Anabolic androgenic steroids and aggression: studies using animal models.

Ann N Y Acad Sci. 2004 Dec;1036:399-415.

Anabolic androgenic steroids and aggression: studies using animal models.

McGinnis MY.

Department of Biology, University of Texas at San Antonio, 6900 North Loop 1604
West, San Antonio, Texas 78249, USA. mmcginnis@utsa.edu

The use of anabolic androgenic steroids (AASs) has escalated in teenagers and is
associated with increased violence. Adolescent exposure to chronic high levels of
AASs is of particular concern because puberty is a hormonally sensitive period
during which neural circuitry for adult male patterns of behavior develop. Thus,
teenage AAS use may have long-term repercussions on the potential for displaying
aggression and violence. Animal models have contributed valuable information on
the effects of AAS use. For example, studies in rodents confirmed that exposure
to the AASs testosterone and nandrolone, but not stanozolol, does indeed increase
aggression. A side effect of AAS use reported in humans is "'roid rage,"
characterized by indiscriminate and unprovoked aggression. Results of animal
studies demonstrated that pubertal rats receiving AASs respond appropriately to
social cues as they are more aggressive toward intact males than are castrates.
Also, testosterone-treated males recognize appropriate environmental cues as they
are most aggressive in their home cage. Thus, adolescent AAS exposure increases
aggressive behaviors, but does not induce indiscriminate aggression. To assess
whether AAS exposure increases aggression after provocation, rats were tested
following a mild tail-pinch. In adolescent males, provocation increased
aggression after withdrawal from testosterone, nandrolone, and stanozolol, an
effect which persisted for many weeks. The data suggest that AASs sensitize
animals to their surroundings and lower the threshold to respond to provocation
with aggression. Thus, in humans, pubertal AAS exposure may not cause violent
behaviors, but may increase the likelihood that aggressive acts will result in
violence. This may persist into adulthood.

Assessment of attentional bias and mood in users and non-users of anabolic-androgenic steroids

Drug Alcohol Depend. 1995 Mar;37(3):241-5.

Assessment of attentional bias and mood in users and non-users of
anabolic-androgenic steroids.

Bond AJ, Choi PY, Pope HG Jr.

Department of Psychiatry, Institute of Psychiatry, University of London, UK.

Forty-six male strength athletes took part in a study to measure the effects of
anabolic-androgenic steroids on attentional bias to aggressive cues. They were 16
current users of anabolic steroids, 16 former users and 14 non-users.
Testosterone, deca-durabolin and anadrol were the three most commonly taken
steroids during the last cycle. Users generally took 2-3 drugs during each cycle;
the average cycle lasted 8-11 weeks and they had completed 3-4 cycles. The
subjects completed visual analogue scales of current feelings and were presented
with a modified Stroop Colour Word Conflict Task containing sets of neutral,
verbally aggressive and physically aggressive words. Current users tended to rate
themselves more negatively. Users took longer than former users to name the
colours of all word sets but there were no significant differences between word
sets. Therefore, attentional bias did not differ between groups but current
steroid use produced subtle mood changes and slowed performance compared to users
not currently taking steroids.

Rupture of the triceps tendon associated with steroid injections.

Am J Sports Med. 1993 May-Jun;21(3):482-5.

Comment in:
    Am J Sports Med. 1995 Nov-Dec;23(6):778.

Rupture of the triceps tendon associated with steroid injections.

Stannard JP, Bucknell AL.

Orthopaedic Surgery Service, Brook Army Medical Center, Fort Sam Houston, Texas.

Rupture of the triceps mechanism is an uncommon injury that has been recognized
with increasing frequency in recent years. It has been proposed that such
injuries commonly accompany fractures of the radial head and must be actively
evaluated in the presence of such a fracture. We present a unique case of
isolated rupture of the triceps tendon in an athlete who was lifting weights.
This case was complicated by a history of olecranon bursitis that had been
treated with numerous local steroid injections, as well as a history of anabolic
steroid abuse. Both systemic steroids and local injections may predispose tendons
to rupture. Triceps tendon ruptures may result in uniformly good to excellent
results if recognized and treated surgically. This case also serves as a reminder
of the risks of treating inflamed tissues with local steroid injections,
especially in strength athletes who place high demands on their musculoskeletal
structures. Finally, this case documents a second case of triceps mechanism
rupture in an athlete who has abused anabolic steroids. A study by Hunter et al.
suggests that oral steroid abuse may be associated with detrimental effects on
the mechanical properties of connective tissue, demonstrating another negative
effect of anabolic steroid use in athletes.

