I had the privilege of sitting down with Dr. David Zava, the founder of ZRT Laboratory and someone I’ve had the pleasure of knowing for over 20 years. During our conversation, Dr. Zava shared insights into his fascinating journey from studying environmental chemicals at the University of Tennessee to founding ZRT in Beaverton, Oregon. Over the years, Dr. Zava's pioneering research and unwavering commitment to advancing hormone testing have not only enhanced my practice but also deepened our friendship.

As a practitioner, I’ve always been deeply impacted by Dr. Zava’s work. His relentless pursuit of knowledge and his innovative spirit have influenced not only my clinical practice but also my approach to patient care. One of Dr. Zava's most impactful contributions was his collaboration with Dr. John Lee on the book What Your Doctor May Not Tell You About Breast Cancer, published in 2002. The release coincided with the Women's Health Initiative (WHI) study, which linked hormone replacement therapy to a higher risk of breast cancer, causing widespread concern. Dr. Zava and Dr. Lee's book offered an alternative view, distinguishing between synthetic progestins and natural progesterone and advocating for bio-identical hormones as a safer option. Their work provided clarity during a time of uncertainty and continues to guide informed decisions about hormone therapy.

I encourage you to watch the full interview through the provided link, and for those who prefer to read along, a synopsis of our conversation is included below. This is a unique chance to hear from one of the foremost experts in hormone testing and discover the science and passion fueling ZRT Laboratory’s work. Whether you’re a healthcare professional or simply interested in your own health, Dr. Zava’s insights will leave you with a deeper understanding of hormone health and the cutting-edge approaches being developed to advance it.

Watch Full Video Here:

Read the Synopsis Here:

Kyle: Dr. Zava thank you so much for taking the time to sit down with me today. Having known you for over 20 years, I know how busy you are with all of the work that you do but I do think it is so important that providers and patients learn more about you, your journey and your endless knowledge about biochemistry, hormones, various kinds of testing as well as many diseases.  Please tell me about your academic background and how you wound up here in Beaverton, OR founding this laboratory.

DZ: I started out at the University of TN studying environmental chemicals and their impact on the development of cancer.  The main chemical I studied was dimethylbenzanthracene which causes cancer in certain animal species. Dimethylbenzanthracene looks very similar in chemical structure to estradiol. When we gave rats this chemical, they developed mammary cancers but didn’t develop cancer anywhere else in their bodies. I studied this effect on the mammary glands of rats during my time at the university.

After this, my postdoctoral fellowship was in San Antonio, TX where I began to study the effects of estrogen. This work was with humans and we began to look at the receptors inside breast cancer cells. This led to evaluating both estrogen and progesterone receptors and their relationship to cancer.

My next move was to Switzerland where I worked as the director of

a lab studying basically the same things. At that time, there was an international breast cancer study and we were looking at the effects of Tamoxifen, an anti-estrogenic drug that can inhibit the growth of breast cancer, as well as those of chemotherapy agents on breast cancer.  Our work analyzed women’s breast cancer tumors in terms of their estrogen and progesterone receptors. What we learned is that Tamoxifen does indeed work to inhibit the growth of breast cancer but only for about five years and then its effect diminished. I was very disappointed by this and decided to shift my work towards finding ways to prevent rather than just treat breast cancer.

Kyle: I seem to recall that your work in Switzerland was pivotal in terms of how you viewed the effects of hormones on the development of breast cancer. Can you explain what happened there?

DZ: We were looking at receptors of estrogen and progesterone in breast cancers. What I saw in the tumors, depending on the age of the woman, is that the morphology of the tumors was different, depending on her age. For women in the perimenopause, where you generally tend to have estrogens uncontrolled by progesterone, their tumors were growing faster. So they had a much higher rate of growth, not necessarily more aggressive, but definitely faster growing.  Women in the perimenopause were obviously exposed to excessive amounts of estrogen.

Kyle: So from that research, is it fair to say that women in the perimenopause are at higher risk for breast cancer development?

DZ: Yes if they don’t control the excess estrogen. Estrogen causes down regulation of estrogen receptors and up regulation of progesterone receptors , which in the presence of progesterone would then down regulate the estrogen receptors, which is what happens during a menstrual cycle. This is a feedback loop but during the perimenopause, there is inadequate progesterone so this feedback loop is not working.

Kyle: What did you do after you left Switzerland?

DZ: I moved to California around 1995 and worked at a group called Aaron Life Cycles, again doing work on breast cancer. But not only did I look at estrogen receptors but also how these might be affected by women taking estrogen exogenously as well as getting it from various food sources. I wanted to know if these things would increase a woman’s risk of breast cancer. At that time, there was a lot of interest in these issues and the Women’s Health Initiative was also started around this time. I became very interested in developing assays that could monitor the levels of estrogen in women. I was particularly interested in looking at the phytoestrogens in food, such as soy, to see if they could stimulate the growth of a breast cancer because they are estrogenic and can bind to estrogen receptors.

