Sponsored: In Pursuit of Best Practice for Menopausal Hormone Therapy (MHT)

As a functional medicine clinician and scientist, I absolutely appreciate the deep literature dives my colleagues take. When they come up for air, there is a synthesized body of knowledge that is riveting, satisfying to listen to, trust-worthy and, most importantly, practice changing. Such was my conversation on all things menopausal hormone therapy with Dr. Doreen Saltiel, currently consulting for Precision Analytical (they’re lucky to have her). She spent the bulk of her impressive career as an interventional cardiologist (although confesses she wanted to go into OBGYN) and jumped into integrative and functional medicine after her own “ah-ha” healing journey, involving hormone replacement therapy, relatively early on in her life. The first solid debunking Doreen provides are the findings from WHI. IT’S TIME these ideas are PUT TO BED. I asked Dr. S about the political backstory for the WHI debacle – it’s a good listen, and like me, you’ll probably want to read more. We then dive into the solid body of evidence for transdermal estradiol, oral progesterone. We discuss compounding, dosing, testing, addressing metabolites … and SO MUCH MORE. Keep a pen or your phone handy for note-taking, there’s tons of info in this podcast. Thanks as always, to Precision Analytical, creators of the DUTCH test, for bringing Dr. Saltiel to our listeners. She’s incredible! Please share New Frontiers with your network, and if you would be so kind, leave us a comment and review wherever you listen. Thank you! ~DrKF

There’s a lot of confusion about the safety and efficacy of hormone replacement therapy (HRT) for menopausal women. Dr. Doreen Saltiel, a cardiologist and hormone expert, is on a mission to clear up that confusion and help women protect their health during menopause and beyond. Dr. Saltiel received her medical degree from New York Medical College before completing her Internal Medicine residency at Brooke Army Medical Center in San Antonia and subsequently a Cardiology fellowship at Walter Reed in Washington D.C. She practiced Cardiovascular Medicine for 14 years in the Army and her Army service culminated at Fort George in Georgia, where she was Chief of Cardiology and the South East Regional Consultant in Cardiovascular Disease. In this episode of New Frontiers, Dr. Fitzgerald talks with Dr. Saltiel about hormone replacement therapy and its benefits for women; how the WHI study perpetuated dangerous and inaccurate information about HRT; and dosing hormones and testing serum hormones levels.

Dr. Saltiel received her medical degree from New York Medical College before completing her internal medicine residency at Brooke Army Medical Center in San Antonio, Texas and subsequently a cardiology fellowship at Walter Reed Army Medical Center in Washington, DC. She practiced cardiovascular medicine for 14 years in the Army, and her Army service culminated at Fort Gordon, Georgia where she served as the Chief of Cardiology and the Southeast Regional Consultant in Cardiovascular Disease. Following 20 years as an Interventional Cardiologist, she practiced Phlebology and Functional Medicine in Fort Smith, AR. She is board certified in Internal Medicine and is an Advanced Fellow in Anti-Aging and Regenerative Medicine. Recently Dr. Saltiel served as the Vice-President, Medical Affairs and Chief Medical Officer for Genova Diagnostics and is currently the Medical Director of Peak Health and Wellness in Asheville, NC. She is a member of the CardioSurve Research Panel of the American College of Cardiology and the Metagenics Cardiometabolic Health Advisory Board, and serves as a consultant for Precision Analytical.

• Evidence-Based Opinion Papers and Best Practices for MHRT
• DrKF Blog: In Pursuit of Best Practice: Menopausal Hormone Therapy (MHT)
• Hodis and Sarrel: Menopausal Hormone Therapy and Breast Cancer: What is the Evidence from Randomized Trials?
• New Frontiers with Dr. Dale Bredesen

New Frontiers podcasts with Precision Analytical

• Dutch™ Research And Validation In Peer-reviewed Journal Article
• The Cortisol Awakening Response
• Urine Testing to Monitor Transdermal Estrogen Creams or Gels
• HPA, Organic Acids and the DUTCH Test with Dr. Carrie Jones
• Using Dutch Hormone Test

• DrKF FxMed Clinic: Patient consults with DrKF physicians
• Clinician Professional Development: DrKF FxMed Clinic Immersion
• 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 today is no exception. I am thrilled to be here with Dr. Doreen Saltiel. We’re going to be doing a nice dive into menopausal hormone therapy, just a good survey on the literature. She’s really established herself as an expert in this arena and I, for one, appreciate it. But before I do that, let me give you a little bit of Dr. Saltiel’s background.

She received her medical degree from New York Medical College before completing her Internal Medicine residency at Brooke Army Medical Center in San Antonia and subsequently a Cardiology fellowship at Walter Reed in Washington D.C.

She practiced Cardiovascular Medicine for 14 years in the Army and her Army service culminated at Fort George in Georgia, where she was Chief of Cardiology and the South East Regional Consultant in Cardiovascular Disease.

Following 20 years as an Interventional Cardiologist, she practiced Phlebology and Functional Medicine in Ft. Smith, Arkansas. She’s board certified in Internal Medicine and is an advanced fellow in Anti-Aging and Regenerative Medicine. Recently, Dr. Saltiel served as the Vice President of Medical Affairs and CMO for Genova Diagnostics and she’s currently the Medical Director of Peak Health and Wellness in Asheville, North Carolina. She’s a member of Cardio Survey Research Panel of the American College of Cardiology and the Metagenics Cardiometabolic Health Advisory Board. She also serves as a consultant for Precision Analytical. Dr. Saltiel, welcome to New Frontiers.

