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LE Magazine February 2004
Testosterone Attacked by the Media
Life Extension Reveals the Facts...

Does Testosterone Cause Prostate Cancer?
Mainstream medical practitioners often have stated that prostate cancer, which in 2003 was responsible for the deaths of more than 29,000 men in the US, is caused by testosterone. Fortunately, the Institute of Medicine includes some data showing that optimal levels of testosterone do not cause prostate cancer, and in fact may protect against this major killer of elderly men. On p. 90, the authors state:

“population-based studies clearly document the relationship between aging and both increases in prostate cancer incidence rates and decreases in circulating [and free] testosterone levels. While this relationship does not equal causality, the findings do raise intriguing hypotheses regarding the influence of testosterone on inhibiting prostate carcino-genesis.”

New European Study Supports
Testosterone Supplementation

A report in The Journal of Clinical Endocrinology and Metabolism (November 2003) sheds more light on the beneficial effects of testosterone supplementation in andropausal men. The study authors conducted a rigorous database search of testosterone’s effect on heart disease in men, and identified multiple studies showing that men with low testosterone levels had higher blood pressure, LDL cholesterol levels, triglyceride levels, and body mass index compared to men with optimal testosterone levels. Discussing the potential side effects of testosterone supplementation in elderly men, the authors noted, “the scientific basis for these concerns is scarce.”*

* Muller M, van der Schouw YT, Thijssen JH, Grobbee DE. Endogenous sex hormones and cardiovascular disease in men. J Clin Endocrinol Metab. 2003; 88 (11): 5076-86.

Estrogen’s Role in Prostate Cancer
Unfortunately, while the Institute of Medicine spends 11 pages (pp. 87-98) detailing testosterone’s effect on the prostate, it offers no discussion of the possible effects of estrogen on prostate and its role in prostate cancer. The belief that estrogen, rather than testosterone, is one of the prime hormonal initiators of prostate cancer is based on the fact that while testosterone levels are highest in young men, prostate cancer essentially is never seen in this population. It is only in older men, who have lower levels of testosterone but higher levels of estrogen and its breakdown products, that prostate cancer is a significant health threat. Animal studies have shown that male rats treated with testosterone alone showed significantly less prostate growth compared to animals treated with both testosterone and estrogen.16 A 1993 study showed that men treated with DHT (which cannot convert to estrogen) saw a reduction in the size of their prostate with no sign of prostate cancer.17 An article published in 2003 in the World Journal of Urology sums up the estrogen-prostate cancer link succinctly: “Estrogenic stimulation through estrogen receptor alpha in a milieu of decreasing androgens [testosterone] contributes significantly to the genesis of benign prostates hyperplasia, prostate dysplasia, and prostate cancer.”18

The Institute of Medicine’s Recommendations
With all the positive studies cited by the Institute of Medicine, it would be reasonable to expect the authors to conclude that testosterone supplementation, to even the most conservative-minded researcher, has been shown to be efficacious for a variety of andropause-related symptoms. Unfortunately, that is not the case. In fact, the authors do not even acknowledge that low testosterone contributes to andropause in any way, shape, or form, as seen in the following quote on p. 100:

“Endogenous testosterone levels clearly decline with aging, but it is not clear if lower levels of serum testosterone affect health outcomes in older men.”

Following this remarkable statement, the authors then conclude on p. 100:

“A systematic review of the medical literature on testosterone therapy, particularly placebo-controlled trials in older men, demonstrated that there is not clear evidence for any of the health outcomes examined.”

Scanning electron micrograph of prostatic cancer cell magnified 6000x..

Given the mind-set exemplified by the previous statement, the Institute of Medicine’s recommendations and conclusions should come as no surprise. On pp. 117-167, the authors detail the committee’s key conclusions, considerations, and recommendations, based on their rather skeptical view of testosterone’s effect on the aging process in men and the use of testosterone supplementation. Their first recommendation is to conduct trials of testosterone supplementation only in older men—those aged 65 and above—and to focus on testosterone supplementation as a therapeutic intervention rather than a preventive measure. The problem here is that it is well established—and even acknowledged by the Institute of Medicine—that in most men, testosterone levels begin falling while they are in their forties. While it is certainly worthwhile to try to treat debilitating symptoms of any disease or pathological process, be it an infection or aging, it is almost always better to try to prevent symptoms rather than treat them once they are in place.

The recommendations continue with the idea of starting research trials with studies to determine whether there is any benefit to testosterone supplementation, and if so, then conducting longer-term trials. The glaring problem with these recommendations is that a significant number of clinical trials already have been conducted—many referenced by the Institute of Medicine—that prove the efficacy of testosterone supplementation for treating a variety of andropause-related symptoms. In addition, longer-term studies of up to three years already have been conducted and have established the usefulness of testosterone supplementation in both middle-aged and elderly men. In the journal The Aging Male, researchers recently presented the findings of a three-year study of 122 men, aged 19 to 67, who were treated with testosterone gel.19 As with numerous earlier studies, the study authors found that long-term treatment with testosterone supplementation causes a statistically significant improvement in bone mineral mass and sexual desire, an increase in muscle mass, and a decrease in fat mass.

