if they don’t have a pop off valve, if you don’t have adequate glutathione, if you don’t have adequate methylation. So that’s the first thing I look at.

And then to increase activity down that 2-hydroxy, you can give I3C, you can give DIM. In addition to diet, right? Cruciferous vegetables, not that’s going to make this huge dent, but you want to eat an anti-inflammatory diet because inflammation will push things down that 1B1 4 hydroxy pathway, it will increase aromatase activity and you really don’t want to do that. And as far as methylation, you can talk as well probably better than I can about trimethylglycine and methylated B vitamins, but making sure you’re not over-methylating people because of the consequences and some of them are cardiovascular consequences of over-methylating.

Dr. Kara Fitzgerald: Right, right. So again, we can lean on diet. Of course, anybody listening probably knows I wrote a book about that.

Dr. Doreen Saltiel: Right. I was going to let you talk about that.

Dr. Kara Fitzgerald: So you can get top tips from the Younger You book on how to work with tweaking methylation through diet and lifestyle. But you’re doing a lot of that. And anyway, folks, we’ll link to a Dutch test as well, so that you can take a look at that and what Doreen’s talking about here in case you’re not familiar with it already. So this brings us to the end. And I just want to say, thank you. I love it. I love these deep dives that you do. I look forward to your next one and talking about wherever you go. It’s so helpful to the community, so helpful.

Dr. Doreen Saltiel: Oh, well, it’s my pleasure. And everybody read Kara’s book because in all, honestly I read it, it gave me a lot of good information, which I use on my patients all the time. Lean on the experts, people, and Kara is definitely an expert. And so not only a friend and a colleague, but a well written, well versed expert in that field. So I leaned on her.

Dr. Kara Fitzgerald: Thank you so much, Doreen. All right, well, big virtual hug to you and may our paths cross in real life soon.

Dr. Doreen Saltiel: I’ll talk to you soon.

Dr. Kara Fitzgerald: Okay.