Italiano Farmacia on line: comprare cialis senza ricetta, acquistare viagra internet.
Sudden or unnatural deaths involving anabolicandrogenic steroids
Available online at: onlinelibrary.wiley.com
Shane Darke,1 Ph.D.; Michelle Torok,1 M.Soc.Sci.; and Johan Duflou,1,2,3,4 M.Med.Path. (Forens),F.R.C.P.A.
Sudden or Unnatural Deaths InvolvingAnabolic-androgenic Steroids*
ABSTRACT: Anabolic-androgenic steroids (AASs) are frequently misused. To determine causes of death, characteristics, toxicology, and
pathology of AAS positive cases, all cases (n = 24) presenting to the New South Wales Department of Forensic Medicine (1995–2012) wereretrieved. All were male, and the mean age was 31.7 years. Deaths were mainly due to accidental drug toxicity (62.5%), then suicide (16.7%)and homicide (12.5%). Abnormal testosterone/epitestosterone ratios were reported in 62.5%, followed by metabolites of nandrolone (58.3%),stanozolol (33.3%), and methandienone (20.8%). In 23 of 24 cases, substances other than steroids were detected, most commonly psychostimu-lants (66.7%). In nearly half, testicular atrophy was noted, as was testicular fibrosis and arrested spermatogenesis. Left ventricular hypertrophywas noted in 30.4%, and moderate to severe narrowing of the coronary arteries in 26.1%. To summarize, the typical case was a male polydruguser aged in their thirties, with death due to drug toxicity. Extensive cardiovascular disease was particularly notable.
KEYWORDS: forensic science, steroids, toxicology, psychostimulants, cardiovascular disease, demographics
Anabolic-androgenic steroids (AAS) include exogenous testos-
with increased risk of peliosis hepatitis, cholestasis, and hepatic
terone, synthetic testosterone, and synthetic testosterone deriva-
tumors (1,7,18). AAS are also psychotropic and are associated
tives (1). While such drugs have valid medical applications,
with increased aggressiveness, agitation, paranoid ideation, mood
human and animal AAS are frequently misused to enhance ath-
swings, and depression (1,11,12). In the few steroid positive case
letic performance, strength, and image (e.g., body building)
series that have been conducted, death by violence, from other or
(2–7). Users of these drugs are mostly male, and aged predomi-
to self, formed a substantial proportion of deaths (11,12).
nantly between the late teens and mid-thirties (2–8). Apart from
One final factor that may contribute to premature mortality
muscular development, the regular use of AAS is associated with
among AAS users is polypharmacy. There is emerging evidence,
a number of direct physiological changes, including testicular
among both current users and fatalities, that substance use
atrophy and arrested spermatogenesis, while females may experi-
among this population extends far beyond AAS (3,5,20–22).
ence masculinization (1). There is also evidence of a dependence
There appear to be increased rates of use of opioids and psycho-
syndrome among regular users (9,10). Indeed, in one recent study
stimulants in particular but, apparently, not of cannabis or
of AAS users, 30% met DSM criteria for dependence (10).
There is emerging evidence that the use of AAS is associated
Despite their widespread use, there are few case series of ste-
with increased risk of premature mortality (7,11,12). Much of this
roid positive cases of unnatural or sudden death. This study
risk is thought to arise from the physiological and psychological
aimed to determine the circumstances of death, demographic
sequelae of AAS. There is mounting evidence that these drugs
characteristics, toxicology, and major organ pathology of cases
cause cardiovascular disease, including cardiomegaly, left ventric-
presenting to the Department of Forensic Medicine (DOFM),
ular hypertrophy, cardiomyopathy, ischemic heart disease, fibro-
Sydney, over the period January 1, 1996 to December 31, 2012
sis, and contraction band necrosis (1,12–19). Indeed, it has been
in which anabolic steroids were detected during quantitative
noted that the profile of cardiovascular damage from AAS abuse
is similar to the pathology seen from psychostimulant abuse(1,7,18). Liver disease also appears higher among AAS users,
National Drug and Alcohol Research Centre, University of New South
Wales, Sydney, NSW, 2052, Australia.
All cases autopsied at the DOFM between January 1, 1996 and
Department of Forensic Medicine, South Western Sydney Local Health
District, PO Box 90, Glebe, NSW, 2037, Australia.
