AAS and Cardiovascular Health: Case Study

[CFC]

I thought I'd walk us through an interesting case-study from a few years ago, with potentially wider implications for all AAS-using bodybuilders and powerlifters. I know I keep bringing up these cardiovascular issues, but so few people consider them, and it really is worth having some awareness and an idea of how to ameliorate effects where possible. In particular I've translated some of what the text means for a lay person, and the discussion should be of particular value as a broad summary.

Anyway, have a read...




BMJ Case Reports 2011; doi:10.1136/bcr.12.2010.3650

Anabolic androgenic steroid-induced cardiomyopathy, stroke and peripheral vascular disease

Maged Y Z Youssef, Ahmed Alqallaf, Nabila Abdella


Summary

Acute stroke could be the presentation of unrecognised cardiomyopathy postanabolic androgenic steroid (AAS) abuse. A 39-year-old male patient displayed signs of acute stroke, which were associated with AAS abuse over the last 3 years. Despite the absence of symptoms and signs of congestive heart failure at presentation, AAS-induced cardiomyopathy with a thrombus in the left ventricle was discovered to be the aetiology of his stroke and peripheral vascular disease. Awareness of the complications of AAS led to the prompt treatment of the initially unrecognised dilated cardiomyopathy, and stroke.


Background

Acute presentation of stroke in a young patient with prolonged anabolic steroid use should alert us to underlying cardiomyopathy with thromboembolic events and peripheral vascular disease.


Case presentation

A 39-year-old male body builder presented with dizziness and expressive aphasia for the last 6 h.

Three months earlier, the patient presented to medical emergency with a transient ischaemic attack in the form of sudden loss of vision in left eye associated with weakness and numbness in the left upper and lower limbs lasting less than 1 h. The patient had intermittent claudication in the left lower limb. Neurological examination at the time, followed by CT of the head was completely normal. The patient refused admission to the hospital and was discharged on aspirin and follow-up which he did not pursue. [A rookie mistake which too many 'indestructable' bodybuilders repeat!]

The patient had no medical issues, 3 weeks prior to admission at the hospital. However, the patient admitted to have been abusing anabolic androgenic steroids (AAS) for the last 3 years, which were administered as intramuscular injections of nandrolone twice weekly [I think we can fairly assume that's not all he took! ]

On physical examination, he was alert and conscious with motor aphasia. Heart rate was 100/min, and blood pressure 140/100 mm Hg. Chest, heart and abdomen were normal. Jugular venous pressure was not elevated, and no peripheral oedema was noted. Peripheral pulsations were present on right side and absent dorsalis pedis pulsation on left side. Pupils were normal to exam. His fundi were normal with no visual field defects and no nystagmus. Right facial palsy, upper motor neuron lesion. No motor weakness was detected. Deep reflexes were normal in upper and lower limbs. Plantar reflexes were normal.


Investigations

Complete blood picture, erythrocyte sedimentation rate and C reactive protein were within normal range. Fasting blood sugar, liver function test, kidney profile and serum electrolytes were normal. Troponin, and coagulation profile were normal and his creatine kinase was 500 U/l (normal range 5–130 U/l).

Serum triglycerides 1.8 mmol/l (normal <2.20 mmol/l), total serum cholesterol 5.4 mmol/l (normal <5.2 mmol/l), high density lipoprotein-C 0.85 mmol/l (normal >0.9 mmol/l), low density lipoprotein-C (LDL-C) 4.19 mmol/l (normal < 3.37 mmol/l) [A typically poor lipid profile as regularly seen in AAS users - incidentally Deca doesn't appear to negatively affect lipids so we can assume it's whatever else he's taking], apolipoprotein B 1.29 mg/dl (normal range 0.60–1.33 mg/dl). Full thrombophilia screen, antiphospholipid antibodies, virology screen and immunology screen were negative. Urinalysis and microscopy was normal. Ankle brachial index: right side=1.2, 1eft side=0.69. Chest x-ray showed cardiomegaly [FYI: enlarged heart]. ECG showed sinus rhythm. Q waves were present in leads II, III and AVF. Poor R waves were observed in V1–V3. CT and MRI of brain showed left frontal infarction [Tissue death - due to the prior stroke]. Echocardiography showed dilated left ventricle (LV) with global hypokinaesia. Left ventricular cavity size was enlarged, end diastolic diameter was 6.9 cm and end systolic diameter was 5.7 cm. Left ventricular ejection fraction was 35% [very poor/inefficient] and there was an apical thrombus[A huge clot inside the left ventricle of the heart]. The left apical thrombus was mobile, measuring 1.6×1.5 cm. Left atrium diameter was 4.1cm. Carotid Doppler ultrasound showed no significant stenosis. Dipyridamol stress test of heart ruled out myocardial ischaemia. Magnetic resonance angiogram of left lower limb showed that there was an abrupt cut-off at the left superficial femoral artery at the beginning of the left popliteal artery, with total occlusion of left popliteal artery [piece of clot lodged in leg causing total aterial blockage].


Outcome and follow-up

Patient was managed with intravenous unfractionated heparin infusion, statins, angiotensin converting enzyme inhibitors and β-blockers. Repeat CT showed no evidence of haemorrhagic transformation with progressive improvement of motor aphasia. In addition to the previously mentioned medications, the patient was discharged on aspirin and warfarin as well.

Upon follow-up after 3 months, review echo showed resolution of thrombus with partial improvement of ejection fraction ( 40–45% ).

Upon follow-up after 6 months, ankle brachial index was improved, right side=1.20 and left side=0.82. The patient’s symptoms improved and he was able to resume work.


