RubricPart3 Conductingalitreview RubricPart2 RubricPart1 CapstonePaper1 x
 

• Type of paperThesis
• SubjectOther
• Number of pages26
• Format of citationAPA
• Number of cited resources26
• Type of serviceEditing

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PA 18 Capstone Project PA 18 Capstone Draft Paper

Final Paper Rubric_edited

CRITERIA SCALES

0.00
Information is not organized, and
paragraphs are not well-
constructed.

4.00
Information is organized with well-
constructed paragraphs but lacks
clearly indicated subheadings.

8.00
Information is very organized with
well-constructed paragraphs and
subheadings.

0.00
Paper is less than 15 pages in
length and does not contain
substantive or relevant content.

4.00
Paper is less than 18 pages in
length but contains substantive and
relevant content.

8.00
Paper is 18-22 pages and not more
than 30 pages in length and
contains substantive and relevant
content.

0.00
Many grammatical, spelling, or
punctuation errors.

4.00
Almost no grammatical, spelling or
punctuation errors

8.00
No grammatical, spelling or
punctuation errors.

0.00
Percentage of matches are greater
than or equal to 40% and is not
acceptable.

4.00
Percentage of matches are less
than 40% but greater than 20% and
is tolerable.

8.00
Percentage of matches are less
than or equal to 20% and is
acceptable.

0.00
The purpose and theme of the
research project is somewhat

4.00
The research project has a clearly
stated purpose and theme, but may

8.00
The research project has a well-
stated clear purpose and theme

Organization
How well information is

organized with attention to

well-constructed paragraphs

and subheadings.

Length
Length of paper is

considered here based on

syllabus requirement but

also considered here is

l d

Grammar
Grammatical, spelling or

punctuation errors are

considered.

Originality
This is based on the

Turnitin Originality report

with “Quoted or

Bibliographic Material

Content
Whether the research project

has a well-stated clear purpose

Limited Acceptable Proficient

Close

THE LITERATURE REVIEW: A FEW TIPS ON CONDUCTING IT

What is a review of the literature? A literature review is an account of what has been published on
a topic by accredited scholars and researchers. Occasionally you will be asked to write one as a
separate assignment (sometimes in the form of an annotated bibliography—see the bottom of the
next page), but more often it is part of the introduction to an essay, research report, or thesis. In
writing the literature review, your purpose is to convey to your reader what knowledge and ideas
have been established on a topic, and what their strengths and weaknesses are. As a piece of writing,
the literature review must be defined by a guiding concept (e.g., your research objective, the
problem or issue you are discussing, or your argumentative thesis). It is not just a descriptive list of
the material available, or a set of summaries.

Besides enlarging your knowledge about the topic, writing a literature review lets you gain and
demonstrate skills in two areas:

1. information seeking: the ability to scan the literature efficiently, using manual or computerized

methods, to identify a set of useful articles and books

2. critical appraisal: the ability to apply principles of analysis to identify unbiased and valid

studies.

A literature review must do these things:

a) be organized around and related directly to the thesis or research question you are developing

b) synthesize results into a summary of what is and is not known

c) identify areas of controversy in the literature

d) formulate questions that need further research

Ask yourself questions like these:

1. What is the specific thesis, problem, or research question that my literature review helps to

define?
2. What type of literature review am I conducting? Am I looking at issues of theory?

methodology? policy? quantitative research (e.g. on the effectiveness of a new procedure)?
qualitative research (e.g., studies )?

3. What is the scope of my literature review? What types of publications am I using (e.g., journals,
books, government documents, popular media)? What discipline am I working in (e.g., nursing
psychology, sociology, medicine)?

4. How good was my information seeking? Has my search been wide enough to ensure I’ve
found all the relevant material? Has it been narrow enough to exclude irrelevant material? Is the
number of sources I’ve used appropriate for the length of my paper?

5. Have I critically analysed the literature I use? Do I follow through a set of concepts and
questions, comparing items to each other in the ways they deal with them? Instead of just listing
and summarizing items, do I assess them, discussing strengths and weaknesses?

