Misguided MedicineJune 2015
By William Faloon
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 the 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 early observations.49-53
Insufficient 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 increased 317% 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 enzyme aromatase.
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 testosterone.
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 aged 69-80 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 ranges.69
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.
Misinterpretation Of The Massachusetts General Hospital Study
The doctors who conducted the study at Massachusetts General Hospital extolled their findings about the adverse effects seen in men prescribed the absurdly high dose of anastrozole.
They noted the increased percentage of abdominal fat as well as decreased sexual desire and erectile function seen in their estrogen-deficient study subjects. These doctors extrapolated that since abdominal fat mass is associated with diabetes and metabolic syndrome, that the marked increase in visceral fat seen in men prescribed high-dose anastrozole could portend increases in cardiovascular disease.
The problem is that estradiol was artificially suppressed down to levels not seen in the real world. Thus it is not surprising that these men with virtually no estrogen suffered unwanted side effects.
The doctors who performed this study concluded that men need sufficient levels of estrogen, as well as testosterone, to stay healthy. The media made it appear as if a major discovery had occurred, i.e. a newly found role for estrogen in males. This is not a new finding!
Scientists long ago identified men’s biological requirements for estrogen, and published studies of aging men clearly demonstrate the lethal impact when estradiol levels are too high or too low.43,69
The implication from this study’s findings was that doctors should use caution when prescribing estrogen-suppressing drugs to their male patients. Nowhere do they mention that the study subjects were grossly overdosed on anastrozole to the point that estradiol levels dropped to virtually nonexistent levels.
In today’s sound bite environment, practicing physicians will be even less likely to prescribe the proper dose of anastrozole (1 mg a week) to men whose estradiol levels are over 30 pg/mL. At Life Extension®, we sometimes see aging men with estradiol levels over 60 pg/mL. These men are in urgent need of aromatase-inhibition using the proper dose of anastrozole, yet their doctors might erroneously refuse to prescribe it because they will recall the misinterpretation of this study emanating from esteemed Massachusetts General Hospital.
On a positive note, doctors at Massachusetts General Hospital stated in their concluding remarks that some of the deleterious effects of aging may be related to changes in testosterone and estrogen levels that “may be preventable with appropriate replacement.”
At least the medical authorities are recognizing that aging men do indeed require testosterone and estrogen.
Our Early Battles With Medical “Authorities”
When Life Extension® first recommended that aging men restore their testosterone to youthful levels, a firestorm of criticism erupted.
The medical establishment proclaimed that by interfering with the natural decline in testosterone secretion, men risked all kinds of terrible fates. When Life Extension® members asked their doctors for testosterone prescriptions, they ran into objections such as, “I don’t prescribe steroids,” “testosterone causes heart attacks,” and “testosterone causes prostate cancer.”
We countered these criticisms with hundreds of scientific citations showing that testosterone deficiency is an underlying cause of many age-related diseases. We also demonstrated that none of the paranoid fears about natural testosterone had ever been substantiated.
Low Testosterone Increases Prostate Cancer Risk
Fear of prostate cancer was the leading reason why aging men historically shied away from restoring their testosterone.
To dispel this concern, Life Extension® analyzed every published study in the 1990s and found there was no basis for asserting that testosterone causes prostate cancer.86-91
Our observations from the thousands of blood tests we perform each year for members corroborate this. What we found is that men with low testosterone appear to be more likely to contract prostate cancer.
In the book Testosterone for Life, authored by Harvard researcher Abraham Morgentaler, MD, the misleading notion about testosterone causing prostate cancer was exposed in meticulous detail.
Dr. Morgentaler dropped a bombshell on the medical establishment in 2008 showing that men with low testosterone levels have an increased percentage of prostate cancer-positive biopsies.92 This and other findings have led to the record number of aging men being prescribed natural testosterone today.
Critical Importance Of Blood Testing
Today’s conventional physicians prescribe blood tests to check glucose, cholesterol, and triglycerides, but rarely check their male patients’ testosterone and estradiol levels.
