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This is a very interesting read by a guy working for ZRT labs about the pros

and cons of saliva testing. I was particularly interested in the

progesterone part since my levels keep coming back high in my saliva tests

even though I am symptomatic of low progesterone and having to supplement

with cream which helps. Didn't answer my issue but was interesting to see

the difference between blood serum and saliva testing.

The full article can be found here

http://www.encyclopedia.com/printable.aspx?id=1G1:112728019 but I just

clipped some excerpts below. Figure 4 of the link is particularly

interesting because it matches symptoms to deficiency or excess for sex

hormones and cortisol. Not that I agree with the match-up totally (cortisol

seems really off and I think Dr. Rind's is more accurate) but it was

interesting nonetheless.

Cheri

Saliva hormone testing.

From: Townsend Letter for Doctors and Patients | Date: 1/1/2004 |

Author: Zava,

Perceived disadvantage.

Another " perceived " disadvantage to saliva testing is that when a

hormone is administered topically via creams or gels, salivary hormone

levels often are very high, even higher than serum levels. Out of

frustration, many health care providers are left to conclude that this

anomaly in high salivary hormone levels is the result of an unexplained

artifact of saliva testing unique to topical hormone delivery. For lack of

explanation in the medical literature concern has arisen over the validity

of saliva hormone testing when hormones are delivered topically. This odd

phenomenon, and the failure of some saliva testing laboratories to reset the

expected ranges, has driven many health care providers away from saliva

testing. As I will discuss below, when steroids are delivered topically,

serum testing grossly underestimates bioavailable hormone levels and is not

reflective of either tissue uptake or response. Saliva hormone levels, on

the other hand, closely parallel tissue uptake of the hormone.

The Paradox: Salivary Hormone Levels Often are Higher than Serum

Levels when Hormones are Delivered Topically

One of the most perplexing issues surrounding saliva testing is the

odd phenomenon that topically delivered steroids cause a dramatic increase

in salivary hormones without a concomitant increase in serum levels. (11),

(12) For example, 30 mg topical progesterone supplementation results in an

average rise in salivary levels from about 50 pg/ml (0.05 ng/ml) to 500 to

3000 pg/ml (0.5 to 3 ng/ml), a 10 to 60-fold increase. This increase is

proportionally even greater when progesterone is supplemented at 100 to 200

mg, a common topical dose used by many doctors, resulting in salivary

progesterone levels rising to as high as 10,000 to 100,000 pg/ml (10-100

ng/ml). Under the same conditions, serum progesterone levels only increase

about 4-fold, from about 0.5 to 2-3 ng/ml. (12), (13) The same

disproportionate increase in salivary hormone levels is seen with topical

delivery of all the other steroid hormones (eg. estradiol. testosterone.

DHEA. etc.). (11)

The remarkable increase in salivary hormone levels observed with

topical hormone delivery raises a number of questions. First, if salivary

hormones are derived from blood, how could saliva hormone levels be higher

than serum or plasma levels? The numbers just don't add up. Second, if this

is some unexplained artifact, how does the hormone get into saliva and by

what mechanism?

Questioning Assumptions

To answer these questions it is worthwhile to take a step back and

question the assumptions made when testing hormones in saliva and serum. It

is assumed that hormones measured in serum or plasma represent all the

hormones in whole blood. Serum (or plasma) comprises only about half of the

blood volume, the remainder is made up of blood cells, mostly erythrocytes,

which are removed by sedimentation. It is assumed that the blood cells are

inert and play no role in hormone transport in the bloodstream. This, in

fact, is not so.

Blood cells as hormone transporters

Blood cells, particularly erythrocytes, play an important role in

steroid hormone transport. In fact, early studies with red blood cells

demonstrated that when progesterone was added directly to whole blood, about

80% associated with erythrocytes and was removed from serum by

sedimentation. (14) In contrast, only about 5% of aldosterone associated

with the erythrocytes under the same conditions. Progesterone is a non-polar

steroid that seeks out a non-polar, lipophilic environment such as the

plasma membrane of the red blood cells. In contrast, aldosterone is a more

oxidized and polar version of progesterone and would more likely find its

way to a hydrophilic portion of blood, such as plasma.

Koeford and Braun (15) studied the permeability of red blood cells to

steroids and concluded that steroids bind avidly to red blood cells and

serve as a transport mechanism for them. They determined that when

steroid-laden red blood cells enter capillaries of tissues much of the

steroid payload is delivered to adjacent tissues within milliseconds. From

this, it is not difficult to envision a nonpolar steroid entering the

bloodstream directly through the skin, hitching a ride on red blood cells,

and being delivered almost instantaneously to tissues throughout the body.

One of these tissues would be the salivary gland, duct, and saliva.

Studies show topical delivery of hormones results in increased tissue

hormone levels without parallel increase in serum levels.

