Poorly Done Testosterone Studies Fuel Concerns and Lawsuits

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Nelson Vergel

Founder, ExcelMale.com
A study published at the end of 2013 and a previous one from the Veterans Administration Hospital System (see below post) show what happens when older men are given suboptimal testosterone replacement without proper monitoring and management of factors that can affect their health.

Testosterone replacement can increase red blood cells (and hematocrit which is the total red cell volume) and estradiol production, two important factors for men's health when present in normal levels (red blood cells carry oxygen and estradiol maintains healthy bones, cognitive function, and sex drive). However, due to genetics, age or other factors, some men can have excessive production of both. High hematocrit and estradiol are more common in older men on testosterone since testosterone-related aromatization and erythrocytosis are worse in that population. In excess, both variables have been linked to cardiovascular risks in older men. Not a single one of the studies reporting higher cardiovascular risks in men on testosterone have managed either important factors.

Additionally, this latest nonrandomized study states that "No data were available on indications for T prescription, race, laboratory findings, occupational, environmental, or lifestyle factors."

Many clinics are managing hematocrit by recommending blood donation or phlebotomies to men with a hematocrit over 53. They are also recommending treatment with low dose anastrozole for men with estradiol over 50 pg/mL. However, an alarming number of medical practices and research studies chose not to follow basic recommendations from the 4 current guideline groups that, in my opinion, may still need revision to add estradiol monitoring. The table below shows a summary of the monitoring required by the main 4 guidelines groups in the world.

It is also imperative that future studies at least follow the minimum requirements of the current guidelines. The last few studies that concluded that testosterone may increase cardiovascular risks did not monitor or report hematocrit blood levels. Most guidelines recommend monitoring hematocrit at months 3, 6 and then annually. Are these studies liable for not following minimum guidelines and exposing their volunteers to increased risks?. I do not why I do not see discussions on this alarming fact. Institutional review boards (IRB's) need to educate themselves about this problem so that no more studies are allowed that do not properly monitor men on testosterone replacement. Would a class action lawsuit be required to change this malpractice? Some are already popping up: Testosterone Treatment Lawsuit Information

It is time to revise the current guidelines for testosterone treatment in men to include monitoring and managing estradiol with the same frequency as hematocrit. It is also time to enforce guidelines compliance in all testosterone studies.

I encourage all men currently on testosterone replacement or thinking about starting it to familiarize themselves with the table below and demand that guidelines (along with estradiol monitoring) are followed by their physicians. And, please, do not sign a study consent form if you see that they do not specify the monitoring frequency and side effect management options the researchers are offering.

I also encourage Abbvie (makers of Androgel), Auxillum (makers of Testim), Endo Pharmaceuticals (makers of Fortesta), Lilly (makers of Axiron) to wake up to this fact before they lose millions due to negligent practices that do not follow minimum guidelines.

I am looking forward to the day when a research group will perform a good study that uses a protocol that not only gives testosterone to men but also one that retests them periodically to manage dose, high hematocrit, and estradiol blood levels. It should not be a difficult task and it is the only responsible thing to do to come up with conclusions that we can trust.

For options on how to prevent and reverse potential side effects of testosterone replacement: click here


Reference: Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men



table5guidelines.jpg
 
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Defy Medical TRT clinic doctor

Nelson Vergel

Founder, ExcelMale.com
This is a press release that describes issues with a previous study from the veterans administration hospital that also fails to monitor hematocrit and estradiol (and in which the majority of veterans were not monitored after starting testosterone). When will large medical groups get it?

ExcelMale.com Identifies Major Flaws in Recently Published VA Testosterone Study


A men's health grassroots and education group advocates for better testosterone replacement therapy of veterans of the U.S. Armed Forces


Houston, TX -- (SBWIRE) -- 11/14/2013 -- Last week's Journal of American Medical Association (JAMA) published a retrospective study (1) that was performed at the Veteran's Administration (VA) hospital system. While it has long been known that testosterone replacement therapy (TRT) improves sexual function, bone density, lean body mass, and lipids, this study concluded that testosterone therapy may increase the risk of cardiovascular problems in men with a history of heart disease. It cautioned that men with pre-existing cardiovascular problems and testosterone deficiency should avoid TRT. ExcelMale.com, an education website for men, identified major flaws in this study that wrongly alarmed patients, physicians and the media.

