Hormones work as chemical messengers in our bodies, continually circulating through the blood stream. The body produces very active and different hormones throughout our lives, all of which serve necessary biologic functions, from organizing thoughts and memory to producing energy.

As we age, though, our hormones go through a gradual and steady descent. The endocrine and sex glands produce fewer hormones, changing us from vital, active individuals to slower, weaker ones. In fact, every 10 years after the age of 20, we lose 15% of our hormones. A 70-year-old woman, for example, may lose up to 75% of her natural hormones.¹ With 78.2 million baby boomers over age 60 in the United States alone, hormone deficiencies may play a larger role in health problems than we previously thought.²

If you're involved in hormone replacement, you need to arm yourself with the facts about accurate testing. Serum and saliva testing each have their pros and cons. But before delving into these, let's first look at the different forms of hormones in the body.

More than 95% of the hormones in our bloodstream are bound hormones. This means they're loosely bound to albumin and tightly bound to cortisol binding globulins (CBG) and sex hormone-binding globulins (SHBG). These are glycoproteins that bind to hormones, such as testosterone and all forms of estrogen. Bound hormones are biologically inactive and don't help the body stay vital and active as it ages.

The remaining hormones in our bloodstream - a tiny fraction - are called unbound or free hormones, which are readily available for the receptors of organs and tissues. They are, in fact, the only hormones our bodies can use.

Saliva's Role With Hormones
Saliva is produced by three major glands: The parotid gland, the sublingual gland and the submandibular gland. The parotid is located in front of the ears on the lateral portion of the mandible and produces 30% to 40% of our saliva (70% when stimulated).

The sublingual gland is located within the oral cavity underneath the tongue and produces 25% of our saliva (50% to 70% when stimulated with food). The submandibular is located under the jaw and produces only about 5% of our saliva. An average person produces about 1.5 liters of saliva per day. But as we age, saliva production decreases to less than 0.5 liters per day, possibly due to salivary gland atrophy and hormonal imbalance.

Saliva is produced when blood (possessing hormones, both bound and free) and lymphatic components pass through membrane barriers on their way to the glands. According to Vining and McGinley, "unconjugated plasma steroids, such as estradiol, testosterone, progesterone and other related steroids, are able to cross the salivary gland wall and to diffuse to saliva regardless of the salivary flow rate."³

How can these hormones cross the salivary gland wall? Any hormone less than 1,900 molecular weight (mw) can penetrate the filtration membrane. Hormones, such as testosterone, DHEA, cortisol and melatonin typically weigh 300 mw. The average albumin weighs 66,000 mw, a CBG approximately 50,000 mw and a SHBG sex hormone 115,000 mw. These are much too heavy to breach the membrane barriers, leaving only the free hormones to cross over and enter the saliva with ease.

So it's clear that active and free hormones are present in our saliva. In fact, published findings show that measurements of salivary testosterone reflect plasma testosterone levels accurately.⁴ Salivary measures of testosterone, estrogen and progesterone will accurately reflect what's in the body. In fact, these tests have gone beyond CLIA approval and have received FDA approval for accuracy and clinical application.⁵

The Established Method
Serum testing is the oldest and most widely used form of testing in the medical community. Several advantages exist for this testing. There's a long history and accumulated data with serum use. Serum testing is usually paid for by major insurance companies. Testing is easily available through hospitals, laboratories and clinics and is generally accepted by health care providers worldwide. Most published research data are based on serum testing. Patients and the medical community trust it.

On the other hand, problems exist. Serum testing is painful, which can cause anxiety and difficulties for patients. Furthermore, a professional needs to draw a serum sample, so testing can be inconvenient.

Aside from these issues, the real heart of the criticism is that serum testing is not always reliable, particularly when measuring testosterone in children and women.⁶ Because so many bound inactive hormones circulate in our bloodstream (approximately 95%), a serum sample will reflect the majority of these bound and useless hormones, rather than the more important free hormones (less than 5%).

Testosterone, estrogen, progesterone, DHEA and other hormones in their free state are not directly measured. Rather, they're calculated by measuring the existing total hormones in the serum sample and using mathematical equations with assumed statistics based on general populations for SHBG. For serum testing to be more precise, additional serum samples would have to be extracted from the patient to calculate individual levels of SHBG.

Furthermore, hormones are not produced all at once, but rather are released in 2-hour interval spurts. The difference between a high hormone output and a low one can range from 300% to 500%, which is significant. Using a single random serum test is like throwing a dart in the dark at a dartboard. The results from one random serum hormone test, added to the problem of using calculations from a mathematical formula with an assumed constant SHBG, significantly advance the chance of inaccuracy.