Medical Policy: 02.04.05
Original Effective Date: May 1998
Reviewed: September 2015
Revised: October 2014
Benefit determinations are based on the applicable contract language in effect at the time the
services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary
based on contract, and individual member benefits must be verified. Wellmark determines medical
necessity only if the benefit exists and no contract exclusions are applicable. This medical
policy may not apply to FEP. Benefits are determined by the Federal Employee Program.
This Medical Policy document describes the status of medical technology at the time the document
was developed. Since that time, new technology may have emerged or new medical literature may
have been published. This Medical Policy will be reviewed regularly and be updated as scientific
and medical literature becomes available.
Saliva is produced primarily by the parotid, sublingual and submandibular glands. Salivary fluid may contain various amounts of hormones, depending on the ability of these hormones to leave the blood, penetrate through or around the salivary cell membranes, and diffuse into the saliva. Lipid-soluble hormones can pass directly through cell membranes via passive diffusion and are commonly found in the saliva. Small, water-soluble hormones may be able to enter the saliva through the tight junctions between salivary cells in a process called ultrafiltration. Salivary cells do not appear to use active transport to place hormones into the saliva.
Salivary tests may help to identify hormonal imbalances in either females or males which can occur at any age and effect how a person feels on a daily basis. The slightest dysfunction of an individual’s hormones can result in weight gain, mood changes, low libido, poor memory or concentration, depression, bone loss, migraines or headaches and sleep disorders. Salivary testing can also be used to monitor the outcomes of hormonal replacement therapy.
A number of laboratory tests are now being offered to consumers as home-based testing. Among these tests, saliva testing for certain hormones (e.g. estrogen (estradiol), progesterone, testosterone, DHEA and cortisol) has been proposed for the screening, diagnosis, and monitoring of menopause and other conditions.
The saliva used for hormone testing may be collected in the clinic setting or by the individual at home. The sample is then sent to a laboratory for evaluation. The results of the test may then be used to determine the need for vitamins, herbs, and phyto-hormones (e.g. phytoestrogen and phytotestosterone). These may be manufactured products (e.g. vitamins, topical creams) or products compounded specifically for the individual.
Practice Guidelines and Position Statements
The 2012 Hormone Therapy Position Statement of The North American Menopause Society: The use of bioidentical hormones (BHT) has escalated in recent years, along with the use of salivary hormone testing, which has been proven to be inaccurate and unreliable.
American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Menopause (2011)
Salivary hormone level testing is recommended by many bioidentical hormone proponets as a means of providing patients with “individualized” therapy. Yet these methods are not approved by either the FDA or the Clinical Laboratory Improvement Amendments (the US Health and Human Services agency regulating laboratory standards). Accurate studies have revealed large intra-subject variability in salivary hormone concentrations, which fluctuate depending on numerous variables, including diet, hydration and circadian rhythm. These conditions are difficult to standardize. Standardized blood tests, which are available for sex steroids, are well established but have limited clinical value in evaluating menopausal hormone therapy (MHT). (Evidence Level: 4 no evidence (theory, opinion, consensus or review)).
The American College of Obstetricians and Gynecologists (ACOG)
Committee Opinion Number 532, August 2012
Compounded Bioidentical Menopausal Therapy
There is no evidence that hormonal levels in saliva are biologically meaningful. In addition, whereas saliva is an ultrafiltrate of the blood and in theory should be amendable to testing for “free” (unbound) concentrations of hormones, salivary testing does not currently offer an accurate or precise method of hormone testing. There are several problems with salivary testing and monitoring of free hormone levels. First, salivary levels do not consistently provide a reasonable representation of endogenous, circulating serum hormones. There is within patient variability in salivary hormone concentrations, especially when exogenously administered hormones are given. Salivary hormone levels vary depending on diet, time of testing, and the specific hormone being tested. Second, because the pharmacokinetics of exogenously administered compounded hormones cannot be known, it is not possible to estimate with reliability how and when to test saliva to obtain a representative result. Third, saliva contains far lower concentrations of hormone than serum and its prone to contamination with blood, infectious agents, and epithelial cells all of which may affect the level of hormone to be measured.
Although more sensitive testing is becoming available through the use of mass spectrometry, there are few indications for the measurement of hormone levels to ascertain success of therapy when treating postmenopausal woman with hormones. If treatment is initiated for symptom control, subjective improvement in symptoms is the therapeutic end point, and there is no need to assess hormone levels. Hormone therapy should not be titrated to hormone levels (serum, urinary or salivary).