Dr. Doreen Saltiel: Thank you for having me. I’m delighted to be here.

Dr. Kara Fitzgerald: And it’s really lovely to be able to connect with you again and to dive into this all important topic of menopausal hormone therapy. But before we do, I just want to learn a little bit about your background. You’ve been practicing functional medicine for a long time. Actually, you’ve got an incredibly impressive medical career with 20 years of functional medicine in there. So just talk to me about that. What got into integrative/functional medicine?

Dr. Doreen Saltiel: It’s actually an interesting story. I was teaching for a vein company how to do venous procedures and I was teaching all over the United States and a bunch of OBGYN’s came to my office, one of whom actually became a good friend of mine, and we were chatting and I was teaching them how to do venous ablation and I said to them, “I cannot lose this 15 pounds that I’ve got around my gut.” And he said, “You need hormones.” And I said, “I’m not taking no hormones. After the WHI, I am not taking hormones.” And he said, “You need hormones.” He said, “How long are you menopausal?” And I said, “Well, I had premature menopause and had a hysterectomy at 40.” And he said, “You definitely need hormones.”

And so he and I chatted about hormones and he basically sent me all the literature to read on bioidentical hormones and then I went to his office in Houston where I actually proctored him on venous procedures and he put a testosterone and Estradiol pellet in me because I had a complete Hysterectomy. And he gave me oral progesterone and it changed my life.

Dr. Kara Fitzgerald: Wow.

Dr. Doreen Saltiel: And I said, “Wow. If this did this to me and I didn’t really think I felt bad, imagine what this could do for others.” And he said, “You pass people all the time. You could put pellets in people.” And I said, “No, no, no, no. I need to learn. I haven’t practiced anything other than cardiology for 25 years or so and I just can’t just do that. That’s not who I am.”

And so I found Pam Smith online and the AM4 Fellowship and I went through the entire fellowship plus more and realized that it wasn’t just about hormones, it was about inflammation and I transitioned both my cardiology and venous practice into a preventive cardiology and venous practice and, at the same time, incorporated all the functional medicine stuff that I learned throughout the years. So that was my transition, and I didn’t like staying up all night anymore.

Dr. Kara Fitzgerald: Right, right. And that was quite a while ago. You were really sort of really a doctor of this medicine and like many of us, coming with your own experience, your own personal experience. Wow.

Dr. Doreen Saltiel: And aside from that, I wanted to be an OBGYN when I was a kid. I didn’t want to be an interventional cardiologist. I wanted to be an OBGYN until a doctor I was rotating with said, he used to call me kid, he was my mom’s OBGYN. He said, “Kid, you don’t want to be up all night.”

Dr. Kara Fitzgerald: Ah.

Dr. Doreen Saltiel: And look what happens. I go and become an interventional cardiologist and I’m up all night. So I’m actually now in my second or third life actually following a real passion of mine.

Dr. Kara Fitzgerald: Good to hear. And I’ll tell you what, it’s essential that we’ve got leaders like  you committed to teasing through the literature because nowhere is it more confusing for clinicians and regular folks, patients alike, than in to take or not to take hormone therapy.

So let’s dive in and just talk to me first of all the big giant question is what does the science say regarding MHT and cancer risk? Give me the overview, talk to me, bottom line, whether or not we’re concerned about cancer these days.

Dr. Doreen Saltiel: Well, and you and I can just stipulate up front, most things in excess may not be good for you. Whether it be too much sleep, too much exercise, and hormones are included in that. So, the answer to the cancer question is no. It doesn’t increase. Estrogens, hormones, menopausal hormone therapy, does not increase cancer in the right patient at the right time and, of course, giving her or him the right dose delivery and ongoing surveillance. So I think the WHI really did a disservice to the medical community when they put out the data that they put out prematurely.

Dr. Kara Fitzgerald: Yes.

Dr. Doreen Saltiel: Because as you know, the WHI was not a study looking at breast cancer.

Dr. Kara Fitzgerald: Yes.

Dr. Doreen Saltiel: It was a study to evaluate whether the benefits we saw in younger women who took hormones could be translated to older women who were more likely to get that disease, I.e. cardiovascular disease, cancer, osteoporosis, whether those benefits translated. Unfortunately, there was a ton of politics around the WHI and it got all turned around and translated into an increased breast cancer risk.

But let’s start with the most straight forward cancer, which is endometrial cancer. It’s very clear, nobody will argue that unopposed estrogen increases endometrial cancer risk. So the question then becomes, what progesterone dose and delivery will mitigate that risk? And across the board, the largest and really only randomized trial was the PEPPY Trial, which looked at 200 mg of oral micronized progesterone.

However, they’re a large, randomized trial that looked at 100 mg of oral micronized progesterone with higher doses of, say EstroGel, like one and a half milligrams, than we would use today. So I am comfortable saying with the low doses that we use today, 100 mg is safe. Vaginal micronized progesterone is a great option, right? Because it avoids first path, it saturates the endometrium and you probably don’t need to use as high a dosage as you do an oral preparation and you’ll get the endometrial protection, and then all the Estradiol alone benefits that you see in the literature as we march through this.

