Androgen Replacement

[Michael Scally MD]

Liao PW, Wu CC, Chen KC, et al. Testosterone Threshold for Increased Cardiovascular Risk in Middle-Aged and Elderly Men: A Locally Weighted Regression Analysis. J Sex Med. http://www.jsm.jsexmed.org/article/S1743-6095(16)30459-3/abstract

INTRODUCTION: Although testosterone deficiency has a well-known association with increased risk of cardiovascular disease (CVD), the threshold remains to be determined.

AIM: To investigate whether there is a discriminatory testosterone level below which the CVD risk increases.

METHODS: The study included 876 men 45 to 74 years old who underwent a general health checkup. The Framingham Risk Score was used to estimate the 10-year CVD risk; a high-sensitivity C-reactive protein (hsCRP) level of at least 1 mg/L was considered an indicator of increased CVD risk. Aging symptoms and sexual function were evaluated with the Aging Males' Symptom Scale.

MAIN OUTCOME MEASURES: Locally weighted regression was performed to determine the testosterone threshold for Framingham CVD risk and increased hsCRP.

RESULTS: The mean age was 56.6 +/- 7.0 years. The mean total testosterone level was 394.3 +/- 115.7 ng/dL. The mean 10-year Framingham CVD risk was 16.6 +/- 10.7%, and 169 (19.3%) had increased hsCRP. The locally weighted regression showed that total testosterone levels of 440 and 480 ng/dL were associated with increased Framingham CVD risk and an increased probability of increased hsCRP, respectively.

Men with sexual dysfunction (poor sexual performance, decreased morning erection, and loss of libido) had significantly greater CVD risk. Their risk appeared to increase at a relatively higher testosterone level, and it reached a plateau at a testosterone level of 300 to 350 ng/dL.

In contrast, the risk in those with no or less sexual dysfunction remained low at a higher testosterone level, and a threshold level of 425 to 475 ng/dL was associated with increased CVD risk. A similar pattern and threshold were identified in the analyses of the relation between testosterone and hsCRP.

CONCLUSION: These data showed that a testosterone threshold of 440 ng/dL was associated with increased Framingham 10-year CVD risk in middle-aged and elderly men. Poor sexual performance, decreased morning erection, and loss of libido had an impact on the testosterone threshold for CVD risk. The threshold level was higher in men with sexual dysfunction. Further study is required to evaluate the validity of these testosterone thresholds for CVD risk.

 

[MR10X]

Abstract
AIMS:
The aim of this study was to assess cardiovascular (CV) safety of testosterone replacement therapy (TRT) in a large, diverse cohort of European men with hypogonadism (HG).
METHODS:
The Registry of Hypogonadism in Men (RHYME) was designed as a multi-national, longitudinal disease registry of men diagnosed with hypogonadism (HG) at 25 clinical sites in six European countries. Data collection included a complete medical history, physical examination, blood sampling and patient questionnaires at multiple study visits over 2-3 years. Independent adjudication was performed on all mortalities and CV outcomes.
RESULTS:
Of 999 patients enrolled with clinically diagnosed HG, 750 (75%) initiated some form of TRT. Registry participants, including both treated and untreated patients, contributed 23 900 person-months (99.6% of the targeted) follow-up time. A total of 55 reported CV events occurred in 41 patients. Overall, five patients died of CV-related causes (3 on TRT, 2 untreated) and none of the deaths were adjudicated as treatment-related. The overall CV incidence rate was 1522 per 100 000 person-years. CV event rates for men receiving TRT were not statistically different from untreated men (P=.70). Regardless of treatment assignment, CV event rates were higher in older men and in those with increased CV risk factors or a prior history of CV events.
CONCLUSIONS:
Age and prior CV history, not TRT use, were predictors of new-onset CV events in this multi-national, prospective hypogonadism registry.
Testosterone treatment is not associated with increased risk of adverse cardiovascular events: results from the Registry of Hypogonadism in Men (RH... - PubMed - NCBI

 

[tenpoundsleft]

