Hormone Testing and Dosing - Saliva Better than Serum?

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Hormone Balance in Males

TESTOSTERONE, MALE MENOPAUSE AND HORMONE BALANCE IN MEN

by John R. Lee, M.D.

Commentary on an Article by Jerome Groopman, published in the New Yorker magazine, July 29, 2002

Mr. Groopman discusses the commercialization of “andropause,” a moniker that implies a fall in androgen hormones similar to the menopausal fall of estrogen in women. The commercialization comes via Unimed, a division of Solvay, a Belgian conglomerate that includes pharmaceuticals. Unimed hopes to broaden the concept of andropause to include men with symptoms of fatigue, low sex drive, depressed mood, or poor erections. Their product, AndroGel, is a 1% transdermal gel, i.e., containing 1 mg of testosterone per gram of gel. Their recommended dose, as listed by their three page ad in this weeks TIME magazine, is 5 grams of gel (5 mg of testosterone).

The author points out that FDA approval of AndroGel was given for treating rather rare disorders such as Klinefelter’s syndrome (a rare genetic disorder causing underdeveloped testes), or testes damaged by viral inflammation or trauma, and pituitary disorders that lead to loss of testicular function, and not for “andropause.” Once a drug is approved for sale, however, physicians can legally prescribe it for any clinical condition he thinks might benefit from it.

Mr. Groopman’s article describes the dichotomy between physicians who find it useful (and remunerative) for practically every man entering their offices, and medical scientists who are still uneasy about the definition of andropause and question the use of supplemental testosterone. Points of difference include the questionable value of blood tests and the wide variability of testosterone levels in men without any sign of andropause symptoms, the subjective nature of so-called benefits, as well as testosterone’s potential risk of heart attacks and prostate cancer, and the claims that testosterone prevents aging. Unfortunately, Mr. Groopman does not seem to understand that risk of hormone side effects is largely a matter of dosage.

In his conclusion, the author regards the present surge of testosterone replacement therapy by approximately a quarter of a million American men to be a vast, uncontrolled experiment, whose consequences remain uncertain. He feels that what is needed is large scale study involving “many thousands of men” over a period of many years, such as was done for women in the Women’s Health Initiative (WHI) study of conventional HRT.

Medicine’s Lack of Understanding about Male Hormone Balance

I find the article, written in the cool, cosmopolitan style so adored by the New Yorker magazine, to be glib and mistaken in its underlying hypotheses. Yes, there is a parallel with the problems uncovered by the recently stopped WHI study. The major problem is conventional medicine’s lack of understanding of the realities of hormone balancing. Any single hormone does not work in isolation – it works something like a member of a large orchestra with many different players. The question of testosterone’s role can not be determined, in most cases, by knowing merely its serum concentration. What is the right level for one person may not be right for another person. Absolute levels are deceptive. Far more relevant is the ratio between testosterone and estradiol concentrations. Testosterone is an antagonist of estradiol; it acts to oppose estradiol’s actions. Thus, a given estradiol level will lead to breast growth in a man with low testosterone, and not in a man with higher testosterone levels.

Testosterone and Estrogen in Men

It is well known that the estradiol level in 55-year old men, for example, is usually a bit higher than that of a 55-year old woman. The man, however, does not develop breasts because he has a higher testosterone level than women do. As men age, their estradiol levels gradually rise, whereas their progesterone and testosterone levels gradually fall. The hormone balance changes. These gradual changes lead to reduction in testosterone benefits and eventually to estrogen dominance. That is, his estradiol effects emerge since his testosterone level is not sufficient to block or balance them. Estrogen dominance stimulates breast cell growth and endometrial cell proliferation in women. In men, estrogen dominance stimulates breast cell growth and prostate hypertrophy. Estrogen dominance is responsible for the majority of breast cancers and is the only known cause of endometrial cancer in women. Since the male prostate is the embryonic equivalent of the uterus, is should not be surprising that estrogen dominance is also a major cause of prostate cancer.

Testosterone Supplementation in Men

Testosterone supplementation is the obvious treatment for men with testosterone deficiency relative to their estradiol levels. If the estradiol, progesterone, and testosterone balance that prevails in younger men (when they do not get prostate cancer) is a healthy one, why not restore the hormone levels in older men to that same healthy balance?

To achieve this desired goal of a healthy balance between these major sex hormones, one must learn how to accurately measure their levels. All steroid hormones are fat-soluble. When they circulate through the liver they wrapped up, so-to-speak, by a protein coating, a process known as protein binding. When protein-bound, the hormones are water soluble but less bioavailable. Being water-soluble, the protein-bound hormones pass through the kidneys and are excreted in the urine. The non-protein-bound hormone (referred to a “free” hormone) on the other hand, is the bioavailable form of the hormone. It is fat-soluble and is carried in blood by red blood cells rather than in the serum, that is the watery, non-cellular portion of the blood. When the blood circulates through the tissue of the salivary glands, the “free” hormone, whether in red blood cells or in the serum, filters through into the saliva, whereas the protein-bound form does not. If one wished to know the concentration of “free” bioavailable hormone in the blood, it is obvious that saliva hormone levels are more accurate and more relevant than serum hormone levels.