December 31, 2012 were identified in which anabolic steroids
3School of Medical Sciences, University of New South Wales, Sydney,
were detected in urine taken at autopsy. Police death investigation
summaries and autopsy reports of all such cases were retrieved
4Sydney Medical School, University of Sydney, NSW, 2008, Australia.
from the database of the DOFM. The DOFM is located in central
*The National Drug and Alcohol Research Centre at the University of
Sydney and is the primary forensic pathology center in New South
NSW is supported by funding from the Australian Government.
Wales (NSW), conducting between 2000 and 2500 autopsies per
Received 18 Dec. 2012; and in revised form 25 April 2013; accepted 24
year during this time period. Permission to inspect the files was
2014 American Academy of Forensic Sciences
received from the Sydney Local Health District Human Research
TABLE 1––Characteristics of cases of sudden or unnatural death in which
Ethics Committee. All cases were reviewed by the authors.
anabolic-androgenic steroids were detected.
In NSW, a case must be reported to the coroner where a per-
son dies a violent or unnatural death. The majority of such casesundergo a standardized forensic autopsy, with examination of all
major organs and quantitative toxicological analysis. Cause of
death is determined by the forensic pathologist on the basis of
circumstances of death, the autopsy findings, and the toxicologi-
cal analyses. Circumstances of death, and case histories, were
obtained from accompanying police reports to the coroner.
All autopsy blood samples were taken peripherally (femoral or
alcohol, cannabis (determined by the presence of D-9-THC), opi-
oids (e.g., morphine, methadone, buprenorphine, oxycodone,
hydrocodone, tramodol), psychostimulants (methamphetamine,
cocaine, benzoylecgonine, 3,4methylenedioxymethamphetamine
[MDMA]), benzodiazepines (e.g., diazepam, oxazapam, temaze-
pam, flunitrazepam, alprazolam), gammahydroxybutyrate (GHB),
antidepressants (e.g., amitriptyline, citalopram, moclobemide,venlafaxine, sertraline, dothiepin, imipramine, fluoxetine), andantipsychotic medications (e.g., thioridazine, chlorpromazine,olanzapine, lithium). In cases where there was prolonged hospi-
relationship. Two-thirds were employed, the most common occu-
talization prior to death, antemortem toxicology taken at admis-
pations being security guard (n = 5) and personal fitness trainer
sion was reported, and drugs administered by hospital and
(n = 4). Bodybuilding was noted in a fifth of cases. The mean
medical staff excluded. All samples were screened by immuno-
BMI was 29.6 kg/m2, with 45% exceeding the cutoff for obesity
assay and either by gas chromatography or by high-performance
(>30 kg/m2). Evidence of recent injecting drug use was noted in
liquid chromatography (HPLC) for drugs of abuse and common
54.2% of cases. Two cases were hepatitis C virus (HCV) posi-
therapeutic substances. All analyses of blood were conducted by
tive, and one was HIV positive on serologic testing.
the Forensic Toxicology Laboratory of the NSW Forensic &
The most common direct cause of death was drug toxicity
Analytical Science Service (formerly the Division of Analytical
which, in conjunction with combined drug toxicity/cardiovascu-
lar disease, constituted two-thirds of cases. Psychostimulant tox-
Urine samples taken at autopsy were screened for AAS metab-
icity was the direct cause of death in eight cases (33.3%) and
olites by the Australian Sports Drug Testing Laboratory, using
opioid toxicity in 7 (29.2%). Arsenic poisoning was diagnosed
gas chromatography and mass spectrometry, there being no cur-
in one case – the manner of death in this case was not able to
rent blood test. In addition, abnormalities in steroid profiles were
be determined, but homicide was suspected. Violent death (sui-
examined for evidence of exogenous testosterone use, with a tes-
cide, homicide) constituted a quarter of cases. Three of the four
tosterone/epitestosterone ratio of >4 considered evidence of
suicides were by gunshot, with one hanging. All three definite
exogenous use by the Australian Sports Drug Testing Laboratory
homicides were gunshot victims. The sole accidental death was
(23). As is the case in other forensic institutes (11,12), AAS are
of a pilot of a light aircraft with controlled flight into terrain,
not routinely screened for by the NSW Forensic & Analytical
situational unawareness being the likely cause of the crash.
Science Service. Such tests are conducted at the request of the
There were no deaths solely attributable to natural causes.
forensic pathologist when there are signs (e.g., a pronounced,overdeveloped musculature), or circumstances indicating sus-
pected AAS use (e.g., substances discovered at the death scene).