Abstract
AIMS:
The aim of this study was to assess cardiovascular (CV) safety of testosterone replacement therapy (TRT) in a large, diverse cohort of European men with hypogonadism (HG).
METHODS:
The Registry of Hypogonadism in Men (RHYME) was designed as a multi-national, longitudinal disease registry of men diagnosed with hypogonadism (HG) at 25 clinical sites in six European countries. Data collection included a complete medical history, physical examination, blood sampling and patient questionnaires at multiple study visits over 2-3 years. Independent adjudication was performed on all mortalities and CV outcomes.
RESULTS:
Of 999 patients enrolled with clinically diagnosed HG, 750 (75%) initiated some form of TRT. Registry participants, including both treated and untreated patients, contributed 23 900 person-months (99.6% of the targeted) follow-up time. A total of 55 reported CV events occurred in 41 patients. Overall, five patients died of CV-related causes (3 on TRT, 2 untreated) and none of the deaths were adjudicated as treatment-related. The overall CV incidence rate was 1522 per 100 000 person-years. CV event rates for men receiving TRT were not statistically different from untreated men (P=.70). Regardless of treatment assignment, CV event rates were higher in older men and in those with increased CV risk factors or a prior history of CV events.
CONCLUSIONS:
Age and prior CV history, not TRT use, were predictors of new-onset CV events in this multi-national, prospective hypogonadism registry.
Testosterone treatment is not associated with increased risk of adverse cardiovascular events: results from the Registry of Hypogonadism in Men (RH... - PubMed - NCBI

Wow, that was exceedingly intelligible, couldn't have been written by anyone with an MD.

Good info

 

[Michael Scally MD]

‘Forever Young’ — Testosterone Replacement Therapy: A Blockbuster Drug Despite Flabby Evidence and Broken Promises

In the last decade, testosterone replacement therapy (TRT) has been increasingly prescribed to treat a controversial condition known as ‘late-onset hypogonadism (LOH)’.

This syndrome is diagnosed in men who, for no discernible reason other than older age, obesity or ill health have serum testosterone concentrations below the normal range for healthy young men and report one or more of the following symptoms: muscle weakness or wasting, mood, behaviour and cognition-related symptoms and sexual function or libido impairment.

However, recent evidence has demonstrated that testosterone drugs do not substantially ameliorate these symptoms and, more worryingly, that their long-term use may be associated with severe adverse effects (i.e. increased risk of prostate cancer, stroke and myocardial infarction, worsening of benign prostatic hyperplasia symptoms and testicular atrophy).

Nonetheless, testosterone drugs have exhibited extraordinary commercial success and their pharmaceutical sales are steadily rising.

Behind this apparently unjustifiable trend there are deliberate, well designed direct and indirect pharmaceutical marketing initiatives that exploit the conviction rooted in contemporary society that testosterone can reverse the effects of ageing and ensure social accomplishment.

Commercial mechanisms have laid the foundation for disease mongering of LOH and also have resulted a considerable expansion of the indications for treatment.

This promotion model deserves particular attention since it is applicable to any drug with a purportedly favourable risk-benefit ratio not supported by evidence.

Busnelli A, Somigliana E, Vercellini P. ‘Forever Young’†—Testosterone replacement therapy: a blockbuster drug despite flabby evidence and broken promises. Hum Reprod. 2017;1-6. ‘Forever Young’†—Testosterone replacement therapy: a blockbuster drug despite flabby evidence and broken promises | Human Reproduction | Oxford Academic

 

[BBC3]

WELL.....................

Thats because ALL I CAN THINK/SAY,, IS IT FUCKING WORX....!

And there is a REAL MEDICAL SCIENTIFIC REASON BEHIND IT TOO, that DUMBSHIT "MEDICAL SCIENCE" hasn't the WHEREWITHAL to muster...
( i think their new name is "CUNTZ IN COATZ".....)
L............. O.............L.................

And I was on the trail years back but even the best get side tracked.... Something to do with RECEPTOR COMPETITION meaning that MORE MIGHT JUST BE BETTER... FUK U ALL...

I will tell you this. I don't get a bit as androgenic in a negative sense until I lower my test dose down below 100mgs./wk. Next thing you know my scalp is bubbling with horseshit hairloss.

And I'm big and VOLUMETRIC as a mutherfucker and I can honestly say MY DAMN FEET HAVENT HURT SINCE THAT DAY I WOKE UP AT AGE 32 WHEN THEY FIRST DID AND I SAID FUK THIS I'm GETTING SOME TEST>....!!! And I'll drag my 275lb ASS out on the RacBall court and move like you never seen mid 40's... Fuk-U-Very-Much....!

Perhaps ESTROGEN IS GOOD, ..... When properly tempered with ANDROGENS.... or was that VISA-VERSA....!

