AAS and Cardiovascular/Pulmonary Function

[Michael Scally MD]

[OA] Impact of Medical Castration on Malignant Arrhythmias in Patients With Prostate Cancer

Clinical Perspective

What Is New?

Medical castration prolonged the QT and corrected QT intervals in most patients with prostate cancer and could rarely cause torsade de pointes and ventricular fibrillation.

An increase in the corrected QT interval of >50 ms might become a predictor of malignant arrhythmias during medical castration in patients with prostate cancer.

What Are the Clinical Implications?

Much attention should be paid to the corrected QT interval throughout all periods of medical castration to prevent torsade de pointes, ventricular fibrillation, and sudden death in patients with prostate cancer.

Background Medical castration, gonadotropin-releasing hormone agonists, and antiandrogens have been widely applied as a treatment for prostate cancer. Sex steroid hormones influence cardiac ion channels. However, few studies have examined the proarrhythmic properties of medical castration.

Methods and Results This study included 149 patients who underwent medical castration using gonadotropin-releasing hormones with/without antiandrogen for prostate cancer. The changes in the ECG findings during the therapy and associations of the electrocardiographic findings with malignant arrhythmias were studied.

The QT and corrected QT (QTc) intervals prolonged during the therapy compared with baseline (QT, 394±32 to 406±39 ms [P<0.001]; QTc, 416±27 to 439±31 ms [P<0.001]). The QTc interval was prolonged in 119 (79.9%) patients during the therapy compared with baseline. In 2 (1.3%) patients who had no structural heart disease, torsade de pointes (TdP) and ventricular fibrillation (VF) occurred ≥6 months after starting the therapy.

In patients with TdP/VF, the increase in the QTc interval from the pretreatment value was >80 ms. However, in patients without TdP/VF, the prevalence of an increase in the QTc interval from the pretreatment value of >50 ms was 11%, and an increase in the QTc interval from the pretreatment value >80 ms was found in only 4 (3%) patients.

Conclusions Medical castration prolongs the QT/QTc intervals in most patients with prostate cancer, and it could cause TdP/VFs even in patients with no risk of QT prolongation before the therapy. An increase in the QTc interval from the pretreatment value >50 ms might become a predictor of TdP/VF. Much attention should be paid to the QTc interval throughout all periods of medical castration to prevent malignant arrhythmias.

Hasegawa K, Ito H, Kaseno K, Miyazaki S, Shiomi Y, Tama N, Ikeda H, Ishida K, Uzui H, Ohno S, Horie M, Yokoyama O, Tada H. Impact of Medical Castration on Malignant Arrhythmias in Patients With Prostate Cancer. J Am Heart Assoc. 2021 Feb 18:e017267. doi: 10.1161/JAHA.120.017267. Epub ahead of print. PMID: 33599136. https://www.ahajournals.org/doi/10.1161/JAHA.120.017267

 

[Michael Scally MD]

[OA] Impact of Medical Castration on Malignant Arrhythmias in Patients With Prostate Cancer

Clinical Perspective

What Is New?

Medical castration prolonged the QT and corrected QT intervals in most patients with prostate cancer and could rarely cause torsade de pointes and ventricular fibrillation.

An increase in the corrected QT interval of >50 ms might become a predictor of malignant arrhythmias during medical castration in patients with prostate cancer.

What Are the Clinical Implications?

Much attention should be paid to the corrected QT interval throughout all periods of medical castration to prevent torsade de pointes, ventricular fibrillation, and sudden death in patients with prostate cancer.

Background Medical castration, gonadotropin-releasing hormone agonists, and antiandrogens have been widely applied as a treatment for prostate cancer. Sex steroid hormones influence cardiac ion channels. However, few studies have examined the proarrhythmic properties of medical castration.

Methods and Results This study included 149 patients who underwent medical castration using gonadotropin-releasing hormones with/without antiandrogen for prostate cancer. The changes in the ECG findings during the therapy and associations of the electrocardiographic findings with malignant arrhythmias were studied.

