Test Results and Interpretation

Turnaround Time of Test Results
Test results are generated and mailed within 5-7 working days from date of receipt of the specimen to the laboratory, often sooner, depending on the panel requested. One copy is always sent to the healthcare provider and one may be sent to the patient at the discretion of the provider. Patients receiving a copy of test results tend to play a more active role in their own health care and may be more likely to adhere to proposed hormone replacement intervention.

Saliva Hormone Report Form
Aeron LifeCycles Clinical Laboratory reports serially up to five sets of patient results. Test results consist of three sheets:

Page 1: Contains patient and provider information with saliva hormone levels for a particular date and time. Next to each of the values is the section, "Assay Value Ranges for Females and Males" for a quick comparison. On the reverse side are more detailed ranges addressing age and gender specific groups as well as supplementation.

Page 2: A graphic display of test results.

Page 3: Contains the patient's personal information from the requisition form including current hormone usage.

Interpretation of Saliva Hormone Ranges
Laboratory values can only be fully interpreted in the context of the complete clinical picture. Specific diagnoses cannot be made on the basis of laboratory values alone. In addition, for diurnally variable hormones or supplementation, the timing of collection of the specimen is critical. Normal ranges as established by Aeron were calibrated relative to a specific time of day (early AM) and to specific times relative to dosing of supplementation (trough levels). The normal ranges may not be valid for different collection regimens (i.e. PM collection or to capture peak levels).

Derivation of Ranges
The detailed "Expected Hormone Ranges in Saliva by Gender, Age and Treatment" is on the reverse side of Page1 of the test results. Ranges can also be found for each hormone under the 'Saliva Analysis' section of this website. These ranges were determined by testing both volunteers representing designated populations and drawing from an extensive patient database. Each range is based on as many as 800 analyses. These salivary hormone ranges capture 90% of normal female and male values leaving 5% below and 5% above the normal range. Correlation of these ranges with those in the literature for saliva steroid hormones is excellent.

Unsupplemented salivary hormone ranges represent normal physiologic levels for the groups of patients described (i.e. premenopausal, postmenopausal, specific age groups and gender for androgens). These ranges do not necessarily represent optimal levels for health since physiologically normal levels can be risk factors for pathologic processes in certain groups (postmenopausal low levels of estrogen put women at risk for bone fracture due to increased bone turnover).

Supplemented salivary hormone ranges are derived from groups of people on usual dose ranges of standard medications. Thus, these ranges are expected rather than optimal ranges as delineated by clinical endpoints. Dose levels tend to be high rather than low and physiologic effect (i.e. relief of symptoms, decrease in bone turnover rates) can be expected from the lower end of expected dose ranges for supplementation in most patients.

Individual and Physiological Variability
Some ranges may seem broad but this variation aptly demonstrates the wide individuality of hormone levels. As to be expected, women have higher levels of the estrogens and progesterone than men, and cycling women have higher levels than menopausal women. Men, in general, have higher DHEA and testosterone levels than women, and in both sexes, the level of each drops dramatically with age. There is some indication in the literature that melatonin levels also drop with age. Healthy state cortisol levels remain constant throughout life, regardless of sex or age.

Time of Collection
The ranges represent saliva hormone levels from specimens collected in the early morning unless otherwise noted. Since testosterone, DHEA and cortisol express diurnal variation with levels highest just after waking, it is extremely important that patients indicate the time of collection for an effective hormonal evaluation. Saliva hormone ranges were developed with early AM collections (between 6-8 AM), and they may not be valid for collections taken outside this window of time. For patients taking supplementation, there is obvious pharmacokinetic variation relative to the time of dosing. If peak levels are desired, one may adjust the timing of collection to coincide with peak supplemented hormonal levels. However, Aeron LifeCycles Clinical Laboratory ranges are not adjusted to interpret peak levels.

Hormone Levels Low or Below Normal Physiologic Range
Low saliva hormone levels present the patient with the option to supplement from a wide variety of hormone replacement preparations. Ideal HRT target levels for supplementation can either be aimed towards the patient age-specific range or to a more youthful range.

Hormone Levels Above Normal Physiologic Range
Reasons for a high value include the following:

Hormone Replacement Thearpy (HRT) Pharmacokinetics

Delivery Systems
1. Oral HRT: Taken as tablets or capsules, oral HRT levels follow a cyclic pattern following ingestion. Oral doses, on average, result in peak levels about 2-6 hours following dosage, falling to the lowest, trough levels between 8-12 hrs.

2. Patch HRT: HRT patches provide a continuous, steady-state delivery and are applied every 3-7 days depending on the patch. Saliva levels reflecting an estradiol patch delivery are very close to normal, cycling premenopausal levels. Patch-delivered hormones usually reach a peak by 24 hours followed by continuous levels for the duration of the recommended patch interval.

3. Transdermal HRT: Hormones can be delivered transdermally or transmucosally (mouth, vagina or rectum) with a cream or gel. Saliva levels of hormones delivered transdermally (such as progesterone which is readily available over the counter in creams) are high relative to physiologic levels because of the following:

4. Sublingual HRT: Sublingual delivery is similar to transdermal and the above explanation applies. However, caution during sample collection must be taken since occasionally the mouth will not clear the preparation and the saliva will be directly contaminated with hormone. If this is a problem, a PM collection prior to the next dose allows the mouth to clear during the day with increased oral activity. This collection modification will solve the problem in most cases.

Transdermal Hormone Delivery
As stated above, the expected concentration of steroid hormones in saliva is 1-10% of serum levels. When salivary steroids were measured initially by Aeron LifeCycles Clinical Laboratory, a certain proportion of those patients tested had very high levels of hormone - beyond normal physiologic levels. This phenomenon was first noticed with progesterone where saliva levels were equivalent or higher than luteal phase serum levels for premenopausal women. Further investigation found that these women were using transdermal progesterone creams. These salivary progesterone levels approached or significantly exceeded blood levels when blood and saliva were collected simultaneously. These high salivary hormone levels occur not only with transdermal progesterone but also with other steroids such as estradiol, testosterone and DHEA when used in a transdermal or transmucosal fashion.

The current belief is that transdermal application of the steroid leads to rapid absorption and thus the binding globulins are saturated locally leading to a high concentration of free steroid in the blood. Because these are highly hydrophobic compounds, steroids do not like to be in the aqueous serum fraction, and they find a haven in the red cell membrane mass which is a readily available hydrophobic environment of high capacity. The literature indicates that a significant proportion of an intravenously delivered glucocorticoid dose can be found in the red cell membrane mass. The ancillary hypothesis is that the red cell steroid is freely available to the tissues (salivary gland cells and by extrapolation all other cells of the body). This hypothesis would explain why blood (i.e. serum) levels are relatively low in comparison to salivary levels and that serum levels might be an underestimation of total available steroid. 

As for pharmaceutical patches, they deliver very small amounts of estradiol slowly, thus do not overwhelm the binding capacity of the binding globulins. As expected, patches do not show a transdermal cream pattern but give levels that look like endogenous production or oral replacement at about 2 % of serum values.

Suggested Schedule for Saliva Hormone Testing
As with thyroid medication, it is a good idea to follow a rigorous and timely saliva hormone testing schedule. 

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