Androgen Replacement

[Michael Scally MD]

[I do not envision ANY SARM ever being FDA Approved. This is more so in light of the importance of Estradiol. SARMs are HPTA suppressive that will lead to the adverse effects and consequences of a decreased Estradiol. Add to this the potential for misuse.]

Coss CC, Jones A, Hancock ML, Steiner MS, Dalton JT. Selective androgen receptor modulators for the treatment of late onset male hypogonadism. Asian J Androl. Selective androgen receptor modulators for the treatment of late onset male hypogonadism Coss CC, Jones A, Hancock ML, Steiner MS, Dalton JT, - Asian J Androl

Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism.

Selective androgen receptor modulators (SARMs) have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defined clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism.

 

[Michael Scally MD]

Cooper LA, Page ST. Androgens and prostate disease. Asian J Androl. Androgens and prostate disease Cooper LA, Page ST, - Asian J Androl

A growing body of literature has established the anabolic benefits of testosterone (T) therapy in hypogonadal men. However, there remains a paucity of data regarding the risks of exogenous androgen use in older men and the potential for adverse effects on the prostate gland.

Whether T therapy in older, hypogonadal men might worsen lower urinary tract symptoms or exacerbate, unmask, or even incite prostate cancer development has tempered enthusiasm for T therapy, while known prostatic disease has served as a relative contraindication to T therapy.

Androgens are necessary for the development and maintenance of the prostate gland. However, epidemiologic studies do not consistently find a positive relationship between endogenous serum androgen concentrations and the risk of prostate disease. Recent data demonstrate that 5alpha-reductase inhibitors decrease the risk of low-grade prostate cancer, suggesting that modifying androgen metabolism may have beneficial effects on prostate health, yet similar reductions in high-grade disease have not been observed, thereby questioning the true clinical benefits of these agents for chemoprevention.

Knowing how to best investigate the relationship between androgens and the development of prostate disease given the lack of large, randomized trials is difficult. Accumulating data challenges the assumption that alterations in serum androgens have parallel effects within the prostate hormonal environment or change androgen-regulated processes within the gland.

Long-term intervention studies are needed to truly ascertain the effects of androgen manipulation on prostate tissue and disease risk. However, available data do not support the notion that restoring serum androgens to normal physiologic ranges drives prostate disease.

 

[Michael Scally MD]

Can Testosterone Levels Influence Mortality Risk?
http://www.medscape.org/viewarticle/817442?src=cmemp

 

[Michael Scally MD]

NEJM Journal Watch Year in Review 2013

This annual collection includes original content that examines the 13 most important clinical topics in General Medicine of 2013, as chosen by the NEJM Journal Watch physician-editors.

INCLUDES: "Questions About Risks and Benefits of Testosterone Therapy."

 

[Michael Scally MD]

Association of Ringside Physicians Releases Consensus Statement on Therapeutic Use Exemptions for Testosterone Replacement Therapy
http://www.associationofringsidephysicians.org/ (Association of Ringside Physicians)

The Association of Ringside Physicians (ARP), an international, non-profit organization dedicated to the health and safety of the boxer and mixed martial arts athlete, has released a consensus statement on therapeutic use exemptions for testosterone replace therapy in professional combat sport athletes, as follows:

The incidence of hypogonadism requiring the use of testosterone replacement therapy (TRT) in professional athletes is extraordinarily rare. Accordingly, the use of an anabolic steroid such as testosterone in a professional boxer or mixed martial artist is rarely justified. Steroid use of any type, including unmerited testosterone, significantly increases the safety and health risk to combat sports athletes and their opponents. TRT in a combat sports athlete may also create an unfair advantage contradictory to the integrity of sport. Consequently, the Association of Ringside Physicians supports the general elimination of therapeutic use exemptions (TUE) for testosterone replacement therapy.