Prognostic factors and evolution of acquired aplastic anemia in childhood. A prospective analysis of 48 androgen-treated cases

Am J Pediatr Hematol Oncol. 1982 Fall;4(3):273-83.

Prognostic factors and evolution of acquired aplastic anemia in childhood. A
prospective analysis of 48 androgen-treated cases.

Najean Y, Girot R, Baumelou E.

Forty-eight cases of acquired aplastic anemia in children were analyzed in
comparison to 26 cases of genetic aplastic anemia and 483 cases of aplastic
anemia in adults. All were gathered from similar institutions and all were
similarly followed and treated with androgens. The following conclusions were
drawn: 1) Initial severity is greater in children than in adults, and is greater
in acquired than in genetic aplastic anemia; 2) even in cases of similar initial
severity, the early death rate is higher in children than in adults; 3) a
multiparametric index allows the correct prediction of short-term evolution in
70% of the cases and thus aids in providing an indication for bone marrow graft;
its sensitivity is similar to that of the classical parameters proposed by
Camitta, et al., but its specificity significantly higher; 4) most deaths
occurred during the first 3-4 months and the chance for long-term improvement
appears similar in the more severe than in the less severe cases if they survive
this delay; 5) some data (relapse after androgen withdrawal and
androgen-dependence and failure of corticoid therapy alone) suggest that androgen
therapy in children is useful, as it is in adults, and that corticosteroids do
not modify the course of the disease at its usual dosage (1 mg/kg/day); and 6)
very few side effects, particularly concerning height, of androgens were noted in
the survivors at adult age after long-term androgen therapy prescribed before
puberty.

A comparison of androgens for anemia in patients on hemodialysis

N Engl J Med. 1981 Apr 9;304(15):871-5.

A comparison of androgens for anemia in patients on hemodialysis.

Neff MS, Goldberg J, Slifkin RF, Eiser AR, Calamia V, Kaplan M, Baez A, Gupta S,
Mattoo N.

To compare the erythropoietic effects of nandrolone decanoate, testosterone
enanthate, oxymetholone, and fluoxymesterone, we performed a randomized clinical
trial in patients with anemia who were receiving maintenance hemodialysis (the
women were not given testosterone enanthate). After a control period of at least
two months, patients received one of the drugs for six months and then returned
to control status; a second and third drug were administered in a similar
fashion. Seventy-seven patients completed the first drug period, 56 the second,
and 35 the third. The response to nandrolone and testosterone enanthate, the two
drugs given by injection, was clearly superior to the response to oxymetholone or
fluoxymesterone, given by mouth, in terms of the percentage of patients
responding and the mean rise in hematocrit. Approximately half the patients had
an increase of at least 5 percentage points in hematocrit after an injectable
androgen was given; more than half the women responded. Patients who required
transfusions regularly and those who had bilateral nephrectomies did not respond.

Androgen therapy of aplastic anaemia--a prospective study of 352 cases

Scand J Haematol. 1979 Apr 4;22(4):343-56.

Androgen therapy of aplastic anaemia--a prospective study of 352 cases.

