Massachusetts General Hospital consistently ranks as one of the world's top medical facilities. It conducts the largest hospital-based research program in the United States. Case reports from Massachusetts General Hospital are routinely published in the prestigious New England Journal of Medicine.
Doctors at Massachusetts General Hospital observed that prescription sales of testosterone increased by 500% in the United States between years 1993 and 2000 and continue to surge.1 This prompted
these doctors to study the effects of testosterone and estrogen on body composition, strength, and sexual function in men.2
The results of this study published in the New England Journal of Medicine confirm Life Extension's long-standing position that restoring testosterone blood levels to youthful range reduces body fat,3 increases lean muscle,4 improves strength,5 and enhances sexual function.6
This study also helped corroborate the adverse impact when estrogen levels are out of range in men.
What troubles us, however, is the medieval manner in which this study at Massachusetts General Hospital was
designed, why the doctors overdosed study subjects on an estrogen-suppressing drug, and why the media treated certain
findings as a discovery when they're not new.
The men in this study who were overdosed on the estrogen-suppressing drug had their estrogen drop to dangerously low levels. This led the study doctors to proclaim that men need estrogen and testosterone.
We fear this study will cause physicians to avoid appropriately prescribing estrogen-suppressing drugs, which will result in
tragedies as estrogen overload is a serious condition in many aging men (as is estrogen deficit).
"Authorities" are often viewed as reliable sources of expert information. This editorial exposes errors committed by mainstream doctors who attempted to study the effects of aggressive testosterone and estrogen modulation in
males. These medical "authorities" appear to have made little effort in identifying clinically validated methods of optimizing hormone status in aging men.
Aging is accompanied by an imbalance of hormones required to sustain life.
As a man's testosterone declines, his risk of dying greatly increases.7-9
Heart disease,10-13 osteoporosis,14,15 and muscle wasting16,17 are strongly linked to testosterone deficiency, as are chronic inflammatory18-20 and neurodegenerative disorders.21-25 Doctors are often surprised to
learn that men with low testosterone show an increased incidence of prostate cancer.26-30
Long before life prematurely ends, testosterone deficit can manifest in the form of psychological disturbances
such as depression,23,31,32 reduced sexual desire,33-35 and a loss of sense of well-being.32,36
Life Extension® has long urged male members to have their blood tested for testosterone and to restore levels to youthful ranges if they are low.
Estrogen Balance Critical To Aging Men
When Life Extension started offering comprehensive blood test panels back in 1996, men did not understand why we were checking their estrogen levels. Back in those days, estrogen was viewed as a
hormone of importance only to women.
We tested estrogen blood levels in men based on published data indicating that when estrogen levels are unbalanced
, the risk of degenerative disease in aging men skyrockets.37-40 Of concern to us 18 years ago were reports showing that excess estrogen contributes to the development of atherosclerosis.41,42 Human clinical studies
conducted more than a decade later confirmed our suspicions. Men with even slightly elevated estrogen levels doubled their risk of stroke and had far higher incidences of coronary artery disease.43-45
Our early observations also revealed that men presenting with benign prostate enlargement or prostate cancer had higher blood estrogen levels (and often low testosterone).46-48 Subsequent clinical and laboratory studies helped confirm our
estrogen, on the other hand, predisposes men to ailments such as osteoporosis and bone fracture.54,55
The fact that 99% of men today have no idea what their blood estrogen levels are helps explain the epidemic
of age-related disease that is bankrupting this nation's medical system.
Higher Mortality In Men With Unbalanced Estrogen
Conventional doctors tend to ignore hard science even after it appears in their own medical journals.
A study published in the Journal of the American Medical Association (JAMA) measured blood estradiol (a
dominant estrogen) in 501 men with chronic heart failure. Compared to men in the balanced estrogen quintile, men in the lowest estradiol quintile were 317% more likely to die during a three-year follow-up, while men in the highest estradiol
quintile were 133% more likely to die.56
The men in the balanced quintile-with the fewest deaths-had serum estradiol levels between 21.80 and 30.11 pg/mL. This is virtually the ideal range that Life Extension® has long
recommended aging men strive for.