While it is commendable that the VA hospital system collected data on the use of testosterone in over 8,000 veterans with cardiovascular disease, the study highlights deficiencies in the hospital system's testosterone management protocol.

The VA study showed that 40% of patients did not have their testosterone blood levels retested after they started testosterone. This lack of follow up contradicts a review of guidelines published on 2011 by the American College of Cardiology Foundation that The Endocrine Society, the American Association of Clinical Endocrinologists, the American Society of Reproductive Medicine, and the European Association of Urology recommendations of monitoring patients' blood analysis 3 months after initiation of testosterone therapy (2) to determine TRT dose adjustments and potential side effects.

A previously study (3) also published in JAMA in 2009 showed that men with total testosterone blood levels below 550 ng/dl had a significant increase in their risk of cardiovascular disease, while men with levels above 550 ng/dl reduced their risk by 30%. Monitored participants in the VA study were only able to increase their total testosterone blood levels to 332 ng/dl, a value considered sub-optimal by all testosterone treatment medical guidelines.

Another shortcoming of the VA hospital system's TRT protocol highlighted by the study is the lack of monitoring and managing of hematocrit (red cell volume) and estradiol (a female hormone produced in the body from testosterone). TRT can increase hematocrit and estradiol is a minority of men resulting in increased blood viscosity and cardiovascular risks as documented in the previously mentioned 2009 JAMA study (4). Fortunately, both variables can be easily managed if patients are properly monitored.

The majority of participants in the VA study used testosterone patches. Once a popular method of testosterone delivery, testosterone patches are no longer used due to their poor absorption and inconvenience. This is reflected in the VA study where most of the participants continued to have testosterone deficiency and increased cardiovascular risk.

"Publishing flawed studies only increases the current misconceptions surrounding this important therapy and unnecessarily alarms TRT patients and their physicians", said Nelson Vergel, founder of ExcelMale.com. "We encourage patients, physicians and the media to closely examine studies for misleading information that could increase barriers to life saving therapies", added Vergel.

"We urge the VA hospital system to revise their TRT protocol and to follow current testosterone guidelines. We want only the best for the men who have served our country", said Keith Willse, co-founder of ExcelMale.com.

ExcelMale.com is a peer reviewed and moderated safe platform where men can privately and securely share information and experiences about health and productivity. It is moderated daily for content and enforcement of a code of conduct and provides well organized archives of articles, forum chats, product reviews, and videos related to:

- Testosterone replacement,
- erectile dysfunction and sex drive,
- fat loss and muscle gain,
- energy boosters,
- exercise,
- nutrition,
- supplementation,
- diagnostics,
- pharmaceuticals,
- and all things related to men's health and productivity.

For more information and patient/clinician education on testosterone, visit http://www.ExcelMale.com

References:

1- JAMA. 2013;310(17):1829-1836.
2- J Am Coll Cardiol. 2011;58(16):1674-1681.
3- JAMA. 2009 May 13;301(18):1892-901.
4- JAMA. 2009 May 13;301(18):1892-901.
 

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Kelly

Member
Seems like it's becoming the new media football to kick around.

Did Lyle Alzado come back to life?
 
I have also being seeing the attorney ads for "victims" who had heart attacks while on TRT. Unfortunately our entitled society has been conditioned to blame someone else for their own faults. Not only is the study this misinformation is based upon simply wrong, but more than likely that patients heart attack was caused by their life-style and habits. The poorly monitored TRT only potentiated the already existing risk due to elevated H/H.

People wonder why physicians have to charge so much. Always have to keep an attorney on retainer and be able to defend yourself against fished law-suits. The drug companies already consider legal pay-outs into their margins, and the margins are so large they can afford to pay. Its probably cheaper than actually putting up a fight.

Great to see the experts starting to debunk this information.
 

Bass

New Member
^^^ I agree. elevated hematocrit, RBC, hemoglobin and E2 can cause health issue not testosterone, testosterone causes them to elevate and that's why is it important and should be prescribed by the doctor to do a mandatory blood letting or donation. of course its should be based on BW, but there is no harm whatsoever to donate even if you don't need to.
 