[No authors listed]

A prospective study of 352 patients with aplastic anaemia on androgen therapy has
been performed. The following main observations have been obtained: The actuarial
mortality rate at the 20th month is 52%, half the deaths being observed during
the first 3 months; these figures are similar to those previously published, from
smaller series of androgen-treated patients, and lower than those of
non-androgen-treated cases. Differences in survival and improvement were observed
between groups of patients treated for more than 3 months with either alkylated
or non-alkylated drugs. Signs of liver damage were observed no matter which was
the drug used. Continous improvement can be observed even in the 2nd year of
treatment indicating that full-dose androgen therapy should be continued up to 20
months in not fully improved patients. The degree of initial disease activity is
a clear prognostic parameter for the mortality in the first quarter of the
course. In case of survival of severe cases, improvement can be obtained to the
same extent as in milder cases. This stress the need for adequate maintenance
therapy in all types of patients. Addition of glucocorticoids harms the
prognosis, mainly in most granulocytopenic patients. Glucocorticoids have no
effect upon the liver damage induced by androgens.

Acquired aplastic anaemia in adults. II. Conventional treatment: retrospective study in 40 patients

Acta Haematol. 1977;58(6):339-52.

Acquired aplastic anaemia in adults. II. Conventional treatment: retrospective
study in 40 patients.

Haak HL, Hartgrink-Groeneveld CA, Guiot HF, Speck B, Eernisse JG, von Rood JJ.

The effect of conservative treatment of aplastic anaemia was evaluated
retrospectively in 40 patients. No significant beneficial effect was provided by
long-term high-dose oxymethalone in 20 patients or by metenolone, adrenstonolone,
or testosterone in 14 patients. Splenectomy gave no improvement in the majority
of cases, although in some it decreased the transfusion requirement.
Immunosuppressive treatment was successful in 1 patient with a positive LE
phenomenon. Until a specific treatment becomes available, the possibility offered
by alternative treatment, e.g. bone marrow transplantation, in cases with poor

Effects of use of anabolic steroids on the masticatory system: a pilot study.

J Oral Sci. 2008 Mar;50(1):19-24.

Effects of use of anabolic steroids on the masticatory system: a pilot study.

Barros TS, Santos MB, Shinozaki EB, Santos JF, Marchini L.

Department of Dentistry, University of Vale do Paraíba - UNIVAP, São José dos
Campos, Brazil.

The use of androgenic anabolic steroids (AAS) has increased significantly among
athletes in Brazil and other countries. These drugs alter the physiological
behavior of bone and muscles, also affecting these structures in masticatory
system. This paper aims to evaluate bone and dental changes in users of AAS, as
well as the incidence of temporomandibular dysfunction (TMD), compared to
athletes not using AAS. Eight athletes were equally divided in two groups, AAS
users and non-users. The groups were evaluated using Helkimo index, McNamara
cephalometric tracing and cast analysis. The AAS users presented more intense TMD
signs and symptoms (Di total value, P = 0.096, Mann-Whitney test), increased
cephalometric measures (Co-A, P = 0.020, Mann-Whitney test) and Angle Class II
malocclusion, compared to the non-users. These results suggested that the use of
AAS alters masticatory structures and increases the incidence of TMD.

Impaired vasoreactivity in bodybuilders using androgenic anabolic steroids.

Eur J Clin Invest. 2006 Jul;36(7):483-8.

Impaired vasoreactivity in bodybuilders using androgenic anabolic steroids.

Lane HA, Grace F, Smith JC, Morris K, Cockcroft J, Scanlon MF, Davies JS.

Department of Endocrinology, University Hospital of Wales, Heath Park, Cardiff
CF14 4XW, Wales, UK. laneha@cf.ac.uk

BACKGROUND: Anabolic androgenic steroids are used by some bodybuilders to enhance
performance. While the cardiovascular implications of supraphysiological androgen
levels requires further clarification, use is associated with sudden death, left
ventricular hypertrophy, thrombo-embolism and cerebro-vascular events.

MATERIALS
AND METHODS: To further understand the effect of androgenic anabolic steroid
abuse on vascular function, this study assessed vascular stiffness (pulse-wave
analysis) and cardiovascular risk factors in 28 male, bodybuilding subjects, of
whom ten were actively receiving anabolic agents (group A; 26.4 +/- 7.2 years)
and eight had undergone a 3-month "wash-out" period (group B; 32.1 +/- 7.1
years). The remaining ten bodybuilding subjects (group C; 24.4 +/- 4.4 years)
denied any past use of anabolic steroids or other performance enhancing drugs.
Comparisons were made with ten sedentary male controls (group D, 29.3 +/- 4.7
years).