How to Restore Youthful Testosterone Levels

Unlike the Institute of Medicine’s dismissive report, Life Extension long ago identified and resolved potential problems associated with testosterone replacement therapy, enabling thousands of aging men to safely enjoy the remarkable rejuvenation effects that can occur when sex hormone levels are restored to youthful ranges.

In 1999, the Life Extension Foundation published an extensive protocol that describes how aging men can restore youthful sex hormone levels. Minor modifications were made to the protocol, which is contained in the fourth edition of Disease Prevention and Treatment and also can be accessed at www.lef.org/test.

The Institute of Medicine’s final recommendation concerns the safety of the men participating in the testosterone supplementation trial. To accomplish this, the committee would set up strict exclusion criteria, mandate careful monitoring of markers of prostate function such as PSA (prostate specific antigen) levels, and seek to ascertain whether long-term testosterone supplementation can cause a rise in prostate cancer. While these recommendations are commendable, significant omissions also are obvious, such as failing to include monitoring of SHBG and estrogen levels along with the use of estrogen blockers (aromatase-inhibitors).

It is puzzling, at the very least, why the Institute of Medicine fails to even mention the significant effect of rising estrogen levels on prostate cancer when a substantial amount of well-researched literature has been published on this very subject.

Conclusions of the Institute of Medicine
In the Institute of Medicine book’s final pages (pp. 163-7) preceding the appendixes, the authors cast a derisive eye on the myriad reports showing the effectiveness of testosterone supplementation, concluding:

“The trials that have been conducted do not show definitively that there are benefits of testosterone therapy for older men…the committee recommends short-term efficacy trials to determine if there are benefits of testosterone therapy in older men.”

Apparently, at the cost of the health and possibly lives of many thousands of middle-aged and elderly men, the Institute of Medicine committee has decided that yet another trial of testosterone supplements should be conducted, a trial that will take years and be funded by taxpayers, while those very same taxpayers are suffering from the very real, and often very debilitating symptoms, of andropause-induced testosterone deficiency.

Instead of reading the Institute of Medicine’s book, the media instead chose to malign the multiple benefits of testosterone replacement and exaggerate its potential side effects. Testosterone and Aging cites numerous clinical studies showing significant anti-aging effects, but the media reported only the disparaging conclusions made by certain committee members that had little or no basis in fact.

Unlike the mainstream media, we actually read the book, which provides solid scientific evidence that aging men should seek to maintain youthful testosterone levels.

Low Testosterone = Higher Blood Pressure

In a recent study, Italian researchers compared plasma testosterone levels of 119 elderly men with isolated systolic hypertension to those of 106 nonhypertensive elderly men.* All the study participants were 60 to 79 years old, non-obese, nondiabetic, and nonsmokers. The hypertensive men were found to have 14% lower levels of testosterone compared to the nonhypertensive men. In both the hypertensive and nonhypertensive men, low testosterone levels correlated with higher blood pressure values.

These findings are vastly magnified by the results of another study, which reviewed data to determine how blood pressure affects cardiovascular disease risk.** After reviewing a meta-analysis of data from 61 prospective studies involving almost 1 million participants and 56,000 vascular deaths, the researchers stated: “Persons aged 40 to 69 years had a doubling of risk of stroke or coronary mortality with every 20-mm Hg increment in [systolic blood pressure] (or 10-mm Hg higher [diastolic blood pressure]) throughout the entire range of [blood pressure].” The researchers’ conclusions were:

“There is overwhelming evidence of a continuous, graded influence of [systolic blood pressure] on [cardiovascular disease] morbidity and mortality at all ages…It is the level of [blood pressure] that kills, not arbitrarily defined hypertension…The importance of what appear to be trivial differences in [blood pressure], even within the high-normal [blood pressure] range, should not be underestimated. The extra effort needed to lower the [blood pressure] down to the recommended goals for avoiding [cardiovascular disease] is worthwhile.”

Taken together, these two studies point to a conclusion that could only escape a committee of government experts: With hypertension linked to impaired testosterone levels, and with higher blood pressure values in turn linked to increased risk of cardiovascular disease in both men and women of all ages, aging men would be well advised to consider taking all measures necessary—including testosterone supplementation—to bring their blood pressure values into the optimal ranges.

The Institute of Medicine researchers note in their report that testosterone’s role in heart and vascular diseases “has yet to be determined”—a conclusion squarely contradicted by many published studies.

* Fogari R, Malacco E, Preti P, et al. Plasma testosterone in isolated systolic hypertension. Hypertension. 2003 Oct;42(4). Epub 2003 Sep 15.

** Kannel WB, Vasan RS, Levy D. Is the relation of systolic blood pressure to risk of cardiovascular disease continuous and graded, or are there critical values? Hypertension. 2003 Oct;42(4):453-6. Epub 2003 Sep 15.

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