Nelson Vergel

Founder, ExcelMale.com
I am very happy to see that several researchers have sent letter to the editors that support our views.

Letters to the Editor & Reply


Dhindsa S, Batra M, Dandona P. Deaths and Cardiovascular Events in Men Receiving Testosterone. JAMA. 2014;311(9):964. http://jama.jamanetwork.com/article.aspx?articleid=1835494


Riche DM, Baker WL, Koch CA. Deaths and Cardiovascular Events in Men Receiving Testosterone. JAMA. 2014;311(9):963-964. http://jama.jamanetwork.com/article.aspx?articleid=1835493


Katz J, Nadelberg R. Deaths and Cardiovascular Events in Men Receiving Testosterone. JAMA. 2014;311(9):963. http://jama.jamanetwork.com/article.aspx?articleid=1835496


Jones T, Channer KS. Deaths and Cardiovascular Events in Men Receiving Testosterone. JAMA. 2014;311(9):962-963. http://jama.jamanetwork.com/article.aspx?articleid=1835497


Morgentaler A, Traish A, Kacker R. Deaths and Cardiovascular Events in Men Receiving Testosterone. JAMA.2014;311(9):961-962. http://jama.jamanetwork.com/article.aspx?articleid=1835495


Ho P, Barón AE, Wierman ME. Deaths and Cardiovascular Events in Men Receiving Testosterone—Reply. JAMA. 2014;311(9):964-965. http://jama.jamanetwork.com/article.aspx?articleid=1835499
 

Nelson Vergel

Founder, ExcelMale.com
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Nelson Vergel

Founder, ExcelMale.com
[h=2]Experts, Androgen Study Group petition JAMA to retract testosterone article[/b]
Three medical organizations and an international group of over 130 scientists and physicians have issued a letter to the Journal of the American Medical Association requesting the retraction of an article which associated testosterone therapy with cardiovascular disease.

Associate Clinical Professor of Urology Abraham Morgentaler, MD, of Harvard Medical School, and chairman of the Androgen Study Group said, "To have several professional societies and so many of the most accomplished experts in the field unite in this action indicates the seriousness of the article's errors, and the magnitude of damage this article has caused to the public's perception of testosterone therapy.”

http://www.healio.com/endocrinology...petition-jama-to-retract-testosterone-article
 

Nelson Vergel

Founder, ExcelMale.com
26 Medical Groups Petition to Retract Misleading Testosterone Study

Twenty-Five Medical Societies Join Androgen Study Group to Petition JAMA to Retract Misleading Testosterone Study



In an unprecedented action, twenty-five international medical societies have petitioned the Journal of the American Medical Association to retract the article that precipitated recent concerns regarding cardiovascular risks with testosterone therapy, citing "gross data mismanagement" rendering the study "no longer credible." Twenty-two societies have added their names since the original petition was submitted to JAMA two weeks ago. The article by Rebecca Vigen and colleagues from the University of Colorado, published in the November 13, 2013 issue of JAMA, is entitled "Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels." The results were widely reported as new evidence that testosterone therapy is associated with cardiovascular risks, resulting in a Food and Drug Administration safety bulletin issued January 31, 2014.

The 25 medical societies represent US and international groups dedicated to education and research in endocrinology, men's health, andrology, and sexual medicine. These medical societies join more than 160 of the world's leading figures in urology, endocrinology, and andrology from 32 countries, from every continent except Antarctica. Individual signers include 8 emeritus professors, 9 journal editors, and 67 full professors. Societies recommending retraction are:

American Society for Men's Health

Brazilian Society of Endocrinology and Metabolism
Canadian Men's Sexual Health Council
Canadian Society for the Study of Men's Health
European Society for the Study of the Aging Male
European Society for Sexual Medicine
Indonesian Andrologist Association
International Society for Men's Health
International Society for Sexual Medicine
International Society for the Study of the Aging Male
Italian Society of Andrology
Italian Society of Andrology and Sexual Medicine
Japan ASEAN Council for Men's Health and Aging
Korean Society for Sexual Medicine and Andrology
Latin American Society for Sexual Medicine
Malaysian Men's Health Initiative
Malaysian Society of Andrology and the Study of the Aging Male
Men's Health Initiative of British Columbia (Canada)
Middle East Society for Sexual Medicine
Russian Society for Men's Health
South Asian Society for Sexual Medicine
Sexual Medicine Society of North America
The Society for Men's Health, Singapore
Society for the Study of Androgen Deficiency
Society for the Study of Andrology and Sexology, Singapore
Click here to see the full list.