6. Have I cited and discussed studies contrary to my perspective?
7. Will the reader find my literature review relevant, appropriate, and useful?

Ask yourself questions like these about each book or article you include:

1. Has the author formulated a problem/issue?
2. Is it clearly defined? Is its significance (scope, severity, relevance) clearly established?
3. Could the problem have been approached more effectively from another perspective?
4. What is the author’s research orientation (e.g., interpretive, critical science, combination)?
5. What is the author’s theoretical framework (e.g., psychological, developmental, feminist)?
6. What is the relationship between the theoretical and research perspectives?
7. Has the author evaluated the literature relevant to the problem/issue? Does the author include

literature taking positions she or he does not agree with?
8. In a research study, how good are the basic components of the study design (e.g., population,

intervention, outcome)? How accurate and valid are the measurements? Is the analysis of the
data accurate and relevant to the research question? Are the conclusions validly based upon the
data and analysis?

9. In material written for a popular readership, does the author use appeals to emotion, one-sided
examples, or rhetorically-charged language and tone? Is there an objective basis to the
reasoning, or it the author merely Aproving@ what he or she already believes?

10. How does the author structure the argument? Can you “deconstruct” the flow of the argument to
see whether or where it breaks down logically (e.g., in establishing cause-effect relationships)?

11. In what ways does this book or article contribute to our understanding of the problem under
study, and in what ways is it useful for practice? What are the strengths and limitations?

12. How does this book or article relate to the specific thesis or question I am developing?

Final Notes:

• A literature review is a piece of discursive prose, not a list describing or summarizing one piece

of literature after another. It’s usually a bad sign to see every paragraph beginning with the name
of a researcher. Instead, organize the literature review into sections that present themes or
identify trends, including relevant theory. You are not trying to list all the material published, but
to synthesize and evaluate it according to the guiding concept of your thesis or research question.

• If you are writing an annotated bibliography, you may need to summarize each item briefly,

but should still follow through themes and concepts and do some critical assessment of material.
Use an overall introduction and conclusion to state the scope of your coverage and to formulate
the question, problem, or concept your chosen material illuminates. Usually you will have the
option of grouping items into sections—this helps you indicate comparisons and relationships.
You may be able to write a paragraph or so to introduce the focus of each section.

Prepared by Dena Taylor, Health Sciences Writing Centre, and Margaret Procter, Writing Support

Over 50 other files giving advice on university writing are available at www.writing.utoronto.ca

http://www.writing.utoronto.ca/advice

PA 18 Capstone Project PA 18 Capstone Draft Paper

Final Paper Rubric_edited

CRITERIA SCALES

0.00
There is not any logical flow of
information and often strays

from the controlling idea. *Few
paragraphs have topic
sentences with support

4.00
The paper was moderately clear
and had a fair amount of supportive
and substantive detail.

8.00
There is a consistent and logical
flow of information relating to the
controlling idea. *Each

paragraph contains a topic

0.00
Conclusion does not bring paper to
a close and does not re-establish
the the controlling idea of the paper.

4.00
Conclusion attempts to bring paper
to a

close by re-establishing the

controlling idea of the paper.

8.00
Conclusion brings paper to a
satisfactory close by re-establishing
the controlling idea of the paper.

0.00
Does not meet requirements:
double-

spaced, 12pt font, page

header, title page, abstract, main
body, references

4.00
Mostly meets or exceeds
requirements: double-spaced, 12pt
font, page header, title page,
abstract, main body, references

8.00
Exactly meets or exceeds
requirements: double-spaced, 12pt
font, page header, title page,
abstract, main body, references

0.00
Information is not organized, and
paragraphs are not well-
constructed.

4.00
Information is organized with well-
constructed paragraphs but lacks
clearly indicated subheadings.

8.00
Information is very organized with
well-constructed paragraphs and
subheadings.

0.00
Paper is less than 15 pages in

4.00
Paper is less than 18 pages in

8.00
Paper is 18-22 pages and not more

h l t d

Discussion
How consistent and logical

the flow of information

relating to the controlling

idea is and whether or not

Conclusion
How well the conclusion brings

the paper to a satisfactory

close by re-establishing the

controlling idea and final ideas.