 

[Michael Scally MD]

Finkle WD, Greenland S, Ridgeway GK, et al. Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men. PLoS ONE 2014;9(1):e85805. PLOS ONE: Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men

Background - An association between testosterone therapy (TT) and cardiovascular disease has been reported and TT use is increasing rapidly.

Methods - We conducted a cohort study of the risk of acute non-fatal myocardial infarction (MI) following an initial TT prescription (N = 55,593) in a large health-care database. We compared the incidence rate of MI in the 90 days following the initial prescription (post-prescription interval) with the rate in the one year prior to the initial prescription (pre-prescription interval) (post/pre). We also compared post/pre rates in a cohort of men prescribed phosphodiesterase type 5 inhibitors (PDE5I; sildenafil or tadalafil, N = 167,279), and compared TT prescription post/pre rates with the PDE5I post/pre rates, adjusting for potential confounders using doubly robust estimation.

Results - In all subjects, the post/pre-prescription rate ratio (RR) for TT prescription was 1.36 (1.03, 1.81). In men aged 65 years and older, the RR was 2.19 (1.27, 3.77) for TT prescription and 1.15 (0.83, 1.59) for PDE5I, and the ratio of the rate ratios (RRR) for TT prescription relative to PDE5I was 1.90 (1.04, 3.49). The RR for TT prescription increased with age from 0.95 (0.54, 1.67) for men under age 55 years to 3.43 (1.54, 7.56) for those aged ?75 years (ptrend = 0.03), while no trend was seen for PDE5I (ptrend = 0.18). In men under age 65 years, excess risk was confined to those with a prior history of heart disease, with RRs of 2.90 (1.49, 5.62) for TT prescription and 1.40 (0.91, 2.14) for PDE5I, and a RRR of 2.07 (1.05, 4.11).

Discussion - In older men, and in younger men with pre-existing diagnosed heart disease, the risk of MI following initiation of TT prescription is substantially increased.

 

[Michael Scally MD]

FDA evaluating risk of stroke, heart attack and death with FDA-approved testosterone products
http://www.fda.gov/Drugs/DrugSafety/ucm383904.htm

Safety Announcement

[01-31-2014] The U.S. Food and Drug Administration (FDA) is investigating the risk of stroke, heart attack, and death in men taking FDA-approved testosterone products.

We have been monitoring this risk and decided to reassess this safety issue based on the recent publication of two separate studies that each suggested an increased risk of cardiovascular events among groups of men prescribed testosterone therapy.

We are providing this alert while we continue to evaluate the information from these studies and other available data, and will communicate our final conclusions and recommendations when the evaluation is complete.

At this time, FDA has not concluded that FDA-approved testosterone treatment increases the risk of stroke, heart attack, or death. Patients should not stop taking prescribed testosterone products without first discussing any questions or concerns with their health care professionals.

Health care professionals should consider whether the benefits of FDA-approved testosterone treatment is likely to exceed the potential risks of treatment. The prescribing information in the drug labels of FDA-approved testosterone products should be followed.

 

[Millard]

Finkle WD, Greenland S, Ridgeway GK, et al. Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men. PLoS ONE 2014;9(1):e85805. PLOS ONE: Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men

FDA evaluating risk of stroke, heart attack and death with FDA-approved testosterone products
http://www.fda.gov/Drugs/DrugSafety/ucm383904.htm

What was the other study referenced by FDA?

 

[Michael Scally MD]

What was the other study referenced by FDA?

Vigen R, O’Donnell CI, Barón AE, et al. Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels. JAMA. 2013;310(17):1829-1836. JAMA Network | JAMA | Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels

Importance Rates of testosterone therapy are increasing and the effects of testosterone therapy on cardiovascular outcomes and mortality are unknown. A recent randomized clinical trial of testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety.

Objectives To assess the association between testosterone therapy and all-cause mortality, myocardial infarction (MI), or stroke among male veterans and to determine whether this association is modified by underlying coronary artery disease.