Read more: http://www.digitaljournal.com/pr/1843239#ixzz2yUwxAgJx

Read ExcelMale's position on the two studies that linked testosterone replacement with higher cardiovascular events: http://www.excelmale.com/forums/75-Press-Releases-and-Position-Statements-from-ExcelMale-com
 

Nelson Vergel

Founder, ExcelMale.com
The Life Extension Foundation's View on Flawed Testosterone Analysis That Spured Misleading Media Headlines

".... on November 5, 2013, we were startled to see headlines like "Testosterone Treatments Linked to Heart Risks" in the major news media. This headline and others like it were prompted by a retrospective, observational study by Vigen and colleagues published in the September 5, 2013, issue of the Journal of the American Medical Association (JAMA). The study suggests testosterone therapy may increase risk of death and certain cardiovascular events. However, there are several significant shortcomings in the study's design and methodology, and the results conflict with an existing body of research.

Woefully Inadequate Testosterone Replacement

The goal of testosterone restoration in most cases is to restore youthful blood levels of the hormone. Typically, Life Extension® suggests men target a blood level of testosterone between 700 and 900 ng/dL for optimal health.

In studies designed to assess the impact of testosterone replacement therapy, one of the most important considerations is to measure subjects' blood levels of testosterone regularly throughout the study period. This allows the scientists conducting the study to make sure subjects are taking their testosterone as directed and that their blood levels are rising as expected.

Unbelievably, in the flawed analysis by Vigen, only 60% of study subjects receiving testosterone had a follow-up blood test to assess their testosterone levels. Among them, average testosterone levels rose from a very low level of 175.5 ng/dL at baseline to a still far-from-optimal level of 332.2 ng/dL during testosterone therapy.

Raising testosterone levels from a paltry 175.5 ng/dL to only 332.2 ng/dL is unlikely to deliver robust health benefits. In fact, research has shown that restoring testosterone levels to 500 ng/dL or higher is associated with pronounced health benefits, whereas benefits may be less evident at lower levels. "
 
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Excel Male

Administrator
Staff member
The Androgen Study Group
http://www.androgenstudygroup.org/


The Androgen Study Group is a newly formed multidisciplinary group of clinicians and researchers dedicated to education and accurate reporting on the science of testosterone deficiency in men and its treatment.


The impetus for the formation of The Androgen Study Group was the publication of several flawed testosterone trials whose conclusions have already caused unnecessary concern and confusion among healthcare providers and their patients.


With the media attention that testosterone therapy is attracting it is critical that clinical trials are properly conducted and analyzed, and that results are presented in a way that is not misleading.


It is our mission to ensure that the results of research regarding testosterone deficiency and its treatment is presented accurately and fairly within medical literature and to the public.
 

Nelson Vergel

Founder, ExcelMale.com
Another Study Review Debunks Two Prior Flawed Papers That Linked Testosterone and Heart Attacks

Can Urol Assoc J. 2014 May-Jun; 8(5-6): E356–E357.
Published online May 21, 2014. doi: 10.5489/cuaj.1962

PMCID: PMC4039601


A critical analysis of testosterone supplementation therapy and cardiovascular risk in elderly men

Jason Scovell, BBA,* Ranjith Ramasamy, MD,* and Jason R. Kovac, MSc, MD, PhD, FRCSC†


Hypogonadism has become a common diagnosis in elderly men, with increasing prevalence from 20% in the sixth decade of life to 50% in the ninth.1,2 Declines in serum testosterone affect up to 40% of men;3,4 about 3.75% of men ≥60 years of age are on some form of testosterone supplementation therapy (TST).3,5–7
The use of TST in elderly men has been justified given that hypogonadism is an independent risk factor for cardiovascular disease and all-cause mortality.8–11 Furthermore, improvements following TST in body weight, waist circumference,12–18 HbA1c,17,19 and total cholesterol levels17,18contribute to decreases in cardiovascular adverse events (CVAEs). However, several recent population-based studies have raised concerns regarding the safety of TST in elderly (≥65 years old) men.20–23