It should be noted that the field of AAS use, and the detection
Abnormal testosterone/epitestosterone ratios >4 were reported
of such use, is in constant flux as new drugs are developed, and
in 15 of 24 cases, indicative of exogenous testosterone use, the
testing menus are likely to vary over time.
most common indicator of AAS, followed by with metaboliteswere of nandrolone, stanozolol, and methandienone (Table 2). Inone case, a significantly increased concentration of dehydroepi-
androsterone was reported. Tamoxefin was also present, a drug
For continuous distribution means, standard deviations (SD)
frequently used in AAS steroid cycles (25). The presence of
and ranges were reported. All analyses were conducted using
increased dehydroepiandrosterone and of tamoxifen in this case
is strongly suggestive of exogenous steroid use. Nandrolone maybe present in low concentrations in urine from exogenous andendogenous sources. We did not have access to more detailed
data on nandrolone concentrations or specific metabolites. In 12of these 14 cases, however, metabolites of other AAS were
detected and/or increased testosterone/epitestosterone ratios, con-
A total of 24 cases were identified, all male, with a mean age
sistent with AAS use, while in the remaining two cases, other
in their early thirties (Table 1). The majority were in a sexual
TABLE 2––Toxicology of cases of sudden or unnatural death in which
TABLE 3––Major autopsy findings of cases of sudden or unnatural death in
anabolic-androgenic steroids were detected.
which anabolic-androgenic steroids were detected.
Abnormal testosterone/epitestosterone ratio
Moderate–severe atherosclerotic occlusion
injection of tablet preparations or other insoluble materials) wasdetected in a quarter of cases. Other pulmonary pathology was
Blood toxicology was available for all cases. In all but one
noted in six cases (26.1%), most commonly bronchopneumonia.
case (95.8%), psychoactive substances other than steroids were
Renal pathology was diagnosed in three cases (13.0%). No pre-
detected. The most prevalent substances were psychostimulants,
existing intracranial pathology was identified, and there were no
present in two-thirds of cases. Opioids were detected in 37.5%
tumors typically associated with AAS use.
of cases, with morphine present in all these cases. A quarter hadalcohol detected, with a mean concentration of 0.093 g/100 mL
(SD 0.095, range 0.010–0.247 g/100 mL). Benzodiazepines weredetected in nearly half of cases, most commonly diazepam. Ven-
The cases in this series were exclusively male and aged on
lafaxine was present in one case, as was ketamine, while no case
average in their early thirties, characteristics consistent with ear-
lier case studies and series (7,11–13,15–17). There was extensivephysical evidence of steroid abuse, most notably testicular atro-phy, and fibrosis, as well as arrested spermatogenesis. Muscular
overdevelopment was present in almost all cases, with half hav-
Muscular physique was noted in 21 cases (87.5%). In nearly
ing BMIs in the obese range. As reported elsewhere (4), these
half of cases, testicular atrophy, testicular fibrosis, and arrested
high BMIs were not due to obesity, but to muscle volume and
spermatogenesis were noted (Table 3). No case exhibited
density. A large proportion of cases were employed as security
gynecomastia, acne, or prostate enlargement.
guards or as personal trainers, occupations in which AAS may
Cardiac pathology was diagnosed in 11 cases (47.8%). The
mean heart weight was 467.7 g (SD 107.7, range 304–760 g),
Exogenous testosterone appeared to be the most frequent form
with left ventricular hypertrophy present in seven cases (30.4%).
of AAS use, as evidenced by metabolites of nandrolone, stanozo-
Moderate to severe stenosis (>50%) of the coronary arteries was
lol, and methandienone. An outstanding feature of these cases
diagnosed in a quarter of cases. Fibrosis of the myocardium was
was their extensive polypharmacy. All but a single case had psy-
noted in three cases (13.0%). Psychostimulants were present in
choactive substances other than AAS detected in blood, and death
all six cases who exhibited moderate–severe coronary artery ste-
was due to drug toxicity nearly two-thirds. Half were injecting
nosis, 6 of 7 cases of left ventricular hypertrophy, 2 of 3 cases
substances other than steroids, and a quarter showed evidence of
of fibrosis of the myocardium, 1 of 1 case of cardiomyopathy, 2
likely injection of tablet preparations. Most prominent were the
of 3 cases of myocyte necrosis, and 2 of 2 cases of myocarditis.
psychostimulants, although opioids were also prevalent. In terms
Clinically significant hepatic pathology was diagnosed in six
of the latter, in eight of the nine morphine positive cases, the evi-
cases (26.1%). Two cases had cirrhotic livers, one of which was
dence was of the injection of opioids and of heroin in particular.