Serum vs. Saliva Holds True for Men Too

For reasons that escape rational thinking, conventional medicine persists in using serum tests rather than saliva tests. The results have been disastrous. When using hormone creams or gels, the hormone is absorbed through the skin and into the blood without first passing through the liver. Thus, they are essentially all absorbed in the “free” form. When given orally, they pass first through the liver and 90% of them become protein-bound. For this reason, transdermal dosing is at least 10 times more efficient than oral dosing. If one uses serum testing to measure the blood levels achieved by transdermal dosing, the test will fail to measure all the hormone carried by red blood cells. As a consequence, physicians are apt to greatly over-dose their patients.

When using saliva testing, it is found that the transdermal dose of testosterone when treating someone with testosterone deficiency is only 0.25-0.5 mg in women, and 1-2 mg in men. As the New Yorker article indicated, the transdermal doses of testosterone ranged from 5 mg to 100 mg a day. The same is observed in estrogen replacement therapy – the doses are generally all greatly excessive. The same hormone that brought good health without side effects when in normal endogenous levels will bring on very bad side effects when given in grossly excessive doses.

The problem is not the hormone, per se, the problem is the dosing.

Some physicians have attempted to measure “free” hormones in serum. Regardless of how well this is done, such tests fail to measure the “free” hormone being carried by red blood cells.

Use Only Bio-identical, Natural Hormones

The final correction that must be made is equally obvious – when treating someone with a hormone deficiency, use only bio-identical hormone. Altered, synthetic versions of our natural hormones will not do – they are foreign to the body, do not convey the same benefits as the real hormone, and all are fraught with undesirable side effects not conveyed by the real hormone.

Our problems in using hormones can be solved by the four guidelines summarized below:

Learn how to measure total “free” hormone.
Use physiologic doses rather than pharmacologic doses.
Use only bio-identical hormones.
Learn how to achieve hormone ratios that produce proper hormone balance.
Failure to follow these three guidelines is the principal cause of the problems exposed by the Women’s Health Initiatives. The makers of AndroGel use bio-identical testosterone but their dosing regulations are faulty and dangerous. Any good compounding pharmacist can make up a testosterone cream that will more easily supply the right dose of testosterone in men with estrogen dominance due to testosterone deficiency.

For more information on this topic, please read Hormone Balance for Men a booklet by John R. Lee, M.D.

Correct.

Correct, apart from the fact that it is androgens and not merely testosterone that balances out estrogens effects. That is why it is the androgen to estrogen balance or ratio that is important, with the potent androgen and testosterone metabolite dihydrotestosterone playing an important part

Again it should be noted that it is the Androgen levels that are important and not just the testosterone level.

This is a complete fallacy and total rubbish.

First of all free hormones can be measured via blood tests something the author conveniently fails to mention. Secondly free testosterone obtained by equilibrium dialysis IS the gold standard and most reliable free testosterone assay in existence. Thirdly and this one is the one that seals it for me is the fact that Most free testosterone assays via saliva are VERY poor in terms of methodology and highly inaccurate hence the reason you are highly unlikely to find a hospital that uses them.

I personally have used them and had wild and bizarre results that were completely off the scale and at complete odds with far more reliable blood assays.

Rubbish.

Restandol is an oral form of testosterone replacement and it does not have a first pass on the liver, it is drained via the lymphatic system. Gels and creams are absorbed in their free form according to the author. No they are not, this is categorically untrue. They are absorbed by the skin and enter the blood steam, that is the mechanism of action, but a high percentage of the hormone is bound in the same manner that occurs with endogenous production. This is ably demonstrated by the fact that men with very high SHBG levels suffer from testosterone deficiency even on testogel testosterone replacement. The problem remains until the level of SHBG is reduced and the amount of supplemented hormone freed so that it is able to act in the body. In terms of efficiency of dosing, the author makes no reference of the half life of the differing medications which is highly relevant, no mention of the differing T/DHT/E2 ratios or any mention of the fact that some people simply do better on certain forms of TRT due to the complicated interactions of ancillary hormones involved. There is no point in saying that gels are better than injections or oral forms of medication or vice versa because it is all dependent on the highly individual response. In terms of gels and dosing, what is being said again is a complete fallacy. First of all dosing is usually conservative and secondly it is often based upon symptoms as opposed to bloods. In fact one of the advantages of transdermal gels is that it is usually very easy to ascertain the correct dose via trial and error given the nature of daily application.