‘Forever Young’ — Testosterone Replacement Therapy: A Blockbuster Drug Despite Flabby Evidence and Broken Promises

In the last decade, testosterone replacement therapy (TRT) has been increasingly prescribed to treat a controversial condition known as ‘late-onset hypogonadism (LOH)’.

This syndrome is diagnosed in men who, for no discernible reason other than older age, obesity or ill health have serum testosterone concentrations below the normal range for healthy young men and report one or more of the following symptoms: muscle weakness or wasting, mood, behaviour and cognition-related symptoms and sexual function or libido impairment.

However, recent evidence has demonstrated that testosterone drugs do not substantially ameliorate these symptoms and, more worryingly, that their long-term use may be associated with severe adverse effects (i.e. increased risk of prostate cancer, stroke and myocardial infarction, worsening of benign prostatic hyperplasia symptoms and testicular atrophy).

Nonetheless, testosterone drugs have exhibited extraordinary commercial success and their pharmaceutical sales are steadily rising.

Behind this apparently unjustifiable trend there are deliberate, well designed direct and indirect pharmaceutical marketing initiatives that exploit the conviction rooted in contemporary society that testosterone can reverse the effects of ageing and ensure social accomplishment.

Commercial mechanisms have laid the foundation for disease mongering of LOH and also have resulted a considerable expansion of the indications for treatment.

This promotion model deserves particular attention since it is applicable to any drug with a purportedly favourable risk-benefit ratio not supported by evidence.

Busnelli A, Somigliana E, Vercellini P. ‘Forever Young’†—Testosterone replacement therapy: a blockbuster drug despite flabby evidence and broken promises. Hum Reprod. 2017;1-6. ‘Forever Young’†—Testosterone replacement therapy: a blockbuster drug despite flabby evidence and broken promises | Human Reproduction | Oxford Academic

 

[Michael Scally MD]

Elsherbiny A, Tricomi M, Bhatt D, Dandapantula HK. State-of-the-Art: a Review of Cardiovascular Effects of Testosterone Replacement Therapy in Adult Males. Curr Cardiol Rep 2017;19(4):35. https://link.springer.com/article/10.1007%2Fs11886-017-0838-x

PURPOSE OF REVIEW: According to an Endocrine Society Clinical Practice Guideline published in June 2010, testosterone replacement therapy (TRT) should be administered only to men who are hypogonadal with documented low testosterone level on two morning measurements. This recommendation was based on previous studies that did not show an increased risk in cardiovascular events with TRT. In contrast, recent studies did show an increased risk which prompted the FDA to investigate further.

RECENT FINDINGS: Multiple studies suggested an increased risk in cardiovascular events among groups of men prescribed TRT.

SUMMARY: There is recent evidence that TRT can be associated with higher cardiovascular risks, while these risks are still not well established, and more well-designed trials are needed. Physicians should always be cautious when prescribing TRT to their patients. Potential risks should be discussed with each patient, and TRT requires regular monitoring to help minimize side effects.

 

[Superman125]

Association of Testosterone Replacement With Cardiovascular Outcomes Among Men With Androgen Deficiency.
Cheetham TC1, An J2, Jacobsen SJ1, Niu F3, Sidney S4, Quesenberry CP4, VanDenEeden SK4.
Author information
1
Southern California Permanente Medical Group, Department of Research & Evaluation, Pasadena.
2
Western University of Health Sciences, Pharmacy Practice and Administration, Pomona, California.
3
Kaiser Permanente Southern California, Drug Information Service, Downey.
4
Kaiser Permanente Northern California, Division of Research, Oakland.
Abstract
IMPORTANCE:
Controversy exists regarding the safety of testosterone replacement therapy (TRT) following recent reports of an increased risk of adverse cardiovascular events.

OBJECTIVE:
To investigate the association between TRT and cardiovascular outcomes in men with androgen deficiency.

DESIGN, SETTING, AND PARTICIPANTS:
A retrospective cohort study was conducted within an integrated health care delivery system. Men at least 40 years old with evidence of androgen deficiency either by a coded diagnosis and/or a morning serum total testosterone level of less than 300 ng/dL were included. The eligibility window was January 1, 1999, to December 31, 2010, with follow-up through December 31, 2012.

EXPOSURES:
Any prescribed TRT given by injection, orally, or topically.