The first study to identify an association between TST and cardiovascular risk was the Testosterone in Older Men (TOM) trial.20 The TOM trial was designed to evaluate muscle strength improvements in men aged ≥65 years (n = 209) with limited mobility. The authors included frail men with mobility limitations, including difficulty walking 2 blocks or climbing 10 steps.20 Since the study was designed to examine strength improvements, treatment was solely based on serum total testosterone and free testosterone values without considering hypogonadal symptoms.20 The trial was halted due to CVAEs ranging from elevated blood pressure (n = 3) and peripheral edema (n = 5) to stroke (n = 1) and myocardial infarction (MI) (non-fatal n = 2, fatal n = 1).20 The greatest concerns arose given the increased number of CVAEs in men on TST (n = 23) compared to placebo (n = 5).20 While drawing attention to the use of TST in elderly men, the TOM trial was not designed to address CVAEs. Furthermore, there were no differences in the number of serious, life-threatening adverse events between the testosterone and placebo arms of the study. Given that many men reached supra-physiological levels of serum testosterone, and a disproportionate amount of CVAEs occurred in these patients, correlates were drawn.


Recently, several studies have examined the relationship between CVAEs and TST in more detail. For example, a meta-analysis by Xu and colleagues24 noted an increased risk of CVAEs in men on TST (odds ratio 1.54, p < 0.05). Another large (n = 8709) retrospective national cohort study in elderly males (&#8805;60 years old) analyzed TST outcomes in hypogonadal men (serum testosterone <300 ng/dL) with previous coronary angiography.22 In this study, men who began TST had an absolute risk increase of 5.8% (p < 0.05) for a CVAE when compared to matched peers not receiving TST.22 Unfortunately, one of the major drawbacks of the study was that despite TST, most men remained hypogonadal (mean serum testosterone 332.2 ng/dL; delta = 175.5 ng/dL from baseline).22Furthermore, 17.6% of patients in the testosterone group filled only 1 prescription and no testosterone levels were measured after therapy, which raised the question of therapy adherence and the generalizability of the findings.
In another study, Finkle and colleagues21 determined that men &#8805;65 years old had an increased risk of non-fatal MI within 90 days of TST initiation. In this trial, the pre-TST prescription MI-event rate in men &#8805;65 years old was 5.27 (95% confidence interval CI] 3.81&#8211;7.27).21 Following the start of TST, these rates increased to 11.52 (95% CI 7.43&#8211;17.86) in men &#8805;65, while men <65 did not change (pre-TST MI-event rate of 3.22 CI 2.75&#8211;3.77 vs. post-TST MI-event rate of 3.76 CI 2.81&#8211;5.04).21 Unfortunately, in this population-based study, the lack of evaluation of serum hormones and hematocrit levels significantly limited the validity of the conclusions regarding the relationships between TST, serum testosterone and MI. In addition, men on TST were compared to men using PDE5 inhibitors, which is potentially confounding since PDE5 inhibitors benefit men with coronary artery disease, hypertension, heart failure, pulmonary arterial hypertension, and diabetes mellitus.25

Currently, the exact mechanisms for increased CVAEs in men on TST remain unknown. Testosterone stimulates erythropoiesis in a dose-dependent manner &#8211; an effect that is more prominent in elderly men.26TST also induces a hyper-coagulable state via increases in thromboxane A2 and platelet thromboxane A2 receptor density with decreases in prostaglandins.27 In the Tampere Adult Population Cardiovascular Risk study (TAMRISK), the authors demonstrated a relationship between borderline polycythemia and an increased risk of cardiovascular mortality.28,29 Taken together, it is tempting to speculate that TST may exacerbate cardiac risks in men with atherosclerosis by increasing blood viscosity and platelet counts leading to CVAEs in susceptible elderly patients.