This is hilariously bad science/endocrinology. The author could make money as an after dinner speaker at reproductive endocrine conferences, he would have them laughing in the aisles.

First of all the transdermal dose does not range from 5 to 100mgs a day. Testogel and Testim come in 5 gram packets and each packet contains 50mgs of testosterone. So dosing is 50mgs, 75mgs or 100mgs a day. Secondly a eugonadal or health man produces about 7 to 10 mgs of testosterone a day, not quite 1-2mgs is it!!! Thirdly his ratio of supposed requirement when looking at men and women is just ludicrous, it would mean that the differences that we see between men and women simply wouldn’t exist. In fact men would have undeveloped genitals and eunuchoid body proportions at such levels if that was what occurred throughout puberty. You would expect to see the average male height to be around 6 foot 3 due to a lack of closure of the growth plates. Again I point to the fact that dosing particularly with gels is usually based upon symptomatic response as opposed to simply blood tests and symptoms are a far more reliable indicator of hormonal action in the body than any objective test, because of the limitations of almost all testing. Again though the idea that people should turn to saliva testing on the basis of reliability is just downright hilarious. In terms of why many men of TRT struggle, that is simple. There is not one method of testosterone replacement is existence that comes close to replicating or being as good at as a fully functioning HPTA with correctly working testicles. All forms of TRT produce differing hormonal ratios and effects on ancillary hormones, many of which you do not see with the human form. Furthermore many men are only on basic TRT and do not measure or control hormones affected by TRT. Last but not least without an individuals optimal levels, measured in youth, we have no idea what exactly would represent health testosterone, SHBG, Estradiol, DHT level levels or ratios in that individual. And of course we invariably do not have these levels as endocrine evaluations only tend to occur when illness has already set-in. This is a very real and unfortunate fact and as a result trial and error with differing forms of imperfect TRT and possibly ancillary meds are required. Of course none of this has anything to do with testing and nothing that could be corrected with even the best testing methods and certainly it has nothing to do with inadequate testing with piss poor methodology and piss poor accuracy of saliva testing.

Retarded blanket statement, bloody lazy and stupid to boot.

The fact is the problems inherent in treating hypogonadism are not simply down to methods of testing and free testosterone assays by equilibrium dialysis absolutely piss all over saliva tests in terms of accuracy, that is not an opinion, that is a FACT. Furthermore most blood assasy are vastly superior in comparison to saliva assays when it comes to measuring sex hormones and the methodology in even a limited total testosterone assay is of FAR greater use and value than a typical saliva assay.

Correct for the most part.

Measuring the free hormone can certainly be helpful and I would strongly advise that to be able to do that one should not touch a saliva assay with a barge pole.

This is semantical claptrap; it is a statement that actually doesn’t say anything of any meaning whatsoever. The fact is one would want to use the correct dose, but that equally conveys nothing of any worth to anyone.

The key when it comes to dosing is to follow the prescribing guidelines and to dose according to symptoms in accordance with correct hormonal pathology evaluation with due consideration paid to ancillary hormones with a view to obtaining hormonal balance that leave the individual as close to well being as possible.

Fairly obvious.

Absolutely hilarious. Apart from your basic testosterone to estrogen ratio and a view to altering dosage and meds based on any obvious problem such as high estradiol or low DHT, you won’t get a real idea of the ratios of your hormones. The fact is the interactions are so complex and the free levels of hormones such as Estradiol so difficult to evaluate that this is simply a stupid statement.

And now he suddenly mentions estrogen dominance as though that has been the mainstay of his article, how odd.

Firstly excess estrogen, normally estradiol should be treated in its own right via aromatase inhibitors or the like and has little to do with TRT. Secondly there is not a single compounding pharmacist in the world that can successfully treat estrogen dominance with testosterone. This is a cripplingly stupid statement and shows a fundamental lack of understanding of the issues at hand. In terms of his comments regarding the dosages of Androgel, firstly I presume he is going to provide the relevant evidence that backs up his claims and takes Androgel off the market? If he hasn’t got this evidence then I presume he is not going to continue to print articles for very much longer as he will be sued out of professional existence. If only the author realized that A) estrogen dominance should not be treated by simply used TRT and B) that in fact gels are the worst form of TRT in such circumstances as they inherently increase both the levels of estradiol and the ratio of estradiol beyond that seem in many other forms of TRT. Something not only detailed by the makers of Androgel but also detailed by world leading andrologist Dr Malcolm Carruthers in his book Androgen Deficiency In The Adult Male.

One should not be treating estrogen dominance with TRT, certainly not alone and transdermal gel is one of the worst forms of TRT when dealing with estrogen dominance because the mechanism of delivery ensures that testosterone comes into contact with the aromatase enzyme.

He would be well advised to attend a conference with Dr Shippen and Dr Carruthers so that he could be educated on the reality of matters.

Did some one, at least gave it a try???