MAIN OUTCOMES AND MEASURES:
The primary outcome was a composite of cardiovascular end points that included acute myocardial infarction (AMI), coronary revascularization, unstable angina, stroke, transient ischemic attack (TIA), and sudden cardiac death (SCD). Multivariable Cox proportional hazards models were used to investigate the association between TRT and cardiovascular outcomes. An inverse probability of treatment weight, propensity score methodology, was used to balance baseline characteristics.

RESULTS:
The cohorts consisted of 8808 men (19.8%) ever dispensed testosterone (ever-TRT) (mean age, 58.4 years; 1.4% with prior cardiovascular events) and 35 527 men (80.2%) never dispensed testosterone (never-TRT) (mean age, 59.8 years; 2.0% with prior cardiovascular events). Median follow was 3.2 years (interquartile range [IQR], 1.7-6.6 years) in the never-TRT group vs 4.2 (IQR, 2.1-7.8) years in the ever-TRT group. The rates of the composite cardiovascular end point were 23.9 vs 16.9 per 1000 person-years in the never-TRT and ever-TRT groups, respectively. The adjusted hazard ratio (HR) for the composite cardiovascular end point in the ever-TRT group was 0.67 (95% CI, 0.62-0.73. Similar results were seen when the outcome was restricted to combined stroke events (stroke and TIA) (HR, 0.72; 95% CI, 0.62-0.84) and combined cardiac events (AMI, SCD, unstable angina, revascularization procedures) (HR, 0.66; 95% CI, 0.60-0.72).

CONCLUSIONS AND RELEVANCE:
Among men with androgen deficiency, dispensed testosterone prescriptions were associated with a lower risk of cardiovascular outcomes over a median follow-up of 3.4 years.

 

[Michael Scally MD]

[OA] Testosterone Treatment and Cardiovascular Events in Prescription Database Studies

Over the past decade, there has been a substantial increase in the number of men who are treated with testosterone.

Despite this increase in the use of testosterone, the risks of adverse cardiovascular events are unclear as meta-analyses have reported conflicting findings and no clinical studies have been large enough or long enough to adequately assess for cardiovascular risks.

The goal of this paper is to review large prescription database studies of testosterone treatment and adverse cardiovascular events and mortality with the aim of providing some guidance for clinicians and researchers in this controversial area.

Shores MM. Testosterone treatment and cardiovascular events in prescription database studies. Asian J Androl. http://www.ajandrology.com/preprintarticle.asp?id=212903

 

[Michael Scally MD]

Second U.S. jury finds AbbVie misrepresented risks of AndroGel
Second U.S. jury finds AbbVie misrepresented risks of AndroGel

(Reuters) - A U.S. jury on Thursday ordered AbbVie Inc to pay more than $140 million to a man who claimed the company misrepresented the risks of its testosterone replacement drug AndroGel, causing him to suffer a heart attack, the plaintiff’s lawyer said in a statement.

The verdict, handed down in federal court in Chicago, came in a lawsuit Tennessee resident Jeffrey Konrad and his wife filed in 2015. It is the second verdict against AbbVie to come out of more than 6,000 similar lawsuits against AbbVie and other companies consolidated in the Chicago court.

“We are disappointed with today’s verdict and we intend to appeal,” Chicago-based AbbVie said in a statement.

Thursday’s verdict was comprised of $140 million in punitive damages, intended to deter the defendant and others from engaging in similar behavior, and $140,000 in compensatory damages, according to David Buchanan, an attorney for Konrad.

Konrad’s case is part of a series of test trials aimed at helping plaintiffs and manufacturers of AndroGel gauge the range of damages and define a legal strategy and settlement options.

Plaintiffs across the country claim AndroGel can cause heart attacks, strokes and other injuries.

AbbVie has said that its marketing of AndroGel adhered strictly to uses approved by the Food and Drug Administration and that it was in full compliance with applicable standards.

A federal jury in another case in July found AbbVie fraudulently misrepresented the drug’s risk and ordered the company to pay $150 million in punitive damages.

That jury’s decision to award punitive damages without granting compensatory damages was unusual and both sides continue to fight over the verdict’s validity in court.

Konrad, 56, had been using AndroGel for two months in 2010 when he suffered a heart attack. He has since recovered from his injuries.

In court papers, the company contended that Konrad’s heart attack was caused by other factors, such as obesity and high blood pressure. It also said it made no misrepresentations about AndroGel’s safety.

 

[Dr JIM]

A "heart attack" and a windfall of 140 MILLION bucks awarded as "punitive damages".