When we talk about breast cancer, go ahead.

Dr. Kara Fitzgerald: Okay, so plenty of women are using oral, for the potential brain benefits, for the anxiolytic properties, etc. Speak to that, do you have any thoughts?

Dr. Doreen Saltiel: Yeah, actually I use oral micronized progesterone most of the time. And most of the times I use it is, number one, because of the randomized control trial, and all the other trials that support its use. And then, number two, the sleep and anxiolytic properties through its metabolism to allopregnanolone and it’s attachment to the GABA receptor.

Unfortunately, there’s not a lot of data on progesterone and cognition. It doesn’t do any harm, but as much as we’d like to think that it does benefit, the data’s just not there yet.

Dr. Kara Fitzgerald: Okay, okay. What about traumatic brain injury, out of curiosity? Have you-

Dr. Doreen Saltiel: Yes, yes. That’s a whole different scenario, because now the brain hardware and the brain network has been altered. Especially in acute traumatic brain injury, right? Because it’ll put a break on all that hyper-reactivity that occurs in the brain that you want to squelch with all those reactive oxygen species etc.

Dr. Kara Fitzgerald: Etc. Right, right. I mean, it’s a leap, and probably I know you’re just really nicely rooted in the evidence, but it’s an extreme inflammation and certainly some of the cognitive impairment, that I was just talking to Dale Bredesen yesterday, we were on this very topic, is inflammation driven, in many, many cases.

Dr. Doreen Saltiel: Yes, yes.

Dr. Kara Fitzgerald: So, we could make the leap that it’s likely beneficial. Would you agree with that statement?

Dr. Doreen Saltiel: Yes. Especially since progesterone is an anti-inflammatory.

Dr. Kara Fitzgerald: Yes.

Dr. Doreen Saltiel: Absolutely.

Dr. Kara Fitzgerald: Okay.

Dr. Doreen Saltiel: Absolutely, I would take that leap.

Dr. Kara Fitzgerald: Well then let me ask you this, too, I just don’t want to forget. Vaginal micronized progesterone dosing, where would you start?

Dr. Doreen Saltiel: 100 mg.

Dr. Kara Fitzgerald: Okay.

Dr. Doreen Saltiel: The data that, the indirect data, on 45 mg, which is Crinone, the four percent Crinone, the eight percent is 90 mg, which is what was used in the elite trial, which is a cardiovascular trial, probably is okay. But there’s really not a lot of robust data.

Dr. Kara Fitzgerald: Got it.

Dr. Doreen Saltiel: And so, when I dose progesterone, I also look at serum level of Estradiol, which we can talk about when we talk about Estradiol in a bit.

Dr. Kara Fitzgerald: Okay, okay, perfect. Give me just your run down on, just a list of benefits, of MHT. I mean obviously it turned your world around profoundly, changed your career, and you weren’t doing bad.

Dr. Doreen Saltiel: Yeah.

Dr. Kara Fitzgerald: So, just give me the benefits of considering this.

Dr. Doreen Saltiel: Oh, there’s the benefit of vasomotor symptom, vulva-vaginal atrophy, bone mineral density, and hard endpoint cardiovascular disease, and soft endpoint, I’d say cognitive improvement.

So, my answer to why I give hormones to women who are outside of that golden less than 10 years, and less than 60, is for their bones, their brain, and their heart.

Dr. Kara Fitzgerald: Good, okay. What about increased cardiovascular risk for women on MHT?

Dr. Doreen Saltiel: Actually, Estradiol alone decreases cardiovascular events. There are a number of studies, once again, the WHI sort of freaked people out. Because remember, the majority of women in the WHI were 60 to 70 years old.

Dr. Kara Fitzgerald: Mh-hmm (affirmative).

Dr. Doreen Saltiel: It had a neutral effect on cardiovascular events in that population. In the very small population of 50 to 59 year old women, which was about 10 to fifteen percent of the population, there was a 40 percent decrease in cardiovascular risk.

Dr. Kara Fitzgerald: Just massive.

Dr. Doreen Saltiel: Yeah, and then as women got older, greater than 70 in the WHI, there was an increasing trend. But remember, this was with synthetics.

Dr. Kara Fitzgerald: Yes, that’s right.

Dr. Doreen Saltiel: But when you go to the finished trial, which was a very large observational study where they used oral bioidentical hormones, transdermal bioidentical hormones, it was all bioidentical hormones. Much more similar to doses in what we use. There was an up to 54 percent decrease mortality from cardiovascular disease in those women who took estrogen based therapy.

Dr. Kara Fitzgerald: That were bioidentical estrogen based?

Dr. Doreen Saltiel: Yes, yes, yes.

Dr. Kara Fitzgerald: Good.

Dr. Doreen Saltiel: So, the answer is no worries.

Dr. Kara Fitzgerald: Yes, well no worries in benefit.

Dr. Doreen Saltiel: Lot’s of benefits, correct.

Dr. Kara Fitzgerald: Extraordinary benefit. And so, do you think it’s clear at this point in time that the literature is strong enough to state really unequivocally bioidentical is better than synthetic?

Dr. Doreen Saltiel: Yes. I think even the guidelines that are very conservative, basically say transdermal Estradiol is the better choice. Oral micronized progesterone is the better choice.