A further factor to consider is the level of serum testosterone in the aging male since it appears that both sub-, and supra-physiological levels of testosterone carry risk. This was illustrated in the population-based cohort study recently done on 3690 men.30,31 The authors found that men whose serum testosterone was in the middle 2 quartiles (Q2 and Q3; testosterone 283 ng/dL to 453 ng/dL) of the population had the lowest incidence of death from any cause (Q2 vs. Q1, adjusted hazard ratio
0.82; Q3 vs. Q1, HR 0.78; Q4 vs. Q1, HR 0.86).30

In summary, the preponderance of the evidence suggests that TST should be used judiciously in elderly males, with a paradigm focused on returning serum testosterone levels to normal limits, rather than treating with supra-physiological doses (i.e., injections). Furthermore, it is essential to choose the proper TST modality and to schedule regular (i.e., every 3 months) visits to monitor hematocrit, platelet and serum estradiol levels with an experienced TST specialist.

Go to:
Footnotes

Competing interests: Dr. Scovell, Dr. Ramasamy and Dr. Kovac all declare no competing financial or personal interests.
This paper has been peer-reviewed.


Go to:
References

1. Harman SM, Metter EJ, Tobin JD, et al. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. J Clin Endocrinol Metab. 2001;86:724&#8211;31.http://dx.doi.org/10.1210/jcem.86.2.7219. [PubMed]
2. Surampudi PN, Wang C, Swerdloff R. Hypogonadism in the aging male diagnosis, potential benefits, and risks of testosterone replacement therapy. Int J Endocrinol. 2012;2012:625434. [PMC free article][PubMed]
3. Mulligan T, Frick MF, Zuraw QC, et al. Prevalence of hypogonadism in males aged at least 45 years: The HIM study. Int J Clin Pract.2006;60:762&#8211;9. http://dx.doi.org/10.1111/j.1742-1241.2006.00992.x.[PMC free article] [PubMed]
4. Wu FC, Tajar A, Beynon JM, et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med.2010;363:123&#8211;35. http://dx.doi.org/10.1056/NEJMoa0911101. [PubMed]
5. Baillargeon J, Urban RJ, Ottenbacher KJ, et al. Trends in androgen prescribing in the United States, 2001 to 2011. JAMA Intern Med.2013;173:1465&#8211;6. http://dx.doi.org/10.1001/jamainternmed.2013.6895.[PubMed]
6. Bassil N, Alkaade S, Morley JE. The benefits and risks of testosterone replacement therapy: A review. Ther Clin Risk Manag. 2009;5:427&#8211;48.[PMC free article] [PubMed]
7. Nigro N, Christ-Crain M. Testosterone treatment in the aging male: myth or reality? Swiss Med Wkly. 2012;142:w13539. [PubMed]
8. Corona G, Mannucci E, Petrone L, et al. Psychobiological correlates of smoking in patients with erectile dysfunction. Int J Impot Res.2005;17:527&#8211;34. http://dx.doi.org/10.1038/sj.ijir.3901351. [PubMed]
9. Corona G, Rastrelli G, Balercia G, et al. Testosterone and cardiovascular risk in patients with erectile dysfunction. J Endocrinol Invest. 2012;35:809&#8211;16. [PubMed]
10. Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev.2005;26:833&#8211;76. http://dx.doi.org/10.1210/er.2004-0013. [PubMed]
11. Maggio M, Basaria S. Welcoming low testosterone as a cardiovascular risk factor. Int J Impot Res. 2009;21:261&#8211;4.http://dx.doi.org/10.1038/ijir.2009.25. [PMC free article] [PubMed]
12. Moncada I. Testosterone and men's quality of life. Aging Male.2006;9:189&#8211;93. http://dx.doi.org/10.1080/13685530601003180.[PubMed]
13. Snyder PJ, Peachey H, Berlin JA, et al. Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab.2000;85:2670&#8211;7. [PubMed]
14. Wang C, Alexander G, Berman N, et al. Testosterone replacement therapy improves mood in hypogonadal men--a clinical research center study. J Clin Endocrinol Metab. 1996;81:3578&#8211;83. [PubMed]
15. 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;89:2085&#8211;98.http://dx.doi.org/10.1210/jc.2003-032006. [PubMed]