APA
How well the paper meets

or exceeds APA

requirements: double-

spaced, 12pt font, page

h d titl b t t

Organization
How well information is

organized with attention to

well-constructed paragraphs

and subheadings.

Length
Length of paper is

Limited Acceptable Proficient

Close

PA 18 Capstone Project PA 18 Capstone Draft Paper

Final Paper Rubric_edited

CRITERIA SCALES

0.00
Information clearly relates to the
main topic. Not a lot of supporting
details and/or examples are given.

4.00
Information clearly relates to the
main topic. It provides 1-2
supporting details and/or examples.

8.00
Information clearly relates to the
main topic. It includes several
supporting details and/or examples.

0.00
Introduction does not orient the
audience to what will follow. Does
not connect to the controlling idea.

4.00
Introduction shows some structure
but does not create a strong sense
of what is to follow. It is too vague
or contains too many varied details
in relation to the controlling idea.

8.00
Introduction presents the overall
topic and draws the audience into
the paper. Effectively connects to
the controlling idea.

0.00
The controlling idea is too vague or
not present as the last sentence of
the introduction.

4.00
The controlling idea is clearly stated
but not placed as the last sentence
of the introduction.

8.00
The controlling idea is clearly stated
and is

properly placed as the last

sentence in the introduction.

0.00
Most sources (information and
graphics) are not accurately
documented in the desired APA
format. Has less than 5 sources
most of which are not relevant

4.00
Most sources (information and
graphics) are accurately
documented in the desired APA
format. Has at least five sources
most of which are relevant and

8.00
All sources (information and
graphics) are accurately
documented in the desired APA
format. Has at least five sources
all of which are relevant and

0.00
There is not any logical flow of
information and often strays

4.00
The paper was moderately clear
and had a fair amount of supportive

8.00
There is a consistent and logical
flow of information relating to the

Accuracy
How well the information

relates to the main topic

and whether or not It

includes supporting details

d/ l

Introduction
How well the introduction

presents the overall topic

and draws the audience

into the paper in additon to

h ff ti l it t

Thesis
How well the controlling idea is

stated and whether or not is

properly placed as the last
sentence in the introduction.

Sources
How well the sources

(information and graphics)

are documented in the

desired APA format and

h l t d

Discussion
How consistent and logical

Limited Acceptable Proficient

Close

RUNNING HEAD: ANABOLIC-ANDROGENIC STEROID USE IN ATHLETES 1

Anabolic-Androgenic Steroid Use in Athletes and the

Associated Cardiovascular and Metabolic Effects

Michael W. McClellan

Des Moines University

Abstract

Anabolic-androgenic steroid use has become a popular drug for athletes and bodybuilders to use in order to improve their athletic performance despite health consequences associated with its use. The use of anabolic-androgenic steroids has been associated with adverse outcomes in prior studies, particularly in regards to cardiovascular and metabolic systems. In order to further evaluate the scientific data behind this proposition many studies reviewed were small, retrospective-prospective studies that systemically reviewed anabolic-androgenic steroid use and the cardiovascular effects associated such as hypertension, left ventricular hypertrophy, and myocardial infarction. Dyslipidemia was the only metabolic component reviewed due to the close interaction and indication it has for cardiovascular function. Past data collected on this topic has been very controversial and conflicting due to ethical limitations placed on anabolic-androgenic steroid use within the athletic community. Findings from this review will help athletes globally to understand the adverse effects associated with anabolic-androgenic steroid use. Healthcare providers will be able to identify potential steroid abuse, and educate these patients on the adverse outcomes associated, so they can help prevent future misuse and abuse.