Discussion

Some athletes whether in competitive or non-competitive sports, abuse AAS to improve their performance or even their appearance as body builders.1

Abusers typically use 5–15 times the recommended medical doses of AAS. Athletes abusing AAS for years have high potential for arterial hypertension, cardiovascular, cerebrovascular disease and lipid metabolism disorder.2

We reported a 39-year-old man, who developed dilated cardiomyopathy, embolic stroke and peripheral vascular disease after self-administration of AAS for 3 years.

Several studies show that high doses of AAS such as nandrolone, may lead to growth-promoting effects on cardiac tissue, as seen in hypertrophic cardiomyopathy, followed by apoptotic cell death which is mediated by membrane-receptor second messenger cascades that increase intracellular Ca2+ influx [Hence the potential utility of Calcium Channel Blockers for AAS users] and mobilisation, leading to the release of apoptogenic factors.3 4

AAS abuse associated with sudden cardiac death, myocardial infarction, ventricular remodelling and cardiomyopathy is related to apoptosis.5 This relation may explain the clinical observations that AAS can lead to myocardial death without coronary thrombosis or atherosclerosis.6 7

Several studies in isolated human myocytes have shown that AAS bind to androgen receptors and may directly cause hypertrophy, via tissue upregulation of the renin-angiotensin system.8 [Hence part of the rationale for using Angiotensin Receptor Blockers EG: Losartan - other important reasons include inhibtion and reversal of AAS-induced scarring and fibrotic tissue accumulation in the heart and cardiovascular system]

AAS abuse causes decrease in high density lipoprotein cholesterol by 20% and increase in LDL cholesterol by 20% due to lipolytic degradation of lipoproteins and their removal by receptors through modification of apolipoprotein A-I and B synthesis.9 Apolipoprotein B has been experimentally linked to the development of atherosclerosis, mediating the interaction between LDL-C and the arterial wall.1

These lipoprotein abnormalities increase the risk for coronary artery disease by three to sixfold and may occur within 9 weeks of AAS self-administration.8 10 Fortunately, lipid effects seem to be reversible after discontinuation.1

AAS enhance platelet aggregation and thrombus formation by increasing platelet production of thromboxane A2, decreasing production of prostacyclin and increasing fibrinogen levels.1

Ischaemic stroke can occur as a result of atherothrombosis or embolisation either in the carotids or the heart as AAS has been associated with changes in vascular reactivity, lipid profile, haemostasis and platelet aggregation.1 Accordingly, peripheral vascular disease can occur through the same mechanism.1

Our case is unique as our patient developed an embolic stroke and peripheral vascular disease in the absence of any risk factors for either of the diseases, but rather as a complication of dilated cardiomyopathy with LV thrombus formation. These complications were deduced to be the result of AAS abuse after ruling out other aetiological factors.


References

Santamarina RD, Besocke AG, Romano LM, et al. Ischemic stroke related to anabolic abuse. Clin Neuropharmacol 2008;31:80–5.

Lane HA, Grace F, Smith JC, et al. Impaired vasoreactivity in bodybuilders using androgenic anabolic steroids. Eur J Clin Invest 2006;36:483–8.

D’Ascenzo S, Millimaggi D, Di Massimo C, et al. Detrimental effects of anabolic steroids on human endothelial cells. Toxicol Lett 2007;169:129–36.

Achar S, Rostamian A, Narayan SM. Cardiac and metabolic effects of anabolic-androgenic steroid abuse on lipids, blood pressure, left ventricular dimensions, and rhythm. Am J Cardiol 2010;106:893–901.

Zaugg M, Jamali NZ, Lucchinetti E, et al. Anabolic-androgenic steroids induce apoptotic cell death in adult rat ventricular myocytes. J Cell Physiol 2001;187:90–5.

Fineschi V, Baroldi G, Monciotti F, et al. Anabolic steroid abuse and cardiac sudden death: a pathologic study. Arch Pathol Lab Med 2001;125:253–5.

Wysoczanski M, Rachko M, Bergmann SR. Acute myocardial infarction in a young man using anabolic steroids. Angiology 2008;59:376–8.

Liu PY, Death AK, Handelsman DJ. Androgens and cardiovascular disease. Endocr Rev 2003;24:313–40.

Hartgens F, Rietjens G, Keizer HA, et al. Effects of androgenic-anabolic steroids on apolipoproteins and lipoprotein (a). Br J Sports Med 2004;38:253–9.

Maravelias C, Dona A, Stefanidou M, et al. Adverse effects of anabolic steroids in athletes. A constant threat. Toxicol Lett 2005;158:167–75.

 

[GrymReefer]

The patient had no medical issues, 3 weeks prior to admission at the hospital. However, the patient admitted to have been abusing anabolic androgenic steroids (AAS) for the last 3 years, which were administered as intramuscular injections of nandrolone twice weekly

I never understood those who still have to half-truth an issue especially in reference to a diagnosis and possibly successful treatment afterwards. If they don't know everything you did then they may miss something else due to how small the spectrum of usage was described.

In regards to lipid profiles, I have only gotten my profile done on the cycles that included trenabolone due to its harsh nature. I'm thinking about including that now at the same frequency I get full hormone panels. (before, during, after cycle) Definitely an interesting study. Thanks for the post and nice breakdown on all the medical jargon. Definitely helps not having to look up every single ailment that I'm unfamiliar with.

I never really put into perspective how detrimental having poor lipid profiles could be. I always thought being predisposed to certain cardiovascular issues was the common denominator, but seeing this makes me change my views. Soooo many variables still such little knowledge.