RESULTS: Endothelial independent dilatation in response to glycerol
trinitrate was significantly impaired in the group currently using anabolic
steroids (group A) compared with the other three groups [A (5.63 +/- 3.24%)
versus; B (11.10 +/- 4.91%), C (17.88 +/- 9.2%) and D (14.46 +/- 3.9%), P <
0.0005, respectively], whereas no significant differences in
endothelial-dependent dilatation were detected between the groups [A (5.0 +/-
3.0%), B (7.4 +/- 3.4%), C (9.6 +/- 4.5%) and D (8.2 +/- 3.3%), P < 0.059,
respectively].

CONCLUSIONS: Previous studies described a decline in vascular
reactivity occurring in bodybuilding subjects which is independent of anabolic
steroid use and may result from smooth muscle hypertrophy with increased vascular
stiffness. This study revealed impaired vascular reactivity associated with
anabolic agents and that improvement in vascular function may occur following
their discontinuation.

Stacking anabolic androgenic steroids (AAS) during puberty in rats: a neuroendocrine and behavioral assessment.

Pharmacol Biochem Behav. 2006 Mar;83(3):410-9. Epub 2006 Apr 17.

Stacking anabolic androgenic steroids (AAS) during puberty in rats: a
neuroendocrine and behavioral assessment.

Wesson DW, McGinnis MY.

The University of Texas at San Antonio, Department of Biology, 6900 North Loop
1604 West, San Antonio, TX 78249, USA.

Anabolic androgenic steroid (AAS) abuse is increasing in teenagers. We examined
the effects of stacked AAS in adolescent male rats. Stacking, in which multiple
AAS are taken simultaneously, is commonly employed by humans. Beginning at
puberty gonadally intact male rats received testosterone, nandrolone, or
stanozolol. Additional groups received stacked AAS: testosterone + stanozolol,
nandrolone + stanozolol, or nandrolone + testosterone. Injections continued
during tests for sexual behavior, vocalizations, scent marking, partner
preference, aggression and fertility. Body and reproductive tissue weights were
taken. Sexual and aggressive behaviors were increased by testosterone yet
inhibited by stanozolol; nandrolone had no effect. Stacking testosterone with
stanozolol prevented the inhibitory effects of stanozolol. Body weight was
decreased by testosterone and all stacked AAS. Cell nuclear androgen receptor
binding in brain was significantly increased in nandrolone males and decreased in
stanozolol males; testosterone males were slightly higher than controls. Androgen
receptors in stacked groups were intermediate between individual AAS suggesting
that stanozolol competed with other AAS for androgen receptors despite its low
affinity. The results indicate that stacking AAS influences the effects of
individual AAS on behavioral and endocrine measures, and levels of androgen
receptor occupation are not directly correlated with AAS effects on behavior.

Management of male sterility in patients taking anabolic steroids

 Arch Esp Urol. 2005 Apr;58(3):241-4.

[Management of male sterility in patients taking anabolic steroids]

[Article in Spanish]

de la Torre Abril L, Ramada Benlloch F, Sánchez Ballester F, Ordoño Domínguez F,
Ulises Juan Escudero J, Navalón Verdejo P, López Alcina E, Ramos de Campos M,
Zaragoza Orts J.

Servicio de Urología, Consorcio Hospital General Universitario, Valencia, España.
Luitorrr@hotmail.com

OBJECTIVES/METHODS: To review the incidence of male infertility secondary to
intake of anabolic products and our experience and outcomes with treatment. There
is a variety of such substances (testosterone, nandrolone, stanozolol, etc.) in
their intake may be unique or combinations, both orally or parenterally.
Comparisons between patients and case series are difficult because of the hiding
of this practice and various consumption practices and doses employed.
RESULTS/CONCLUSIONS: Most of the patients recover normal spermatogenesis does by
stopping intake of anabolic substances. The period of time until recovery is 6.35
months. Patients not recovering after six months were given tamoxifen 20
mg/24-hour, if having a normal or inhibited hypothalamus-hypophysis axis.
Duration of abuse, doses, and anarchical consumption maderesponse to treatment
with antiestrogen drugs or gonadotropins unpredictable in patients not responding
to conservative treatment.