HCV positive on serological testing. Pulmonary edema was pres-
In one case, it would appear that a codeine preparation was con-
ent in 16 cases (69.4%), 14 of which were drug overdoses. Pul-
sumed. It is clear that there is a strong association between the
illicit use of AAS and the illicit use of other substances, and with
injecting drug use more broadly. As is commonly seen among
5. Larance B, Degenhardt L, Copeland J, Dillon P. Injecting risk behaviour
psychostimulant and opioid users (26), there was widespread use
and related harm among men who use performance- and image-enhanc-ing drugs. Drug Alcohol Rev 2008;27:679–86.
of benzodiazepines. In contrast, no case was positive for canna-
6. Petersson A, Bengtsson J, Voltaire-Carlsson A, Thiblin I. Substance
bis, consistent with reports elsewhere of low rates of cannabis
abusers’ motives for using anabolic androgenic steroids. Drug Alcohol
use (20–22). This is clearly not a drug that appeals to this popula-
tion, who appear to prefer injectables.
7. Di Paolo M, Agozzino M, Chiara T, Luciani AB, Bassi A, Molendini L,
While there were no deaths solely attributable to natural
et al. Sudden anabolic steroid abuse-related death in athletes. Int J Car-diol 2007;114:114–7.
causes, an outstanding feature of these cases was widespread car-
8. Hakansson A, Mickelsson K, Wallin C, Berglund M. Anabolic andro-
diovascular disease. These findings are consistent with earlier
genic steroids in the general population: user characteristics and associa-
work associating AAS use with such pathology (1,12–19). The
tions with substance use. Eur Addict Res 2012;18:83–90.
etiology of these pathologies is uncertain, however, given the
9. Kanayama G, Brower KJ, Wood RI, Hudson JI, Pope HG. Treatment of
anabolic-androgenic steroid dependence: emerging evidence and its
extensive use of psychostimulants seen in this and other studies
implications. Drug Alcohol Depend 2010;109:6–13.
(20–22), and that both AAS and psychostimulants are associated
10. Kanayama G, Brower KJ, Wood RI, Hudson JI, Pope HG. Anabolic–
with similar pathology. Certainly, as noted above, there were
other physical manifestations of steroid abuse. The majority of
cases who exhibited cardiovascular disease were, however, posi-
11. Petersson A, Garle M, Granath F, Thiblin I. Morbidity and mortality in
patients testing positively for the presence of anabolic androgenic ste-
tive for psychostimulants. It may be that the combination of AAS
roids in connection with receiving medical care. A controlled retrospec-
and psychostimulants increases the risk of cardiovascular disease.
tive cohort study. Drug Alcohol Depend 2006;8:215–20.
Finally, death from violence occurred in over a quarter of
12. Thiblin I, Lindquist O, Rajs J. Cause and manner of death amongst users
these cases, similar in proportion to the few case series con-
of anabolic androgenic steroids. J Forensic Sci 2000;45:16–23.
13. Petersson A, Garle M, Holmgren P, Druid H, Krantz P, Thiblin I. Toxi-
ducted to date (11,12). As noted earlier, AAS use is associated
cological findings and manner of death in autopsied users of anabolic
with increased aggressiveness and depression (1,11,12). The
androgenic steroids. Drug Alcohol Depend 2006;81:241–9.
association with illicit drug use may also be of relevance here,
14. Baggish AL, Weiner RB, Kanayama G, Hudson JI, Picard MH, Hutter
as death due to homicide and suicide comprises a significant
AM, et al. Long-term anabolic-androgenic steroid use is associated with
proportion of fatalities among psychostimulant and opioid users,
left ventricular dysfunction. Circ Heart Fail 2010;3:472–6.
