Laboratory Section - Salivary Hormone Testing for Menopause and Aging

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PLEASE NOTE: Contracts exclude from coverage, among other things, services or procedures that are considered investigational or cosmetic. Providers may bill members for services or procedures that are considered investigational or cosmetic. Providers are encouraged to inform members before rendering such services that the members are likely to be financially responsible for the cost of these services.

Description

For several decades, there has been interest in testing various hormone levels using saliva as the specimen rather than blood, plasma or urine. Salivary testing has been viewed as potentially more advantageous due to its noninvasive nature and the relative ease and convenience of sample collection, which can be done in the home.

Consumers now have the ability to order home saliva tests over the Internet for some hormones such as estrogen, progesterone, testosterone, melatonin, cortisol, and dehydroepiandrosterone (DHEA). A physician's prescription is not required for these saliva tests, which are primarily promoted for the evaluation of menopause and aging.

Policy/Criteria

Salivary hormone testing for the screening, diagnosis and/or monitoring of menopause and aging is considered investigational; salivary hormone tests for aging and menopause include but are not limited to:

1. Cortisol
2. DHEA
3. Estrogen
4. Melatonin
5. Progesterone
6. Testosterone

Scientific Background

Validation of any new diagnostic technique involves the following steps:

1. Technical feasibility of the test must be demonstrated, including assessment of its reproducibility and precision. For comparison among studies, a common standardized protocol is necessary.
   

   Hormone concentrations in saliva are subject to a number of factors, which influence their correlation with the total plasma concentration, or the unbound ("free") fraction of hormone. Such factors include: binding affinity for specific protein carriers; saliva flow; use of pharmacologic agents, which may disturb the ratio of free to bound hormone by displacing the bound hormone; metabolism of the hormone by salivary gland epithelial cells or oral bacteria; circadian rhythms; and contamination of the saliva specimen with blood, food, gingival fluid or tissue debris. (1,2) Despite these variables, the technical feasibility of measuring some salivary hormone levels has been demonstrated in some published studies; however, it is not clear that standardized protocols for measuring salivary hormone levels are used. (1,3) There also continues to be a need for a protocol for sample collection and handling. Whembolua and colleagues studied the saliva sample of 19 healthy adults who provided saliva samples upon rising in the morning, rinsed their mouths with water, and donated a second specimen ten minutes later. (4) Samples were either left untreated or passed through a 0.22-microm filter and then frozen at -80 degrees C or incubated at room temperature for ten days. Aliquots of each sample were cultured on agar to determine baseline and post-incubation (or freezing) bacteria load.  Bacteria counts were not significantly influenced by rinsing (with water), were substantially reduced by filtration, and increased by incubation at room temperature. Average levels of salivary testosterone and cortisol, but not DHEA, were significantly lower in samples stored at room temperature than samples frozen the day of collection. The change in bacteria count induced by storing samples at RT was associated with a change in testosterone but not cortisol or DHEA.  When samples were passed through a 0.22-microm filter bacteria counts were reduced, and the association between bacteria and testosterone was reduced to non-significant. These findings contribute to a growing body of literature revealing that the process of sample collection, storage, and handling can dramatically influence the accuracy of information generated when salivary biomarkers are integrated into research and clinical diagnostics.

2. Normal and abnormal values as studied in different clinical situations must be established. For accurate interpretation of study results, sensitivities, specificities, and positive and negative predictive values compared to a gold standard must be known.

   There are no published studies documenting sensitivity, specificity, or positive and negative predictive values for any salivary hormones when used to diagnose, treat or monitor menopause or aging.

3. The clinical utility of both positive and negative tests must be established. The clinical utility of a diagnostic technique is related to how the results of that study can be used to benefit patient management. Relevant outcomes of a negative test (i.e., suspected pathology is not present) may be avoidance of more invasive diagnostic tests or avoidance of ineffective therapy. Relevant outcomes of a positive test (i.e., suspected outcome is present) may also include avoidance of a more invasive test plus the institution of specific, effective therapy.

   There are no published clinical trials that demonstrate how the results of salivary hormone testing can be used clinically to direct patient treatment of menopause or aging. In addition, clinical practice guidelines from the North American Menopause Society and the Institute for Clinical Systems Improvement consider evidence to be insufficient to consider salivary hormone testing reliable. (8,9) The American College of Obstetrics and Gynecologists states that "salivary hormone level testing used by proponents to “tailor” this therapy isn't meaningful because salivary hormone levels vary within each woman depending on her diet, the time of day, the specific hormone being tested, and other variables". (10) There are no published national practice guidelines that advocate the use of salivary hormone testing in the diagnosis, treatment or monitoring of menopause or aging.

In summary, there is insufficient evidence in the published scientific literature to permit conclusions concerning the use of salivary hormone testing for the diagnosis, treatment or monitoring of menopause and aging. An updated search of the MEDLINE database through February 11, 2009 identified no new published data that alter this conclusion.

References

1. Saliva as a diagnostic fluid. Conference proceedings. Panama City Beach, Florida, October 22-25, 1992. Ann N Y Acad Sci 1993;694:1-348
2. Lawrence HP. Salivary markers of systemic disease: noninvasive diagnosis of disease and monitoring of general health. J Can Dent Assoc 2002;68(3):170-4
3. Vining RF, McGinley RA. The measurement of hormones in saliva: possibilities and pitfalls. J Steroid Biochem 1987;27(1-3):81-94
4. Whembolua GL, Granger DA, Singer S, et al. Bacteria in the oral mucosa and its effects on the measurement of cortisol, dehydroepiandrosterone, and testosterone in saliva. Horm Behav. 2006;49(4):478-83
5. Rakel, David. Integrative Medicine 1st edition. Philadelphia: Elsevier Science 2003
6. Thiedke CC. Menopause. Clinics in Family Practice.   2002;4(4):1-16
7. Boothby LA, Doering PL, Kipersztok S. Bioidentical hormone therapy: a review. Menopause 2004;11(3):356-67
8. The American Menopause Society. The role of testosterone therapy in postmenopausal women: position statement of the North American Menopause Society. Menopause 2005;12(5):497-511
9. Institute for Clinical Systems Improvement (ISCI). Menopause and hormone therapy (HT): collaborative decision-making and management. 2008;64:198 (Verified 2/11/09)
10. ACOG News Release: ACOG Reiterates Stance on So-Called “Bioidentical” Hormones. The American College of Obstetrics and Gynecologists; 2009 http://www.acog.org/from_home/publications/press_releases/nr02-03-09.cfm (Verified 2/11/09)

Cross References

None

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