Hepatocellular adenomas associated with anabolic androgenic steroid abuse in bodybuilders: a report of two cases and a review of the literature.

Br J Sports Med. 2005 May;39(5):e27.

Hepatocellular adenomas associated with anabolic androgenic steroid abuse in
bodybuilders: a report of two cases and a review of the literature.

Socas L, Zumbado M, Pérez-Luzardo O, Ramos A, Pérez C, Hernández JR, Boada LD.

Department of Radiology, Cajal Clinical Centre, Las Palmas de Gran Canaria,
Canary Islands, Spain.

Anabolic androgenic steroids (AAS) are used illicitly at high doses by
bodybuilders. The misuse of these drugs is associated with serious adverse
effects to the liver, including cellular adenomas and adenocarcinomas. We report
two very different cases of adult male bodybuilders who developed hepatocellular
adenomas following AAS abuse. The first patient was asymptomatic but had two
large liver lesions which were detected by ultrasound studies after routine
medical examination. The second patient was admitted to our hospital with acute
renal failure and ultrasound (US) studies showed mild hepatomegaly with several
very close hyperecogenic nodules in liver, concordant with adenomas at first
diagnosis. In both cases the patients have evolved favourably and the tumours
have shown a tendency to regress after the withdrawal of AAS. The cases presented
here are rare but may well be suggestive of the natural course of AAS induced
hepatocellular adenomas. In conclusion, sportsmen taking AAS should be considered
as a group at risk of developing hepatic sex hormone related tumours.
Consequently, they should be carefully and periodically monitored with US
studies. In any case, despite the size of the tumours detected in these two
cases, the possibility of spontaneous tumour regression must also be taken in
account.

The anti-doping hot-line, a means to capture the abuse of doping agents in the Swedish society and a new service function in clinical pharmacology.

Eur J Clin Pharmacol. 2003 Nov;59(8-9):571-7. Epub 2003 Sep 12.

The anti-doping hot-line, a means to capture the abuse of doping agents in the
Swedish society and a new service function in clinical pharmacology.

Eklöf AC, Thurelius AM, Garle M, Rane A, Sjöqvist F.

Department of Clinical Pharmacology, Huddinge University Hospital, 14185
Stockholm, Sweden.

With the support of the Swedish National Institute of Health a national
information service was started in 1993 aiming to capture the abuse of doping
agents in the general public. It was organized as a telephone service, called the
Anti-Doping Hot-Line, from our department and managed by trained nurses
co-operating with clinical pharmacologists. Important information collected about
all callers (anonymous) was: date of call, its origin, category of caller, doping
experience and main question being asked. Abusers were asked about their age,
sex, affiliation, abused drug(s), duration of abuse, habit of administration and
adverse reactions (ADRs). Between October 1993 and December 2000 25,835 calls
were received with a peak during spring and autumn. Most calls (12,400) came from
non-abusers, 60% being males. Callers connected with gyms represented the largest
group (30%). Most calls about specific drugs concerned anabolic androgenic
steroids (AAS). Other drugs or products included ephedrine, clenbuterol and
creatine. The most commonly abused anabolic steroids were testosterone,
nandrolone-decanoate, methandienone and stanozolol. The ten most commonly
reported ADRs of AAS were aggressiveness (835), depression (829), acne (770),
gynecomastia (637), anxiousness (637), potency problems (413), testicular atrophy
(404), sleep disorders (328), fluid retention (318) and mood disturbances (302).
Female side effects included menstruation disturbances, hair growth in the face,
lower voice and enlarged clitoris. During the period 1996-200, totally 4339
persons reported about 10,800 side effects. This figure should be compared with
the very low number of ADRs (27) reported by prescribers to the Swedish ADR
committee during the same period. Abuse of doping agents appears to be a new
public health problem that needs detection, medical care and prevention.

