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Townsend Letter for Doctors and Patients, Jan, 2004 by Stanford Field
Now that we know something about the nature of steroid hormones and blood, what is it like for those hormones to travel in the bloodstream?
Let us use testosterone as an example that is representative of all steroid hormones. Over 90% of the testosterone in the bloodstream is carried by water-soluble proteins (sex hormone binding globulin [SHBG] and albumin). The testosterone bound to those proteins is not readily bioavailable to target tissues because it is on its way to the liver for excretion in bile which enters the intestines when fat is eaten. Along the intestines, about 90% of the bile and testosterone is reabsorbed and recycled to the liver for new processing--thus conserving these valuable biochemicals.
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Part of the testosterone-SHBG and testosterone-albumin complexes that went to the liver is converted into water-soluble chemicals that are excreted in the urine. Sometimes, a urine specimen is used to estimate the testosterone in the blood.
Less than 10% of total testosterone is bioavailable. More than 80% of this bioavailable (called "free") testosterone travels in the blood attracted to (adsorbed on) fatty red blood cell membranes. The other 20% of bioavailable testosterone (2% of total testosterone) is unbound, traveling in the plasma, and is readily available to stimulate target tissues.
When blood is drawn from a vein (low pressure going to the heart), it contains plasma and red and white blood cells. To analyze the blood, the plasma is separated from the blood cells by centrifugation. Since the plasma still contains clotting factors, an anticoagulant is added. This, then, is the plasma used for blood analysis. If the blood is allowed to coagulate, the cell-depleted fluid phase, devoid of fibrinogen, is called "serum." The serum may also be used for analysis. In either case, the blood being analyzed does not contain the red blood cells that held the free testosterone. What is being analyzed is testosterone that is attached to binding proteins and is not bioavailable.
When testosterone is applied transdermally, it is absorbed into the bloodstream as "free" testosterone, It has not been packaged with a binding protein by the liver because the liver did not have access to the testosterone, Most of the "free" testosterone is taken up by the red blood cell membranes which are not analyzed by a common blood test.
Conclusion: Common blood tests that use plasma or serum are not accurate for assessing bioavailable steroid hormone concentrations because neither the plasma nor the serum contain the red blood cells which hold the bioavailable hormones.
Direct Comparison of Plasma and Saliva Levels After Topical Progesterone Application
A technical paper entitled "Absorption of Progesterone after Topical Application: Plasma and Saliva Levels" was presented by Dollbaum and Duwe in 1997 at the 7th Annual Meeting of the American Menopause Society. An abstract of the presentation follows:
Creams with varying concentrations of progesterone were applied to menopausal women, after which both plasma and saliva levels were measured, as shown in the following table:
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