Introduction

The development of anabolic-androgenic steroids (AAS) were first seen in the early 1930’s when it was isolated from testosterone (Kanayama & Pope Jr., 2017). Soon after, there were many synthetic androgens developed such as testosterone propionate, stanozolol, and nandrolone, which are a few of the most common subtypes (Gheshlaghi, Piri-Ardakani, Masoumi, Behjati, & Paydar, 2015). As athletes and bodybuilders discovered the enhanced anabolic effects of each of these testosterone derivatives, it was not long until they became popular throughout the elite athletic population (Kanayama & Pope Jr., 2017). The improved performance seen throughout these individuals became the primary foundation for their use and eventually, abuse. The United States Food and Drug Administration has approved the use of anabolic-androgenic steroids as a form of hormone replacement therapy for men who have low testosterone production due to hypogonadism (Safety alerts for human medical products – testosterone and other anabolic androgenic steroids (AAS): FDA statement – risks associated with abuse and dependence.2016)). However, studies have shown that it is more commonplace for these synthetic drugs to be abused for cosmetic and personal performance rather than for any serious medical condition.

In a study conducted by Mitchell, it was found that over 30 major league baseball players reported the abuse of anabolic-androgenic steroids and performance enhancing drugs within the last 4 years. These players underwent anonymous questionnaires that allowed them to openly discuss their inappropriate use of AAS despite the ban placed on these drugs in all major league sports (Grossman, Kimsey, Moreen, & Owings, 2007). The study found that professional players had been administering AAS at much higher doses to create an offensive advantage on the baseball field (Grossman et al., 2007). On the other spectrum, bodybuilders have utilized these drugs to increase overall muscle workload and decrease muscular fatigue, which helps increase strength as well as develop a more aesthetic physique (Kanayama & Pope Jr., 2017). Bodybuilders use AAS to improve their overall appearance for the International Federation of Bodybuilder competitions. Despite the use of AAS for performance enhancing reasons in all major athletic sports and bodybuilding competitions, these drugs have many adverse effects at the heart, liver, brain, and endocrine system that can potentially impair the health of those who abuse AAS (Safety alerts for human medical products – testosterone and other anabolic androgenic steroids (AAS): FDA statement – risks associated with abuse and dependence.2016)).

Side effects of AAS and performance enhancing drugs are not common when used at therapeutic levels, but bodybuilders and athletes tend to use at levels that are nearly ten times higher than the standard dose. When AAS is administered at such high doses the most common effects include gynecomastia, reduced testicular function, hepatotoxicity, and psychological dependence (Safety alerts for human medical products – testosterone and other anabolic androgenic steroids (AAS): FDA statement – risks associated with abuse and dependence.2016). Cardiovascular effects, however, remain controversial within the literature and more recent studies. Elevated blood pressure and peripheral vascular resistance are two of the more widely studied effects of AAS abuse, whereas severe cardiac morbidity and mortality from arrhythmias and myocardial infarction are more controversial cardiovascular topics. The objective of this study is to analyze, synthesize, and report the data pertaining to AAS abuse in athletes and the associated cardiovascular effects.

Anabolic-Androgenic Steroids

Anabolic-androgenic steroids (AAS) represent a large number of synthetic derivatives of testosterone that are used to maximize anabolic effects while limiting the androgenic, sex-linked effects (Pope et al., 2014). The anabolic properties would primarily consist of muscle tissue building and the sexual characteristics consist of voice changes through enlargement of the pharynx, hair growth at the pubic, axillary, and facial regions, along with increases in sebaceous gland activity, and CNS involvement. Most AAS composition tries to enhance the anabolic properties while limiting the androgenic effects. These drugs can be administered in a variety of different routes for the body to metabolize and utilize such as oral, parenteral and transdermal. Access to these drugs can be done through pharmacy’s oversea where AAS are not FDA regulated. This allows users such as athletes and bodybuilders to purchase online through third party vendors.