Imagine what the awards would be if AAS were FDA "approved" for use as PEDS!

Not surprising in an almost identical case a Chicago jury awarded "Jessie Mitchell"
150 MILLION dollars as punitive damages in spite of the fact, Mr Mitchell had every cardiac risk factor under the sun including, according to his own physician;
"HTN, Smoking, obesity, high cholesterol, high triglycerides, family HX of heart disease, and a lack of exercise".

But TRT was deemed the proximate cause of Mr Mitchell's "heart attack" --- NUTS

Finally since ABVIE Androgel sales approximated 700 million last year, and some 6000 cases remain, will the end result will follow the silicone breast implant debacle and bankrupt ABVVIE. -------- The lawyers were paid millions while on a comparative basis the patients got next to nothing!

 

[tenpoundsleft]

A "heart attack" and a windfall of 140 MILLION bucks awarded as "punitive damages".

Imagine what the awards would be if AAS were FDA "approved" for use as PEDS!

Not surprising in an almost identical case a Chicago jury awarded "Jessie Mitchell"
150 MILLION dollars as punitive damages in spite of the fact, Mr Mitchell had every cardiac risk factor under the sun including, according to his own physician;
"HTN, Smoking, obesity, high cholesterol, high triglycerides, family HX of heart disease, and a lack of exercise".

But TRT was deemed the proximate cause of Mr Mitchell's "heart attack" --- NUTS

Finally since ABVIE Androgel sales approximated 700 million last year, and some 6000 cases remain, will the end result will follow the silicone breast implant debacle and bankrupt ABVVIE. -------- The lawyers were paid millions while on a comparative basis the patients got next to nothing!

Do I detect antipathy toward the liberal legal profession? Interesting.

 

[eryximachus]

Do I detect antipathy toward the liberal legal profession? Interesting.

Liberalism, fundamentally, is a consequence of baseline testosterone levels. You will rarely find a man in the upper quintile of testosterone levels who is a liberal. One can attend any "liberal" event, and it entirely consists of degenerate effete creatures who allegedly have penises and extremely large, often obese, females with masculine features and demeanors.
The politics of testosterone and biological sex is fascinating and beyond the scope of this site. But, bottom line: liberals are pussies. Men who are pussies have low testosterone levels. Case closed.

 

[tenpoundsleft]

Liberalism, fundamentally, is a consequence of baseline testosterone levels. You will rarely find a man in the upper quintile of testosterone levels who is a liberal. One can attend any "liberal" event, and it entirely consists of degenerate effete creatures who allegedly have penises and extremely large, often obese, females with masculine features and demeanors.
The politics of testosterone and biological sex is fascinating and beyond the scope of this site. But, bottom line: liberals are pussies. Men who are pussies have low testosterone levels. Case closed.

Oh, I agree with you.

And I agree with Dr Jim's critique too, just pointing out his rare moment of clarity - normally he's sucking the liberal teat 24/7.

 

[eryximachus]

Oh, I agree with you.

And I agree with Dr Jim's critique too, just pointing out his rare moment of clarity - normally he's sucking the liberal teat 24/7.

He's a boomer. No matter how smart they are, they were indoctrinated from a young age in Marxist ideology. No matter what they say, they cannot accept that human behavior is almost entirely biological and that social conditioning has little impact on life outcomes.

 

[Michael Scally MD]

Testosterone Therapy and [No] Risk of Acute Myocardial Infarction

Background - There are some ongoing debates on the potential link between testosterone therapy (TT) and risk of acute myocardial infarction (MI).

Aim - To investigate the association between acute MI and TT use compared with non-use in men having documented hypogonadism (diagnostic International Classification of Diseases, Ninth Revision codes 257.2, 257.8, 257.9, 758.7) in patient claims records.

Methods - This retrospective cohort study used a real-world US-based administrative health care claims database (MarketScan 2004–2013; Truven Health Analytics, Ann Arbor, MI, USA) to compare MI rates between TT-treated men and a cohort of untreated hypogonadal men matched by a calendar time-specific propensity score. Subgroup analyses were performed by route of administration, age, and prior cardiovascular disease (CVD).

Outcomes - Incidence rates of MI (per 1,000 person-years) and hazard ratio.