The QT and corrected QT (QTc) intervals prolonged during the therapy compared with baseline (QT, 394±32 to 406±39 ms [P<0.001]; QTc, 416±27 to 439±31 ms [P<0.001]). The QTc interval was prolonged in 119 (79.9%) patients during the therapy compared with baseline. In 2 (1.3%) patients who had no structural heart disease, torsade de pointes (TdP) and ventricular fibrillation (VF) occurred ≥6 months after starting the therapy.

In patients with TdP/VF, the increase in the QTc interval from the pretreatment value was >80 ms. However, in patients without TdP/VF, the prevalence of an increase in the QTc interval from the pretreatment value of >50 ms was 11%, and an increase in the QTc interval from the pretreatment value >80 ms was found in only 4 (3%) patients.

Conclusions Medical castration prolongs the QT/QTc intervals in most patients with prostate cancer, and it could cause TdP/VFs even in patients with no risk of QT prolongation before the therapy. An increase in the QTc interval from the pretreatment value >50 ms might become a predictor of TdP/VF. Much attention should be paid to the QTc interval throughout all periods of medical castration to prevent malignant arrhythmias.

Hasegawa K, Ito H, Kaseno K, Miyazaki S, Shiomi Y, Tama N, Ikeda H, Ishida K, Uzui H, Ohno S, Horie M, Yokoyama O, Tada H. Impact of Medical Castration on Malignant Arrhythmias in Patients With Prostate Cancer. J Am Heart Assoc. 2021 Feb 18:e017267. doi: 10.1161/JAHA.120.017267. Epub ahead of print. PMID: 33599136. https://www.ahajournals.org/doi/10.1161/JAHA.120.017267

[OA] The Role of Testosterone and Gonadotropins in Arrhythmogenesis

Nearly 100 years ago, prof. Henry Bazett described a shorter heart rate corrected QT interval (QTc) in adult men compared with women. In the past decades, we have learned that this difference is not present during the first months of life but arises during puberty. Throughout puberty, the QTc shortens in male but not in female adolescents. This sex difference decreases with age during adulthood because of progressive QTc lengthening in men. As a result, no clear sex differences are present in the age group of >60 years.

It is thus thought that sex hormones play a role in the relationship between QTc, age, and sex. However, the mechanisms underlying the influence of sex hormones on the repolarization are complex and still incompletely resolved. It has been suggested that the presence of nuclear and cytosolic receptors for sex hormones within the cardiovascular system and neuroregulatory tissues exerts direct and indirect effects on the cardiovascular system and may regulate gene expression.

From observational studies, we have learned that testosterone decreases the L‐type calcium current and increases certain potassium channel currents, and may shorten the action potential and consequently QTc through these mechanisms. The concentration of testosterone is regulated by the hypothalamic‐pituitary‐gonadal axis. During puberty, the hypothalamic‐pituitary‐gonadal axis becomes activated and therefore a higher concentration of testosterone is found during this period compared with childhood, presumably resulting in a QTc shortening in male subjects. In adulthood, the level of testosterone gradually decreases with age in men, explaining why with aging, the QTc in men gradually lengthens and approximates that of women.

What makes the influence of sex hormones on the repolarization even more complex is that there also seems to be an interaction between sex hormones and gonadotropins. Especially, follicle‐stimulating hormone (FSH) appears to independently prolong ventricular repolarization, resulting in QTc prolongation, although the exact mechanisms by which the ion currents involved in cardiac repolarization are affected are still under study.

In secondary hypogonadotropic hypogonadal men (presenting with both low FSH and testosterone concentrations), no difference in QTc was seen compared with healthy controls, which could be because of opposing actions of low FSH and low testosterone on repolarization. In contrast, men with peripheral hypogonadism (presenting with high FSH and low testosterone concentrations) had longer QTc compared with healthy men.