Serum is the standard specimen used for measurement of hormones. Because saliva is similar to a blood ultrafiltrate, it has been theorized that salivary hormone concentrations may correlate with free/unbound serum concentrations. However, the promotion of saliva testing has been criticized. Critics site a lack of scientific evidence supporting the use of salivary hormone levels for determining and monitoring hormone therapy. They also claim that hormone concentrations in saliva are highly variable and may not correlate with biological or clinical response to treatment, that salivary hormone levels may not reflect free hormone levels in blood, and that the large variability associated with salivary hormone assays makes them unreliable. Therefore, the medical literature fails to demonstrate that salivary tests are appropriate for screening, diagnosing or monitoring patients with menopause and other conditions and therefore is considered investigational.
The use of Saliva hormone tests including but not limited to estrogen (estradiol), progesterone, testosterone, cortisol or dehydroepiandrosterone (DHEA)) in males or females of any age is considered investigational for all indications.
Based on the peer reviewed literature there is lack of clinical evidence to indicate its validity as an appropriate form of testing and also fails to demonstrate that this testing is appropriate for screening, diagnosing, or monitoring patients with menopause or other conditions and therefore, is considered investigational.
Procedure Codes and Billing Guidelines:
- To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.
- S3650 Saliva test, hormone level; during menopause.
- Lewis, J.G., McGill, H., Patton, V.M., Elder, P.A. Caution on the use of saliva measurements to monitor absorption of progesterone from transdermal creams in postmenopausal women. Maturitas 2002; 41:1-6.
- Wren, B.G., McFarland, K., Edwards, L., O'Shea, P., Sufi, S., Gross, B., Eden, J.A. Effect of sequential transdermal progesterone cream on endometrium bleeding pattern, and plasma progesterone and salivary progesterone levels in postmenopausal women. Climactric 2000; 3:155-160.
- O'Leary, P., Feddema, P., Chan, K., Taranto, M., Sith, M., Evans, S. Salivary, but not serum or urinary levels of progesterone are elevated after topical application of progesterone cream to pre-and postmenopausal women. Clinical Endocrinology 2000; 53:615-620.
- Griscgek, M., Wagner, R., Tauh, M., Dorr, H.G. Stability of salivary steroids: the influences of storage, food and dental care. Steroids 2001; 66:737-741.
- Kaufman E, Lamster IB. The diagnostic applications of saliva--a review. Crit Rev Oral Biol Med. 2002;13(2):197-212.
- Warren MP, Stanczyk FZ. Custom-compounded hormone therapy: Is there science to support the claims? Council on Hormone Education, University of Wisconsin Medical School, Newsletter 2004, Vol. 2 No. 4.
- Institute for Clinical Systems Improvement (ICSI). Menopause and hormone therapy (HT): collaborative decision-making and management. 2006 Oct.
- AACE Menopause Guidelines Revision Task Force. Medical guidelines for clinical practice for the diagnosis and management of menopause. American Association of Clinical Endocrinologists. Endocrine Practice 2006; 12(3).
- ACOG Committee on Gynecologic Practice. ACOG Committee Opinion #322: Compounded bioidentical hormones. Obstet Gynecol. 2005 Nov;106(5 Pt 1):1139-40.
- ECRI Institute. Accuracy of Salivary Hormone Tests Compared to Serum Hormone Tests. Plymouth Meeting (PA): ECRI InstituteExternal Site; 2009 Sept 29. 10p. [ECRI hotline response].
- ECRI. Salivary Hormone Tests for Menopause and Aging in Adult Women. Plymouth Meeting (PA): ECRI Health Technology Assessment Information ServiceExternal Site; 2011 July 25. [Hotline Response].
- ECRI. Accuracy of Salivary Hormone Tests Compared to Serum Hormone Tests. Plymouth Meeting (PA): ECRI Health Technology Assessment Information ServiceExternal Site; 2011 July 25. [Hotline Response].
- ECRI. ECRI Health Technology Assessment Information ServiceExternal Site 2012. [Hotline Response].
- Menopause: The Journal of the North American Menopause Society Vol. 19, No.3, pp. 257-271. The 2012 Hormone Therapy Position Statement of The North American Menopause Society.
- American Association of Clinical Endocrinologists (AACE) Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Menopause. Endocrine Practice Vol 17 (Suppl 6) November/December 2011.
- The American College of Obstetricians and Gynecologists (ACOG), Committee Opinion, Number 532, August 2012. Compounded Bioidentical Menopausal Hormone Therapy. (Replaces No. 387, November 2007 and No. 322, November 2005, Reaffirmed 2014).
- Maas C, Ringwald C, Weber K, et al. Relationship of salivary and plasma cortisol levels in preterm infants: Results of a prospective observational study and systematic review of the literature. Neonatology. 2014;105(4):312-318.
September 2015 - Annual Review, Policy Renewed
October 2014 - Annual Review, Policy Revised
December 2013 - Annual Review, Policy Renewed
May 2013 - Annual Review, Policy Renewed
May 2012 - Annual Review, Policy Renewed
June 2011 - Annual Review, Policy Renewed
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*Current Procedural Terminology © 2012 American Medical Association. All Rights Reserved.