Endocrine Profiles Test Prep

Medications and Supplements May Impact Results

Should a patient discontinue a medication or supplement prior to testing?

Genova never recommends that patients discontinue medically necessary medications or supplements in order to complete testing.

There may be times when a patient may stay on a medication or dietary supplement during testing in order to evaluate its effectiveness, especially if a long-term medication. Discontinuing a substance is intended to establish a baseline finding. If you choose to discontinue a medication, a good rule of thumb is to take the biological half-life of the drug times 5 to allow for 'clearance' before testing. With certain medications, the drug itself may have cleared the body, but the effect of the medication may be longer lasting.

How will a medication or supplement impact hormone levels?

In many instances, it is unknown what potential impact a medication or supplement may have on test results.

Any questions regarding a medication or supplement impact on biomarker results can be researched by contacting the manufacturer, pharmacist, and/or searching the literature (PubMed, Google Scholar) for relevant information. Drug databases such as drugs.com, rxlist.com, Epocrates, and pdr.net, or laboratory textbooks such as Fischbach's A Manual of Laboratory and Diagnostic Tests may provide additional information.

Medication Interferents

The medications listed below are direct interferants to hormone assays resulting in falsely low or falsely elevated findings. Testing may not be appropriate for patients who cannot discontinue these medications.

Interfering Medications/ Supplements	Possible Impact on Results
Biotin - high dose (RDI is 30 mcg)	Direct assay interferant for Thyroglobulin Antibody, free T3, free T4, serum DHEA-S, and SHBG1 May result in falsely elevated FT3 and FT4 and falsely low levels of TSH. The American Thyroid Association recommends holding for at least 2 days prior to testing.2
Immunotherapy (i.e., cancer, autoimmune, and other condition treatments)	Immunotherapy or diagnostic procedures utilizing immunoglobulins or immunoglobulin fragments may produce antibodies that interfere with immunoassays. Such interfering antibodies may cause erroneous results.3 For additional information, visit the section on 'Immunoassay Interferents' below.
Steroids	Different steroids have differing effects on hormone levels, with some being direct assay interferents.1,4 See Adrenocortex Stress Profile test prep page for more info.

Immunoassay Interferents

For all assays utilizing antibodies (i.e., immunoassays), the possibility exists for interference by heterophile antibodies in the patient sample. Patients who have regularly been exposed to animals or have received immunotherapy or diagnostic procedures utilizing immunoglobulins or immunoglobulin fragments may produce antibodies, e.g. HAMA, that interfere with immunoassays. Such interfering antibodies may cause erroneous results. Additionally, rheumatoid factor, endogenous alkaline phosphatase, fibrin and proteins capable of binding to alkaline phosphatase can act as interferants.³ The following article thoroughly discusses hormone immunoassay interference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8368230/

• Profiles using immunoassays include:
  • Salivary hormones E1, E2, E3, P, T, cortisol, DHEA, melatonin
  • Serum hormones E1, E2, E3, P, T, DHEAs, SHBG
  • Thyroid Panel

Medication Influencers

The medications listed below will not interfere with Genova's ability to run the assays but may influence biomarker levels.

Influencing Medications/ Supplements	Possible Impact on Results
Ketoconazole, antibiotics, cimetidine, fibrates (gemfibrozil), metformin, statins, antiepileptics, digoxin	These are examples of medications that are generally prescribed for non-hormone related conditions that can alter hormone levels and/or metabolism.1,4-20 This list is not exhaustive. There is no recommendation to discontinue.
Leuprolide, clomiphene, aromatase inhibitors (Anastrozole, Letroxole, Exemestane), tamoxifen, finasteride, spironolactone	These are examples of medications that are generally prescribed to intentionally alter hormone levels and/or metabolism.1,4,18,21-29 This list is not exhaustive. There is no recommendation to discontinue.
Hormone Replacement Therapy (HRT)	Genova's assays detect bio-identical hormones, but not synthetic or non-bioidentical hormones. Synthetic hormones, such as those from oral contraceptives, are generally not recommended for any of Genova's sex steroid hormone testing platforms - blood, urine, or saliva. Synthetic hormones may create unpredictable results that often do not reflect the patient's physiologic levels. For additional information, visit the section on 'Hormone Therapy and Test Considerations' below.

* There are numerous medications and other factors that influence thyroid hormone results. A very informative article covering this topic can be found by following the link: https://www.ncbi.nlm.nih.gov/books/NBK285560/

Hormone Therapy and Testing Consideration FAQs

When should my patient take their hormones prior to testing?

The answer depends on several factors including the hormone delivery type, dosing intervals, specimen type, what information the clinician is hoping to glean, etc. In general, many clinicians opt to test their patients 8-12 hours following their last dose of hormones. Some clinicians wait 24 hours following transdermal cream application.

Published standardized guidelines and best practices are lacking regarding timing of supplementation with testing. The time to reach peak and trough levels, as well as time to steady state varies with each hormone and hormone delivery method. Furthermore, peak and trough levels may vary depending on the sample type evaluated (saliva, blood, urine). Pharmacokinetic studies exist for FDA-approved hormone products and provide information about half-life and time to steady state. The same kinds of studies do not exist for custom compounded hormones, making it challenging to know the best time to test. Most of the published literature utilizes serum to conduct the pharmacokinetic studies; information on half-life and timing of saliva or urine sampling is sparse. Some sources suggest that measuring the trough level is ideal.

