Monitoring Topical Hormone Therapy in Saliva - Understanding the Ranges

If you've used saliva testing for topical hormones, you know that it can be a challenge. Why? Because "normal" levels of hormones like progesterone are supraphysiological, even at modest doses. Why is this? That has been covered in a previous blog, and if you're new to this topic it may be worth your time to read. To make sense of topical hormones, you need to know what women's levels typically are given the particular dosage of interest. ZRT Laboratory can provide this data and it will help you to make sense of salivary results.

You can find a more comprehensive listing of progesterone, estradiol, and testosterone (men) here. For the purpose of this blog, let's just consider progesterone.

- You need to have tested 12 or 24 hours after the last dose (ranges for other time points are not available) and select the appropriate graph.

- Find the dose used (x-axis) and move vertically until you find the patient's result (y-axis).

This will tell you how your patients results compare to what is expected given this particular scenario. The data has been generated from tens of thousands of saliva results from individuals using hormonal supplementation. The line in the middle represents the average (median) patient's result on the relevant dosage. The top and bottom lines make a reference range for the particular dosage of interest. The top line represents the 80th percentile, and the bottom line represents the 20th percentile. This effectively gives a reference range for all dosage found on the x-axis at either 12 or 24 hours after supplementation. Values significantly higher than the 80th percentile may be due to sample contamination. Note: being within the reference range for a particular dosage is, in no way, an endorsement of that particular supplementation regiment.

Here is an example for your consideration:

Topical Progesterone, 12 hours:

Topical Progesterone, 24 hours:
Please see ZRT Laboratory Ranges & Dosage for more information

Salivary cortisol testing

Lena Edwards, MD, internist, Balance Health & Wellness Center, discusses salivary cortisol testing which is increasingly being used in the diagnosis and treatment of patients with hypothalamic pituitary adrenal dysfunction. The pattern of cortisol release is important and salivary testing allows this to be analyzed.

Watch the video: http://www.thedoctorschannel.com/video/4137.html

Your Spit May Hold Key to Predicting Burnout

By Wallace Immen
from CTV News
2/22/2011

Go ahead: Spit if you feel frustrated about your job. What your saliva reveals could alert doctors to whether you’re at risk of burnout at work, according to new Canadian research.

And testing saliva could also help people with symptoms of burnout avoid being put on medication that might actually make the condition worse, said Robert-Paul Juster, a doctoral student at McGill University in Montreal who helped design the research.

A clue that someone is suffering burnout is lowered levels of cortisol, often referred to as the “stress hormone” because it is secreted when we feel anxious or agitated. But if we are under continual stress, our bodies can shut down production of the hormone rather than try to keep up with the constant demand.

“We wanted to … find a simple way to find low levels of the hormone showing up in people who have not yet had problems, and how that may predict risk of burnout,” Mr. Juster said.

Normally, cortisol tends to spike in the morning as people wake up, which is the body’s way of revving up after a night’s sleep. Levels usually decline during the day. “But we find that people with high stress don’t have that boost of cortisol in the morning,” Mr. Juster said. “They report feeling exhausted in the morning, even though they’ve had a full night’s sleep.”

Burnout, clinical depression, or anxiety-related issues in the workplace affect at least 10 per cent of North Americans and Europeans, according to estimates prepared by the International Labour Organization.

The Montreal research included a random sample of 30 middle-aged workers in a variety of professions. They took samples of their saliva at home and at work a total of five times a day; using a questionnaire, they also rated their stress levels and any physical symptoms they were experiencing.

Read more ...

What Testing to Use? by guest blogger - Jim Paoletti, Pharmacist

Jim Paoletti, Pharmacist, FAARFM, talks about his preferred methods of laboratory testing, and when to use saliva and blood spot testing.

UPDATE: IOM's Report: Vitamin D Daily Intake Recommendation

The Institute of Medicine of the National Academies offered up new recommendations for daily intake of vitamin D and calcium late last year. The new Recommended Dietary Allowance (RDA) is 600 IU/day. They define the RDA as “levels of intake that are likely to meet the needs of about 97.5% of the population.” The Upper Level Intake is listed as 4,000 IU/day, which is an increase.