Dr. Kara Fitzgerald: Good, okay, good.

Dr. Doreen Saltiel: So, I think that’s a given.

Dr. Kara Fitzgerald: I want to go… if you can, you can certainly turn me down on this question, but I think some of our listeners, and myself included, can you give sort of a high level sketch of the WHI politics and why, all of these horrible-

Dr. Doreen Saltiel: Oh, absolutely.

Dr. Kara Fitzgerald: These are decades long misinformation that have negatively informed clinical practice, and for women. Go ahead.

Dr. Doreen Saltiel: It was really very political. When the WHI was published, well, before the WHI, before it was published, they set out, the NIH set out to do three studies. An observational study, the hormone study, and then the dietary study.

There was some concern amongst congressional leaders and doctors that the NIH was going to spend all this money. So, they asked a group to look at it and see whether it was worth doing. The group said yes, it is worth doing. Then, as the data started to collect, and remember the primary goal was cardiovascular disease, and all the statistical analysis was set forth based on a cardiovascular disease model. But for whatever reason, the original authors of the WHI papers were not the original investigators.

So, let me pause. The original authors were not the original investigators. And in fact, they wrote a manuscript, that was accepted by JAMA that basically said there’s an increase in breast cancer.

Now, this study wasn’t powered to look at breast cancer. And then the analysis that they used was an analysis that was set forth for cardiovascular disease. So, there were analytical flaws throughout. And then the results that they called statistically significant were not really statistically significant.

And then they clumped all of the people on CEE and MPA together. What is clear, is that CEE alone, and I will extrapolate that, to transdermal estrogens, do not increase breast cancer. Period. Do not. All of the studies to date, even the study that was just published that I’m writing a blog about because it irritates me, they basically said that after 20 years, CEE alone, so estrogen alone, does not increase breast cancer. In fact, it decreases breast cancer and Hodis and Sarrel wrote a great review article pointed out that by 45 percent after 18 years of follow-up.

Dr. Kara Fitzgerald: Wow.

Dr. Doreen Saltiel: However, the WHI authors continue to perpetuate the falsities about, for example, CEE and MPA. What the data actually showed is that in the group who never used hormones, hormone naïve, there was no difference between placebo and the CEE and MPA group. But in the group who had used prior hormones, who were asked to wash hormones out, they used prior hormones, they had a washout, and then they were randomized to either CEE and MPA or placebo, the placebo had an unusually low breast cancer incident. Lower than all the other placebo groups in all the other WHI studies.

So the diverging curves, which they called an increase in breast cancer risk, was actually not. Because that curve superimposed on the hormone naïve group, and it was actually the divergent of this lower placebo group that the divergents of those curves that lead the WHI authors that there’s an increase in breast cancer with CEE and MPA. And actually there was a null effect.

But, I constantly say, we really don’t care, because we don’t use CEE. And we don’t use MPA. Nobody uses progestins anymore.

Dr. Kara Fitzgerald: Right, right, right. Just in case anybody doesn’t know, it’s conjugated equine estrogen and medroxyprogesterone acetate.

Dr. Doreen Saltiel: Right, it’s Premarin and Provera. And that’s really the very sad point of all of this.

Dr. Kara Fitzgerald: Yeah.

Dr. Doreen Saltiel: Is that instead of focusing on the data that has shown that when you add OMP, oral micronized progesterone, to transdermal Estradiol, even continued for greater than ten years, there is no increase in breast cancer.

Dr. Kara Fitzgerald: And is there a decrease, is there any benefit, or is it just?

Dr. Doreen Saltiel: Yeah. And that’s the hard part, whether the sustained decrease that you see with estrogen alone is maintained, nobody knows. But it certainly doesn’t increase breast cancer.

Dr. Kara Fitzgerald: Okay. And is that because too many women are stopping after a certain time, again, because of the WHI?

Dr. Doreen Saltiel: Yes. Yes.

Dr. Kara Fitzgerald: Isn’t that fascinating. Wow. Well thank you for outlining that, I really appreciate it. And why did they have a different group authoring? Just out of curiosity.

Dr. Doreen Saltiel: Politics. They wanted this study to go away. And actually, there are a ton of editorials written about this and the disservice that was done because of the WHI.

Dr. Kara Fitzgerald: Well, I’m going to imagine that some of our folks are going to want to read about it. Incidentally, people, since Dr. Saltiel is mentioning many, many papers, we will link to access to those, so you’ll be able to do a drill down into the same data that she’s been talking about. We’ll also link to our blog, she wrote a great blog for us that has a bunch of citations on it as well. And if you can link us to a good read on this WHI story I think it would just be compelling for some of the audience.

Dr. Doreen Saltiel: Absolutely.

Dr. Kara Fitzgerald: Okay.

Dr. Doreen Saltiel: Absolutely.

Dr. Kara Fitzgerald: Okay, all right, perfect. So let’s move over and talk about the literature on transdermal Estradiol. Actually, if there’s… Go ahead.

Dr. Doreen Saltiel: What I was going to say is, a lot of the studies are, that’s the unfortunate thing, they’re small studies, but the patch studies, for example, the FDA approved patches, which are all bioidentical, the FDA approved gels, are all bioidentical. Those studies clearly show symptomatic relief of vasomotor symptoms, osteoporosis prevention, vulvo-vaginal atrophy prevention, and there are some really small studies that demonstrated cognitive improvement.