Vink AS, Postema PG. The Role of Testosterone and Gonadotropins in Arrhythmogenesis. J Am Heart Assoc. 2021 Feb 18:e020300. doi: 10.1161/JAHA.120.020300. Epub ahead of print. PMID: 33599137. https://www.ahajournals.org/doi/10.1161/JAHA.120.020300

 

[Ss99]

[OA] The Role of Testosterone and Gonadotropins in Arrhythmogenesis

Nearly 100 years ago, prof. Henry Bazett described a shorter heart rate corrected QT interval (QTc) in adult men compared with women. In the past decades, we have learned that this difference is not present during the first months of life but arises during puberty. Throughout puberty, the QTc shortens in male but not in female adolescents. This sex difference decreases with age during adulthood because of progressive QTc lengthening in men. As a result, no clear sex differences are present in the age group of >60 years.

It is thus thought that sex hormones play a role in the relationship between QTc, age, and sex. However, the mechanisms underlying the influence of sex hormones on the repolarization are complex and still incompletely resolved. It has been suggested that the presence of nuclear and cytosolic receptors for sex hormones within the cardiovascular system and neuroregulatory tissues exerts direct and indirect effects on the cardiovascular system and may regulate gene expression.

From observational studies, we have learned that testosterone decreases the L‐type calcium current and increases certain potassium channel currents, and may shorten the action potential and consequently QTc through these mechanisms. The concentration of testosterone is regulated by the hypothalamic‐pituitary‐gonadal axis. During puberty, the hypothalamic‐pituitary‐gonadal axis becomes activated and therefore a higher concentration of testosterone is found during this period compared with childhood, presumably resulting in a QTc shortening in male subjects. In adulthood, the level of testosterone gradually decreases with age in men, explaining why with aging, the QTc in men gradually lengthens and approximates that of women.

What makes the influence of sex hormones on the repolarization even more complex is that there also seems to be an interaction between sex hormones and gonadotropins. Especially, follicle‐stimulating hormone (FSH) appears to independently prolong ventricular repolarization, resulting in QTc prolongation, although the exact mechanisms by which the ion currents involved in cardiac repolarization are affected are still under study.

In secondary hypogonadotropic hypogonadal men (presenting with both low FSH and testosterone concentrations), no difference in QTc was seen compared with healthy controls, which could be because of opposing actions of low FSH and low testosterone on repolarization. In contrast, men with peripheral hypogonadism (presenting with high FSH and low testosterone concentrations) had longer QTc compared with healthy men.

Vink AS, Postema PG. The Role of Testosterone and Gonadotropins in Arrhythmogenesis. J Am Heart Assoc. 2021 Feb 18:e020300. doi: 10.1161/JAHA.120.020300. Epub ahead of print. PMID: 33599137. https://www.ahajournals.org/doi/10.1161/JAHA.120.020300

I’ve seen this from my own ECGs, my QTc (Bazett) on my last steroid cycle was around 365 or so, and before ever using steroids it trended around the 400-410 mark. I believe a certain study also found that the majority of AAS users had a QTc of under 380.

Is it safe to say with extended androgen abuse the action potential duration will continue to get shorter unless by the odd chance cardiomyopathy or significant pathaological cardiac remodelling occurs leading to the trend reversing and the QTc subsequently increasing?

 

[Michael Scally MD]

[OA] The Cardiac Effects of Performance-Enhancing Medications: Caffeine vs. Anabolic Androgenic Steroids

Several performance-enhancing or ergogenic drugs have been linked to both significant adverse cardiovascular effects and increased cardiovascular risk. Even with increased scrutiny on the governance of performance-enhancing drugs (PEDs) in professional sport and heightened awareness of the associated cardiovascular risk, there are some who are prepared to risk their use to gain competitive advantage.

Caffeine is the most commonly consumed drug in the world and its ergogenic properties have been reported for decades. Thus, the removal of caffeine from the World Anti-Doping Agency (WADA) list of banned substances, in 2004, has naturally led to an exponential rise in its use amongst athletes. The response to caffeine is complex and influenced by both genetic and environmental factors. Whilst the evidence may be equivocal, the ability of an athlete to train longer or at a greater power output cannot be overlooked. Furthermore, its impact on the myocardium remains unanswered.