AAS Mechanism of Action and Pathophysiology

The mechanism of action of these prohormones still remains very controversial due to limited studies within the human population, but testosterone’s similar mechanism has been attributed to anabolic steroid’s mechanism of action. Testosterone is produced in the testicles under the direct influence of the luteinizing hormone. There is a negative feedback loop between testosterone production, the hypothalamus, the anterior pituitary, and the testicles. Testosterone as well as dihydrotesosterone (DHT) and estrogen all function at the hypothalamus by exerting a negative feedback on gonadotropin releasing hormone (GnRH). GnRH stimulates the follicle stimulating hormone (FSH) and luteinizing hormone (LH) in the anterior pituritary which can also exert a negative Feedback on the hypothalamus. When FSH and LH are not being inhibited then they function to act on the testicles to help produce and potentiate spermatogenesis and oogenesis.

The pathophysiology of steroids at the cellular level involves the binding of these synthetic testosterone hormones to their corresponding nuclear androgen receptor within the cytoplasm of the target tissue. Different tissues have different enzymes that convert the synthetic form into a consumable form for the body to utilize. Following this binding, the hormone is released into the tissue where a series of enzymes are activated that involve protein metabolism. This protein metabolism enhances protein synthesis while inhibiting protein degradation simultaneously. These two mechanisms working together allows for increased muscle to tensile strength, which generates enhanced muscle growth. The drugs optimal situation would be to completely isolate anabolic activity from the androgenic activity, however, molecular biologists remain unable to completely isolate the two properties in vitro. Recent pharmacological manipulation of androgens has allowed for this concept to be utilized but not refined to perfection.

Although the use of androgenic anabolic steroid use has been shown to be beneficial for certain medical conditions like gynecomastia and hypogonadism. It remains unknown whether short or long-term use of these drugs have potentially harmful or fatal side effects at low and high doses. Specifically, in regards to the cardiovascular and metabolic systems.

Hypertension

The effects of anabolic androgenic steroid use on blood pressure is one area of concern. There has been an associated link between AAS and increased blood pressure readings. The mechanism behind this link associates AAS use with sodium retention in the kidneys (Achar, Rostamian, & Narayan, 2010). With that being said, the proposed effect of anabolic androgenic steroid use would cause a dose-dependent and timewise step approach to increasing blood pressure (Achar et al., 2010; P. Angell et al., 2014). The length of time athletes and bodybuilders are utilizing AAS should directly affect how high their blood pressure increases. Same concept applies with increased dosing of AAS and increased blood pressure. Many retrospective studies look at AAS users and measure their systolic and diastolic blood pressure reading throughout the course of their steroid use. This in turn can be utilized to show the mean systemic arterial hypertension, which is compared amongst all steroid users and non-users. This review will address each of the studies to better understand the effects of AAS use and the precipitating effects it has on blood pressure.

Left Ventricular Hypertrophy

Another parameter to understand when analyzing athletes who use anabolic steroids is the effect that these synthetic forms of testosterone have on cardiac remodeling. Specifically, in regards to left ventricular hypertrophy (LVH), which is a common condition that causes the muscles of the left ventricle to become thickened (P. Angell et al., 2014). LVH is observed through electrocardiogram (EKG) and echocardiographic observation in studied participants (P. Angell et al., 2014). This process is believed to be a direct response from elevated blood pressure as well as underlying congenital heart disorders. As LVH develops, it causes the heart to work harder and less efficiently than a typical, normal functioning heart should. Stress on the heart over time can eventually lead to poor outcomes such as myocardial infarction, angina, dilated cardiomyopathy, and heart failure (Sabzi & Faraji, 2017). This topic seems to be the most relevant within the recent literature in human and animal studies. Understanding the link between AAS use and abuse in athletes will help provide more insight to potential effects that these drugs have on cardiac remodeling.