Can custom compounded bioidentical hormones be monitored with testing?

Many clinicians prefer to monitor patients on custom compounded formulas so they can adjust accordingly. Hormone compounding can result in variations depending on the base ingredients as well as actual dose of the active hormone. Genova has observed erroneously elevated levels of hormones in patients particularly being prescribed custom compounded formulations. These erroneous levels are not typically observed in baseline, unsupplemented samples. It is important to work closely with your compounding pharmacist to understand the formulations, pharmacokinetics, and pharmacodynamics. Pharmacokinetic studies exist for FDA-approved bioidentical hormones and provide information about half-life and time to steady state. These studies are sparse for custom compounded hormones. Blending more than one hormone in a regimen is another variable that affects the drug's kinetics, potentially resulting in unpredictable findings.

What impact does hormone cream have on testing?

Hormone creams tend to be underrepresented in serum and overrepresented in salivary samples. Progesterone is very lipophilic and accumulates in subcutaneous fat cells. Red blood cells passing through the capillaries play a role in transporting progesterone to salivary glands and other tissues.³⁰ As such, we can see elevated progesterone in salivary samples for several months after complete cessation of transdermal therapy, before the progesterone depot is depleted. The degree of impact that transdermal hormone therapies may have on an individual's salivary hormone levels are determined by many factors: dose, route of administration, site of administration, pharmacokinetics of the preparation, patient compliance, adiposity, and patient metabolic individuality. Anecdotally, we have noticed salivary progesterone levels persisting for up to a year after discontinuation of transdermal creams in some patients.

Additionally, creams can directly contaminate samples. For example, a vaginal hormone cream can contaminate a urine sample. Residual cream on the fingers after application can contaminate tube caps, lips, or mouth before spitting into a tube. Sublingual hormones can directly contaminate salivary collections if they haven't been fully absorbed.

Can a patient test while taking synthetic, non-bioidentical hormones?

Synthetic hormones, such as those from oral contraceptives, are generally not recommended for any of Genova's sex steroid hormone testing platforms - blood, urine, or saliva. The assays are not designed to detect the molecular structure of synthetic hormones, only bio-identical and endogenously produced hormones. Synthetic hormones may create unpredictable results that often do not reflect the patient's physiologic levels. Hormone therapy impacts the hypothalamic-pituitary-gonadal axis via negative feedback as well as affecting binding protein levels, which then results in altered levels of endogenous hormones.³¹ Testing while on synthetic, non-bioidentical hormones may produce results that are not clinically useful.

How long after discontinuing oral contraceptives can a patient test hormone levels?

Prior to testing, it is preferred that there be at least two menstrual bleeds after discontinuing contraception (i.e., oral contraceptive pill, depo-medroxy-progesterone acetate, hormonal IUD like Mirena or Kyleena, etc.).^32-34 Testing sooner may not assess the natural baseline menstrual cycle as the body needs time to readjust. Recent discontinuation of oral contraceptives may delay ovulation and prolong the follicular phase and thus overall cycle length.³² The overall duration of contraceptive use does not significantly affect the return of fertility after discontinuation.³⁵

Unintentional hormone exposure can elevate levels

Patients should be instructed to avoid skin-to-skin exposure with close friends/family members that use hormone creams to avoid unintentional exposure. Exposure can be from close contact with others using prescription or over the counter transdermals including family members or occupational (i.e., massage therapy, pharmacies, health care facilities), and exposure to items that a person using transdermals touched including gym equipment, towels, doorknobs, sheets, etc.^36,37 Anti-aging, anti-wrinkle creams, and other cosmetics and body care products may contain hormones even if not disclosed on the label. Additionally, over-the-counter products containing hormones can be purchased directly by consumers.^38,39

Bleeding Gums and Salivary Testing

Salivary samples visibly contaminated with blood should be recollected. This can result in a false elevation of hormones. Blood concentrations of steroid hormones are several-fold higher than saliva levels.^40,41 For this reason, brushing and flossing is discouraged for 1 hour prior to salivary collection. Additionally, if the patient has a condition that causes gums to bleed easily, such as gingivitis or periodontitis, or has dentures and other oral appliances, a plan should be in place to ensure gums do not bleed during testing.

Urinary Creatinine Levels and Kidney Function

All urine hormone results are ratioed to urinary creatinine. If urinary creatinine is out of range, it can impact the levels of reported urine analytes. Several medications influence creatinine concentration. The collection instructions recommend not to drink more than six, 8-ounce glasses of liquid (48 ounces) 24 hours prior to sample collection because it can dilute the urine impacting the reported urine analytes. Below are considerations for altered urinary creatinine:

• Elevated Creatinine: High muscle mass, heavy exercise or increased physical activity, increased protein intake, significant dehydration, and increased renal clearance.
• Low Creatinine: Poor renal clearance or dysfunction, low muscle mass (i.e. physical inactivity or muscle wasting disease), diluted urine (use of diuretics), malnutrition/protein insufficiency, and hypothyroidism.

We do not recommend urine hormone testing in a patient with known kidney dysfunction, defined by abnormal serum testing.

Pediatric Patients

The reference ranges for all of Genova's endocrine profiles are based off a healthy cohort of patients aged greater than 18. Genova does not have pediatric reference ranges. A literature search may provide further insight into pediatric reference ranges.

References

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