In contrast, anabolic androgenic steroids are recognised PEDs that improve athletic performance, increase muscle growth and suppress fatigue. Their use, however, comes at a cost, afflicting the individual with several side effects, including those that are detrimental to the cardiovascular system.

This review addresses the effects of the two commonest PEDs, one legal, the other prohibited, and their respective effects on the heart, as well as the challenge in defining its long-term implications.

Sivalokanathan S, Małek ŁA, Malhotra A. The Cardiac Effects of Performance-Enhancing Medications: Caffeine vs. Anabolic Androgenic Steroids. Diagnostics (Basel). 2021 Feb 17;11(2):324. doi: 10.3390/diagnostics11020324. PMID: 33671206. https://www.mdpi.com/2075-4418/11/2/324/htm

 

[Bumble]

I’ve seen this from my own ECGs, my QTc (Bazett) on my last steroid cycle was around 365 or so, and before ever using steroids it trended around the 400-410 mark. I believe a certain study also found that the majority of AAS users had a QTc of under 380.

Is it safe to say with extended androgen abuse the action potential duration will continue to get shorter unless by the odd chance cardiomyopathy or significant pathaological cardiac remodelling occurs leading to the trend reversing and the QTc subsequently increasing?

Prolonged QT is typically what we care about. I've never come across shortened QT being a thing.

Can you explain in simple terms.

 

[Michael Scally MD]

View: https://twitter.com/skathire/status/1369269584168157190?s=20

 

[Michael Scally MD]

[OA] Anabolic Steroid-Induced Myocardial Infarction

Misuse of androgenic-anabolic steroids (AAS) has been well known to increase the risk for a cardiac problem, including acute myocardial infarction (MI). Steroids once thought a magic drug providing immediate relief to patients, also have a darker aspect of its severe side effects. AAS are widely used these days, especially in teenagers, bodybuilders, and athletes. MI is thought to be a disease of old age, but young patients with MI without risk factors draw attention to the possibility of drugs such as cocaine, AAS abuse, and amphetamine.

In this article, we report the case of a 38-year-old African-American male, with a history of AAS abuse, who arrived at the emergency department with complaints of severe chest pain radiating to the left arm. An electrocardiogram (ECG) revealed ST-elevation MI (STEMI) and elevated troponin. The patient was transferred to the cardiac catheterization lab for an emergent catheterization which showed 100% stenosis of the left anterior descending artery and a drug-eluting stent was placed. An echocardiogram showed an ejection fraction of 35%. All blood workup was negative. The patient was discharged on aspirin, ticagrelor, statin, ACE inhibitor, and B-blocker after three days.

Chest pain in a young patient population secondary to MI is not uncommon these days and the most important thing to evaluate is drug history, including AAS use. Athletes, bodybuilders, and others who use steroids or other drugs that are responsible for MI should be under the supervision of physicians so that the complications of steroids are ascertained, and if steroids are needed for any medical illness, proper dosage and follow-up should be emphasized. Therefore, while taking history from a patient, it is essential for physicians to be aware of this association of steroids with coronary artery disease.

Samreen F, Popal U, Qutrio Baloch ZA. Anabolic Steroid-Induced Myocardial Infarction in a Young Male. Cureus. 2021 Feb 1;13(2):e13054. doi: 10.7759/cureus.13054. PMID: 33680596; PMCID: PMC7925058. Anabolic Steroid-Induced Myocardial Infarction in a Young Male

 

[Michael Scally MD]

[OA] Testosterone in Cardiovascular Prevention: From Association to Action

The importance of framing accurately the role of testosterone in primary and secondary prevention is clearly embodied by two articles published in the European Journal of Preventive Cardiology.(4-5) In particular, Zeller et al highlighted the significant association between blood testosterone levels and long-term risk of atrial fibrillation and stroke.(4)

