Life Extension Magazine November 2010
Mainstream Doctors’ Ineptitude Put on Display in the New England Journal of Medicine
By Steven Joyal, MD
A study published online in the June 30, 2010 edition of the New England Journal of Medicine1 confirms how little conventional doctors know about prescribing testosterone to aging men.
The Life Extension Foundation® long ago recognized that maturing men have a propensity to convert (aromatize) testosterone into estrogen. When you see an overweight man growing breasts, it is not directly because he eats too much. This phenomenon is instead caused by the testosterone he converts to breast-enlarging estrogen.2
When men are prescribed testosterone gels or creams, they sometimes have to take an aromatase-inhibiting drug (like Arimidex®) to prevent their estrogen (measured as estradiol in the blood) from climbing to dangerous levels.3
Optimal estradiol blood levels in men are between 20-30 pg/mL.4 Elderly males can have much higher estradiol levels that place them at substantial risk for developing coronary atherosclerosis and thrombotic stroke.5,6
If elderly men are prescribed large doses of topical testosterone gel or cream, their estradiol blood levels have to be tested and properly controlled. Failure to manage estradiol in men receiving high-dose testosterone gel or cream can result in a catastrophic estrogen surge that increases vascular disease risk and premature death.
Enormous Tax Dollars Squandered on Flawed Testosterone Study
The federal government provided a financial grant to an armada of doctors to evaluate the effects of high-dose testosterone on men who were so severely debilitated that they struggled to climb more than 10 stairs or walk the equivalent of two city blocks.
These men suffered numerous risk factors such as obesity, diabetes, hypertension, and elevated blood lipids that placed them at higher risk for cardiovascular events. Obese men tend to produce loads of estrogen in their abdominal fat—and typically have higher estradiol levels than thinner men.
The men with the worst vascular risk factors (such as the highest triglyceride levels) were placed on a dose of topical testosterone that is TWICE the standard starting dose. These debilitated men were given testosterone in a way that is more likely to aromatize through the skin into estrogen.
Men with fewer vascular risk factors were given a placebo gel.
It should be no surprise to learn that this study was halted prematurely because the debilitated men given the high-dose testosterone (with no aromatase inhibitor) suffered more “atherosclerosis-related events” such as heart attack, stroke, and sudden death.1
The official title of this study is “Adverse Events with Testosterone Administration.” A more accurate title may have been: “Elevated Estrogen Leads to Cardiovascular Events in Older Men.”
To read Life Extension’s recent review about the dangers of estrogen imbalance in aging men published in the May 2010 magazine issue, visit: www.lef.org/maleestrogen
Life Extension Writes a Letter to These Doctors
The day this study was published, Life Extension® wrote the doctors who conducted it asking if there were any data regarding baseline and post-baseline blood estradiol levels. We have waited over eight weeks, and the authors of the New England Journal of Medicine study have not responded to our repeated requests as to whether estradiol levels were ever measured.
From what was written in the paper, it does not appear that any attention was paid to the estrogen levels in these debilitated men. The authors wrote in the discussion section of the paper, “Testosterone and associated increases in estradiol may promote inflammation, coagulation, and platelet aggregation.”1 Yet these doctors don’t appear to have done anything to evaluate estradiol levels in the unfortunate study subjects given double-dose testosterone with no aromatase inhibitor to suppress the expected estrogen surge.
This Study Had Numerous Other Flaws
Leaving aside the failure to manage estradiol levels in men given high-dose testosterone gel, there were numerous design flaws that call into question any conclusion that can be drawn from this study.
As mentioned earlier, the testosterone group at baseline was at greater risk for cardiovascular events as manifested by a greater proportion of men in the testosterone group with dyslipidemia who were undergoing statin and antihypertensive drug treatment.
In addition, triglyceride levels (higher) and HDL levels (lower) were trending against the testosterone group. Clearly, the baseline cardiovascular risk for the testosterone group was higher than the placebo group. The authors claim that a sensitivity analysis, as well as controlling for cardiovascular risk factors, did not change the results, but the small sample size and relatively short trial duration serve to magnify, not minimize, differences due to chance.
The study was not designed to systematically assess for cardiovascular events, and given the small sample size, lack of consistent pattern of events, diversity of serious events, and small number of serious adverse cardiac events (10 vs. 1) in the two treatment groups before study stoppage in this short-duration trial strongly suggest that the results are due to chance. Another explanation, of course, is that the adverse vascular events were caused by the uncontrolled conversion of the topically-applied testosterone to estradiol in men who were already likely to have dangerously high estradiol blood levels to begin with.
Fodder for the Media
The published scientific data document low testosterone as being an independent risk factor for heart attack and a host of other age-related ailments.
The authors of this study acknowledge the benefits the testosterone group obtained from the drug and openly admitted the limitations of this study in providing guidance about the effects of testosterone on different population groups.
The media, however, has a propensity to publicize one negative study while ignoring hundreds of positive ones. We will not be surprised to see this horrifically flawed study used for decades to discredit the safety and efficacy of properly prescribed testosterone cream and aromatase-inhibition therapy.
Importance of Blood Testing in Men Supplementing with Testosterone
In response to overwhelmingly favorable studies, record numbers of aging men are rubbing testosterone creams or gels on their skin each day to restore this vital hormone to youthful levels.
Within 45-60 days of initiating testosterone replacement therapy, the following blood tests should be done to ensure safety and efficacy:
These tests can be done at your doctor’s office, or you can order them all directly from Life Extension by calling 1-800-208-3444 (24 hours a day). These tests can retail for over $500 at commercial labs, but Life Extension members pay only $125 (Test code LC100001).
To review Life Extension Magazine® articles from July 2008 and December 2008 describing benefits of testosterone replacement in aging men, visit:
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at
1. Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010 Jul 8;363(2):109-22. Epub 2010 Jun 30.
2. Narula HS, Carlson HE. Gynecomastia. Endocrinol Metab Clin North Am. 2007 Jun;36(2):497-519.
3. Rhoden EL, Morgentaler A. Treatment of testosterone-induced gynecomastia with the aromatase inhibitor, anastrozole. Int J Impot Res. 2004 Feb;16(1):95-7.
4. Jankowska EA, Rozentryt P, Ponikowska B. Circulating estradiol and mortality in men with systolic chronic heart failure. JAMA. 2009 May 13;301(18):1892-901.
5. Abbott RD, Launer LJ, Rodriguez BL, et al. Serum estradiol and risk of stroke in elderly men. Neurology. 2007 Feb 20;68(8):563-8.
6. Dunajska K, Milewicz A, Szymczak J, et al. Evaluation of sex hormone levels and some metabolic factors in men with coronary atherosclerosis. Aging Male. 2004 Sep;7(3):197-204.