Androgenic/Anabolic steroid-induced toxic hepatitis.

J Clin Gastroenterol. 2002 Oct;35(4):350-2.

Androgenic/Anabolic steroid-induced toxic hepatitis.

Stimac D, Milić S, Dintinjana RD, Kovac D, Ristić S.

Division of Gastroenterology, Department of Internal Medicine, Clinical Hospital
Center Rijeka, Rijeka, Croatia. davor.stimac@ri.hinet.hr

Athletes and bodybuilders often misuse androgenic/anabolic steroids. When used in
therapeutic doses, these drugs produce clinical jaundice in just a small number
of recipients. We present a 26-year-old male bodybuilder who self-administered
high doses of androgenic/anabolic steroids that induced liver damage. One month
before admission to the hospital, he used testosterone enanthate (500 mg
intramuscularly, twice weekly), stanozolol (40 mg/d), and methylandrostenediol
(30 mg/d by mouth, for 5 weeks). On admission, his bilirubin level was 470
micromol/L (direct, 360 micromol/L), his aspartate aminotransferase (AST) level
was 5,870 IU/L, his alanine aminotransferase (ALT) level was 10,580 IU/L, his
alkaline phosphatase (ALP) level was 152 IU/L, his gamma-glutamyl-transpeptidase
level was 140 IU/L, his albumin level was 27.6 g/L, and his prothrombin time was
29%. During the patient's prolonged hospitalization, multiple tests and liver
biopsy were performed, showing only toxic hepatic lesions. The patient was
provided with supportive medical treatment. Clinical signs and laboratory
findings improved substantially 12 weeks after the patient discontinued
androgenic/anabolic steroids. The reasons for presenting this case were the much
higher values of AST and ALT levels than reported in other studies, although the
values of bilirubin and ALP were similar to those found in the literature. To our
knowledge, it is the first case of toxic hepatitis induced by androgenic/anabolic
steroids with predominantly hepatocellular necrosis instead of intrahepatic
cholestasis.

Masseteric hypertrophy associated with administration of anabolic steroids and unilateral mastication: a case report.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001 Nov;92(5):515-8.

Masseteric hypertrophy associated with administration of anabolic steroids and
unilateral mastication: a case report.

Skoura C, Mourouzis C, Saranteas T, Chatzigianni E, Tesseromatis C.

Department of Oral and Maxillofacial Surgery, General District Hospital of Athens
KAT, Greece.

In this report we present a patient with unilateral masseteric hypertrophy who
used anabolic steroids and was chewing entirely unilaterally for 1 month.
Computed tomography and histologic examination were used to confirm the
diagnosis. The combined action of unilateral mastication and anabolic steroid use
is probably responsible for the rapid development of unilateral masseteric
hypertrophy.

Building your body to survive: the use of anabolic steroids for HIV therapy.

Posit Aware. 1998 Mar-Apr;9(2):37-41.

Building your body to survive: the use of anabolic steroids for HIV therapy.

Vergel N.

AIDS: The loss of lean body mass (LBM) that is commonly associated with wasting
syndrome has been linked to death in HIV disease. Bioelectrical Impedance
Analysis (BIA) is a simple, inexpensive and painless technique used to assess
body composition. The test gives a good reading of body cell mass, fat mass, and
body water, and can be used to detect loss of LBM when it first occurs. BIA is a
useful tool in managing and preventing wasting. Other factors that influence LBM
include testosterone levels and anabolic steroids. Anabolic steroids, synthetic
analogs of testosterone, are a Class III regulated drug. The use of anabolic
steroids is controversial, and abuse by athletes led to the drugs being banned
for many uses. A list of approved steroids, their actions, and potential problems
associated with their use is included. Another table rates the major steroids for
their effectiveness in AIDS therapy.

Anabolic steroid abuse and cardiac sudden death: a pathologic study.

Arch Pathol Lab Med. 2001 Feb;125(2):253-5.

Anabolic steroid abuse and cardiac sudden death: a pathologic study.

Fineschi V, Baroldi G, Monciotti F, Paglicci Reattelli L, Turillazzi E.