Results - After 1:1 calendar time-specific propensity score matching, 207,176 TT-treated men and 207,176 untreated hypogonadal men were included in the analysis (mean age = 51.8 years). Incidence rates of MI were 4.20 (95% CI = 3.87–4.52) in the TT-treated cohort and 4.67 (95% CI = 4.43–4.90) in the untreated hypogonadal cohort. Cox regression model showed no significant association between TT use and MI when comparing TT-treated with untreated hypogonadal men overall (hazard ratio = 0.99, 95% CI = 0.89–1.09), by age, or by prior CVD. A significant association was observed when comparing a subgroup of injectable (short- and long-acting combined) TT users with untreated hypogonadal men (hazard ratio = 1.55, 95% CI = 1.24–1.93).

Clinical Implication - In this study, there was no association between TT (overall) and risk of acute MI.

Strengths and Limitations - Strengths included the use of a comprehensive real-world database, sophisticated matching based on calendar blocks of 6 months to decrease potential bias in this observational study, carefully chosen index dates for the untreated cohort to avoid immortal time bias, and implemented sensitivity analysis to further investigate the findings (stratification by administration route, age, and prior CVD). Key limitations included no information about adherence, hypogonadism condition based solely on diagnosis (no information on clinical symptoms or testosterone levels), lack of information on disease severity, inability to capture diagnoses, medical procedures, and medicine dispensing if corresponding billing codes were not generated and findings could contain biases or fail to generalize well to other populations.

Conclusion - This large, retrospective, real-world observational study showed no significant association between TT use and acute MI when comparing TT-treated with untreated hypogonadal men overall, by age, or by prior CVD; the suggested association between injectable TT and acute MI deserves further investigation.

Li H, Mitchell L, Zhang X, et al. Testosterone Therapy and Risk of Acute Myocardial Infarction in Hypogonadal Men: An Administrative Health Care Claims Study. J Sex Med 2017;14:1307–17. http://www.jsm.jsexmed.org/article/S1743-6095(17)31427-3/abstract

 

[Michael Scally MD]

Testosterone Therapy and Risk of Acute Myocardial Infarction in Hypogonadal Men

BACKGROUND: There are some ongoing debates on the potential link between testosterone therapy (TT) and risk of acute myocardial infarction (MI). AIM: To investigate the association between acute MI and TT use compared with non-use in men having documented hypogonadism (diagnostic International Classification of Diseases, Ninth Revision codes 257.2, 257.8, 257.9, 758.7) in patient claims records.

METHODS: This retrospective cohort study used a real-world US-based administrative health care claims database (MarketScan 2004-2013; Truven Health Analytics, Ann Arbor, MI, USA) to compare MI rates between TT-treated men and a cohort of untreated hypogonadal men matched by a calendar time-specific propensity score. Subgroup analyses were performed by route of administration, age, and prior cardiovascular disease (CVD).

OUTCOMES: Incidence rates of MI (per 1,000 person-years) and hazard ratio.

RESULTS: After 1:1 calendar time-specific propensity score matching, 207,176 TT-treated men and 207,176 untreated hypogonadal men were included in the analysis (mean age = 51.8 years). Incidence rates of MI were 4.20 (95% CI = 3.87-4.52) in the TT-treated cohort and 4.67 (95% CI = 4.43-4.90) in the untreated hypogonadal cohort.

Cox regression model showed no significant association between TT use and MI when comparing TT-treated with untreated hypogonadal men overall (hazard ratio = 0.99, 95% CI = 0.89-1.09), by age, or by prior CVD.

A significant association was observed when comparing a subgroup of injectable (short- and long-acting combined) TT users with untreated hypogonadal men (hazard ratio = 1.55, 95% CI = 1.24-1.93).

CLINICAL IMPLICATION: In this study, there was no association between TT (overall) and risk of acute MI.

STRENGTHS AND LIMITATIONS: Strengths included the use of a comprehensive real-world database, sophisticated matching based on calendar blocks of 6 months to decrease potential bias in this observational study, carefully chosen index dates for the untreated cohort to avoid immortal time bias, and implemented sensitivity analysis to further investigate the findings (stratification by administration route, age, and prior CVD).

Key limitations included no information about adherence, hypogonadism condition based solely on diagnosis (no information on clinical symptoms or testosterone levels), lack of information on disease severity, inability to capture diagnoses, medical procedures, and medicine dispensing if corresponding billing codes were not generated and findings could contain biases or fail to generalize well to other populations.

CONCLUSION: This large, retrospective, real-world observational study showed no significant association between TT use and acute MI when comparing TT-treated with untreated hypogonadal men overall, by age, or by prior CVD; the suggested association between injectable TT and acute MI deserves further investigation.