The largest study was the Finnish study that looked at both cardiovascular disease and breast cancer and found that both cardiovascular disease and breast cancer were decreased using transdermal Estradiol products. Both up to a 54 percent decrease. And of course the younger the woman, the earlier you start, the greater the benefit.

Dr. Kara Fitzgerald: So, how early can one start? When would you initiate-

Dr. Doreen Saltiel: Hormones?

Dr. Kara Fitzgerald: Yeah. Would you initiate during perimenopause, as soon as symptoms kick in? What are you thinking around it?

Dr. Doreen Saltiel: I typically don’t give estrogen to women who are perimenopausal, and partially because of the ups and downs of estrogen.

Dr. Kara Fitzgerald: Sure.

Dr. Doreen Saltiel: And I always give progesterone to perimenopausal women. Now, the data on, interestingly, progesterone and vasomotor symptoms, the answer is yes it works. On bone mineral density, yes it’s necessary. Those are the two, and then cardiovascular disease, there’s no harm. But I typically start perimenopausal women anywhere between 100 and 200 mg. And the higher their serum Estradiol is, the more apt I am to give 200 mg at night, before bedtime.

Dr. Kara Fitzgerald: Good, so you’re going oral? Or would you use vaginal?

Dr. Doreen Saltiel: Oh, no, I would do oral in those women.

Dr. Kara Fitzgerald: Okay.

Dr. Doreen Saltiel: Partially because of, most of these women, as you know, have anxiety, they can’t sleep, they have hot flashes. And oral progesterone works for all of those.

Dr. Kara Fitzgerald: Okay. And then once they hit the year transition to full, to being post-menopausal, are you going to initiate estrogen at that time?

Dr. Doreen Saltiel: I actually may do it at six or eight months, not wait for the magic year. If somebody hasn’t had a cycle in six or eight months and I check an Estradiol level, and don’t check FSH, because that bounces all over the place, and their Estradiol level on a couple of occasions is low, I may start a really, really low dose estrogen.

Dr. Kara Fitzgerald: Now, is that based on their symptoms or just the potential benefit? Or both?

Dr. Doreen Saltiel: Both.

Dr. Kara Fitzgerald: Okay.

Dr. Doreen Saltiel: Both, because the bone mineral density, especially. Because women who are perimenopausal really are, at that point, they pose an increased risk of osteoporotic fractures, because it’s during that first few years of menopause that bone loss goes up. And then it stabilizes, and then when they become frail later in life, it goes up again.

Dr. Kara Fitzgerald: Right, right.

Dr. Doreen Saltiel: So, you really want to kind of protect their bones as early as possible. And I’ll also give testosterone to women. I don’t talk a lot, I don’t have it yet, we can do a whole different podcast on testosterone, but I also give testosterone to women because it helps bones. It helps with vasomotor symptoms.

Dr. Kara Fitzgerald: Yes.

Dr. Doreen Saltiel: And so, it does a lot of good things.

Dr. Kara Fitzgerald: Yes.

Dr. Doreen Saltiel: So then it’s deciding how to give the three at once, do I wait? Do I not wait? So, in a perimenopausal woman I may give her testosterone and progesterone.

Dr. Kara Fitzgerald: How are you dosing the testosterone?

Dr. Doreen Saltiel: I’m a pelleter. So, in women and men I’ll pellet, but I typically start with a cream, I typically start at about a half a mg in a woman.

Dr. Kara Fitzgerald: Okay.

Dr. Doreen Saltiel: And partially, if they have none, it’s going to help. Whatever you give a woman is going to help.

Dr. Kara Fitzgerald: Yes.

Dr. Doreen Saltiel: The question is to what degree and how patient you and they are going to be. Because I hate to over dose people. And I’ve done it, you know, we all have, because then when you back down it’s miserable for the patient and it’s miserable for you.

Dr. Kara Fitzgerald: Yeah. So, titrating up is how you approach it?

Dr. Doreen Saltiel: Yes. Start low and go slow.

Dr. Kara Fitzgerald: Yup, good. Okay, so incidentally, again, you’ll have a host of resources where Doreen goes into more prescribing detail. We’ll continue to talk about that, but her thoughts on those are available on the links and our show notes.

I just wanted to ask you, though, on that front, how low you’re starting transdermal E2 in a perimenopausal woman? Like six months out.

Dr. Doreen Saltiel: I will start with, say, I’ll take a .025 mg patch and I’ll cut in half. Or, if I’m dosing a cream, a bias is the .125 mg. It’s really tiny, I’m just trying to get her over, not to be as symptomatic, and the data as shown that a .014 mg patch improves bone mineral density, vasomotor symptoms, vulvo-vaginal atrophy, so really low doses work.

And then I follow urine and before I start I follow serum, because here’s the data on serum. In a woman who you’re going to start hormones on, if they’re serum Estradiol level is really low, less than five picograms per mil, that woman, when you initiate Estradiol, is more apt to spot.

Her vaginal wall is atrophic, so she’s going to spot. If her serum Estradiol is greater than ten, this came out of the [Bejuba ? ] trials that they did for the combo oral progesterone, oral Estradiol pill that was approved by the FDA. That what they found is that women whose serum Estradiols were greater than ten picograms per mil, when initiating therapy, they were more likely to have a proliferative endometrium.