The men in the highest quintile who suffered 133% increased death rates had serum estradiol levels above 37.39 pg/mL. The lowest estradiol group that suffered a 317% increased death rate had serum estradiol levels under 12.90 pg/mL.
The dramatic increase in mortality in men with unbalanced estrogen (estradiol levels either too high or too low) is nothing short of astounding. It uncovered a gaping hole in conventional medical practice that is easily correctable.
Massachusetts General Hospital Doctors Overlooked These Studies
The study I just described revealing the dangers of estrogen imbalance was published in the May 13, 2009, issue of the Journal of the American Medical Association. This JAMA study corroborated previous studies validating the critical
importance for aging men to maintain their estradiol blood levels in optimal ranges.
Yet doctors at Massachusetts General Hospital seemed oblivious to this JAMA study when they overdosed their
study subjects on the estrogen-suppressing drug "anastrozole." The brand name of this
drug is Arimidex®.
Recall that when estradiol levels drop below 12.90 pg/mL, death rates increased317% in heart-failure patients. Also recall that optimal estradiol blood levels are between 20-30 pg/mL.
By overdosing the study subjects on the estrogen-suppressing drug, doctors at Massachusetts General Hospital caused estradiol blood levels to plummet to a frighteningly low range of 1.0 to 2.8 pg/mL.
This is 10 times lower than the optimal estradiol threshold.
When the arm of the study that was overdosed on the estrogen-suppressing drug developed adverse effects, the doctors at Massachusetts General Hospital proclaimed that men indeed require estrogen, as if this were a surprising discovery.
The media picked up on this misinterpreted data and undermined the value of estrogen-suppressing drugs when properly prescribed
to men suffering estrogen overload.
How Much Of An Overdose?
There is no question that men require a certain amount of estrogen, as they do testosterone, to sustain life. Most
estrogen in men is produced through the aromatization (conversion) of testosterone to estrogen in the body. This transformation occurs in response to the
When men have high levels of aromatase, they convert too much testosterone into estrogen, which can cause them to be low on
testosterone and high on estrogen. These men need a drug like anastrozole to inhibit the aromatase enzyme. The
typical dose an aging man needs of anastrozole is 0.5 mg twice per week. In some cases, a man may need 1.0 mg of anastrozole twice a week.
In contrast, doctors at Massachusetts General Hospital gave men in the estrogen-suppressing group an outlandish dose of 7.0 mg per week of anastrozole. This anastrozole dose is seven times higher than what has been
shown to safely reduce elevated estradiol to optimal ranges in most aging men.
We at Life Extension have no idea why such a high dose of anastrozole would ever be given to men. Perhaps since
it's sold in 1 mg tablets, the physicians who designed the study thought the men should take one per day. This dose of 1 mg/day is what female breast cancer patients sometimes take to suppress estrogen production in their bodies. It is an egregiously
excessive dose for men to take, as evidenced by the suppression of estradiol in these study subjects to virtually non-existent levels (1.0 to 2.8 pg/mL of blood).
The estrogen-suppressing drug (anastrozole) was given to every man in the estrogen-suppressing arm of the study, regardless of
what the man's estradiol blood level was. This meant many of these men were taking this potent drug when they did not even need it.
Unethical Use Of Testosterone-Suppressing Drug And Excess Radiation Exposure
The study conducted at Massachusetts General Hospital was performed in a way that raises medical ethical issues. The doctors took a group
of healthy men aged 20-50 years with normal testosterone levels and initially gave them a powerful drug ( Zoladex®) that drastically suppressed their testosterone.
We at Life Extension have long been aware of the negative impact this kind of hormone depletion creates. Prostate cancer patients
who undergo "androgen deprivation" suffer rapid bone loss,57-60 muscle atrophy,61-63 abdominal fat gain,64,65 and a host
of other adverse changes that are not always reversible.