Design, Setting, and Patients A retrospective national cohort study of men with low testosterone levels (<300 ng/dL) who underwent coronary angiography in the Veterans Affairs (VA) system between 2005 and 2011.

Main Outcomes and Measures Primary outcome was a composite of all-cause mortality, MI, and ischemic stroke.

Results Of the 8709 men with a total testosterone level lower than 300 ng/dL, 1223 patients started testosterone therapy after a median of 531 days following coronary angiography. Of the 1710 outcome events, 748 men died, 443 had MIs, and 519 had strokes. Of 7486 patients not receiving testosterone therapy, 681 died, 420 had MIs, and 486 had strokes. Among 1223 patients receiving testosterone therapy, 67 died, 23 had MIs, and 33 had strokes. The absolute rate of events were 19.9% in the no testosterone therapy group vs 25.7% in the testosterone therapy group, with an absolute risk difference of 5.8% (95% CI, ?1.4% to 13.1%) at 3 years after coronary angiography. In Cox proportional hazards models adjusting for the presence of coronary artery disease, testosterone therapy use as a time-varying covariate was associated with increased risk of adverse outcomes (hazard ratio, 1.29; 95% CI, 1.04 to 1.58). There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease (test for interaction, P?=?.41).

Conclusions and Relevance Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of adverse outcomes. These findings may inform the discussion about the potential risks of testosterone therapy.


Also, see:

Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, et al. Adverse events associated with testosterone administration. N Engl J Med 2010;363:109–22. MMS: Error

BACKGROUND: Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied.

METHODS: Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter (3.5 to 12.1 nmol per liter) or a free serum testosterone level of less than 50 pg per milliliter (173 pmol per liter) were randomly assigned to receive placebo gel or testosterone gel, to be applied daily for 6 months. Adverse events were categorized with the use of the Medical Dictionary for Regulatory Activities classification. The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group.

RESULTS: A total of 209 men (mean age, 74 years) were enrolled at the time the trial was terminated. At baseline, there was a high prevalence of hypertension, diabetes, hyperlipidemia, and obesity among the participants. During the course of the study, the testosterone group had higher rates of cardiac, respiratory, and dermatologic events than did the placebo group. A total of 23 subjects in the testosterone group, as compared with 5 in the placebo group, had cardiovascular-related adverse events. The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period. As compared with the placebo group, the testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load.

CONCLUSIONS: In this population of older men with limitations in mobility and a high prevalence of chronic disease, the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events. The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy.

 

[Millard]

Thanks! So, putting aside the news reports and the FDA warning, do these studies suggest TRT is really safe for those without pre-existing cardiovascular issues?

 

[Michael Scally MD]

Thanks! So, putting aside the news reports and the FDA warning, do these studies suggest TRT is really safe for those without pre-existing cardiovascular issues?

This is how I read it, BUT the question is what is/are pre-existing CVD issues? This is a catch all phrase too commonly used with no clear parameters. For example, when someone has a newly discovered MI do they have pre-existing disease? How about someone with HTN? Or, obesity?

As noted in the forum, Glueck raises the concern of clotting problems. Some are posting about a connection to hematocrit or estradiol, which, IMO, is tenuous.

I have even seen posts that see an effort to restrict TRT. This is absurd suggestive of a conspiracy. These researchers are running up against a BILLION DOLLAR sales bonanza.

 

[MR10X]

For what its worth:
I am a long time AAS user,started in 1980. Although my doses back then were now considered low,i did 2 to 3 8 week cycles for about 5 years,all with no PCT.I used small amounts through the years so i have done well over 35 cycles since 1980.2009 and 2010 i did 3 cycles a year 600 mg Test,600 mg EQ,and 350 mg Tren A weekly. My blood pressure was slightly elevated during these cycles and im not on blood pressure medication and it would return to normal ranges when i was off cycle.I was 63 and 64 years old during these cycles. I have had yearly exams since then and all my blood results were in normal ranges except this year my Thyroid levels were low so now im on T4 to get my levels in range.It appears to me it depends on your health as it does with any drug there may be complications. I even had hepatitus when i was in my late 20's,started AAS when i was 34 and i never had and liver problems while using AAS.Given the extreamly high doses of AAS i took when i was 63 and 64 with no problems,i even had normal test levels after PCT. It appears to me if your in good health you would have no issues taking low dose Test 80 to 100 mg a week to maintain normal test levels even at a higher age like me.