That doesn’t mean I run off and send people for trans-vaginal ultrasounds or anything like that. What I will do with that woman, is I will start her on progesterone before I start her on Estradiol.

Dr. Kara Fitzgerald: And are you-

Dr. Doreen Saltiel: Let me get some progesterone on board.

Dr. Kara Fitzgerald: Yup. Are you cycling it?

Dr. Doreen Saltiel: No. No, no. Women hate that, well at least the women I deal with. None of them want to cycle.

Dr. Kara Fitzgerald: Okay.

Dr. Doreen Saltiel: So, I do continuous hormones. And for our entire lives until we become menopausal we did continuous hormones, even when we cycle, we still have a little bit of estrogen and progesterone. And testosterone is independent of that.

Dr. Kara Fitzgerald: Right. All right, talk to me about estrone and estriol, are you using these at all?

Dr. Doreen Saltiel: Estrone, never. Because in some of the metabolism breast cancer studies they found that women with higher estrone levels were more apt to have and develop breast cancer. So, no, I never use either one. E3 I do use. Interesting, I go back and forth, it’s kind of interesting, I go back and forth with E3.

Because it is breast protective and does work for local vaginal symptoms. So, the question is how much am I worried about a woman’s breasts? Well, I know Estradiol doesn’t increase breast cancer, so if I’m going to do a bias, I may hope that her vaginal symptoms were improved.

But typically, I have to do vaginal estriol.

Dr. Kara Fitzgerald: Okay, so you’ll use E3.

Dr. Doreen Saltiel: It’s really a – yes. So typically I try to get women to use a patch, because insurance carriers pay for it. And the data is so strong in a patch. But a lot of women don’t, they get itchy, and they don’t like adhesive, and they don’t like alcoholic gels. So if I’m going to do a cream I’ll stick E3 in there. But I also give vaginal Estriol for vaginal symptoms, I give a half a mg a day for about two weeks or so, and then I go to every other day for another 2 weeks, and then PRN. Most women end up using it a couple times a week.

Dr. Kara Fitzgerald: Good, okay.

Dr. Doreen Saltiel: And that’s compounded, of course.

Dr. Kara Fitzgerald: Yup, yeah, yeah. That’s my next question for you. You’re obviously taking advantage of insurance covered hormones as much as you possibly can, and that we’ve got more options these days. But you’re compounding as well?

Dr. Doreen Saltiel: Oh, absolutely. I do a mix of both.

Dr. Kara Fitzgerald: Any studies evaluating compounded products?

Dr. Doreen Saltiel: Almost zero. There’s a couple of pharmacokinetic studies looking at serum levels with compounded creams and patches, but there are no really well run studies looking at outcomes.

Dr. Kara Fitzgerald: Well they are expensive….

Dr. Doreen Saltiel: Yes, yes. Number one, they’re expensive. Number two, how are you going to get women to apply it in the same place? I mean there are so many different variables. So you’ve got to extrapolate. You really have to extrapolate the data and I always tell patients, here’s the deal, orals are out, they’re the least safe. Patches have a lot of data, gels have a lot of data. Gels require higher doses to achieve the same thing as a patch will, according to all the studies out there. Same efficacy. And that’s why I try and start with a patch.

And if a patch doesn’t work, then we go to a cream, knowing that I’ll follow urine, and I tell the patient, I may need to follow urine levels much more closely to ensure that I’m achieving what the studies documented for the patch data as being effective. Now, clearly, vasomotor symptoms, vulvo-vaginal atrophy, those are the easy ones, right?

Dr. Kara Fitzgerald: Right.

Dr. Doreen Saltiel: Because people tell you. It’s really osteoporosis. And you want to keep a woman’s serum levels somewhere between 20 and 40, and if you’re using urine, like I do when I use Dutch, it’s .7 to 1.8. And I typically keep people about 1.2, 1.3, using the Dutch test.

Dr. Kara Fitzgerald: Good, okay, good, good. I want to talk about laboratory testing now. Do you use saliva? You start with blood, you then use Dutch, I want to know how you’re using the Dutch. You know what, maybe, why don’t you start with the panel you’re running at baseline in blood, move over to how you’re using Dutch, and are you using saliva in that mix at all?

Dr. Doreen Saltiel: Let me start with saying I used to be a die-hard saliva user.

Dr. Kara Fitzgerald: I see.

Dr. Doreen Saltiel: Until, I dug into the literature and realized that there’s no data. And realized that a salivary E2 level of ABC tells me nothing about a woman’s bones. Tells me nothing about her heart. And that, to me, and it’s mainly that bone density data. Because if you look at the Finnish trial, basically they found that a .025 mg patch up to a .1 and a .25 mg gel, up to 1 mg decreases cardiovascular events.

So, the doses are there, but do doses translate into clinical outcomes? The answer is no, not unless you have studied a dose with a specific outcome, and have some way to measure that. You can’t be doing DEXA scans on everybody all the time. Number one, it’s not healthy. And number two, no one’s going to pay for it.

Dr. Kara Fitzgerald: Right.