 

[CFC]

To be fair, I think most bodybuilders are less than forthcoming about their AAS use to doctors. Generally speaking we know there's a lot of sanctimonious and/or misinformed tabloid-headline crap that bounces around, and your average hospital doctor isn't likely to know much more than some 'roid rage' horror story that he once read about. I say this from years of experience dealing with them! Knowing this, you're likely to just give a dumbed-down story of what you do in the hope they'll focus on your health and not your lifestyle choices. However in this instance, given he'd had a stroke already (!), and then had to be readmitted later with a total blood clot in the leg, honesty may have be the wiser course - although it wouldn't have affected the treatment in any way.

However I think the take-home message from studies like this is less about specifically lipids than how all these vectors interact to cause serious health problems. So, it's not just the lipids that caused his clot - it's the platelet aggregation as the more acute factor. But furthermore, the AAS causing inflexibility of his vascular network (poor vasoreactivity) which promotes atherosclerotic plaque formation and makes the heart pump harder = the enlargement of his heart = inefficient pumping = reduced ejection fraction = relatively stagnant eddies of blood = increased risk of clotting. And of course, not even mentioned in this study is the likely increase in PCV (red blood cell concentration), which would have been an equally important factor. It seems astonishing that they don't seem to be aware of the effect AAS have on RBCs and how that could have aggravated this man's condition, but again that's part of the general lack of knowledge I'm referring to.

 

[Genetic Freak]

To be fair, I think most bodybuilders are less than forthcoming about their AAS use to doctors. Generally speaking we know there's a lot of sanctimonious and/or misinformed tabloid-headline crap that bounces around, and your average hospital doctor isn't likely to know much more than some 'roid rage' horror story that he once read about. I say this from years of experience dealing with them! Knowing this, you're likely to just give a dumbed-down story of what you do in the hope they'll focus on your health and not your lifestyle choices. However in this instance, given he'd had a stroke already (!), and then had to be readmitted later with a total blood clot in the leg, honesty may have be the wiser course - although it wouldn't have affected the treatment in any way.

However I think the take-home message from studies like this is less about specifically lipids than how all these vectors interact to cause serious health problems. So, it's not just the lipids that caused his clot - it's the platelet aggregation as the more acute factor. But furthermore, the AAS causing inflexibility of his vascular network (poor vasoreactivity) which promotes atherosclerotic plaque formation and makes the heart pump harder = the enlargement of his heart = inefficient pumping = reduced ejection fraction = relatively stagnant eddies of blood = increased risk of clotting. And of course, not even mentioned in this study is the likely increase in PCV (red blood cell concentration), which would have been an equally important factor. It seems astonishing that they don't seem to be aware of the effect AAS have on RBCs and how that could have aggravated this man's condition, but again that's part of the general lack of knowledge I'm referring to.

Great post CFC.... I agree, there appears to be more going on than just negative lipid profiles...
I note ECG showed Q wave present in II, III, aVF, (but not how long) that might suggest some necrosis to inferior R ventricle, troponin was normal suggesting previous infarct..
I think I'd be quite concerned about both presence and cause of apical thrombus... Not something I'd want in my L ventricle..

The negative effects of some AAS on cardiovascular tissue are understated or ignored on most popular steroid boards, which is of concern.... GP's either don't fully understand the negative mechanisms involved, and those that do don't generally explain the serious implications to health of long term AAS use to their patients...

You've mentioned the negatives of Nandrolone, what are your thoughts on Masteron, Boldenone, or Trenbolone..?

 

[GrymReefer]

Where would plain old testosterone fit into this equation or is the dosage equally important in the compounding factors? This study is pretty difficult to completely comprehend lol. one day....

 

[CFC]

You've mentioned the negatives of Nandrolone, what are your thoughts on Masteron, Boldenone, or Trenbolone..?

In all honesty GF it's hard to answer with any certainty given the chronic lack of controlled research into compounds aside from nandrolone, stanozolol and testosterone.

We can speculate that since we know nandrolone is more than 10 times more damaging to blood vessel endothelial cells than testosterone (and causes stiffening/reduced vasoreactivity/fibrosis), that testosterone-derived AAS are probably safer from that specific perspective. So boldenone may be relatively safer as a test-derivative. On the other hand winstrol, for example, seems to be no more harmful to myocytes, perhaps less so in fact, than testosterone, although its effect on lipids is worse.

From my own experience, Deca used alone (which I have accidentally done lol) demonstrably raises my blood pressure (presumably from the stiffening effect on blood vessels) moreso than testosterone at similar doses. Yet since Deca is known to have little impact on lipids, possibly because it's also an oestrogen, you might say there is some balancing in that risk equation.

However for me I think issues around lipids - since blood tests are cheap, easy and noticeable - have perhaps become a bit of a diversion from the less obviously visible/measurable risks. Lipids > atherosclerosis > clotting > thrombus formation (in tandem with blood thickening - raised PCV via EPO), are easily reversed post-cycle and/or relatively controllable on-cycle with a combination of venesection/donation, statins, niacin, dietary modifications, fish oils, hydration and aspirin, among others.

In a sense therefore the lipid/thrombus issue is more of an acute concern that diminishes once the cycle is over, and for most people will pass unremarkably assuming they lead an otherwise healthy lifestyle and don't abuse high-dose AAS for prolonged periods (I'm thinking particularly of the Blast-n-Cruise brigade whose cruise dose goes way above TRT, or the 5g of gear/wk meatheads who don't also take suitable pharmaceutical precautions).

However it's the effect of AAS on blood vessels and blood pressure that gets the least attention and is possibly where the really irreversible, chronic issues come in to play, since this is at the root of the deleterious cardiac remodelling we so wish to avoid (be it from fibrotic, apoptotic or hypertrophic causes).