 

[Michael Scally MD]

Don’t Ask Your Doctor About ‘Low T’
By JOHN LA PUMA - FEB. 3, 2014
[John La Puma is an internist and the author of “Refuel: A 24-Day Eating Plan to Shed Fat, Boost Testosterone, and Pump Up Strength and Stamina.”]
http://www.nytimes.com/2014/02/04/opinion/dont-ask-your-doctor-about-low-t.html

SANTA BARBARA, Calif. — A FUNNY thing has happened in the United States over the last few decades. Men’s average testosterone levels have been dropping by at least 1 percent a year, according to a 2006 study in The Journal of Clinical Endocrinology and Metabolism.

Testosterone appears to decline naturally with aging, but internal belly fat depresses the hormone further, especially in obese men. Drugs like steroids and opiates also lower testosterone, and it’s suspected that chemicals like bisphenol A (or BPA, commonly found in plastic food containers) and diseases like Type 2 diabetes play a role as well.

Men feel the loss. Clinical testosterone deficiency, which is variously defined as lower than 220 to 350 nanograms of testosterone per deciliter of blood serum, can cause men to lose sex drive and fertility. Their bone density often declines, and they may feel tired and experience hot flashes and sweats.

But “low T,” as the condition has been labeled, isn’t nearly as common as the drug ads for prescription testosterone would have you believe. Pharmaceutical companies have seized on the decline in testosterone levels as pathological and applicable to every man. They aim to convince men that common effects of aging like slowing down a bit and feeling less sexual actually constitute a new disease, and that they need a prescription to cure it. This is a seductive message for many men, who just want to feel better than they do, and want to give it a shot, literally.

The problem is that prescription testosterone doesn’t just give your T level a boost: it may also increase your risk of heart attack. It can add huge numbers of red blood cells to your bloodstream and shrink your testes. In some men, it increases aggression and irritability. Children who accidentally come in contact with the hormone can develop unwanted pubic hair and genital changes. Last week, a large study published in the journal PLoS ONE found that, within three months, taking the hormone doubled the rate of heart attacks in men 65 and older, as well as in younger men who had heart disease. The Food and Drug Administration has begun an investigation.

The number of testosterone prescriptions given to American men has tripled since 2001. Used clinically since 1937 and approved by the F.D.A. since 1953, testosterone is now administered in at least five forms, including patches, gels and injections. Three million prescriptions were written in 2012 for the market leader AndroGel alone. Sales of all testosterone-boosting drugs are estimated to have been $2 billion in 2012, and are projected to hit $5 billion by 2017.

Too many doctors are now writing testosterone prescriptions without even measuring the patient’s hormone levels, much less re-testing for confirmation and adjusting the dose after prescription. Up to a quarter of these prescriptions are dispensed without a blood test.

From a psychological perspective, this isn’t helping men. From a medical perspective, it’s devastating. In addition to the cardiac risks, prescription T can mean a permanent shut-off in men’s own, albeit diminished, testosterone production. In other words, once you start, you may well be hooked for life.

Instead of heading to the pharmacy to get their fix, men should address the leading cause of the problem. Losing weight is a tried and true way to naturally boost testosterone levels. According to findings presented at the annual meeting of the Endocrine Society in 2012, obese men who lost an average of 17 pounds saw their testosterone levels increase by 15 percent. In general, a man’s waist should be half his height.