The long-term effect of testosterone deprivation was demonstrated later in this study at Massachusetts General Hospital when men whose
testosterone was restored to the higher ranges did not fully recover sexual function lost by this intentional suppression of
Instead of taking healthy men and depleting them of their life-sustaining hormones, the doctors could have chosen to study men over age 50 whose
testosterone levels had already plummeted to ultra-low ranges. By studying younger men who were not testosterone deficient, the researchers lost an
opportunity to directly apply the study outcomes to aging men who are most in need of testosterone restoration.
Another issue we have with this study was the continuous repeated use of DXA and CT body composition scans. While these
scans enable precise body fat measurements,66 they emit huge amounts of radiation that could create cancers later in life.67
The men in this study who were initially deprived of testosterone (and estrogen) may have suffered bone loss and endothelial dysfunction.68 The tragic impact would be an increased risk of fracture and
vascular disease later in life.
The pathological effects of even short-term androgen deprivation are variable, unpredictable, and can result in barbaric consequences. Repeated exposure to
radiation emitting CT and DXA scans is not something that young healthy men should undergo when it is not medically necessary.
This is why I allege at the beginning of this article that this study at Massachusetts General Hospital was designed in a " medieval" manner.
Low Estradiol And Testosterone Predict Mortality In Aging Men
To further substantiate the lethal impact of hormone deficiency, another study published in 2009 evaluated 3,014 men aged69-80 years. Serum levels of testosterone and estradiol were measured during a mean follow-up of 4.5 years.
This study showed that men with low testosterone had 65% greater all-cause mortality, while men with low estradiol suffered 54% more deaths.69 Men low in estradiol and testosterone were almost twice as likely to die (a 96% increase in mortality) compared to men in the optimal
This large study of aged men corroborates prior published reports linking imbalances of testosterone and/or estradiol with greater incidences of degenerative disease and death.10,12,38-40,46,70-76
Why the authorities at Massachusetts General Hospital suppressed estradiol to dangerously low levels (1.0 to 2.8 pg/mL) in their study subjects is beyond our comprehension. It undermined the clinical value of the data they acquired.
Encouraging Findings From Massachusetts General Hospital Study
In the study conducted at Massachusetts General Hospital, groups of men were first given varying doses of the
testosterone-suppressing drug (Zoladex®) for 12 weeks. They were then given various doses of topical testosterone cream for 16 weeks. One group received testosterone cream only, while the other group received testosterone cream plus the estrogen-suppressing drug (anastrozole).
The doctors used some sophisticated techniques to measure parameters such as belly fat, strength, lean muscle, and sexual function. As mentioned earlier, DXA and CT scans were performed
to determine lean mass as well as subcutaneous belly fat and visceral fat. Validated methods were used
to determine sexual function, physical function,vitality, strength, and overall health status of the men enrolled in the study.
In men given the proper dose of testosterone cream, significant anti-aging effects were clearly evident.
In the group of men whose blood levels of total testosterone increased to 805 ng/dL and whose estradiol levels rose nearest the optimal ranges (20-30 pg/mL), there were significant reductions
in belly fat with improvements in lean muscle, strength, and sexual function. The total testosterone blood level (805 ng/dL) in men who attained these benefits falls squarely within the optimal range that Life Extension has advocated since 1996.
These benefits did not occur in the group of men given testosterone plus 7 mg/week of anastrozole. These men in fact suffered a decrease in lean muscle and increased belly fat. Compared to the men who
achieved optimal testosterone and estradiol blood levels, the study subjects who were overdosed on anastrozole experienced decreased sexual function and strength.
Another important finding from this study was that the only group that achieved a significant decrease in body fat was men who achieved total testosterone blood levels averaging 805 ng/dL.
In fact, men who received a placebo or low-dose testosterone showed a substantial increase in subcutaneous belly fat compared to
those who achieved optimal serum total testosterone levels.
Life Extension has long recommended that aging men maintain total testosterone at an optimal range of 700-900 ng/mL.
This Massachusetts General Hospital study helps confirm that the greatest benefits occur when total testosterone and estradiol levels are in ranges that can easily be achieved and monitored utilizing comprehensive blood tests.