From this perspective, I would speculate that highly androgenic steroids and DHT-derivatives are more harmful since they raise blood pressure directly thanks to constantly elevated CNS priming/sympathetic nervous system stimulation. Combine this with stiffer arteries (and apoptosis-fibrosis) and it raises the cardiac load still further.

Of course, the acute issues (thicker blood, poorer lipids, platelet aggregation) feed into this further, hence the annoying circular complexity of it all, and thus presumably the reason so few give a shit about it. But if you control the inotropic/chronotropic (BP and heart rate) effect by limiting both CNS stimulation and arterial stiffening - cut out stimulants, reduce use of highly androgenic AAS, do regular cardio, or alternatively supplement with appropriate pharmaceutical blockers - the acute effects become much less likely to be in a position to cause harm.

Sorry this has become a bit rambling, but the point I was trying to get to is that I would speculatively rank them in terms of presumed overall cardiovascular risk factors (best to worst):

Test > Bold > Winstrol > Mast > Deca > Tren

Tren may actually not be as directly damaging as some of the others (eg doesn't seem to be too bad on lipids for example), but it is an intense CNS stimulant, and that's a huge downside when AAS causes myocyte anabolism. However, it's also hands down one of the best all-round steroids out there for most guys. And rather than avoid it, I'd choose to lessen its side effects.

Also, and since I have little time at the moment to research, if anyone has any papers on cardiovascular risk factors measured against any other AAS, please post them/or links up - even just in vitro stuff. I have a catalogue of papers when I researched this area a few years ago but it's on my other harddrive in storage at present.

 

[CFC]

Where would plain old testosterone fit into this equation or is the dosage equally important in the compounding factors? This study is pretty difficult to completely comprehend lol. one day....

Testosterone actually seems to be one of the safer ones out there. Even more so when you consider that many drugs have been developed specifically for it to control other unwanted side-effects.

You're right about dosage too - as is true for most things. Good can rapidly become 'bad' once you go too crazy. It's why I constantly encourage low(er) doses even for more experienced guys. Unless you have exceptional genetics, the difference between 1g of gear and 5g of gear, or even between 750mg and 1g of gear, is incremental to say the least, and nothing that a slightly superior diet or another couple weeks on cycle wouldn't fix in most cases...

 

[Genetic Freak]

A couple I had on file (LV stuff, not too good), the rest are on another computer I'll check out later..

The impact of anabolic androgenic steroids abuse and type of training on left ventricular remodeling and function in competitive athletes.
Ilić I, Djordjević V, Stanković I, Vlahović-Stipac A, Putniković B, Babić R, Nesković AN.
Abstract
BACKGROUND/AIM:
Long-term intensive training is associated with distinctive cardiac adaptations which are known as athlete's heart. The aim of this study was to determine whether the use of anabolic androgenic steroids (AAS) could affect echocardiographic parameters of left ventricular (LV) morphology and function in elite strength and endurance athletes.
METHODS:
A total of 20 elite strength athletes (10 AAS users and 10 non-users) were compared to 12 steroid-free endurance athletes. All the subjects underwent comprehensive standard echocardiography and tissue Doppler imaging.
RESULTS:
After being indexed for body surface area, both left atrium (LA) and LV end-diastolic diameter (LVEDD) were significantly higher in the endurance than strength athletes, regardless of AAS use (p < 0.05, for both). A significant correlation was found between LA diameter and LVEDD in the steroid-free endurance athletes, showing that 75% of LA size variability depends on variability of LVEDD (p < 0.001). No significant differences in ejection fraction and cardiac output were observed among the groups, although mildly reduced LV ejection fraction was seen only in the AAS users. The AAS-using strength athletes had higher A-peak velocity when compared to steroid-free athletes, regardless of training type (p < 0.05 for both). Both AAS-using and AAS-free strength athletes had lower e' peak velocity and higher E/e' ratio than endurance athletes (p < 0.05, for all).
CONCLUSIONS:
There is no evidence that LV ejection fraction in elite athletes is altered by either type of training or AAS misuse. Long-term endurance training is associated with preferable effects on LV diastolic function compared to strength training, particularly when the latter is combined with AAS abuse.

http://www.ncbi.nlm.nih.gov/pubmed/24783419

Anabolic androgenic steroid use is associated with ventricular dysfunction on cardiac MRI in strength trained athletes.
Luijkx T1, Velthuis BK, Backx FJ, Buckens CF, Prakken NH, Rienks R, Mali WP, Cramer MJ.
Author information
Abstract
BACKGROUND:
Uncertainty remains about possible cardiac adaptation to resistance training. Androgenic anabolic steroids (AAS) use plays a potential role and may have adverse cardiovascular effects.
OBJECTIVE:
To elucidate the effect of resistance training and of AAS-use on cardiac dimensions and function.
PARTICIPANTS:
Cardiac magnetic resonance (CMR) were performed in 156 male subjects aged 18-40 years: 52 non-athletes (maximum of 3exercise hours/week), 52 strength-endurance (high dynamic-high static, HD-HS) athletes and 52 strength (low dynamic-high static, LD-HS) trained athletes (athletes ≥ 6 exercise hours/week). 28 LD-HS athletes denied and 24 admitted to AAS use for an average duration of 5 years (range 3 months-20 years).
RESULTS:
No significant differences were found between non-athletes and non-AAS-using LD-HS athletes. AAS-using LD-HS athletes had significantly larger LV and RV volumes and LV wall mass than non-AAS-using LD-HS athletes, but lower than HD-HS athletes. In comparison to all other groups AAS-using LD-HS athletes showed lower ejection fractions of both ventricles (LV/RV EF 51/48% versus 55-57/51-52%) and lower E/A ratios (LV/RV 1.5/1.2 versus 1.9-2.0/1.4-1.5) as an indirect measure of diastolic function. Linear regression models demonstrated a significant effect of AAS-use on LV EDV, LV EDM, systolic function and mitral valve E/A ratio (all ANOVA-tests p<0.05).
CONCLUSIONS:
Strength athletes who use AAS show significantly different cardiac dimensions and biventricular systolic dysfunction and impaired ventricular inflow as compared to non-athletes and non-AAS-using strength athletes. Increased ventricular volume and mass did not exceed that of strength-endurance athletes. These findings may help raise awareness of the consequences of AAS use.