When looking at the higher mortality rates associated with imbalances of these critical hormones, it becomes strikingly apparent that a significant number of heart attacks, strokes, bone fractures, and other degenerative diseases are easily preventable.
One reason these hormone blood tests are not normally prescribed is their high retail cost, and the fact that insurance companies may not routinely pay for them.
As a member of the Life Extension Foundation®, you don’t have to be victimized by conventional medical ignorance, high prices, or insurance company indifference.
Take Charge Of Your Health
An all-inclusive blood test panel that includes total testosterone, free testosterone, estradiol, and PSA can be very expensive at commercial labs. Life Extension® members obtain these tests at a huge discount.
If your blood test result reveals imbalanced testosterone and/or estradiol, you are in a position to initiate immediate corrective action. Not only can restoring youthful hormone balance save your life, but men (and women) often experience an enhancement in their quality of life after their hormones are adjusted to optimal ranges.
A description of the Male and Female Blood Test Panels can be found on the page to the right. As you’ll readily see, these panels contain many important tests (such as 25-hydroxyvitamin D, homocysteine, C-reactive protein, and DHEA) that mainstream doctors seldom check for.
When you order these tests, a requisition form is sent listing blood drawing stations in your local area. Appointments are usually not necessary, meaning you can have your blood drawn at your convenience. Results are mailed (or emailed) to you usually within five days.
Annual Blood Test Super Sale
High prices charged by commercial labs for comprehensive blood testing preclude most people from having them done. The tragic result is that aging humans needlessly suffer the ill effects of hormone imbalances.
Life Extension® breaks down these price barriers by offering Male and Female Blood Test Panels at the lowest prices anywhere. Once a year, we discount the popular Male and Female Blood Test Panels—far less than what commercial labs charge.
The Blood Test Super Sale ends June 1, 2015, so please order your requisition kit to take advantage of these extra discounted prices. You can have your blood drawn any time after receiving your requisition kit.
The results of your blood tests are rapidly sent directly to you. If you have any questions, you are welcome to call our health advisor helpline.
Annual blood testing is the single most effective method of detecting abnormalities before they lead to serious illness or death. A call to 1-800-208-3444 is all you have to do to order these comprehensive tests at extra discounted prices.
- Available at: http://www.massgeneral.org/about/pressrelease.aspx?id=1617.Accessed February 17, 2014.
- Finkelstein JS, Lee H, Burnett-Bowie SA, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013 Sep 12;369(11):1011-22.
- Katznelson L, Finkelstein JS, Schoenfeld DA, Rosenthal DI, Anderson EJ, Klibanski A. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab. 1996 Dec;81(12):4358-65.
- Page ST, Amory JK, Bowman FD, et al. Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T. J Clin Endocrinol Metab. 2005 Mar;90(3):1502-10.
- Wang C, Eyre DR, Clark R, et al. Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, and increases bone formation markers in hypogonadal men--a clinical research center study. Clin Endocrinol Metab. 1996 Oct;81(10):3654-62.
- Steidle C, Schwartz S, Jacoby K, Sebree T, Smith T, Bachand R. AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J Clin Endocrinol Metab. 2003 Jun;88(6):2673-81.
- Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans. Arch Intern Med. 2006 Aug 14;166(15):1660-5.
- Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab. 2008 Jan;93(1):68-75.
- Khaw KT, Dowsett M, Folkerd E, et al. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation. 2007 Dec 4;116(23):2694-701.
- Jankowska EA, Biel B, Majda J, et al. Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Circulation. 2006 Oct 24;114(17):1829-37.
- English KM, Mandour O, Steeds RP, Diver MJ, Jones TH, Channer KS. Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms. Eur Heart J. 2000 Jun;21(11):890-4.
- Hak AE, Witteman JC, de Jong FH, et al. Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study. J Clin Endocrinol Metab. 2002 Aug;87(8):3632-9.