These conclusions are in sharp contrast to the vitamin D zealots of the world, the most aggressive of whom are calling for 5,000-10,000 IU/day to achieve the health benefits of vitamin D sufficiency. I happened to be at the CDC recently for a meeting with some folks very involved in vitamin D research. These are fairly conservative research types (not to be confused with the vitamin D zealots, which I am one) and the group of renowned epidemiologists was disappointed with the ruling, to say the least. The difference of opinion between the vitamin D research world and the IOM is vast, so let’s break this down, so you can make some reasonable decisions for you, your family, and your patients.

First, let me just say that this is NOT the result of some new study. All of the amazing studies over the past decade on the correlations between vitamin D levels and various diseases are as legitimate today as they were before this release. This is simply the IOM’s attempt to digest all of the studies and make public health recommendations. It is important to understand the public health philosophy at play here. This approach really has little to do with individualized medicine. Consider the following statements the IOM makes:

“An important aspect of Dietary Reference Intake (DRI) development is its grounding in public health applications and the concept of distributions of risk. This approach may appear strange to some and may be disconcerting to those with a clinical orientation who are familiar with the medical model in which the goal is to treat the patient in the most efficacious manner to enhance a positive outcome. This report [is] therefore in contrast to a medical model approach.”

If you’re slow like me you may need to read that again, but let me highlight one point – this report is “in contrast to a medical approach.” A “medical approach” is defined as one “in which the goal is to treat the patient in the most efficacious manner to enhance a positive outcome.”

The above is a HUGE distinction to me. It doesn’t mean I ignore the results of this recommendation or become outraged, but we have to realize that if you are involved in individualized medicine (through a physician or simply in dealing with yourself), the philosophical approach taken here is admittedly different, but this isn’t the most important observation from these recommendations.

The IOM has concluded from their review that there is insufficient evidence to promote vitamin D with respect to its protective properties against anything not related to bone health. That means that all of the interesting and compelling epidemiological studies showing decreased risk for cancers, autoimmune disease, etc did not impress the group enough to affect their recommendations. I personally am compelled by the epidemiology and find it very relevant that risks for some of the most common cancers are reduced by higher levels of vitamin D. Levels that imply protection from colon cancer to autoimmune diseases (to name a few) are realized at levels that greatly exceed what this committee considers acceptable. Remember vitamin D levels required to achieve bone health is considerably lower than the amount it takes to achieve protection against other D-related conditions. If the IOM reached their tipping point and conceded that these other issues are relevant to their recommendations, they would likely be making major jumps in their recommendations.

You can see from their statement below that this committee considers 12 ng/ml to be sufficient for most of the population.

“This committee’s review of data suggests that persons are at risk of deficiency at serum 25OHD levels of below 12 ng/mL. Some, but not all, persons are potentially at risk for inadequacy at serum 25OHD levels from 12 to less than 20 ng/mL. Practically all persons are sufficient at levels of 20 ng/mL and above. Serum concentrations of 25)HD above 30 ng/mL are not associated with increased benefit. There may be reason for concern at serum 25OHD
levels above 50 ng/mL."


Remember to read the above statement through the filter that this committee only considers vitamin D status to be relevant with respect to issues of bone health. If we want to prevent only rickets and osteomalacia, I agree with the above statement. There has been a huge increase in concern for vitamin D levels over the past decade. This increase is largely due to the compelling nature of the epidemiological studies that show the preventive power of vitamin D (the relationship to bone health has been known for almost 100 years). The IOM is simply not impressed by these same studies. If overall risk reduction is the goal, I believe the evidence is plenty strong to encourage us to keep our levels well above 30 ng/mL. Some experts think 40-60 ng/mL is a fine range and I take no issue with that.

If 40 ng/mL is good, 60 or 80 ng/mL should be even better, right? What about the concern over folks with higher levels? This is a relevant discussion and I think moderation is a reasonable approach. Personally, I do not subscribe to the theory that we should be getting the general population to levels above 60 ng/mL. I do, however, agree that there may be benefits to these levels. Colon cancer and common flue/cold bugs may well be positively affected by high levels. There may also be some increased risks from these levels and we should not ignore this possibility. The IOM brings up increased risk for pancreatic cancer as an example. This strikes me as partially a good point and partially hypocritical. There is a study that has linked higher levels of vitamin D to pancreatic cancer risk. This should be considered. At the same time, if you are going to let one study of that type sway you away from higher levels, shouldn't you also consider the weight of the evidence for the protective benefits of having higher levels? The IOM has considered all of the benefit evidence as not sufficiently strong yet the single study on pancreatic cancer (there are many on colon cancer benefits) is sufficiently strong to create concern.