http://www.ncbi.nlm.nih.gov/pubmed/22459398

 

[CFC]

Cheers GF. Nice example of somewhat contradictory findings. I'm sure if I delve in there'll be an answer in the study design though.

 

[Genetic Freak]

Testosterone-induced hypertrophy, fibrosis and apoptosis of cardiac cells--an ultrastructural and immunohistochemical study.
Papamitsou T1, Barlagiannis D, Papaliagkas V, Kotanidou E, Dermentzopoulou-Theodoridou M.
Author information
Abstract
BACKGROUND:
Androgen abuse is an increasing problem amongst professional and amateur athletes. Moreover, testosterone, apart from its widely accepted indications, is used for a variety of other indications such as aging and ischemia. Its actions are mainly attributed to a specific genomic mechanism through the androgen receptor, but emerging evidence reveals non-genomic effects as well. The use of androgens has been linked with several adverse effects. The purpose of this study was to examine the effects of testosterone on the morphology and the ultrastructure of the myocardium and to investigate the possible role of apoptosis.
MATERIAL/METHODS:
We used 12 adult male Wistar rats, separated into 2 groups. Group A consisted of 6 rats that were administered high doses of testosterone enanthate, while group B consisted of 6 male Wistar rats that received placebo (normal saline) intramuscularly. After the last day of treatment, all rats were anesthetized and sacrificed, and the hearts were removed and processed for optical and electron microscopy and immunohistochemical detection of caspase-3, an apoptosis marker.
RESULTS:
We found significant myocardial hypertrophy along with abundant ultrastructural alterations. The immunohistochemical staining of the myocardial cells for caspase-3 was positive in group A (experimental group), which is interpreted as an activation of apoptosis by testosterone treatment.
CONCLUSIONS:
Testosterone abuse has serious adverse effects, including myocardial hypertrophy, myocardial fibrosis and activation of apoptosis. These findings need to be taken into account whenever androgens are prescribed to improve performance or as hormone therapy.

http://www.ncbi.nlm.nih.gov/pubmed/21873939

Androgenic anabolic steroid abuse and the cardiovascular system.
Vanberg P1, Atar D.
Author information
Abstract
Abuse of anabolic androgenic steroids (AAS) has been linked to a variety of different cardiovascular side effects. In case reports, acute myocardial infarction is the most common event presented, but other adverse cardiovascular effects such as left ventricular hypertrophy, reduced left ventricular function, arterial thrombosis, pulmonary embolism and several cases of sudden cardiac death have also been reported. However, to date there are no prospective, randomized, interventional studies on the long-term cardiovascular effects of abuse of AAS. In this review we have studied the relevant literature regarding several risk factors for cardiovascular disease where the effects of AAS have been scrutinized1) Echocardiographic studies show that supraphysiologic doses of AAS lead to both morphologic and functional changes of the heart. These include a tendency to produce myocardial hypertrophy (Fig. 3), a possible increase of heart chamber diameters, unequivocal alterations of diastolic function and ventricular relaxation, and most likely a subclinically compromised left ventricular contractile function. (2) AAS induce a mild, but transient increase of blood pressure. However, the clinical significance of this effect remains modest. (3) Furthermore, AAS confer an enhanced pro-thrombotic state, most prominently through an activation of platelet aggregability. The concomitant effects on the humoral coagulation cascade are more complex and include activation of both pro-coagulatory and fibrinolytic pathways. (4) Users of AAS often demonstrate unfavorable measurements of vascular reactivity involving endothelial-dependent or endothelial-independent vasodilatation. A degree of reversibility seems to be consistent, though. (5) There is a comprehensive body of evidence documenting that AAS induce various alterations of lipid metabolism. The most prominent changes are concomitant elevations of LDL and decreases of HDL, effects that increase the risk of coronary artery disease. And finally, (6) the use of AAS appears to confer an increased risk of life-threatening arrhythmia leading to sudden death, although the underlying mechanisms are still far from being elucidated. Taken together, various lines of evidence involving a variety of pathophysiologic mechanisms suggest an increased risk for cardiovascular disease in users of anabolic androgenic steroids.

http://www.ncbi.nlm.nih.gov/pubmed/20020375

Anabolic androgenic steroids abuse and cardiac death in athletes: morphological and toxicological findings in four fatal cases.
Montisci M1, El Mazloum R, Cecchetto G, Terranova C, Ferrara SD, Thiene G, Basso C.
Author information
Abstract
Anabolic androgenic steroids (AAS) are the main class of doping agents and their consumption produces adverse effects involving several organs and systems. Three cases of sudden cardiac death (SCD) and one of death due to congestive heart failure of previously healthy athletes who were AAS users are herein reported. Concentric cardiac hypertrophy with focal fibrosis (one case), dilated cardiomyopathy with patchy myocyte death (two cases) and eosinophilic myocarditis (one case) were observed and most probably relate to the final event. Molecular investigation for viral genomes was positive in one case (Ebstein virus). Our data confirm previous findings, showing that the most typical cardiac abnormality in AAS abusers is left ventricular hypertrophy, associated with fibrosis and myocytolysis. An exceptional cardiovascular substrate was represented by the case with drug induced eosinophilic myocarditis. These features are at risk of ventricular arrhythmias as well as congestive heart failure. The cause-effect relationship between AAS abuse and cardiac death can be established only by a rigorous methodology with the use of standardized protocols, including precise morphological studies of all target organs to search for chronic toxic effects. Laboratory investigations should focus on AAS searching on a wide range of biological matrices to demonstrate type, magnitude and time of exposure.