- Rosano GM, Leonardo F, Pagnotta P, et al. Acute anti-ischemic effect of testosterone in men with coronary artery disease. Circulation. 1999 Apr 6;99(13):1666-70.
- Tuck SP, Francis RM. Testosterone, bone and osteoporosis. Front Horm Res. 2009 37:123-32.
- Cawthon PM, Ensrud KE, Laughlin GA, et al. Sex hormones and frailty in older men: the osteoporotic fractures in men (MrOS) study. J Clin Endocrinol Metab. 2009 Oct;94(10):3806-15.
- Kamel HK, Maas D, Duthie EH, Jr. Role of hormones in the pathogenesis and management of sarcopenia. Drugs Aging. 2002 19(11):865-77.
- Bhasin S, Storer TW, Berman N, et al. Testosterone replacement increases fat-free mass and muscle size in hypogonadal men. J Clin Endocrinol Metab . 1997 Feb;82(2):407-13.
- Maggio M, Basaria S, Ceda GP, et al. The relationship between testosterone and molecular markers of inflammation in older men. J Endocrinol Invest . 2005 28(11 Suppl Proceedings):116-9.
- Tang YJ, Lee WJ, Chen YT, Liu PH, Lee MC, Sheu WH. Serum testosterone level and related metabolic factors in men over 70 years old. J Endocrinol Invest. 2007 Jun;30(6):451-8.
- Kalinchenko SY, Tishova YA, Mskhalaya GJ, Gooren LJ, Giltay EJ, Saad F. Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: the double-blinded placebo-controlled Moscow study. Clin Endocrinol (Oxf). 2010 Nov;73(5):602-12.
- Lu PH, Masterman DA, Mulnard R, et al. Effects of testosterone on cognition and mood in male patients with mild Alzheimer disease and healthy elderly men. Arch Neurol. 2006 Feb;63(2):177-85.
- Gouras GK, Xu H, Gross RS, et al. Testosterone reduces neuronal secretion of Alzheimer’s beta-amyloid peptides. Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1202-5.
- Almeida OP, Yeap BB, Hankey GJ, Jamrozik K, Flicker L. Low free testosterone concentration as a potentially treatable cause of depressive symptoms in older men. Arch Gen Psychiatry. 2008 Mar;65(3):283-9.
- Hogervorst E, Bandelow S, Combrinck M, Smith AD. Low free testosterone is an independent risk factor for Alzheimer’s disease. Exp Gerontol. 2004 Nov-Dec;39(11-12):1633-9.
- Ready RE, Friedman J, Grace J, Fernandez H. Testosterone deficiency and apathy in Parkinson’s disease: a pilot study. J Neurol Neurosurg Psychiatry. 2004 Sep;75(9):1323-6.
- Morgentaler A, Rhoden EL. Prevalence of prostate cancer among hypogonadal men with prostate-specific antigen levels of 4.0 ng/mL or less. Urology. 2006 Dec;68(6):1263-7.
- Rhoden EL, Morgentaler A. Testosterone replacement therapy in hypogonadal men at high risk for prostate cancer: results of 1 year of treatment in men with prostatic intraepithelial neoplasia. J Urol. 2003 Dec;170(6 Pt 1):2348-51.
- Morgentaler A. Testosterone and prostate cancer: an historical perspective on a modern myth. Eur Urol. 2006 Nov;50(5):935-9.
- Banach-Petrosky W, Jessen WJ, Ouyang X, et al. Prolonged exposure to reduced levels of androgen accelerates prostate cancer progression in Nkx3.1; Pten mutant mice. Cancer Res. 2007 Oct 1;67(19):9089-96.
- Hoffman MA, DeWolf WC, Morgentaler A. Is low serum free testosterone a marker for high grade prostate cancer? J Urol. 2000 Mar;163(3):824-7.
- Pope HG Jr, Cohane GH, Kanayama G, Siegel AJ, Hudson JI. Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am J Psychiatry. 2003 Jan;160(1):105-11.
