And which hormones should be tested with a saliva test, which with a blood test?

What is the difference between a hormone saliva test and a blood test? Saliva is “filtered blood”. In the salivary glands, the blood is filtered and red blood cells are kept outside. Hormones, on the other hand, enter the saliva, as long as they are small enough to pass the membrane. A saliva test is therefore useful for the hormones cortisol, DHEA, melatonin, progesterone, testosterone, estriol and estradiol, because they can pass through the membrane of the salivary glands. On the other hand, blood tests are the number one choice for e.g. thyroid hormones and prolactin.

What exactly does a blood test measure?

When for example sex hormones, such as progesterone, are measured in blood, the test measures the serum or plasma concentration of progesterone. Plasma is the aqueous, non-cellular part of the blood that does not contain the cellular components like red and white blood cells. Serum is plasma without coagulants. Sex hormones like progesterone, estrogen, and testosterone are fat-soluble hormones that bind to binding proteins. Only a small part is available to the cells (so called “free hormones”). Since steroid hormones are bound to binding proteins, it is therefore very important to co-determine the binding proteins (SHBG for sex hormones and transcortin for stress hormones) in order to interpret the proportion of free hormones.

How do sex hormones move through the body?

Let’s take, for example, progesterone. The progesterone produced in the ovaries reaches the cell receptors via the blood. However, most of it is bound to proteins and hence not really available for our body. Only 2-5% of the progesterone measured in the blood is “free” and not bound to proteins. These 2-5% which are available to the cells freely are measured by the saliva test. The level of progesterone measured in the blood doesn’t show the correct amount of what the body can use. But the progesterone levels measured in blood can be useful for other things, e.g. to compare the progesterone production of two women or to check how much progesterone a woman’s ovaries produce overall. If you were to administer progesterone intravenously, 80% of the progesterone would be taken in by red blood cell membranes that are naturally high in fat and therefore available for fat-soluble progesterone molecules. Less than 20 percent would be found in the serum.

What impact does the use of transdermal progesterone (e.g., progesterone creams) have on the saliva test results?

Progesterone is a very lipophilic (fat-loving) molecule that is well absorbed by the skin into the underlying fatty tissue. From there, the progesterone is bit by bit absorbed by the red blood cell membrane in the capillaries. It is then transported through the membrane of the red blood cells into the target tissue and is then e.g. available in saliva. That makes it easy to measure used progesterone in the saliva test. In contrast, only a small part of the progesterone is absorbed by the aqueous serum (and therefore often won’t really show in a blood test).

Why should you always check your progesterone AND estradiol levels toghether?

Progesterone constantly interacts with estrogens, as these hormones have simultaneously balancing effects on each other. Estrogen levels dictate how much progesterone we need. If the ratio of estrogens and progesterone is shifted so much that estrogens are too high compared to progesterone, you suffer from a so called estrogen dominance. The ideal ratio of estradiol and progesterone is more important than the individual values. It is therefore possible to have normal progesterone levels and still showing symptoms of a progesterone deficiency, when the ratio is out of balance. That is why it is always recommended to test these two hormones together.

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»» More Information on Estrogen Dominance
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How much progesterone should I use for hormone substitution therapy?

The goal of any substitution therapy should always be to achieve physiological levels, e.g. of bioavaiable progesterone. As we already established earlier, the progesterone estrogen ratio is important. Women ovulating should stay within a range of 100-450 pg / ml (Verisana reference ranges). The reference ranges ​​of other laboratories may vary, depending on which test method they use (there is more than just “saliva” and “blood”). This range should not be exceeded even with a regular progesterone intake. The body produces between 25-30 mg of progesterone daily. Progesterone supplementation should not be higher than 12-15 mg per day when achieving physiological values ​​is the goal. As a naturopathic laboratory, we do not recommend hormones, not even natural or bioidentical ones. That does not mean they do not make sense in some cases. For fertility treatment or diagnosed luteal weakness, higher doses may be useful under medical supervision.

Do hormones interact/ affect one another?

Yes! The interaction of estradiol and progesterone has already been explained above. But since the entire hormone system is subject to an extremely complex system, other hormones are often affected by an estrogen dominance as well. And the other way around, a deficiency / overproduction of other hormones may lead to an estrogen dominance. Therefore, it is always a good idea to start with a comprehensive overview of the current hormone status, in order to not overlook any problems. For example, increased stress can cause the body to convert progesterone into estradiol, which in turn then leads to an estrogen dominance over time. This often happens with chronic stress or permanent work overload. Stress hormones such as cortisol can be used to detect whether there are any abnormalities. This type of interaction also exists with several other hormones. We therefore always recommend an Enhanced Hormone Health Check, in which the stress hormones cortisol and DHEA are tested in addition to the sex hormones (progesterone, estradiol, estriol and testosterone).