http://www.ncbi.nlm.nih.gov/pubmed/22047750

Left ventricular early myocardial dysfunction after chronic misuse of anabolic androgenic steroids: a Doppler myocardial and strain imaging analysis.
D'Andrea A1, Caso P, Salerno G, Scarafile R, De Corato G, Mita C, Di Salvo G, Severino S, Cuomo S, Liccardo B, Esposito N, Calabrò R.
Author information
Abstract
BACKGROUND:
Anabolic androgenic steroids (AAS) are sometimes used by power athletes to improve performance by increasing muscle mass and strength. Recent bioptical data have shown that in athletes under the pharmacological effects of AAS, a focal increase in myocardial collagen content might occur as a repair mechanism against myocardial damage.
OBJECTIVE:
To investigate the potential underlying left ventricular myocardial dysfunction after chronic misuse of AAS in athletes by use of Doppler myocardial imaging (DMI) and strain rate imaging (SRI).
METHODS:
Standard Doppler echocardiography, DMI, SRI and ECG treadmill test were undertaken by 45 bodybuilders, including 20 athletes misusing AAS for at least 5 years (users), by 25 anabolic-free bodybuilders (non-users) and by 25 age-matched healthy sedentary controls, all men. The mean (SD) number of weeks of AAS use per year was 31.3 (6.4) in users, compared with 8.9 (3.8) years in non-users, and the mean weekly dosage of AAS was 525.4 (90.7) mg.
RESULTS:
The groups were matched for age. Systolic blood pressure was higher in athletes (145 (9) vs 130 (5) mm Hg) than in controls. Left ventricular mass index did not significantly differ between the two groups of athletes. In particular, both users and non-users showed increased wall thickness and relative wall thickness compared with controls, whereas left ventricular ejection fraction, left ventricular end-diastolic diameter and transmitral Doppler indexes were comparable for the three groups. Colour DMI analysis showed significantly lower myocardial early: myocardial atrial diastolic wave ratios in users at the level of the basal interventricular septum (IVS) and left ventricular lateral wall (p<0.01), in comparison with both non-users and controls. In addition, in users, peak systolic left ventricular strain rate and strain were both reduced in the middle IVS (both p<0.001) and in the left ventricular lateral free wall (both p<0.01). By stepwise forward multivariate analyses, the sum of the left ventricular wall thickness (beta coefficient = -0.32, p<0.01), the number of weeks of AAS use per year (beta = -0.42, p<0.001) and the weekly dosage of AAS (beta = -0.48, p<0.001) were the only independent determinants of middle IVS strain rate. In addition, impaired left ventricular strain in users was associated with a reduced performance during physical effort (p<0.001).
CONCLUSIONS:
Several years after chronic misuse of AAS, power athletes show a subclinical impairment of both systolic and diastolic myocardial function, strongly associated with mean dosage and duration of AAS use. The combined use of DMI and SRI may therefore be useful for the early identification of patients with more diffused cardiac involvement, and eventually for investigation of the reversibility of such myocardial effects after discontinuation of the drug.

http://www.ncbi.nlm.nih.gov/pubmed/17178777

 

[Genetic Freak]

Medical Issues Associated with Anabolic Steroid Use: Are They Exaggerated?
Jay R. Hoffman and Nicholas A. Ratamess

Cardiovascular System

In both the medical and lay literature one of the principal adverse effects generally associated with anabolic steroid use is the increased risk for myocardial infarction. This is primarily based upon several case reports published over the past 20 years describing the occurrence of myocardial infarctions in young and middle-aged body builders or weight lifters attributed to anabolic steroid use and/or abuse (Bowman, 1989; Ferenchick and Adelman, 1992; Gunes et al., 2004; Kennedy and Lawrence, 1993; Luke et al., 1990; McNutt et al., 1988).
However, direct evidence showing cause and effect between anabolic steroid administration and myocardial infarction is limited. Many of the case studies reported normal coronary arterial function in anabolic steroid users that experienced an infarct (Kennedy and Lawrence, 1993; Luke et al., 1990), while others have shown occluded arteries with thrombus formation (Ferenchick and Adelman, 1992; Gunes et al., 2004; McNutt et al., 1988).

Still, some of these studies have reported abnormal lipoprotein concentrations with serum cholesterol levels nearly approaching 600 mg·dl-1 (McNutt et al., 1988). Interestingly, in most case studies the effects of diet or genetic predisposition for cardiovascular disease were not disseminated and could not be excluded as contributing factors.

Alterations in serum lipids, elevations in blood pressure and an increased risk of thrombosis are additional cardiovascular changes often associated with anabolic steroid use (Cohen et al., 1986; Costill et al., 1984; Dhar et al., 2005; Kuipers et al., 1991; LaRoche, 1990). The magnitude of these effects may differ depending upon the type, duration, and volume of anabolic steroids used.

Interesting to note is that these effects appear to be reversible upon cessation of the drug (Dhar et al., 2005, Parssinen and Seppala, 2002).

In instances where the athlete remains on anabolic steroids for prolonged periods of time (e.g “abuse”), the risk for developing cardiovascular disease may increase.