Several studies support the evidence that topical progesterone

supplementation significantly increases tissue levels of progesterone

without a parallel increase in serum levels. Three of these studies are

discussed briefly below. These studies are important because they emphasize

that serum hormone testing does not reflect tissue response when hormones

are delivered topically.

It is unfortunate that many physicians refuse to allow their patients

to use topical hormones based on the failure of serum to demonstrate

significant increases in hormone levels. I am confronted daily with letters

and phone calls from women who have benefited enormously from use of about

15-30 mg of OTC topical progesterone but whose physicians refuse to write

prescriptions for it based on their experience with serum testing. Perhaps

it is time to question the assumptions we have made about serum testing of

steroid hormones, especially when they are delivered through the skin.

The Ideal Saliva Hormone Test Report

Ideally, a hormone test report will contain information that serves as

a guide to help an individual and his or her health care provider better

understand how hormonal imbalances could be affecting health and well being

(Figure 3). The hormone test report should also help health care providers

and their patients come to an educated decision about the most effective

treatment strategy (hormonal, nutrition, exercise, stress reduction, etc.).

Progesterone levels differ during the phases of the menstrual cycle

(follicular vs. luteal) and with different delivery systems when taken as

replacement therapy (oral vs. topical). Test results should reflect these

differences; otherwise the results can lead to confusion. For example, a

postmenopausal woman supplementing with topical progesterone will have much

higher salivary progesterone levels than a postmenopausal woman not

supplementing. Therefore, if no information is provided about route of

administration (oral, sublingual, topical, vaginal), or the ranges are not

shifted to a supplemented level, test results can lead to confusion and the

impression that the patient has some hormonal imbalance when, in fact, she

may be enjoying enormous benefit from the hormonal therapy.

The importance of matching symptoms with hormone profiles

The majority of individuals who test their hormones in saliva or blood

have a reason; they are suffering from symptoms that impact the quality of

their life. They recognize that these symptoms often are based on hormonal

imbalances. For example, a woman suffering from PMS and fibrocystic breasts,

which have been getting progressively worse as she approaches menopause,

understands that this is due to hormonal changes. She often wants to verify

this hormonal imbalance by hormone testing to justify some form of

intervention. Or a man who suffers from low energy, muscle loss, apathy,

sagging sex drive, and has lost that " get up and go " as he approaches his

50's recognizes something is wrong and seeks hormone testing to determine if

his problems are related to dwindling testosterone.

There is little question that an individual's symptoms are the primary

driving force that compels them to seek professional help, and spend money

on hormone testing. Documenting these symptoms and understanding their

relationship to hormonal levels has numerous advantages over just simply

knowing an individual's hormone profile. Matching hormone profiles with

symptoms helps confirm that the hormonal imbalance is causing the symptom.

For example, if a woman has normal levels of estradiol, but low progesterone

during the luteal phase of her menstrual cycle and she suffers with symptoms

of estrogen dominance (fibrocystic breasts, water retention, irritability,

PMS) these symptoms help confirm the hormonal imbalance and point to

treatment strategies that can be used to correct the imbalance.

Another reason it is useful for the testing laboratory to document

symptoms is because the health care provider ordering the hormone test often

does not fully understand how to interpret the test results. This frequently

results in a phone call to the testing laboratory to help shed light on the

hormone test results. For a productive and meaningful discussion about the

test results, the health care provider and the professional at the testing

laboratory must both know the patient's age, menopausal status, what

hormones they are taking, and their symptoms. If these parameters are not

documented on the test report, time-consuming conversation often ensues in

order to provide a mutual understanding of the hormone test results in

relationship to the patient's primary complaints. A patient's most pressing

symptoms in relationship to hormonal imbalances are often overlooked in a

conversation where both parties do not have access to this information.

Numerous studies and books (21) have documented symptoms in relation

to hormonal imbalances. Some of the most common symptoms in relationship to

hormonal excesses and deficiencies in women are listed in Figure 4.

http://www.encyclopedia.com/printable.aspx?id=1G1:112728019

Summary

In summary, saliva hormone testing is more convenient, less stressful,

more cost-effective, and more representative of the bioavailable fraction of

hormones in blood than serum hormone testing. When hormones are delivered

topically, serum hormone testing grossly underestimates the bioavailable

fraction of hormones in blood and tissue hormone uptake and response. This

often leads to continued escalation of dosing despite tissue saturation and

symptoms of hormone excess. The ideal saliva hormone test report should

contain patient information not only about an individual's hormone level but

how this relates to symptoms associated with hormonal imbalance. Such

information helps both health care providers and their patients come to a

more educated decision about the most effective treatment strategy

(hormonal, nutrition, exercise, stress reduction, etc.).

by Zava, PhD

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