- Barrett-Connor E, Von Mühlen DG, Kritz-Silverstein D. Bioavailable testosterone and depressed mood in older men: the Rancho Bernardo Study. J Clin Endocrinol Metab. 1999 Feb;84(2):573-7.
- Saad F, Gooren LJ, Haider A, Yassin A. A dose-response study of testosterone on sexual dysfunction and features of the metabolic syndrome using testosterone gel and parenteral testosterone undecanoate. J Androl. 2008 Jan-Feb;29(1):102-5.
- Wang C, Cunningham G, Dobs A, et al. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab. 2004 May;89(5):2085-98.
- Arver S, Dobs AS, Meikle AW, Allen RP, Sanders SW, Mazer NA. Improvement of sexual function in testosterone deficient men treated for 1 year with a permeation enhanced testosterone transdermal system. J Urol. 1996 May;155(5):1604-8.
- Amore M. Partial androgen deficiency and neuropsychiatric symptoms in aging men. J Endocrinol Invest. 2005 28(11 Suppl Proceedings):49-54.
- Lindholm J, Eldrup E, Winkel P. Variability in plasma oestrogen concentrations in men with a myocardial Infarction. Dan Med Bull. 1990 Dec;37(6):552-6.
- Usuki F, Nakazato O, Osame M, Igata A. Hyperestrogenemia in neuromuscular diseases. J Neurol Sci. 1989 Feb;89(2-3):189-97.
- Small M, MacRury S, Beastall GH. Oestradiol levels in diabetic men with and without a previous myocardial infarction. Q J Med. 1987 Jul;64(243):617-23.
- Phillips GB. Evidence for hyperestrogenemia as the link between diabetes mellitus and myocardial infarction. Am J Med. 1984 Jun;76(6):1041-8.
- Phillips GB, Pinkernell BH, Jing TY. The association of hypotestosteronemia with coronary artery disease in men. Arterioscler Thromb. 1994 May;14(5):701-6.
- Jeppesen LL, Jørgensen HS, Nakayama H, Raaschou HO, Olsen TS, Winther K. Decreased serum testosterone in men with acute ischemic stroke. Arterioscler Thromb Vasc Biol. 1996 Jun;16(6):749-54.
- 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.
- 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.
- Wranicz JK, Cygankiewicz I, Rosiak M, Kula P, Kareba W. The relationship between sex hormones and lipid profile in men with coronary artery disease. Int J Cardiol. 2005 May 11;101(1):105-10.
- Suzuki K, Ito K, Ichinose Y, Kurokawa K, Suzuki T. Endocrine environment of benign prostatic hyperplasia prostate size and volume are correlated with serum estrogen concentration. Scand J Urol Nephrol. 1995 Mar;29(1):65-8.
- Krieg M, Nass R, Tunn S. Effect of aging on endogenous level of 5 alpha-dihydrotestosterone, testosterone, estradiol, and estrone in epithelium and stroma of normal and hyperplastic human prostate. J Clin Endocrinol Metab. 1993 Aug;77(2):375-81.
- Gann PH, Hennekens CH, Longcope C, Verhoek-Oftedahl W, Grodstein F, Stampfer MJ. A prospective study of plasma hormone levels, nonhormonal factors, and development of benign prostatic hyperplasia. Prostate. 1995 Jan;26(1):40-9.
- Matsuda T, Abe H, Suda K. Relation between benign prostatic hyperplasia and obesity and estrogen. Rinsho Byori. 2004 Apr;52(4):291-4.
- Ho CK, Nanda J, Chapman KE, Habib FK. Oestrogen and benign prostatic hyperplasia: effects on stromal cell proliferation and local formation from androgen. J Endocrinol. 2008 Jun;197(3):483-91.
- Singh PB, Matanhelia SS, Martin FL. A potential paradox in prostate adenocarcinoma progression: oestrogen as the initiating driver. Eur J Cancer. 2008 May;44(7):928-36.