Sader and colleagues (2001) noted that despite low HDL levels in bodybuilders, anabolic steroid use did not appear to cause significant vascular dysfunction.

Interestingly, athletes participating in power sports appear to have a higher incidence of cardiovascular dysfunction than other athletes, regardless of androgen use (Tikkanen et al., 1991; 1998). Thus, a strength/power athlete with underlying cardiovascular abnormalities that begins using anabolic steroids is at a much higher risk for cardiovascular disease.

However, anabolic steroid-induced changes in lipid profiles may not, per se, lead to significant cardiovascular dysfunction.

The risk of sudden death from cardiovascular complications in the athlete consuming anabolic steroids can occur in the absence of atherosclerosis. Thrombus formation has been reported in several case studies of bodybuilders self-administering anabolic steroids (Ferenchick, 1991; Fineschi et al., 2001; McCarthy et al., 2000; Sahraian et al., 2004). Melchert and Welder, 1995 have suggested that the use of 17α-alkylated steroids (primarily from oral ingestion) likely present the highest risk for thrombus formation. They hypothesized that anabolic steroid consumption can elevate platelet aggregation, possibly through an increase in platelet production of thromboxane A 2 and/or decreasing platelet production of prostaglandin PgI 2, resulting in a hypercoagulable state.

Left ventricular function and anabolic steroid use/abuse has been examined. Climstein and colleagues (2003) demonstrated that highly strength-trained athletes, with no history of anabolic steroid use exhibited a higher incidence of wave form abnormalities relative to recreationally-trained or sedentary individuals. However, when these athletes self-administered anabolic steroids, a higher percentage of wave form abnormalities were exhibited. Further evidence suggestive of left ventricular dysfunction has been reported in rodent models. A study on rats has shown that 8 weeks of testosterone administration increased left ventricle stiffness and caused a reduction in stroke volume and cardiac performance (LeGros et al., 2000).

It was hypothesized that the increased stiffness may have been related to formation of crosslinks between adjacent collagen molecules within the heart. Others have suggested that anabolic steroid use may suppress the increases normally shown in myocardial capillary density following prolonged endurance training (Tagarakis et al., 2000). However, there are a number of interpretational issues with this study. The changes reported were not statistically significant. In addition, the exercise stimulus employed (prolonged endurance training) is not the primary mode of exercise frequently used by anabolic steroid users.

Resistance training, independent of anabolic steroid administration, has been shown to increase left ventricular wall and septal thickness due to the high magnitude of pressure overload (Fleck et al., 1993; Fleck, 2003; Hoffman, 2002). This is known as concentric hypertrophy and does not occur at the expense of left ventricular diameter. In general, cardiac hypertrophy (resulting from a pressure overload, i.e. hypertension) may not be accompanied by a proportional increase in capillary density (Tomanek, 1986). Therefore, the potential for a reduction in coronary vasculature density exists for the resistance- trained athlete. However, it does not appear to pose a significant cardiac risk for these athletes. Recent observations have shown a dose-dependent increase in left ventricular hypertrophy (LVH) in anabolic steroid users (Parssinen and Seppala, 2002). This may have the potential to exacerbate the reduction in coronary vasculature density. However, the authors have acknowledged that their results may have been potentiated by a concomitant use of human growth hormone by their subjects. Other studies have failed to show additive effects of anabolic steroid administration and LVH in resistance-trained athletes (Palatini et al., 1996; Dickerman et al., 1998).

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827559/?report=reader#!po=83.3333

Myocardial infarction with intracoronary thrombus induced by anabolic steroids
Güneş Y, Erbaş C, Okuyan E, Babalik E, Gürmen T.

http://www.anakarder.com/sayilar/32/buyuk/2004-357-358.pdf

Androgen-induced cerebral venous sinus thrombosis in a young body builder: case report
Mohammad Ali Sahraian*, Mahmood Mottamedi, Amir Reza Azimi and Babak Moghimi

Case presentation
In May 2004 a 22 year old male was admitted to our department with chief complaints of headache and vomiting. The patient was well till 10 days prior to admission that developed progressive, intense bitemporal headache exacerbated with bending. The patient also had history of malaise, nausea and several episodes of vomiting from 3 days before admission.
The only objective finding on physical examination was bilateral papilledema. The patient was a body builder doing exercise from 5 years ago who had used nandrolone decaonoate 25 mg once or twice a week during the last 5 months. He had injected 20 ampoules in this period. Brain computed tomography without contrast was done for the patient which showed cord sign, emergency MR imaging including T1 – T2, weighted and MRV showed prominent superior sagital and transverse sinus thrombosis. The C.S.F opening pressure was 480 mm/H2o without any other abnormality. Heparin 80 IU/kg started as loading dose then continued 1000 IU/ hr for 10 days. On the 5th day of treatment headache resolved and warfarin added to heparin.
Laboratory tests including antithrombin III activity, protein C, S factor V leiden, Plasma hemocystein and anticardiolipin were all within normal limits. The patient was discharged in a good condition and was maintained on 6 months warfarin protcol.

Discussion
There are few reports of CVST following androgen therapy [3], but there is just one reported case of CVST in androgen using young body builder [4]. The anabolic activity of
testosterone and its derivatives is primarily manifested in its myotrophic actions which result in greater muscle mass and strength. This has led to widespread use of androgenic anabolic steroids by athletes at all levels. Nandrolone decaonoate is a synthetic anabolic steroid. In focus on homeostasis system the most important factors under testosterone regulation are fibrinogen, Plasminogen activator inhibitor-1 (PAI – 1) and platelet aggregability. The current data indicate that testosterone lowers fibrinogen and PAI – 1, however these anticoagulatory and profibrinolytic may be opposed by proaggregatory effects on platelets because high dosages of androgens were found to decrease cycloxygenase activity and thereby increase platelet functions [5]. Proaggregatory effect of testosterone and other synthetic androgens become more reliable theory for CVST, according to recent publication [6].