Dr. Doreen Saltiel: And so, when I realized that there were no salivary studies, and I thought to myself, why do you measure hormones? Why do we measure hormones? To do no harm. Right? You know, progesterone is to protect the endometrium and no test is going to tell us, really, whether we protect the endometrium. We just have surrogate markers.

But Estradiol, we really want to do no harm and make sure that we’re protecting the endometrium, I mean with estradiol we’re protecting bones. And so, when you look at all the serum data, and you see that urine follows serum, everybody says that.

Dr. Kara Fitzgerald: Yes.

Dr. Doreen Saltiel: It’s easy to translate the data from serum into urine. So, other than cortisol, where I use saliva all the time, I have really switched from saliva monitoring to urine monitoring. And when I, I’ll start with serum labs where I’ll do the typical ultrasensitive E2. I even get E1. I’ll get serum hormone binding globulin, I get prolactin, I get all the typical things we normally would get.

And in a lot of women, if I suspect that her estrogen, or that she’s not detoxifying well, either she doesn’t poop well or sometimes you get a sense that they’re toxic. I will do urine metabolized up front, even though I may only see trends.

So, typically I do serum and urine at the same time.

Dr. Kara Fitzgerald: Okay.

Dr. Doreen Saltiel: To start with.

Dr. Kara Fitzgerald: Yeah, I think it’s worth it to knowing, even if you’re only seeing trends because they don’t have many sex hormones at that point, it’s worth it to get an idea of how they might be metabolizing.

Dr. Doreen Saltiel: Absolutely. And then I try and optimize their detoxification pathways, optimize their re-dox potential, at the same time as I’m initiating hormones so that I actually can have the hormones be as effective as they need to be.

Dr. Kara Fitzgerald: Right.

Dr. Doreen Saltiel: Because if people aren’t detoxifying correctly, and they’re not methylating, even though we’re only doing an indirect, as you know better than I do, an indirect measure of methylation, we’re not measuring DNA methylation. It at least gives you a roadmap to start with.

Dr. Kara Fitzgerald: Right. Well that will be an exciting study, right?

Dr. Doreen Saltiel: Yes.

Dr. Kara Fitzgerald: Compounded individually designed products including a full urine panel with metabolites and addressing that and addressing detox individually. I mean, that would be a pretty exciting study to undertake. I don’t know if we’ll be seeing it any time soon.

Dr. Doreen Saltiel: But I also think you would agree, knowing how somebody metabolizes cortisol and looking at progesterone metabolites, and Estradiol metabolites, even if it’s trends, will certainly help you with your dosing.

Dr. Kara Fitzgerald: Oh, absolutely. Absolutely. And you know the additional supportive interventions that you need to use.

Dr. Doreen Saltiel: Mh-hmm (affirmative). And so I have become a serum and a urine person. And cortisol I do both urine and I do saliva, depending if I want CAR.

Dr. Kara Fitzgerald: Yup, the cortisol awakening response.

Dr. Doreen Saltiel: Yes, yes, yes.

Dr. Kara Fitzgerald: There are other podcasts we can link to on our show now, also conversations I’ve had with Mark Newman over at Precision Analytics as well, and details on CAR and all of that if you want to listen to them. They’re useful if you’re not yet familiar.

Tell me some of your favorite natural products, and when you might use those up front. Just out of curiosity, and are you initiating some? Well, of course you are for thinking about detox pathways, but I’m just curious about what’s in your tool kit that you really like.

Dr. Doreen Saltiel: Well, I certain use a DIM product. I use calcium D-glucarate

Dr. Kara Fitzgerald: Do you use that one everyone, regardless if they’re-

Dr. Doreen Saltiel: No, no.

Dr. Kara Fitzgerald: Okay.

Dr. Doreen Saltiel: I used to use DIM on everybody. Not anymore.

Dr. Kara Fitzgerald: And what changed? Out of curiosity.

Dr. Doreen Saltiel: Looking at pathways, understanding metabolism, and really, if there’s anything I can stress out there, it’s hard. I’m telling you, this stuff is not easy. And it’s kind of funny, Mark always says to me, “Are you done yet?” No, because it’s hard. You know, “What’s taking you so long?” It’s hard.

Dr. Kara Fitzgerald: That’s so funny.

Dr. Doreen Saltiel: Yes.

Dr. Kara Fitzgerald: I feel like he’s one to talk, though. Talk about going in the rabbit hole.

Dr. Doreen Saltiel: Yes, but no, I look at metabolism.

Dr. Kara Fitzgerald: Sure.

Dr. Doreen Saltiel: And, for example, why would I push everybody down to 2-hydroxy pathway if they can’t methylate?

Dr. Kara Fitzgerald: Right.

Dr. Doreen Saltiel: I’m making matters worse, now I’m building a two hydroxy intermediate, which it’s not a strong estrogen. But it’s still an intermediate.

Dr. Kara Fitzgerald: Right, what’s happening with four? You know?

Dr. Doreen Saltiel: Do I give everybody… right, right.

Dr. Kara Fitzgerald: Go ahead.

Dr. Doreen Saltiel: Do I give her resveratrol because it will help decrease DNA adduction? Do I give that to everybody? No. And part of that is because people don’t like to take a thousand pills. And so I try and target what I give to people.