Li H, Mitchell L, Zhang X, Heiselman D, Motsko S. Testosterone Therapy and Risk of Acute Myocardial Infarction in Hypogonadal Men: An Administrative Health Care Claims Study. J Sex Med 2017;14(11):1307-17. http://www.jsm.jsexmed.org/article/S1743-6095(17)31427-3/abstract

 

[Michael Scally MD]

Corona G, Rastrelli G, Dicuio M, Sforza A, Maggi M. Testosterone and Cardiovascular Diseases: Causes or Consequences: The Lesson from the Last 5 Years. Current Sexual Health Reports. https://link.springer.com/article/10.1007%2Fs11930-017-0132-3

Purpose of the Review - The relationship between the age-dependent decline of testosterone (T) and cardiovascular (CV) risk in men is still a matter of intense debate. In particular, over the last 5 years, several scientific reports have shed a new negative light on the association between T treatment (TTh) and forthcoming CV diseases (CVD). Based on this evidence, the US Food and Drug Administration agency has recommended that all T supplementations carry a warning that they may increase the risk of heart attack and stroke.

To better clarify the available data on this topic, we scrutinized and summarized, also by using meta-analytic methods, the data generated during the last 5 years, as derived from the analysis of observational (either longitudinal or pharmaco-epidemiological) studies and from randomized controlled trials (RCTs) on TTh and CVD risk.

Recent Findings - Our analysis shows that there is a clear association between baseline T deficiency and overall mortality and CVD-related mortality when longitudinal surveys were analyzed, although a specific pathogenetic link cannot be made.

When interventional trials were studied, several but not all pharmaco-epidemiological studies reported a possible protective role of TTh on CV risk; however, data from RCTs and their meta-analysis, presented here, do not provide us with sufficient information on this point.

Summary - Present data do not indicate an increased risk with TTh, but there is also insufficient definitive evidence that TTh is protective. Therefore, further and more specific trials are advisable to better clarify the possible relationship between low T, TTh, and CVD in aging men.

 

[Michael Scally MD]

Testosterone Replacement Therapy and The Risk of Stroke

Highlights
· Few studies have evaluated the risk of stroke among testosterone-treated men.
· Existing studies have methodological limitations which preclude valid conclusions.
· The association between testosterone and the risk of stroke in men remains unclear.

In recent years, questions have been raised regarding the cardiovascular safety of testosterone replacement therapy (TRT). The objective of this study was to systematically review the available evidence on TRT safety in men, specifically with respect to the risk of stroke.

We identified publications from MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to May 2017. Articles eligible for review included observational studies evaluating TRT and the risk of stroke among men aged 18 or older. Randomized controlled trials (RCTs) comparing testosterone to placebo in men were also eligible, provided stroke was identified as an adverse event.

Among seven cohort studies of hypogonadal men, one study reported that TRT was associated with a significant decrease in the risk of ischemic stroke (hazard ratio (HR) 0.64; 95% confidence interval (CI) 0.52-0.80). Another reported a similar decrease in risk (HR 0.64; 95% CI 0.43-0.96) among treated men who achieved normalized levels of testosterone. Limitations in study design, including immortal time bias and residual confounding, may have influenced both of these results. The remaining observational studies did not report measures of association to estimate the independent risk of stroke associated with TRT. Among eight RCTs, a low frequency of stroke events (<5) was observed across both testosterone and control groups, thus precluding any definitive conclusions.

Based on these findings, the association between TRT and the risk of stroke in men remains unclear, and further large and methodologically robust studies are needed to establish this relationship.

Loo SY, Chen BY, Yu OHY, Azoulay L, Renoux C. Testosterone replacement therapy and the risk of stroke in men: A systematic review. Maturitas 2017;106:31-7. http://www.maturitas.org/article/S0378-5122(17)30816-2/abstract

 

[Michael Scally MD]

Association Between Testosterone Levels and Risk Factors of Subclinical Atherosclerosis

Introduction & Objectives: It’s suggested that lower testosterone levels contribute to atherosclerosis development in men. However, its exact mechanism is still unclear. The aim of this study was to investigate the association between serum levels of testosterone and risk factors of subclinical atherosclerosis based on data from 119 middle-aged healthy men from the general population.