16. Yassin AA, Saad F. Improvement of sexual function in men with late-onset hypogonadism treated with testosterone only. J Sex Med.2007;4:497&#8211;501. http://dx.doi.org/10.1111/j.1743-6109.2007.00442.x.[PubMed]
17. Hackett G, Cole N, Bhartia M, et al. Testosterone replacement therapy improves metabolic parameters in hypogonadal men with type 2 diabetes but not in men with coexisting depression: The BLAST Study. J Sex Med. 2014;11:840&#8211;56. http://dx.doi.org/10.1111/jsm.12404. Epub 2013 Dec 6. [PubMed]
18. He J, Bhasin S, Binder EF, et al. Cardiometabolic risks during anabolic hormone supplementation in older men. Obesity (Silver Spring)2013;21:968&#8211;75. http://dx.doi.org/10.1002/oby.20081. [PMC free article][PubMed]
19. Corona G, Monami M, Rastrelli G, et al. Type 2 diabetes mellitus and testosterone: A meta-analysis study. Int J Androl. 2011;34:528&#8211;40.http://dx.doi.org/10.1111/j.1365-2605.2010.01117.x. [PubMed]
20. Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363:109&#8211;22. http://dx.doi.org/10.1056/NEJMoa1000485. [PMC free article][PubMed]
21. Finkle W, Greenland S, Ridgeway G. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men.PLoS One. 2014;9:e85805.http://dx.doi.org/10.1371/journal.pone.0085805. [PMC free article][PubMed]
22. Vigen R, O'Donnell CI, Baron AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310:1829&#8211;36.http://dx.doi.org/10.1001/jama.2013.280386. [PubMed]
23. Ramasamy R, Dupree JM, Kovac JR, et al. Risks of testosterone therapy in elderly men. F1000Research. 2014;3:11. [PMC free article][PubMed]
24. Xu L, Freeman G, Cowling BJ, et al. Testosterone therapy and cardiovascular events among men: A systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med. 2013;11:108.http://dx.doi.org/10.1186/1741-7015-11-108. [PMC free article][PubMed]
25. Chrysant SG. Effectiveness and safety of phosphodiesterase 5 inhibitors in patients with cardiovascular disease and hypertension. Curr Hypertens Rep. 2013;15:475&#8211;83. http://dx.doi.org/10.1007/s11906-013-0377-9. [PubMed]
26. Coviello AD, Kaplan B, Lakshman KM, et al. Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. J Clin Endocrinol Metab. 2008;93:914&#8211;9. http://dx.doi.org/10.1210/jc.2007-1692. [PMC free article] [PubMed]
27. Ajayi AA, Mathur R, Halushka PV. Testosterone increases human platelet thromboxane A2 receptor density and aggregation responses.Circulation. 1995;91:2742&#8211;7.http://dx.doi.org/10.1161/01.CIR.91.11.2742. [PubMed]
28. Kunnas T, Solakivi T, Huuskonen K, et al. Hematocrit and the risk of coronary heart disease mortality in the TAMRISK study, a 28-year follow-up. Prev Med. 2009;49:45&#8211;7.http://dx.doi.org/10.1016/j.ypmed.2009.04.015. [PubMed]
29. Sorlie PD, Garcia-Palmieri MR, Costas R, Jr, et al. Hematocrit and risk of coronary heart disease: The Puerto Rico Health Program. Am Heart J. 1981;101:456&#8211;61. http://dx.doi.org/10.1016/0002-8703(81)90136-8. [PubMed]
30. Yeap BB, Alfonso H, Chubb SA, et al. In older men an optimal plasma testosterone is associated with reduced all-cause mortality and higher dihydrotestosterone with reduced ischemic heart disease mortality, while estradiol levels do not predict mortality. J Clin Endocrinol Metab.2014;99:E9&#8211;18. http://dx.doi.org/10.1210/jc.2013-3272. [PubMed]
31. Ramasamy R, Kovac JR, Scovell JM, et al. Re: In older men an optimal plasma testosterone is associated with reduced all-cause mortality and higher dihydrotestosterone with reduced ischemic heart disease mortality, while estradiol levels do not predict mortality. Eur Urol.2014;65:844&#8211;5. http://dx.doi.org/10.1016/j.eururo.2013.12.030.[PubMed]




Articles from Canadian Urological Association Journal are provided here courtesy of Canadian Urological Association
 
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