At the end of the day, this is about risk assessment and cost-benefit analysis. Having higher levels of vitamin D might be associated with slightly higher risk for a few diseases/conditions. It is also associated with significantly lower risk for a fairly lengthy list of etiologies. If 40-60 ng/mL is your goal after considering all of the arguments, the IOM recommendations aren't simply a bit too low, they are entirely irrelevant.

A common sense approach makes sense to me. Common sense tells me that the body begins to use negative feedback to keep vitamin D production reasonable if there is great sun exposure. You simply can't get toxic from sun exposure. Individuals in the sun regularly find their levels routinely above 50 ng/mL. Are we to assume that groups like the IOM will soon be recommending that people be cautious of being overly active outdoors so as not to increase vitamin D to potentially dangerous levels? That doesn't pass the common sense test.

Finally, a note about the new upper limits:

Their upper limits (4,000IU/day) are intended to serve as a lifetime public health measure for free-living, unmonitored population. Unmonitored?

Individual responses to a particular dose of vitamin D differ by a factor of 8! When several people all took the same does of vitamin D, some folks had their levels go up by on 4 ng/mL, whereas some went up by 32 ng/mL. The assumption made by IOM that 4,000IU is the upper max is assuming that nobody is testing their levels. I submit that with testing this is irrelevant. If you are taking 4-10,000IU/day, you should be testing your levels because you could end up anywhere from 15 ng/mL to over 100 ng/mL depending on your individual response.

I think the efforts by the IOM have clearly been very costly, based on the number of folks involved and the thoroughness of the review and it is somewhat regrettable that the scope was so narrow.

For more consideration, please read this viewpoint.

Vitamin D

Listen to Mark Newman's radio interview with Daniel Davis on Beyond 50 radio station, on the importance of Vitamin D. Click here.

New York State Certification for Saliva Testing

We’re really happy to report that ZRT is now certified to perform saliva testing in the state of New York!

New York has its own certification process, which is different from other agencies that oversee labs, such as CLIA. When surveying the lay of the land in NY four years ago, ZRT had two different options in terms of its approach with the State of New York. We took a path that made the journey longer, but we are very glad we did it the way we did. We are now working towards getting bloodspot testing certified in New York.

I thought I would give you a bit of a recap of the process – and some inherent challenges – in getting through this process. Due to some of the internal standards we have established for our testing protocols, it was more difficult for ZRT to be approved by New York.

At the core of the issue is that there are essentially three types of testing systems that can be used by labs to test salivary hormones:
1. FDA “approved” (the FDA prefers the word “cleared”): These have been cleared for sale by the FDA, some reviewed by the FDA (510k) and some not (exempt)
2. Modified FDA approved tests: These are approved, but the lab has modified the procedure to (presumably) improve performance.
3. Tests NOT approved by the FDA: These tests would be considered “research only”

If a lab decides to use only FDA approved tests (#1 above), New York gives the lab a pass on the validation data for that particular test. In this scenario, labs are only required to notify NY that they are participating in a particular test, but the actual performance characteristics of the test are not reviewed. As a laboratory with decades of experience developing laboratory tests for saliva, ZRT has always made a commitment to the highest standards in our testing. As a result, we were coming at all of this with the second scenario noted above as our situation, since we use all FDA cleared products, but have customized our procedures to create what we believe is improved performance and accuracy for our testing.

New York also has a completely separate team that deals with modified methods, so not only are the requirements and requests considerably robust, but the need for patience becomes paramount. While we were not willing to compromise our core testing protocols and standards, we did have to meticulously maneuver to make changes to some aspects of our methods to meet some of the specific requirements of the special laboratory validation unit in NY. As a result of this commitment, the complexity of this issue, and the inherent ‘back-and-forth’ nature of the process, it took nearly four years to complete.

We are very glad to have gone through the process and we have actually been able to implement some improvements to our own quality assurance program, thanks to suggestions made by NY. ZRT is constantly looking for ways to improve the reliability of our testing, and a process like this was another opportunity to put this commitment ‘to the test’. We believe that our judgment in “how” to conduct saliva testing is world-class, and going through this process in addition to other regulatory exercises continues to keep us at the top of our game. We now look forward to providing the physicians and patients of New York the same industry leading standards that the rest of the country has been enjoying for more than ten years.