Conclusions
This case report presents a patient with CVST following exogenous androgen usage with a mechanism which is not completely understood, but it may be related to platelet activation or an increase in coagulation factors. As androgen use may be frequent and hidden in athletes, it may be an underestimated cause of cerebral venous thrombosis in young adults and careful history should be taken in these groups of patients.
Lists of abbreviations

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC539263/pdf/1471-2377-4-22.pdf

Cardiovascular effects of androgenic-anabolic steroids.
Melchert RB1, Welder AA.
Author information
Abstract
Evidence has accumulated over the pst several years which associates androgenic-anabolic steroid (AAS) use with sudden cardiac death, myocardial infarction, altered serum lipoproteins, and cardiac hypertrophy in humans who habitually use these drugs. Even though some experimental data obtained from animals correlate well with the human findings, the adverse cardiovascular effects of AAS use are poorly understood. The evidence presented in this review suggests that there are at least four hypothetical models of AAS-induced adverse cardiovascular effects: 1) an atherogenic model involving the effects of AAS on lipoprotein concentrations; 2) a thrombosis model involving the effects of AAS on clotting factors and platelets; 3) a vasospasm model involving the effects of AAS on the vascular nitric oxide system; and 4) a direct myocardial injury model involving the effects of AAS on individual myocardial cells. Future studies should be directed at determining the exact mechanisms responsible for AAS-induced adverse cardiovascular effects, at determining the relative contribution of each of these models, and at identifying other possible contributing factors such as metabolism of these steroids and the effects of potential metabolites on various target organs.

http://www.ncbi.nlm.nih.gov/pubmed/8531623

 

[GrymReefer]

Would the extent of the use of steroids over a specific period of time dictate the efficiency at which the androgens can create negative ailments? Correct me if I'm wrong, but eventually is there an upregulation of androgen receptor sites because of the excessive flow of AAS within the blood? I found a few studies talking about upregulation, but it wasn't exactly what I was thinking.

upregulation of androgen sites=more active androgen in effect=more changes the androgens can induce on the body?

 

[Serotonin101]

^^^you should be correct. Up regulation does occur which means more side effects as a whole, both desirable ones (increased muscle mass, better recovery, etc) and undesirable as aas aren't specific in which AR they interact with. Now, you have sparked a question I've been pondering about up regulation.

Sarms work in skeletal muscle AR. Would priming with high dose Sarms cause up regulation of skeletal muscle AR which would mean introduction of aas woukd have lower negative sides for a period of time until the other AR sites catch up?

 

[CFC]

Good stuff GF. Lots to read when I get back

Yes AAS appear to up regulate. Not sure about supra physiological doses as I seem to remember those studies were on physiological range or thereabouts. I did read a study where in vitro AAS appeared to cause a downregulation at exceptionally high doses, but that was of overall anabolic and androgenic effect not specifically about receptors.

Not sure about the SARMS idea Sero. Most SARMS so far still seem pretty unselective in all honesty, not much better than regular AAS, yet also of inferior strength. It would certainly be nice if a few studies were conducted though.

 

[Genetic Freak]

An open question to anyone, asked to me on another forum:

Regarding left ventricular hypertrophy combined with fibrosis to cardiac tissue: Can lower intensity cardio have different adaptations than higher intensity cardio.
Will HIIT give you what you call the fibrosis of the heart, the thickening.

To combat that LISS could instead increase the size (rather than thickness) and go someway to compensating for the thickness. So it's not going to reverse fibrosis but it (might) increase the capacity which means the heart doesn't have to work as hard per beat to deliver blood and oxygen....

Thoughts pls...

 

[CFC]

The kind of adaptations we want in the heart are the kind that high intensity cardio bring. It can basically 'enlarge' the capacity of the heart (the chambers) and also improve the ejection fraction. So the heart becomes more efficient per beat, and hence the pulse rate tends to fall - very low in very fit athletes. It does cause a very mild form of hypertrophy, but it arranges the cardiac tissue structurally slightly differently to the type that forms from heavy weight lifting.

So I would always recommend HIIT. LISS doesn't really do much good or bad for the heart. It's not intense enough to cause much positive adaptation, but if you have pre-existing heart conditions, it could aggravate those by drawing on cardiac oxygen capacity.

One of the other positives of HIIT is that it helps to stretch and (theoretically) break up the scarring/fibrotic tissue. We have to bear in mind that intense cardio pumps very large volumes of blood through the heart (unlike weights) which causes a nice eccentric stretch to the cardiac tissue, as opposed to more concentric-focus from weights.

Does that make any sense?

 

[Fractality]

The kind of adaptations we want in the heart are the kind that high intensity cardio bring.....

Interesting...I've always read that LISS cardio is the type that leads to the beneficial heart expansion.

 

[CFC]

Interesting...I've always read that LISS cardio is the type that leads to the beneficial heart expansion.

Where did you read that?

Cardio that doesn't sufficiently provoke adaptation (low intensity) doesn't help the heart much at all. It can even make things worse if you already have cardiovascular health issues.

It's one of the problems with most national exercise recommendations, which have been promoting the idea that adequate cardiovascular fitness can be obtained from at best a few multiple 30-min sessions of modest-intensity cardio a week.

Instead they should be recommending potentially less cardio, but of a very HIIT nature (eg 5 x 30 second all-out sprints, with 2 min recovery between each, 2-3 times a week).