What can falsify the results of a saliva test?
  • Smoking, brushing your teeth, having breakfast or having coffee or other drinks (except for water) immediately before the sample collection
  • Having a dental treatment or having bleeding gums
  • Not stopping hormone replacement therapy on time before doing the test
  • Not stopping the consumption of soy products on time
  • Touching the sample container with the hand you usually use for applying hormone cremas/gels
  • Having/touching a partner who uses hormone creams/gels (the hormones are then transmitted through skin contact)
  • Doing a lot of sports befor collecting the sample

All these things can falsify the results!

Why/when is the collecting time important?

For women, the time is important if they want their sex hormones or total hormone status checked. If you only want to have the stress hormones determined, the day of your cycle is not relevant and you can run the test any day of your cycle.

Women with regular menstruation should collect the samples on the 19th – 21st day of the cycle (calculated from the first day of the menstruation). With irregular menstruation the samples should be collected 5 days before the expected menstruation and without menstruation the samples can be collected any day of the month.

With contraceptives that determine a 21 day cycle with a 7 day pause, the right time is in the first two weeks (calculated from the first day of taking the pill).

Men can collect the samples any day of the month.

Summary:

(1)   Blood tests are unable to differentiate between the protein-bound (inactive) and the freely available and active hormones. Why is that important? Because the blood levels can show normal values, while at the same time, looking at the active hormones, a saliva test can reveal deficiencies or surpluses.

(2)   Blood tests only show the hormone levels outside the cells in the serum and do not reflect the other levels in the body where the hormones are actually active and used.

(3)   If you are using hormone replacement therapy for transdermal (i.e., skin-ingested) hormones, blood levels will not be accurate for testing. This is because hormones, once absorbed through the skin into the blood, bind to the red blood cell membranes to minimize adverse interactions with the aqueous plasma. Once your blood sample is taken, it is usually centrifuged and the red blood cells are removed along with the hormones before analysis. This phenomenon was reported by Stanczyk et al. (2005) (see references) for transdermal progesterone. But it also seems to be the case for all other hormones. Even after several weeks of using transdermal progesterone, blood serum tests show no significant increase in progesterone levels, while saliva tests indicate an increase after a few hours. This can be a problem in monitoring progesterone levels when using transdermal hormone creams.

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Talk to us, we’ll be pleased to advise you!

You have further questions or are unsure which test is right for you?

Call us at (703) 722 6067 (08:00am – 11:30am EST) or write an e-mail to contact@verisana.com

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Scientific studies on the use of saliva tests:

Stanczyk, FZ. et al. (2005): Percutaneous administration of progesterone: blood levels and endometrial protection. Menopause 12(2): 232-237.

O’Leary, P. et al. (2005): Salivary, but not serum or urinary levels of progesterone are elevated after topical application of progesterone one cream to pre- and postmenopausal women. Clin Endo 53: 615-620.

Carey, BJ. et al. (2000): A study to evaluate serum and urinary hormone levels following short and long term administration of two regimens of progesterone cream in postmenopausal women. British J Obstetrics and Gynecology 107: 722-726.

Vining, RF. und McGinley RA. (1986): Hormone in Saliva. 
Critical Reviews in Clinical Laboratory Sciences 23 (2): 95-146.

Dollbaum CM und Duwe GF (1997): Absorption of progesterone after topical application: plasma and saliva levels. Presented at the 7th Annual Meeting of the American Menopause Society, 1997.

Further scientific studies:
  • Ellison, PT. (1993): Measurements of salivary progesterone. Ann NY Acad Sci Sept 20 1993; 694: 161-176.
  • Ellison, PT. (1992): Menstrual variation in salivary testosterone among regularly cycling women. Campbell BC, Horm Res 1992; 37 (4-5): 132-136.
  • Lipson, SF. und Ellison, PT. (1994): Reference values for luteal “progesterone” measured by salivary radioimmunoassay. Fertility and Sterility May 1994; 61 (3): 448-454.
  • Johnson ME, et al. (1995): Permeation of steroids through human skin. J Pharmaceutical Sci 1995; 84: 1144-1146.
Studies regarding “Red Blood Cell Transport” of progesterone:
  • Devenuto F, et al. (1969): Human erythrocyte membrane: Uptake of progesterone and chemical alterations Biochim Biophys Acta, 1969;193:36-47.
  • Koefoed P, Brahm J. (1994): Permeability of human red cell membrane to steroid sex hormones. Biochim Biophys Acta 1994; 1195: 55-62.

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