CONTEXT: Androgenic anabolic steroids (AAS) used for improving physical
performance have been considered responsible for acute myocardial infarction and
sudden cardiac death.

OBJECTIVE: To establish the relationship between AAS and
cardiac death.

DESIGN: Case report.

PATIENTS: Two young, healthy, male
bodybuilders using AAS.

MAIN OUTCOME MEASURES: Pathologic cardiac findings
associated with AAS ingestion.

RESULTS: The autopsy revealed normal coronary
arteries. In one case, we documented a typical infarct with a histologic age of 2
weeks. A segmentation of myocardial cells at the intercalated disc level was
observed in the noninfarcted region. This segmentation was the only anomaly
detected in the second case. No other pathologic findings in the heart or other
organs were found. Urine in both subjects contained the metabolites of
nortestosterone and stanozolol.

COMMENT: A myocardial infarct without vascular
lesions is rare. To our knowledge, its association with AAS use, bodybuilding, or
both lacks any evidence of a cause-effect relationship. The histologic findings
in our 2 cases and in the few others reported in medical literature are
nonspecific and do not prove the cardiac toxicity of AAS. A better understanding
of AAS action on the neurogenic control of the cardiac function in relation to
regional myocardial contraction and vascular regulation is required.

Anabolic steroids induce region- and subunit-specific rapid modulation of GABA(A) receptor-mediated currents in the rat forebrain.

J Neurophysiol. 2000 Jun;83(6):3299-309.

Comment in:
    NIH Guide Grants Contracts. 2007 Aug 17;:NOT-OD-07-086.

Anabolic steroids induce region- and subunit-specific rapid modulation of GABA(A)
receptor-mediated currents in the rat forebrain.

Jorge-Rivera JC, McIntyre KL, Henderson LP.

Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire 03755,
USA.

Anabolic-androgenic steroids (AAS) have become significant drugs of abuse in
recent years with the highest increase reported in adolescent girls. In spite of
the increased use of AAS, the CNS effects of these steroids are poorly
understood. We report that in prepubertal female rats, three commonly abused AAS,
17alpha-methyltestosterone, stanozolol, and nandrolone, induced rapid and
reversible modulation of GABAergic currents in neurons of two brain regions known
to be critical for the expression of reproductive behaviors: the ventromedial
nucleus of the hypothalamus (VMN) and the medial preoptic area (mPOA). All three
AAS significantly enhanced peak synaptic current amplitudes and prolonged
synaptic current decays in neurons of the VMN. Conversely all three AAS
significantly diminished peak current amplitudes of synaptic currents from
neurons of the mPOA. The endogenous neuroactive steroids,
3alpha-hydroxy-5alpha-pregnan-20-one and 5alpha-androstane-3alpha,17beta-diol,
potentiated currents in the VMN as did the AAS. In contrast to the negative
modulation induced by AAS in the mPOA, the endogenous steroids potentiated
responses in this region. To determine the concentration response relationships,
modulation by the AAS, 17alpha-methyltestosterone (17alpha-meT), was assessed for
currents evoked by ultrafast perfusion of brief pulses of GABA to acutely
isolated neurons. Half-maximal effects on currents elicited by 1 mM GABA were
elicited by submicromolar concentrations of AAS for neurons from both brain
regions. In addition, the efficacy of 10(-5) to 10(-2) M GABA was significantly
increased by 1 microM 17alpha-meT. Previous studies have demonstrated a striking
dichotomy in receptor composition between the VMN and the mPOA with regard to
gamma subunit expression. To determine if the preferential expression of gamma(2)
subunit-containing receptors in the VMN and of gamma(1) subunit-containing
receptors in the mPOA could account for the region-specific effects of AAS in the
two regions, responses elicited by ultrafast perfusion of GABA to human embryonic
kidney 293 cells transfected with alpha(2), beta(3), and gamma(2) or alpha(2),
beta(3), and gamma(1) subunit cDNAs were analyzed. As with native VMN neurons,
positive modulation of GABA responses was elicited for alpha(2)beta(3)gamma(2)
recombinant receptors, while negative modulation was induced at
alpha(2)beta(3)gamma(1) receptors as in the mPOA. Our data demonstrate that AAS
in doses believed to occur in steroid abusers can induce significant modulation
of GABAergic transmission in brain regions essential for neuroendocrine function.
In addition, the effects of these steroids can vary significantly between brain
regions in a manner that appears to depend on the subunit composition of GABA(A)
receptors expressed.