15. Fineschi V, Baroldi G, Monciotti F, Reattelli LP, Turillazzi E. Anabolic
and with injecting drug use more generally (27).
steroid abuse and cardiac sudden death. A pathologic study. Arch Pathol
As in all studies, caveats must be made. AAS are not routinely
screened, but conducted where there is reason by the forensic
16. Fineschi V, Riezzo I, Centini F, Silingardi E, Licata M, Beduschi G,
pathologist to suspect AAS use, as is the case in other cases series
et al. Sudden cardiac death during anabolic steroid abuse: morphologicand toxicologic findings in two fatal cases of bodybuilders. Int J Legal
(11,12). It is thus possible that there were undetected cases not
contained in this series, particularly there were no overt reasons
17. Montisci M, El Mazloumn R, Cecchettom G, Terranova C, Ferrara SD,
to order such tests, for example, no pronounced muscularity or
Thiene G, et al. Anabolic androgenic steroids abuse and cardiac death in
AAS found at the death scene. Finally, the field of AAS use, and
athletes: morphological and toxicological findings in four fatal cases.
the detection of such use, is in constant flux as new compound is
18. Wysoczanski M, Rachko M, Bergmann SR. Acute myocardial infarction
developed, and new test is required to detect them. Again, it is
in a young man using anabolic steroids. Angiology 2008;59:376–8.
possible that cases have not been detected. In relation to this, and
19. Denham BE. Association between narcotic use and anabolic-androgenic
the previous point, it must be noted that this is not an epidemio-
logical study, but a clinical study of case presentations where such
20. Dodge T, Hoagland MF. The use of anabolic androgenic steroids and
drugs have been detected. The data also do not allow us to deter-
polypharmacy: a review of the literature. Drug Alcohol Depend
mine the length and severity of AAS use among cases, nor their
polypharmacy histories. Such data would be useful in attributing
21. Garevik N, Rane A. Dual use of anabolic-androgenic steroids and narcot-
causation to the cardiovascular disease seen in this series.
ics in Sweden. Drug Alcohol Depend 2010;109:144–6.
In summary, the typical case in this series was a male poly-
22. Skarberg K, Nyberg F, Engstrom I. Multisubstance use as a feature of
addiction to anabolic-androgenic steroids. Eur Addict Res 2009;15:99–106.
drug user, aged in their early thirties, with drug toxicity the
23. Mareck U, Geyer H, Fussholler G, Schwenkem A, Haenelt N, Piper T,
being most common cause of death. Extensive cardiovascular
et al. Reporting and managing elevated testosterone/epitestosterone
disease was a particularly notable feature.
ratios-novel aspects after five years’ experience. Drug Test Anal2010;2:637–42.
24. IBM. SPSS statistics, 20.0. Chicago, IL: IBM, 2011.
25. Baker JS, Graham MR, Davies B. Steroid and prescription medicine
abuse in the health and fitness community: a regional study. Eur J Intern
The authors wish to thank Vera Alderton and Briony Larance
26. Darke S, Torok M, Kaye S, Ross J, McKetin R. Comparative rates of
violent crime amongst regular methamphetamine and opioid users:offending and victimisation. Addiction 2010;105:916–9.
27. Darke S, Degenhardt L, Mattick R. Mortality amongst illicit drug users:
epidemiology, causes and intervention. Cambridge, U.K.: Cambridge
1. Karch SB. Karch’s pathology of drug abuse, 4th edn. Boca Raton, FL:
2. Brennan BP, Kanayama G, Hudson JI, Pope HG. Human growth hor-
Additional information and reprint requests:
mone abuse in male weightlifters. Am J Addict 2011;20:9–13.
3. Copeland J, Peters R, Dillon P. Anabolic-androgenic steroid use disor-
National Drug and Alcohol Research Centre
ders among a sample of Australian competitive and recreational users.
4. Kao TC, Deuster PA, Burnett D, Stephens M. Health behaviors associ-
ated with use of body building, weight loss, and performance enhancing
supplements. Ann Epidemiol 2012;22:331–9.
Additive effect of rimonabant and citalopram on extracellular serotonin levels monitored with in vivo microdialysis in rat Ortega J.E.a,*, Gonzalez-Lira V.b, Horrillo I.a, Herrera-Marschitz M.b, aDepartment of Pharmacology, University of the Basque Country UPV/EHU and Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain; bMillenium Institute BNI and Programme of
Summary Highly organized and analytical Software Engineer with broad-depth and experience in software development. I have experience in department level support of computer hardware and software applications as well. The past three years have focused on Web interface design for research databases at the University of Vermont. The primary attributes of the systems are to assure accurate and