This work confirms prior research efforts and expands their implications on the complex interplay between cardiac function, gonadal physiology, cerebrovascular events, and cognitive function.(4,6-7)

Notably, Zeller and colleagues do not shy from highlighting the two-face impact of blood levels of testosterone on risk, with this molecule being positively associated with risk (i.e. detrimental) in women, and inversely associated (i.e. protective) in men.(4)

Focusing on secondary prevention, Gencer et al report on the predictive role of admission blood levels of testosterone among men admitted for acute coronary syndromes.(5) Specifically, lower testosterone levels were associated with adverse outcomes, thus confirming the inverse relationship already reported among males by Zeller and colleagues.

Evidently, the next step will be the careful design and conduct of a large and pragmatic randomised trial suitable for quantifying the risk-benefit profile of long-term testosterone supplementation, with substantial precision and external validity.(8)

Testosterone in cardiovascular prevention: from association to action
Comment by Giuseppe Biondi-Zoccai, Population Science and Public Health Section
https://www.escardio.org/Sub-specialty-communities/European-Association-of-Preventive-Cardiology-(EAPC)/News/testosterone-in-cardiovascular-prevention

 

[Michael Scally MD]

Recent Testosterone Drop-Off and Risk of Cardiovascular Events

Low baseline testosterone level has been associated with the development of risk factors for cardiovascular disease such as insulin resistance and obesity. In addition to the absolute testosterone level, remarkable changes in testosterone level may have an acute effect on cardiovascular disease development and progression, which has been rarely investigated.

In this study, we used a clinical dataset of 376 hypogonadal men whose testosterone levels were measured every six months for up to 11 years from a registry study in Germany, and conducted survival analyses to investigate the effect of testosterone changes since the last visit (time-varying) on the risk of cardiovascular events.

Given the potential discrepancies in comorbidity conditions among patients with prior cardiovascular events and those without, all the analyses were stratified by patients' prior cardiovascular event status.

We found the effects were not different among patients with prior cardiovascular events and those without. Regardless of patients' prior cardiovascular event status, patients with larger testosterone declines (≥3.12 nmol/L, 90th percentile) since the last visit were more likely to experience myocardial infarction.

In conclusion, recent pronounced testosterone drop-offs may affect the risk of cardiovascular events among hypogonadal men. Future longitudinal studies are needed to confirm our exploratory study findings.

Zhang X, Zhao H, Horney J, Johnson N, Saad F, Haider KS, Haider A, Xu X. Recent testosterone drop-off and risk of cardiovascular events. Aging Male. 2021 Mar 16:1-9. doi: 10.1080/13685538.2021.1896700. Epub ahead of print. PMID: 33724145. https://www.tandfonline.com/doi/abs/10.1080/13685538.2021.1896700?journalCode=itam20

 

[malfeasance]

A reason not to miss your shots?

 

[DIE KRAFT]

I recently went thru cardiac arrest. It was really bad. I stayed in the hospital for 42 days. On life support for 9 days. During the heart failure I flat-lined for 9 minutes. During CPR they broke 7 ribs. So brutal. The 42 days I kept saying that I want to go home. I have been doing really good. Going to rehab twice per week. Started training last week. Not heavy training yet. But things are looking good. God is truly good.

 

[kosp]

I recently went thru cardiac arrest. It was really bad. I stayed in the hospital for 42 days. On life support for 9 days. During the heart failure I flat-lined for 9 minutes. During CPR they broke 7 ribs. So brutal. The 42 days I kept saying that I want to go home. I have been doing really good. Going to rehab twice per week. Started training last week. Not heavy training yet. But things are looking good. God is truly good.

Geez man, I am happy to hear you are doing Allright now.

What happened? How did it all come?