I give N-Acetylcysteine, you know, to build glutathione stores, I’ll give liposomal glutathione. Of course I always give a multivitamin and all the basic stuff. But I really work hard to limit the number of, whether it be prescriptions, nutraceuticals, so that the patient doesn’t get overwhelmed and really will be compliant. Because remember, in all these people, we’re also giving HPA axis stuff. And we may be giving a probiotic, or other gut healing things.

Dr. Kara Fitzgerald: And you’re doing lifestyle changes and you’re initiating a diet, and so I really appreciate your attention to keep a program doable.

Dr. Doreen Saltiel: Well, part of it is as a patient, myself, when people give me 76 things to take, not only is it expensive, I just get overwhelmed. It’s like I don’t want to do this anymore. How many pills do I have to swallow?

Dr. Kara Fitzgerald: Yes, that’s right. And you end up with an amazingly robust supplement graveyard.

Dr. Doreen Saltiel: Yes. And it’s really interesting, I don’t know if you do this, Kara, I tend to try and get people to do IVs.

Dr. Kara Fitzgerald: It’s a benefit for so many reasons. We don’t offer them here in our office, but I can certainly appreciate it. When I was in Atlanta we used to do them a lot.

Dr. Doreen Saltiel: I don’t offer them, but I know I’m friends with one of the docs who just does that, it’s all she does. And I give what I want, and I develop low protocols for depending on the person, and stuff, and she’ll do it. And they run specials all the time, so for 99 dollars you can get a Meyers with extra C and glutathione, or just extra glutathione if you want. 99 dollars.

Dr. Kara Fitzgerald: That’s a really good price. You’re not on the East Coast anymore, though.

Dr. Doreen Saltiel: Right. Asheville is not that cheap.

Dr. Kara Fitzgerald: No, it’s not. That’s a good price. Good.

Dr. Doreen Saltiel: Yeah, it’s a great price.

Dr. Kara Fitzgerald: And it’s a time to relax, I mean there’s just a lot of benefit from receiving IV. So, when do you do your follow up testing? And you’re just at this point using a Dutch, you’re not using serum? When do you do that?

Dr. Doreen Saltiel: Typically three months after they’ve been on hormones. I want to get things to equilibrate. Now, if I, for example, ultimately put a testosterone pellet in a woman, I’ll check peak levels at four to six weeks. And I am a very low-dose pellet-er. I am like the obnoxiously low-dose pellet-er, because I don’t think women need as much, as a lot of others are getting. The same thing with men.

Other than my first, I’d say, first few months back 10, 12, 15 years ago, I have not had any problems at all. But you really have to, I don’t recommend pelleting to people unless you have trained with somebody. The procedure is easy, whether you have trained with somebody who understands hormone metabolism, and can help you understand how to dose and what the downstream consequences are of bad dosing.

Dr. Kara Fitzgerald: Yeah, that’s a good point. Where would you recommend people get training if they’re interested in learning pelleting?

Dr. Doreen Saltiel: How to actually do it, you can learn how to do it, I think Well’s put something on, A4M puts something on, and if people are really interested, I’d be more than happy to help people. That’s something that Amy and I, and Mark are talking about.

Because I think the pellet industry has been given a really bad name by some overzealous pellet-ers. Just like testosterone has been given a really bad name by all the people who used anabolic steroids and all of those things.

So, to get back, I typically do a urine at four months.

Dr. Kara Fitzgerald: Okay. Are you using a serum testosterone, though? Or are you relying on the urine?

Dr. Doreen Saltiel: Yes.

Dr. Kara Fitzgerald: Okay, so for testosterone.

Dr. Doreen Saltiel: Serum, serum. But I do look at urine metabolites.

Dr. Kara Fitzgerald: Yes, good. Yeah, yeah. Really useful.

Dr. Doreen Saltiel: Yes. But serum is the default for testosterone.

Dr. Kara Fitzgerald: Yeah, okay. And you would do a free and a total, I’m sure.

Dr. Doreen Saltiel: Yes.

Dr. Kara Fitzgerald: Okay. What else do I want to ask you? This has been a useful conversation, and we’ll link to as much as we possibly can. You folks comment on whether you want to learn pelleting and how to do it correctly and we’ll share that with everybody over at Dutch, including Dr. Saltiel.

And you know, any questions you guys have, post on our site and we’ll get there. Dutch is known for such a rich resource of content and I appreciate what you’re contributing there. I was reading some of the documents that you’ve created and they’re just precise, they’re well evidenced, they’re useful, the take home points are clear, they’re just very clinician friendly.

I appreciate you joining me today, and again, puzzling through this and giving us the history of WHI as well. That was quite fascinating, a little bit disappointing, but it seems like we’re finally starting to come out the other side of that. At least in our world.

Dr. Doreen Saltiel: Yeah, and if I can just leave you with the four concerns that the WHI, that were raised by the WHI publications. Venous thromboembolism, myocardial infarction, stroke, breast cancer, are all minimized or negated by using transdermal Estradiol products and oral or vaginal micronized progesterone. So, those studies need to be put to bed. They’re moot.

Dr. Kara Fitzgerald: Yeah. Good. That’s a really good point for us to end on. Scream it from the rooftops.

All right, Doreen, it was lovely to connect with you again. And I look forward to more conversations with you in the future.

Dr. Doreen Saltiel: Oh, it was my pleasure. Thank you so much, have a great weekend.

Dr. Kara Fitzgerald: Thank you, you too.