I developed a methodology for this kind of testing.  I subsequently applied for and received a grant to study this. In order to do this work, I developed assays in saliva as a non-invasive way to monitor the effects of environmental factors(such as from food) on the levels of estrogen and progesterone.

Kyle:  When did you cross paths with Dr. John Lee, the family practice doctor who did a lot of work with progesterone? I know you ended up writing a book with him about breast cancer. Can you tell us about this significant (crucial?) time for you?

DZ: Right around this time, I met Dr. Lee in CA at a lecture that he gave in which he was talking about natural progesterone. By then he had already written three books. The first one was about hormones, the second was “What your doctor may not tell uou about post menopause”, and the third one was about perimenopause. I was probably the only man in the audience amongst a room full of women. 

I became very curious about progesterone at this lecture.  Sharon McFarland was also there with the ‘Progest people’(those who manufactured progesterone) and had been working with wild yams. I took some of their product back to the lab and measured the level of progesterone on it. At that time, around 1998, it was called ‘progest’, not progesterone. Dr. Lee and I began to do lectures together and at some  point, he asked me to co-write a book on breast cancer with him and I agreed. He had extensive experience working as a family practice physician with women and progesterone. I remember hearing that he had a very low incidence of breast cancer in his patients. We went on to write the book

“What your doctor may not tell you about breast cancer”.

Over the years I have heard similar stories from many practitioners who prescribe progesterone for their patients: lower incidence of breast cancer for these patients and in those who do get breast cancer, a less aggressive type. The dose being used is usually between 20-40 mg /day of topical progesterone cream.

When a pathologist looks at a breast cancer tissue specimen under the microscope, on a patient who had been taking progesterone, it was almost not a cancer as it was so well differentiated. I had been the person who often worked with these pathologists and developed  methods to look at the proliferation index, which is how fast a tumor is dividing(using immunohistochemistry, which looks at the chromosomes and cell division).

Kyle: Amazing: you really are ‘the man behind the curtain’. You have all of this knowledge and experience that most people who use your laboratory don’t know about. I heard that you had some pretty humble beginnings when your first started your lab in California. Can you tell us about how that all started?

DZ: I actually was the lab director at a lab in CA and we didn’t agree on some things so I left and came to OR and started the lab here. I was on what they call the “J curve”: no money so I sold my house, took the money from that and moved up here and used that money to get started. At the same time, I was writing that book with

Dr. John Lee, which came out in 2002.

Kyle: That was at the same time that the WHI(Women’s Health Initiative)study halted their project and published their findings. What incredible timing. That most have blown things up. Were people shocked by what your book said versus what the WHI was saying?

DZ:  Correct. WHI was saying ‘get everyone off of hormones, estrogen is bad for you’. That’s what the initial reaction was: taking estrogen(Premarin) caused breast cancer so that everyone thought that estrogen was bad. But it turned out that the women on Premarin alone actually had a lower incidence of breast cancer but those on Premarin plus progestin had a higher incidence. Progestin, NOT progesterone. And it really didn’t matter what kind of synthetic progestin it was.

The companies that make progestins make many different types because they can be patented and that is how they make their money. Progesterone is the same molecule that Mother Nature made a gazillion years ago and it is a substance that is NOT harmful to the human body.  Synthetic progestins can be harmful.

Kyle: As a practitioner at that time,  I had quite a few patients on HRT and when the WHI findings came out, there was quite a bit of panic in the U.S. and I didn’t quite know what to do. I did end up learning about bio-identical hormones from a special on public television and then sought out guidance from a local compounding pharmacist. But this was a very unsettling time and I had a hard time finding people to mentor me. Through a series of events, I found your lab which was incredibly fortunate for me. Your lab is known not only for the excellent testing that you do but also for the educational support you offer to providers and patients.

DZ: The early times were hard for me financially : I had a wife and 2 children to support but failure wasn’t an option and I was interested in what I was doing. I was also working with Dr. Lee and Sharon McFarland at Transitions for Health( they make Pro-gest, topical progesterone). We were on the lecture circuit together and there was a lot of demand for testing levels of estrogen and progesterone so everything was moving in the right direction. Women wanted to know: what’s my level? Is it too high, is it too low, is it just right?

Kyle: How did you know to use saliva as the appropriate body fluid?

DZ: When I was in Europe, I knew somebody who was actually just beginning to develop a methodology for saliva testing. I thought that was very interesting  so I visited him. It is a body fluid that you can collect non-invasively  and it had a good reflection of the bioavailable level of hormones. Many hormones, such as estradiol, progesterone and testosterone are bound up by proteins(about 98% of them are bound)so that only 2% are bioavailable. Saliva represents what is actually bioavailable which is the amount that is going to get into the rest of your body, brain, uterus, breast, skin and every other part of your body.

Part of the problem with early saliva testing is that early on, it wasn’t very accurate so I developed a tool to help standardize testing . We actually then started sending out saliva samples with known amounts of hormones, because by this time, I had developed ‘mass spec technology’, which was extremely accurate. We sent these samples out to other labs so that they could measure their results against this known quantity. Some labs participated, others didn’t of course, but we learned which ones did a better job of measuring hormone levels in saliva. There was no oversight except for cortisol levels. This is why many people cannot get this kind of testing paid for by insurance.