Some diet changes may be useful for reasons other than just weight loss. If you drink too much booze, switch to water — alcohol lowers testosterone levels. Eating more cruciferous vegetables like broccoli and collard greens can also help, by blunting the effects of estrogen in a man’s body. At the end of the day, eating more of the right foods and fewer junk foods improves mood and energy — which may be the only fix many men need.

In the 1990s and early 2000s, middle-aged women went through their own hormone trial, taking synthetic prescription estrogen and progesterone to treat the symptoms of menopause, among other reasons. But by 2002 we knew that those hormones raised the risk of stroke, heart disease, life-threatening blood clots and invasive breast cancer in healthy women.

Luckily, we don’t have to wait 12 more years to learn about the risks of testosterone in healthy men. Men have been drugged by overprocessed foods and gender-bending chemicals like BPA. The last thing they need now is a prescription for a risky drug to treat a trumped-up disease.

 

[Michael Scally MD]

Overselling Testosterone, Dangerously
http://www.nytimes.com/2014/02/05/opinion/overselling-testosterone-dangerously.html?_r=0

A large study has found substantial risks in prescribing testosterone to middle-age and older men for a variety of ailments. One part of the study found that testosterone doubled the risk of cardiovascular disease in more than 7,000 men who were 65 years old or older, essentially confirming findings in previous studies. The other part found that testosterone almost tripled the risk of heart attacks in a group of more than 48,000 middle-age men with previous histories of heart disease. The harm in both cases occurred within 90 days of receiving the prescription.

The new study — conducted by researchers at the University of California, Los Angeles; the National Institutes of Health; and Consolidated Research — analyzed prescription records from a large database of insurance health claims around the country. In a striking comparison, it found that drugs used to treat erectile dysfunction, such as Viagra and Cialis, which are often prescribed for similar purposes, did not increase heart risks.

The study, published last week in the online journal PLOS One, provides the most compelling evidence yet that many American men have embarked on a perilous course of overtreatment. Testosterone is clearly indicated to treat abnormally low levels of the hormone because of genetic or pathological causes, a condition known as hypogonadism. But a huge upsurge in prescriptions in recent years suggests that testosterone is now being prescribed to men who are simply reluctant to accept the fact that they are getting older. In many cases, doctors are prescribing testosterone without even ascertaining whether a patient’s testosterone levels are actually low or whether he has a medical condition that justifies it.

The reason seems clear.

Drug companies have shamelessly pushed the notion, to doctors and to the public, that their testosterone-boosting product can overcome a supposed disease called “low T,” which is characterized by feelings of fatigue, loss of sexual drive, depressed moods, an increase in body fat and decrease in muscle strength, among other symptoms.

Incredibly, AbbVie, which makes the market-leading testosterone gel known as AndroGel, lists “low T” as one of five important health risks facing men, along with high cholesterol, high blood pressure, high blood sugar and high levels of prostate-specific antigen that may indicate prostate cancer.

The overselling is reminiscent of the reckless overprescribing of hormone replacement therapy to millions of American women as an anti-aging elixir until a large federal study in 2002 found that some pills were causing more harm than good.

Men need to recognize the dangers of seeking a quick fix for aging, and doctors need to be more cautious in prescribing. Some experts are calling for a large clinical trial to document the risks and benefits more definitively. The latest study provides enough evidence to persuade regulators to strengthen warning labels and find ways to rein in the industry’s promotional efforts.

 

[Michael Scally MD]

The Risks And Benefits Of Prescribing Testosterone
The Risks And Benefits Of Prescribing Testosterone | The Diane Rehm Show from WAMU and NPR

 

[Michael Scally MD]

Endocrine Society Calls for Large-Scale Studies to Evaluate Testosterone Therapy Risks
https://www.endocrine.org/news-room...tudies-to-evaluate-testosterone-therapy-risks

Aging men weighing treatment should be warned about cardiovascular events
Chevy Chase, MD—According to a statement issued today by the Endocrine Society, the risks and benefits of testosterone therapy for older men with declining levels of the hormone need to be fully evaluated.