Atrial fibrillation and anabolic steroids.

J Emerg Med. 1999 Sep-Oct;17(5):851-7.

Atrial fibrillation and anabolic steroids.

Sullivan ML, Martinez CM, Gallagher EJ.

Department of Emergency Medicine, Jacobi Medical Center, Bronx, New York, USA.

A young male bodybuilder, consuming large doses of anabolic steroids (AS),
presented to the Emergency Department (ED) with symptomatic rapid atrial
fibrillation (AF). Echocardiogram revealed significant septal hypokinesis, and
posterior and septal wall thickness at the upper limit of normal for highly
trained athletes. The atrial fibrillation had not recurred at 10 weeks after
discontinuation of AS use. Consumption of these agents in athletes has been
associated with hypertension, ischemic heart disease, hypertrophic
cardiomyopathy, and sudden death.

Dihydrotestosterone, stanozolol, androstenedione and dehydroepiandrosterone sulphate inhibit leptin secretion in female but not in male samples of omental adipose tissue in vitro: lack of effect of testosterone.

J Endocrinol. 1999 Mar;160(3):425-32.

Dihydrotestosterone, stanozolol, androstenedione and dehydroepiandrosterone
sulphate inhibit leptin secretion in female but not in male samples of omental
adipose tissue in vitro: lack of effect of testosterone.

Piñeiro V, Casabiell X, Peinó R, Lage M, Camiña JP, Menendez C, Baltar J, Dieguez
C, Casanueva F.

Endocrine Section, Department of Medicine, Santiago de Compostela University,
Complejo Hospitalanó de Santiago, Santiago de Compostela, Spain.

Leptin, the product of the Ob gene, is a polypeptide hormone expressed in
adipocytes which acts as a signalling factor from the adipose tissue to the
central nervous system, regulating food intake and energy expenditure. It has
been reported that circulating leptin levels are higher in women than in men,
even after correction for body fat. This gender-based difference may be
conditioned by differences in the levels of androgenic hormones. To explore this
possibility, a systematic in vitro study with organ cultures from human omental
adipose tissue, either stimulated or not with androgens (1 microM), was
undertaken in samples obtained from surgery on 44 non-obese donors (21 women and
23 men). The assay was standardized in periods of 24 h, ending at 96 h, with no
apparent tissue damage. Leptin results are expressed as the mean+/-s.e.m. of the
integrated secretion into the medium, expressed as ng leptin/g tissue per 48 h.
Spontaneous leptin secretion in samples from female donors (4149+/-301) was
significantly higher (P<0.01) than that from male donors (2456+/-428).
Testosterone did not exert any significant effect on in vitro leptin secretion in
either gender (4856+/-366 in women, 3322+/-505 in men). Coincubation of adipose
tissue with dihydrotestosterone (DHT) induced a significant (P<0.05) leptin
decrease in samples taken from women (3119+/-322) but not in those taken from men
(2042+/-430). Stanozolol, a non-aromatizable androgen, decreased (P<0.05) leptin
secretion in female samples (2809+/-383) but not in male (1553+/-671).
Dehydroepiandrosterone sulphate (DHEA-S) induced a significant (P<0.01) leptin
decrease in female samples (2996+/-473), with no modifications in samples derived
from males (1596+/-528). Exposure to androstenedione also resulted in a
significant reduction (P<0.01) of leptin secretion in samples taken from women
(2231+/-264), with no effect on male adipose tissue (1605+/-544). In conclusion,
DHT, stanozolol, DHEA-S and androstenedione induced a significant inhibition of
in vitro leptin secretion in samples from female donors, without affecting the
secretion in samples from men. Testosterone was devoid of activity in either
gender.