Materials & Methods: Systolic and diastolic blood pressure were measured. Serum levels of testosterone, fasting blood glucose, 2-hours glucose tolerance test, HbA1c, Factor VIII, von Willebrand factor antigen (vWF:Ag), von Willebrand factor activity (vWF:RCo), Apolipoprotein A-1 (ApoA-1), Apolipoprotein B (ApoB), and Apolipoprotein B-to-Apolipoprotein A-1 ratio (ApoB-to-ApoA-1 ratio) were assessed. Demographic data regarding BMI, waist-to-hip ratio, smoking, alcohol consumption, and family history of CVD were also collected.

Thereafter, the men were classified into two groups based on serum levels of testosterone; hypogonadal (testosterone ≤ 12 nmol/L) and eugonadal (testosterone > 12 nmol/L). Statistical analyses were done using non parametric Mann-Whitney U test, multivariate regression analysis model, and non parametric Spearmen’s rank correlation test. P-values below 0.05 were considered statistically significant.

Results: BMI, systolic blood pressure, fasting blood glucose, ApoB, and ApoB-to-ApoA-1 ratio were significantly higher in hypogonadal men as compared to eugonadal men (28 kg/cm2 vs. 26 kg/cm2, p = 0.01), (129 mmHg vs. 123 mmHg, p = 0.03), (5.9 mmol/L vs. 5.5 mmol/L, p = 0.03), (1.1 g/L vs. 1.0 g/L, p = 0.03), (0.8 vs. 0.7, p = 0.03), respectively. On the other hand, diastolic blood pressure; levels of Factor VIII; vWF:Ag; vWF:RCo; and ApoA-1 did not differ significantly between groups (p > 0.05).

Using adjusted multivariate regression analysis model, only ApoB showed a negative significant association with testosterone levels (β = -0.011, p = 0.018, 95% CI = -0.019, -0.002). Finally, we found a positive significant correlation between ApoB and BMI (r = 0.299, p = 0.002), systolic blood pressure (r = 0.236, p = 0.018), and 2 –hours blood glucose tolerance test (r = 0.260, p = 0.018).

Conclusions: Low testosterone levels contribute to risk factors of subclinical atherosclerosis. This contribution seems to be mediated through increased levels of ApoB.

Zanjani BR, Borgquist R, Willenheimer RB, Elzanaty S. P26 – Association between testosterone levels and risk factors of subclinical atherosclerosis. European Urology Supplements. 2017;16(13):e3019. https://www.sciencedirect.com/science/article/pii/S1569905617321462

 

[Michael Scally MD]

[OA] British Society for Sexual Medicine Guidelines on Adult Testosterone Deficiency

Background - Testosterone deficiency (TD) is an increasingly common problem with significant health implications, but its diagnosis and management can be challenging.

Aim - To review the available literature on TD and provide evidence-based statements for UK clinical practice.

Methods - Evidence was derived from Medline, EMBASE, and Cochrane searches on hypogonadism, testosterone (T) therapy, and cardiovascular safety from May 2005 to May 2015. Further searches continued until May 2017.

Outcomes - To provide a guideline on diagnosing and managing TD, with levels of evidence and grades of recommendation, based on a critical review of the literature and consensus of the British Society of Sexual Medicine panel.

Results - 25 statements are provided, relating to 5 key areas: screening, diagnosis, initiating T therapy, benefits and risks of T therapy, and follow-up. 7 statements are supported by level 1, 8 by level 2, 5 by level 3, and 5 by level 4 evidence.

Clinical Implications - To help guide UK practitioners on effectively diagnosing and managing primary and age-related TD.

Strengths and Limitations - A large amount of literature was carefully sourced and reviewed, presenting the best evidence available at the time. However, some statements provided are based on poor-quality evidence. This is a rapidly evolving area of research and recommendations are subject to change.

Guidelines can never replace clinical expertise when making treatment decisions for individual patients, but rather help to focus decisions and take personal values and preferences and individual circumstances into account. Many issues remain controversial, but in the meantime, clinicians need to manage patient needs and clinical expectations armed with the best clinical evidence and the multidisciplinary expert opinion available.

Conclusion - Improving the diagnosis and management of TD in adult men should provide somatic, sexual, and psychological benefits and subsequent improvements in quality of life.

Hackett G, Kirby M, Edwards D, et al. British Society for Sexual Medicine Guidelines on Adult Testosterone Deficiency, With Statements for UK Practice. The Journal of Sexual Medicine 2017;14:1504-23. Redirecting