The statement comes in response to recent studies that have raised concerns about the safety of testosterone therapy in older men with a history of heart disease. Two retrospective analyses and one randomized trial supported by the Veterans Health Care System, and the National Institutes of Health found a higher rate of cardiovascular events in men who received testosterone and had preexisting heart problems. The U.S. Food and Drug Administration has announced it plans to evaluate the safety of testosterone therapy.

Testosterone is approved for the treatment of hypogonadism due to known diseases of the testes, pituitary and hypothalamus. Although the use of testosterone therapy is increasing, the treatment has not been approved for the treatment of age-related symptoms or the age-related decline of testosterone levels.

Important safety data are expected from the NIA’s ongoing randomized trial examining testosterone in about 800 older men with unequivocally low testosterone levels and accompanying symptoms, including sexual and physical dysfunction. The trial’s structure and careful monitoring of cardiovascular events will help provide important safety information.

The Society calls for the development of more large-scale randomized controlled trials to determine the true risks and benefits of testosterone therapy in older men.

In the statement, the Society recommends that middle-aged and older men who are considering testosterone supplementation for age-related declines should be informed of the potential cardiovascular risks. The Society also believes that it may be prudent not to administer testosterone therapy to men who have had a cardiovascular event (such as myocardial infarction, stroke or acute coronary syndrome) in the preceding six months.

In cases where men are being treated for hypogonadism as a result of known diseases of the testes, pituitary and hypothalamus, however, patients should consult their health care providers before making any changes to their medication regimen. The Society believes testosterone is generally safe and beneficial when used to treat young, hypogonadal men with these conditions. The Society’s Clinical Practice Guideline on testosterone therapy in this population is available at http://www.endocrine.org/~/media/en...delines/FINAL-Androgens-in-Men-Standalone.pdf.

 

[Michael Scally MD]

The Risk of Cardiovascular Events in Men Receiving Testosterone Therapy - An Endocrine Society Statement
https://www.endocrine.org/~/media/e...nts in Men Receiving Testosterone Therapy.pdf

A recent study by Finkle et al1, published online in PLOS ONE, suggests that the risk of myocardial infarction is increased in men who are receiving testosterone therapy and who have pre-existing heart disease. This report follows on the heels of another study from the Veterans Health Care System2, which also found a higher frequency of death and cardiovascular events in men who had documented coronary artery disease and who were administered testosterone therapy.

In 2010, a randomized placebo-controlled trial of testosterone in older men with mobility limitation, funded by the National Institute on Aging (NIA), was stopped early by the trial’s data and safety monitoring board, due to the higher frequency of cardiovascular-related events in men assigned to the testosterone arm of the trial than in those assigned to the placebo arm3. These studies have heightened concern about the safety of testosterone therapy in older men with pre-existing heart disease.

Finkle and colleagues1 examined the health care records of 55,593 men who had been prescribed testosterone therapy. They found a twofold increase in the relative risk of myocardial infarctions in the 90 days after starting testosterone therapy in men who had heart disease compared to the year before. The increase in myocardial infarctions was even greater in men over the age of 65 than in men under the age of 65.

Another retrospective analysis and a small prospective randomized trial had reported lower cardiovascular events in men who were receiving testosterone than in those who were not receiving testosterone5-6. Retrospective database analyses are limited by their inherent inability to verify the indication for treatment, diagnoses, or other relevant quantitative information that is often not ascertainable from an administrative database.

Nonrandomized retrospective analyses are also susceptible to unmeasured confounding due to a variety of other factors. These factors are particularly important because many patients in the United States are being prescribed testosterone for the treatment of age-related symptoms or age-related decline in testosterone levels, for which testosterone therapy has not been approved by the Food and Drug Administration.

Large scale, prospective, randomized controlled trials are needed to determine the risks and benefits of testosterone therapy in older men with age-related decline in testosterone levels. The NIA-funded T Trials, an ongoing randomized trial of testosterone in older men with unequivocally low testosterone levels and symptoms – sexual dysfunction, physical dysfunction or low vitality – will determine whether testosterone therapy improves these symptoms, and whether it is safe.