- Giton F, de la Taille A, Allory Y, et al. Estrone sulfate (E1S), a prognosis marker for tumor aggressiveness in prostate cancer (PCa). J Steroid Biochem Mol Biol. 2008 Mar;109(1-2):158-67.
- Prins GS, Korach KS. The role of estrogens and estrogen receptors in normal prostate growth and disease. Steroids. 2008 Mar;73(3):233-44.
- Mellström D, Vandenput L, Mallmin H, et al. Older men with low serum estradiol and high serum SHBG have an increased risk of fractures. J Bone Miner Res. 2008 Oct;23(10):1552-60.
- Pernow Y, Hauge EM, Linder K, Dahl E, Sääf M. Bone histomorphometry in male idiopathic osteoporosis. Calcif Tissue Int. 2009 Jun;84(6):430-8.
- Jankowska EA, Rozentryt P, Ponikowska B, et al. Circulating estradiol and mortality in men with systolic chronic heart failure. JAMA. 2009 May 13;301(18):1892-901.
- Moyad MA. Complementary therapies for reducing the risk of osteoporosis in patients receiving luteinizing hormone-releasing hormone treatment/orchiectomy for prostate cancer: a review and assessment of the need for more research. Urology. 2002 Apr;59(4 Suppl 1):34-40.
- Mittan D, Lee S, Miller E, Perez RC, Basler JW, Bruder JM. Bone loss following hypogonadism in men with prostate cancer treated with GnRH analogs. J Clin Endocrinol Metab. 2002 Aug;87(8):3656-61.
- Greenspan SL, Nelson JB, Trump DL, Resnick NM. Effect of once-weekly oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer: a randomized trial. Ann Intern Med. 2007 Mar 20;146(6):416-24.
- Higano CS. Management of bone loss in men with prostate cancer. J Urol. 2003 Dec;170(6 Pt 2):S59-63.
- Galvão DA, Taaffe DR, Spry N, Joseph D, Newton RU. Combined resistance and aerobic exercise program reverses muscle loss in men undergoing androgen suppression therapy for prostate cancer without bone metastases: a randomized controlled trial. J Clin Oncol. 2010 Jan 10;28(2):340-7.
- Sattler F, Bhasin S, He J, et al. Testosterone threshold levels and lean tissue mass targets needed to enhance skeletal muscle strength and function: the HORMA trial. J Gerontol A Biol Sci Med Sci. 2011 Jan;66(1):122-9.
- Kumar RJ, Barqawi A, Crawford ED. Adverse events associated with hormonal therapy for prostate cancer. Rev Urol. 2005 7 Suppl 5:S37-43.
- Smith MR. Changes in fat and lean body mass during androgen-deprivation therapy for prostate cancer. Urology. 2004 63(4):742–745.
- Hamilton EJ, Gianatti E, Strauss BJ, et al. Increase in visceral and subcutaneous abdominal fat in men with prostate cancer treated with androgen deprivation therapy. Clin Endocrinol (Oxf). 2011 Mar;74(3):377-83.
- Jensen MD, Kanaley JA, Reed JE, Sheedy PF. Measurement of abdominal and visceral fat with computed tomography and dual-energy x-ray absorptiometry. Am J Clin Nutr. 1995 Feb;61(2):274-8.
- Sodickson A, Baeyens PF, Andriole KP, et ak. Recurrent CT, cumulative radiation exposure, and associated radiation-induced cancer risks from CT of adults. Radiology. 2009 Apr;251(1):175-84.
- Traish AM, Saad F, Feeley RJ, Guay A. The dark side of testosterone deficiency: III. Cardiovascular disease. J Androl. 2009 Sep-Oct;30(5):477-94.
- Tivesten A, Vandenput L, Labrie F, et al. Low serum testosterone and estradiol predict mortality in elderly men. J Clin Endocrinol Metab. 2009 Jul;94(7):2482-8.
- Laaksonen DE, Niskanen L, Punnonen K, et al. Sex hormones, inflammation and the metabolic syndrome: a population-based study. Eur J Endocrinol. 2003 Dec;149(6):601-8.