 

[malfeasance]

I recently went thru cardiac arrest. It was really bad. I stayed in the hospital for 42 days. On life support for 9 days. During the heart failure I flat-lined for 9 minutes. During CPR they broke 7 ribs. So brutal. The 42 days I kept saying that I want to go home. I have been doing really good. Going to rehab twice per week. Started training last week. Not heavy training yet. But things are looking good. God is truly good.

Since you are in your 60s and had this experience, what are you going to be doing from here on out?

 

[Bork]

@Michael Scally MD What constitutes “long term” in the original study on the first page here? 16 weeks? 1 year? Several years?

Are negative effects significantly less likely to occur on shorter cycles that only happen once or twice in the individual’s life?

I want to say yes, but your recent post here on page 44 indicates some younger people (teenagers, 38 year olds) are ending up in the hospital with severe chest pains.

But at the same time I’m guessing these same people are: 1) taking too much steroids, 2) not watching their bloods, 3) taking too many compounds without trying test first, etc., thus giving a negative impression of “steroids are bad.”

Obviously there are some real negative effects, but are these reports overblown / limited to severe or long term abusers of several years?

 

[Jet Labs]

I recently went thru cardiac arrest. It was really bad. I stayed in the hospital for 42 days. On life support for 9 days. During the heart failure I flat-lined for 9 minutes. During CPR they broke 7 ribs. So brutal. The 42 days I kept saying that I want to go home. I have been doing really good. Going to rehab twice per week. Started training last week. Not heavy training yet. But things are looking good. God is truly good.

Smoker?
Gear history?
Health issues?

Hope you are well sir

 

[malfeasance]

What happened to Michael Scally?

 

[Gbro]

What happened to Michael Scally?

He got sick of the bs

 

[malfeasance]

He got sick of the bs

You know this or just guessing?

 

[Big_paul]

You know this or just guessing?

He got sick of the bullshit. It was obvious. Just not the kind of cat that could hang with some of the lunatics here.

 

[Dr JIM]

[OA] Anabolic Steroid-Induced Myocardial Infarction

Misuse of androgenic-anabolic steroids (AAS) has been well known to increase the risk for a cardiac problem, including acute myocardial infarction (MI). Steroids once thought a magic drug providing immediate relief to patients, also have a darker aspect of its severe side effects. AAS are widely used these days, especially in teenagers, bodybuilders, and athletes. MI is thought to be a disease of old age, but young patients with MI without risk factors draw attention to the possibility of drugs such as cocaine, AAS abuse, and amphetamine.

In this article, we report the case of a 38-year-old African-American male, with a history of AAS abuse, who arrived at the emergency department with complaints of severe chest pain radiating to the left arm. An electrocardiogram (ECG) revealed ST-elevation MI (STEMI) and elevated troponin. The patient was transferred to the cardiac catheterization lab for an emergent catheterization which showed 100% stenosis of the left anterior descending artery and a drug-eluting stent was placed. An echocardiogram showed an ejection fraction of 35%. All blood workup was negative. The patient was discharged on aspirin, ticagrelor, statin, ACE inhibitor, and B-blocker after three days.

Chest pain in a young patient population secondary to MI is not uncommon these days and the most important thing to evaluate is drug history, including AAS use. Athletes, bodybuilders, and others who use steroids or other drugs that are responsible for MI should be under the supervision of physicians so that the complications of steroids are ascertained, and if steroids are needed for any medical illness, proper dosage and follow-up should be emphasized. Therefore, while taking history from a patient, it is essential for physicians to be aware of this association of steroids with coronary artery disease.

Samreen F, Popal U, Qutrio Baloch ZA. Anabolic Steroid-Induced Myocardial Infarction in a Young Male. Cureus. 2021 Feb 1;13(2):e13054. doi: 10.7759/cureus.13054. PMID: 33680596; PMCID: PMC7925058. Anabolic Steroid-Induced Myocardial Infarction in a Young Male

Notwithstanding a less than desirable EF of 35%, this fella was fortunate to survive a complete LAD "widow maker" occlusion. And to that end I query whether AAS were the only PEDs being run.