Until evidence from large randomized trials becomes available, the Endocrine Society believes that patients should be made aware of the potential risk of cardiovascular events in middle-aged and older men who are taking or considering testosterone therapy for age-related decline in testosterone levels and symptoms. Physicians and patients should have a conversation about the risks and benefits of using testosterone, especially in patients who have pre-existing heart disease.

The Endocrine Society recommends that physicians prescribe testosterone in accordance with the Society’s clinical practice guidelines on testosterone therapy in men with hypogonadism. Testosterone therapy should be accompanied by a standardized monitoring plan to optimize the dose and minimize the risk of adverse effects. The Endocrine Society encourages patients with concerns about this report or about their testosterone therapy to contact their health care providers. Patients with hypogonadism who have been on stable testosterone therapy should not stop their medication without consulting their health care provider.

1. Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, Fraumeni JF Jr, Hoover RN. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014 Jan 29;9(1):e85805. doi: 10.1371/journal.pone.0085805

2. Vigen R, O'Donnell CI, Barón AE, Grunwald GK, Maddox TM, Bradley SM, Barqawi A, Woning G, Wierman ME, Plomondon ME, Rumsfeld JS, Ho PM. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013 Nov 6;310(17):1829-36.

3. Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE, Brooks B, Appleman E, Aggarwal S, Bhasin G, Hede-Brierley L, Bhatia A, Collins L, LeBrasseur N, Fiore LD, Bhasin S. Adverse events associated with testosterone administration. N Engl J Med. 2010 Jul 8;363(2):109-22.

4. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM; Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010 Jun;95(6):2536-59.

5. Shores MM, Smith NL, Forsberg CW, Anawalt BD, Matsumoto AM. Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Metab 2012;97(6):2050-8

6. Muraleedharan V, Marsh H, Kapoor D, Channer KS, Jones TH. Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Eur J Endocrinol 2013;169(6):725-33.

 

[Michael Scally MD]

"T"errific or "T"errible? A Review of Testosterone Deficiency
http://www.medscape.com/features/slideshow/testosterone-deficiency

 

[Michael Scally MD]

Putting the 'T'rouble in Testosterone Therapy?
http://www.medscape.com/viewarticle/819766

 

[Michael Scally MD]

Paduch DA, Brannigan RE, Fuchs EF, Kim ED, Marmar JL, Sandlow JI. The Laboratory Diagnosis of Testosterone Deficiency. Urology. The Laboratory Diagnosis of Testosterone Deficiency

The evaluation and treatment of hypogonadal men has become an important part of urologic practice. Fatigue, loss of libido, and erectile dysfunction are commonly reported, but nonspecific symptoms and laboratory verification of low testosterone (T) are an important part of evaluation in addition to a detailed history and physical examination. Significant intraindividual fluctuations in serum T levels, biologic variation of T action on end organs, the wide range of T levels in human serum samples, and technical limitations of currently available assays have led to poor reliability of T measurements in the clinical laboratory setting. There is no universally accepted threshold of T concentration that distinguishes eugonadal from hypogonadal men; thus, laboratory results have to be interpreted in the appropriate clinical setting. This review focuses on clinical, biological, and technological challenges that affect serum T measurements to educate clinicians regarding technological advances and limitations of the currently available laboratory methods to diagnose hypogonadism. A collaborative effort led by the American Urological Association between practicing clinicians, patient advocacy groups, government regulatory agencies, industry, and professional societies is underway to provide optimized assay platforms and evidence-based normal assay ranges to guide clinical decision making. Until such standardization is commonplace in clinical laboratories, the decision to treat should be based on the presence of signs and symptoms in addition to serum T measurements. Rigid interpretation of T ranges should not dictate clinical decision making or define coverage of treatment by third party payers.