- Cutolo M, Seriolo B, Villaggio B, Pizzorni C, Craviotto C, Sulli A. Androgens and estrogens modulate the immune and inflammatory responses in rheumatoid arthritis. Ann NY Acad Sci. 2002 Jun;966:131-42.
- Moffat SD, Zonderman AB, Metter EJ, Blackman MR, Harman SM, Resnick SM. Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. J Clin Endocrinol Metab. 2002 Nov;87(11):5001-7.
- Hogervorst E, Combrinck M, Smith AD. Testosterone and gonadotropin levels in men with dementia. Neuro Endocrinol Lett. 2003 Jun;24(3-4):203-8.
- Traish AM, Saad F, Guay A. The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. J Androl. 2009 Jan-Feb;30(1):23-32.
- Debing E, Peeters E, Duquet W, Poppe K, Velkeniers B, Van Den Branden P. Men with atherosclerotic stenosis of the carotid artery have lower testosterone levels compared with controls. Int Angiol. 2008 Apr;27(2):135-41.
- Muller M, van den Beld AW, Bots ML, Grobbee DE, Lamberts SW, van der Schouw YT. Endogenous sex hormones and progression of carotid atherosclerosis in elderly men. Circulation. 2004 May 4;109(17):2074-9
- Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev. 2005 Oct;26(6):833-76.
- Finkelstein JS, Lee H, Burnett-Bowie SA, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013 Sep 12;369(11):1011-22.
- Longcope C, Kato T, Horton R. Conversion of blood androgens to estrogens in normal adult men and women. J Clin Invest. 1969 Dec;48(12):2191-201.
- Khosla S, Melton LJ 3rd, Atkinson EJ, O’Fallon WM, Klee GG, Riggs BL. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J Clin Endocrinol Metab. 1998 Jul;83(7):2266-74.
- van den Beld AW, de Jong FH, Grobbee DE, Pols HA, Lamberts SW. Measures of bioavailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men. J Clin Endocrinol Metab. 2000 Sep;85(9):3276-82.
- Vermeulen A, Kaufman JM, Goemaere S, van Pottelberg I. Estradiol in elderly men. Aging Male. 2002 Jun;5(2):98-102.
- Available at: http://www.lef.org/magazine/mag2010/may2010_Why-Estrogen-Balance-is-Critical-to-Aging-Men_01.htm. Accessed February 17, 2014.
- de Ronde W, de Jong FH. Aromatase inhibitors in men: effects and therapeutic options. Reprod Biol Endocrinol. 2011 Jun 21;9:93.
- Available at: http://www.renalandurologynews.com/low-estrogen-explains-some-hypogonadal-symptoms-in-men/article/311348/. Accessed February 17, 2014.
- Rhoden EL, Averbeck MA, Teloken PE. Androgen replacement in men under-going treatment for prostate cancer. J Sex Med. 2008 Sep;5(9):2202-8.
- Morgentaler A. Testosterone replacement therapy and prostate cancer. Urol Clin North Am. 2007 Nov;34(4):555-63.
- Miner MM, Seftel AD. Testosterone and ageing: what have we learned since the Institute of Medicine report and what lies ahead? Int J Clin Pract. 2007 Apr;61(4):622-32.
- Raynaud JP. Prostate cancer risk in testosterone-treated men. J Steroid Biochem Mol Biol. 2006 Dec;102(1-5):261-6.
- Tan RS, Salazar JA. Risks of testosterone replacement therapy in ageing men. Expert Opin Drug Saf. 2004 Nov;3(6):599-606.
- Gooren L. Androgen deficiency in the aging male: benefits and risks of androgen supplementation. J Steroid Biochem Mol Biol. 2003 Jun;85(2-5):349-55.
- Available at: http://www.lef.org/magazine/mag2008/dec2008_Destroying-the-Myth-about-Testosterone-Replacement-Prostate-Cancer_01.htm. Accessed February 17, 2014.