Ensuring an Accurate Dose: Testosterone Replacement Therapy

Posted by Ben White on

Testosterone Replacement Therapy

Testosterone replacement therapy cab be useful and it has the potential to drastically improve quality of life of those who need it when it is used correctly. However, many men who begin topical testosterone are given too much of the hormone. Explanations for this erroneous tendency are rooted in incorrect dosing principles that have been established on false assumptions, misconceptions, invalid conclusions and aggressive marketing instead of physiology and science.

Why are testosterone replacement standards and prescribing processes so frequently misguided? 

Testosterone Overdose Begins With Incorrect Dosing Principles

  • For topical application, a physiologic daily dose of any sex steroid (in either sex) is approximately the same as our daily production during our prime—if the person no longer makes any of a hormone endogenously.
  • 50 or 100 mg of topical hormone is a commonly administered dosage, which is 5 to 10 times the amount of testosterone he made at 18 years old! BHRT should be a restoration therapy in the sense that we are dosing enough hormone to restore the level by adding to what the patient is still producing.
  • The physiological production of testosterone in a young adult male is approximately 6 mg per day.
  • A physiologic dose of topical testosterone for a male is 1 to 10 mg daily. Administration of too much hormone will suppress endogenous production and eventually lead to receptor downregulation.

Why Such High Doses

The culprit lies in testing methods. No studies have ever validated the use of serum testing for topically applied hormone, and no correlation has been shown between venous serum levels and bioavailability (available at site of physiologic activity) or long-term efficacy.

In contrast, Dr. Frank Stanczyk has shown that venous serum testing cannot be used to judge the effect of topically applied progesterone in uterine tissue. Applying the principles of evidence based medicine and using the strongest scientific evidence (instead of a manufacturer’s marketing piece), one would avoid using venous serum testing for any topically applied hormone.

Drug manufacturers have led us down the wrong road by relying on irrelevant serum testing methods.

They used venous serum levels to determine how much hormone is "delivered," "absorbed" or is "bioavailable" in their topical products. These three terms have been bastardized by the pharmaceutical industry, which defines them only by the amount of hormone seen in the serum.

In true medical terms:

  • Bioavailability is defined as "the degree and rate at which a substance (a drug) is absorbed into a living system or is made available at the site of physiological activity."
  • Absorb means "to take up especially by capillary, osmotic, solvent or chemical action."
  • Both definitions have to do with the amount of hormone that goes into the system, not the amount left over in venous serum.
  • "Delivered" is a label initiated by the drug manufactures so as to avoid the term "dose" in the context of topical manufactured products.

There is a Better Way

As a result of relying on serum testing for topically applied hormones, doctors and patients are confused as serum levels often go down initially, even if only 5 or 10 mg daily is prescribed. Since most males are still producing at least a fair amount of the original 6 mg daily, even 5 to 10 mg can bring their total level to higher than physiologically normal. This scenario results in decreased endogenous production and downregulation of testosterone receptors, resulting in reduced symptom management.

Venous serum testing only reflects the endogenous hormone level and not the topically applied hormone, so the suppression of production causes a reduction in the serum level. As result, the prescribing practitioner may increase the dose even higher due to the decreased venous serum level. This is blatantly incorrect! We give a patient testosterone and because a level goes down, we give him more? Before increasing the dose further, should one not first be able to explain why the level would go down?

When an educator, such as myself, suggests a topical testosterone dose reduction, resistance is the most common reaction. Similarly, lowering estrogen dosages in women over the past 20 years to 1/10th to 1/20th or what was initially used, also met this type of resistance.

Common reasons for resisting a lower dose include:

  • Lack of knowledge as to any other approach to sufficiently addressing the symptomology.
  • The amount of knowledge, education and time it requires to properly balance all hormones, nutrition and lifestyle factors, in opposition to simply increasing the dose of testosterone.
  • Some prescribers simply state that they do not understand saliva testing and/or that topical testosterone doesn’t work in men. These same practitioners fail to explain why venous serum doesn’t show a linear relationship to topical testosterone dosing, or why testosterone is the only hormone in either sex that doesn’t work topically.

This resistance results from the fact that it is much easier to follow suit and not have to learn and think about how to correct the real problem.

A vital solution to the issue of overprescribing and overdosing testosterone is accurate and indicative hormone level testing and monitoring. Saliva testing and capillary dried blood spot testing present such an answer.

Discerning between free and protein bound hormones is especially important when monitoring topical or transdermal hormone therapy. Studies show that the transdermal method of delivery results in increased tissue hormone levels, thus measurable in saliva, but no parallel increase in serum levels.


With the use of dried blood spot testing, like saliva, hormones are present in the "capillary" blood from the finger and are representative of the hormones delivered to other tissues. When hormones are delivered through the skin as supplements, the capillary dried blood spot hormone level rises in concert with the increase in salivary hormone levels, because hormone delivery to all tissues is well represented.

Blood taken by conventional venipuncture rises very little, not at all, or even decreases in some cases with skin delivery of hormones. This might seem odd, but blood being delivered back to the heart through the veins has already delivered its bioavailable hormone load, and hormones remaining in the bloodstream are tightly bound to serum proteins such as SHBG and albumin.

An easy way to conceptualize capillary blood (teeming with bioavailable hormones) versus venous blood (depleted of bioavailable hormones) is to think of the oxygen content of red blood cells in the capillary beds versus the venous blood returning to the heart. Blood being delivered to the tissues through the arteries, arterioles, and finally through the capillary beds of tissues is charged with oxygen that is released into the tissues. Blood traveling back to the heart is depleted of oxygen. In a similar way, hormones delivered through the skin are picked up by red blood cells, and the hormone-laden red blood cells are then transported within seconds throughout the body to capillary beds of all tissues. There the hormones are released. This is why we see high capillary blood levels of hormones in blood spot testing and much less hormone in venipuncture serum.


Click to see Saliva Hormone Test Kits

Click to see Dried Blood Hormone Test Kits

Click to see Dried Urine Hormone Test Kits

Original of this article was published on ZRT Laboratory Blog. 


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