It is easier to measure cortisol than other hormones as the levels are so much higher. Measuring estradiol is a lot more challenging but we have mastered that.

Kyle: I know that you have faced many obstacles along the way, between the challenges of developing testing assays and of course the controversial nature of hormones in general. How do you stay the course sometimes?

DZ: If I had been in a commercial business, I would have had a hard time with it but we do a tremendous amount of research. That has been very satisfying. Along with our testing, we collect data from patients in terms of symptoms and we have developed a huge data base over time.  Our lab also developed blood spot testing, which is an alternative to saliva testing and serum testing. Particularly during the COVID pandemic, people didn’t want to go in to a lab and have their blood drawn so this kind of testing allowed people to test from home and send their kits in to our lab for evaluation.

Another test we developed was in dried urine looking at metabolites. We can actually see how estradiol is broken down in the body.

Kyle: Can you talk briefly about the estrogen pathway? I know that you have spoken at length about this , how estrogen tends to be broken down along two main pathways. One leads to a higher risk of breast cancer while the other one does not. Can you address this?

DZ: It’s really a story of the “two and the four’ pathways. If your body is exposed to a lot of pollution, the estrogen that you either make or take will then be metabolized to a ‘bad one’, called fork catechol, the 4 hydroxy pathway. This is going to partially oxidize, bind to DNA and cause mutations.  Things that can cause this to happen are trans fats, dry cleaning fluids, heavy metals, pollutants, obesity, etc. This is not something that will happen overnight: it can take years. We talked about this in the book on breast cancer that we wrote.

But if instead, you eat soy, green leafy and cruciferous vegetables, the estradiol will go down the 2 hydroxy pathway. This is the desired route and one that can be influenced by lifestyle. DIM is a supplement that can help drive the estradiol down the 2 OH pathway. In addition, getting more sleep, exercise, dietary changes, taking such supplements as B12, folic acid, B vitamins, vitamin C, D, selenium and iodine can all be quite helpful.

Another main impact on hormone metabolism is stress. When I looked at the cortisol profiles of women with breast cancer, they were flat although the night time cortisol is high at night. This happens after they have been elevated for awhile and then come down. This is another area that we can have an impact on with our interventions.

Kyle:  I can testify to the value of using ZRT’s testing over the last 22 years. I almost always order the Hormone Profile III, which tests estradiol, progesterone, testosterone , DHEA-S and four cortisol levels.  I always love going over these results with my patients and I am able to identify the patterns of stress by looking at their cortisol curves. Patients just love learning why they are feeling the way that are . I can then advise them to take certain supplements as well as hormones that will help make impactful changes in their lives. Thank you for developing these important tests. They have guided so many providers in helping patients leave healthier lives.

DZ: The reports that we generate come from the levels of hormones plus the answers that patients give on the ‘symptom reporting’ section of the questionnaire. This creates augmented intelligence and spits our individualized results.

Kyle: Not only do you give each patient an individualized report but you provide additional resources for them, such as books and references for them to become more educated. People do so appreciate this information.

Kyle: Can you explain why there is still so much controversy about transdermal progesterone? I have often heard that the levels don’t get high enough to protect the endometrial lining.

DZ: The problem is that most providers use serum testing and that doesn’t show accurate levels of transdermal progesterone. They also don’t see it in urine. We see it in saliva and capillary blood, as measured with the blood spot method. And if anyone would bother to read the literature, studies have been done in Taiwan and France that demonstrate that progesterone applied transdermally actually does get into the breast tissue(Inhibiting the growth of mammary epithelial cells) although it doesn’t show up in the serum. The progestereone applied to the skin gets into the lymphatics. This was also seen in the World Anti-Doping Association . They found high levels of testosterone in saliva and in capillary blood but they didn’t find this in serum. In the last five years, they are now using saliva and blood spot to detect doping. 

It is hard to shift people’s paradigms but that is a change.

Kyle: What else are you working on?

DZ: Neurotransmitter testing: we have been doing this for years but now we are looking at ADHD. We are working with OHSU medical school looking at kids with ADHD by measuring levels of neurotransmitters.  We are also beginning work on premenstrual dysphoric disorder and autism.  We test neurotransmitters in dried urine so this can also be done at home.  

Kyle: Recently there was a show on Netflix about the blue zones. They talked about why some people in various regions of the world live to be 100. There are quite a few factors but the main ones were eating a Mediterranean style diet, managing stress, regular exercise, finding joy and most importantly, feeling connected with their community.  Obviously this all segues with the work you have done and have done for a very long time.

Thank you Dr. Zava for taking the time to talk with me today. Your background is pretty incredible and you have worked tirelessly for decades. Not only have you developed innovative laboratory tests but you have been passionate about educating providers and their patients. I hope this conversation helps the public have a greater appreciation of who you are and the work of your staff at ZRT.

DZ: Thank you Kyle as well for all that you have done for women, who you have helped and treated. And thank you for being a friend.