Medical Policy: 02.04.05 

Original Effective Date: May 1998 

Reviewed: August 2021 

Revised: August 2021 

 

Notice:

This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.

 

Benefit Application:

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.

 

Description:

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 individuals which can occur at any age and effects how a person feels daily. 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.

 

Several 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, dehydroepiandrosterone (DHEA) and cortisol) has been proposed for the screening, diagnosis, and/or monitoring of menopause, preterm labor, 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.

 

Menopause

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.

 

Pre-Term Labor

Preterm birth is a major complication of pregnancy and remains a leading cause of neonatal morbidity and mortality worldwide. Improvements in the understanding of the pathophysiology of preterm labor have led to the development of novel diagnostic tools of use to identify women at greatest risk for preterm birth. Currently two FDA-approved biochemical tests are available in the United States:

  • Fetal fibronectin (This is not a salivary test and not applicable to this medical policy)
  • Salivary estriol

 

A practice bulletin from ACOG issued in 2002 (no updated bulletin found in 2021) on preterm saliva testing states the following:

  • Salivary Estriol
    • Observational studies have shown that maternal levels of serum estradiol and salivary estriol increase before the onset of spontaneous term and preterm labor. A test using salivary estriol levels was designed to predict preterm delivery, but maternal estriol levels peak at night and may be suppressed by betamethasone administration. The test carries a high percentage of false-positive results and can add significantly to the cost of prenatal care if used in the low-risk population. Trials with salivary estriol testing have failed to establish its usefulness for anything more than investigational purposes.

 

Patients

The relevant population(s) of interest are patients presenting with hormone changes due to preterm labor or menopause.

 

Interventions

The intervention includes saliva hormone tests including but not limited to estrogen (estradiol), progesterone, testosterone, melatonin, and/or dehydroepiandrosterone (DHEA) which can be used to monitor the outcomes of hormonal replacement therapy.  

 

Comparators

The comparators of interest are standard of care: serum specimen for measurement of hormones.

 

Outcomes

The outcomes of interest are to diagnose and treat the underlying condition correctly.

 

Clinically Valid

A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse). 

 

Clinically Useful

A test is clinically useful if the use of the results informs management decisions that improve the net health outcome of care. The net health outcome can be improved if patients receive correct therapy, or more effective therapy, or avoid unnecessary therapy, or avoid unnecessary testing.

 

Summary of Evidence

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, preterm labor, and other conditions and therefore is considered investigational.   

 

Practice Guidelines and Position Statements

2012, Reaffirmed 2020 The American College of Obstetricians and Gynecologists (ACOG) Committee Opinion Number 532, 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.

  • 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.
  • 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.
  • 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 using 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).

 

2017 North American Menopause Society (NAMS) Hormone Therapy Position Statement:

Compounded hormone therapy (HT) has been prescribed or dosed on the basis of salivary hormone testing; however, salivary testing for HT is considered unreliable because of differences in hormone pharmacokinetics and absorption, diurnal variation, and interindividual and intraindividual variability.

 

2012 North American Menopause Society (NAMS) Recommendations Clinical Care of Midlife Women

Salivary hormone testing with regards to menopausal hormone therapy, stating that salivary hormone testing is "inaccurate and unreliable". The levels in serum, saliva, and tissue are "markedly different" and alludes to the FDA’s statement that there is "no scientific basis for using saliva testing to adjust hormone levels".  The recommendations for clinical care include salivary testing of reproductive hormones is inaccurate and never indicated.

 

2011 American Association of Clinical Endocrinologists (AACE) Medical Guidelines for clinical Practice for the Diagnosis and Treatment of Menopause

Salivary hormone level testing is recommended by many bioidentical hormone proponents 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).

 

Prior Approval:

Not applicable

 

Policy:

The use of salivary testing for individuals with menopause is considered investigational for all indications.

 

The use of salivary testing to assess preterm labor risk is considered investigational for all indications.

 

Based on the peer reviewed literature there is lack of clinical evidence to indicate the treatment decisions made based on the results of salivary testing for menopause and preterm labor risk can be used to enhance patient management and improve beneficial health outcomes.

 

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
  • S3652 Saliva test, hormone level; to assess preterm labor risk

 

Selected References:

  • 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 Health Technology Assessment Information Service 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 Service 2011 July 25. [Hotline Response].
  • ECRI. Accuracy of Salivary Hormone Tests Compared to Serum Hormone Tests. Plymouth Meeting (PA):  ECRI Health Technology Assessment Information Service 2011 July 25. [Hotline Response].
  • ECRI. ECRI Health Technology Assessment Information Service 2012. [Hotline Response].
  • Menopause: The Journal of The North American Menopause Society Vol. 24, No. 7, pp. 728-753 DOI: 10.1097/GME.0000000000000921 2017 by 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 2020).
  • 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.
  • The North American Menopause Society Recommendations for Clinical Care of Midlife Women
  • Liong S, Di Quinzio MK, Fleming G, et al. New biomarkers for the prediction of spontaneous preterm labour in symptomatic pregnant women: A comparison with fetal fibronectin. BJOG. 2015;122(3):370-379.
  • Lockwood CJ. Diagnosis of preterm labor and overview of preterm birth. UpToDate Inc., Waltham, MA. Last reviewed December 2015.
  • Kacerovsky M, Lenco J, Musilova I, et al. Proteomic biomarkers for spontaneous preterm birth: A systematic review of the literature. Reprod Sci. 2014;21(3):283-295.
  • American College of Obstetricians and Gynecologists (ACOG) press release. SalEst™ not recommended as a screening tool for predicting premature labor. Washington, DC; January 31, 2001.
  • Nomura Y, Okada A, Tamaki Y, Miura H. Salivary levels of hemoglobin for screening periodontal disease: A systematic review. Int J Dent. 2018;2018:2541204
  • Ramsey PS, Andrews WW. Biochemical predictors of preterm labor: fetal fibronectin and salivary estriol. Clin Perinatol. 2003 Dec;30(4):701-33. doi: 10.1016/s0095-5108(03)00109-x. PMID: 14714920
  • Am Fam Physician. 2002 Feb 1;65(3):509-510.

 

Policy History:

  • August 2021 - Annual Review, Policy Revised
  • August 2020 - Annual Review, Policy Renewed
  • August 2019 - Annual Review, Policy Renewed
  • August 2018 - Annual Review, Policy Renewed
  • August 2017 - Annual Review, Policy Revised
  • August 2016 - Annual Review, Policy Renewed
  • 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

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

 

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