Myocardial Infarction

The most harmful and fatal cardiovascular phenomenon deals with myocardial infarction (MI) or heart attack from an acute episode of cardiac ischemia due to coronary syndromes and thrombus formation (Poorzand, Jafarzadeh Esfehani, Hosseinzadeh, & Vojdanparast, 2015). Anabolic-androgenic steroid use has been linked to these acute conditions that can potentially be life threatening. The exact mechanism for which this happens is not fully understood, however, the best interpretation is thought to be that cardiac myocyte ischemia develops in response to the increased oxygen demand at maximal intensity exercise during AAS use (Poorzand et al., 2015). This exaggerated response for oxygen demand comes from the anabolic steroids ability to enhance cardiac tissue growth through increased workload over many years of use (Poorzand et al., 2015). This can also be explained from the increased deposition of lipoprotein within the vasculature, which is a metabolic component of concern for AAS use in athletes (Poorzand et al., 2015). Many retrospective studies and pathology reports post-mortem in isolated incidences have linked these myocardial infarctions and sudden death with prior use of anabolic steroids, and raises concern for myocardial infarction induced by anabolic steroid use.

Dyslipidemia

The one metabolic component that this review analyzes deals with blood plasma lipoprotein levels. The evidence based medicine between AAS use and blood plasma lipoproteins indicates a potential increase and decrease in low density lipoprotein (LDL) and high density lipoprotein (HDL), respectively (Gårevik, Skogastierna, Rane, & Ekström, 2012). The long-term sequelae of elevated LDL and decreased HDL is coronary artery disease (Gårevik et al., 2012). Understanding the risks associated with AAS use through evidence can help formulate more concrete risk factors that can be educated to the patient.

Blood plasma lipoprotein levels are more commonly composed of cholesterol, which is synthesized in the liver (Gårevik et al., 2012). The rate-limiting step in cholesterol synthesis is 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) to mevalonate and this process is catalyzed by the enzyme HMG-CoA reductase. This is important because in mammals, HMG-CoA reductase is suppressed by breaking down LDL through LDL receptor activation, which ultimately leads to decreased cholesterol levels in the plasma (Gårevik et al., 2012). The same mechanism of action is used by “statin” medications,” which are used to increase the expression of LDL receptors at the target organ and help induce the breakdown of plasma LDL (Gårevik et al., 2012). Determining whether or not plasma lipoproteins are affected by AAS use can serve as precipitating factor toward cardiovascular disease.

Methods

Anabolic steroids have been around for over 50 years, but studies have not emerged until the last 15 to 30 years. With more public awareness of steroid use in the athletic and bodybuilding community, more research has become available. The examination of potential literature review articles were found through the PubMed search engine. Numerous searches were utilized with terms such as “anabolic androgenic steroid”, “athlete”, “body building”, “cardiovascular effect”, and “metabolic effect.” Extra criteria only included the terms “animal”, and “mice” due to a large number of recent studies being done on animals instead of humans. Several studies included were case reports by athletes and isolated incidents of myocardial damage from anabolic stroids. Anabolic steroids are illegal, which poses an ethical dilemma for acute and chronic AAS users from openly reporting their misuse and abuse. This eliminates the use of randomized control studies in the human population. Also, it only allows for retrospective studies to be reviewed.

Results

AAS Use Induced Hypertension

A retrospective-prospective study comprised of 70 total participants that were all male and divided equally with 35 individuals in each of the experimental and control groups (Solakovic, Totic, Vukas, & Djedovic, 2015). All participants in the study were under the age of 35 and involved in recreational fitness or body-building workouts without competitive motives (Solakovic et al., 2015). They were followed over the course of five years from January 2010 until January 2015 (Solakovic et al., 2015). Each participant had no underlying cardiovascular or metabolic abnormalities (Solakovic et al., 2015). These individuals were not placed on any dietary restrictions and were evaluated through non-invasive procedures such as vascular ultrasound to observe systolic and diastolic blood pressure. The studied participants underwent daily anaerobic exercise training for two hours, four to six times per week to show an understanding of how AAS use can affect blood pressure (Solakovic et al., 2015). In this study, arterial hypertension was observed in 18 of the 35 participants using anabolic steroids. Only 2 of the 35 individuals in the control group were observed to have a statistically significant increase in their blood pressure. The proposed mechanism for this increase was due to damage induced on the surface of the venous system at the saphenous and small saphenous vein, which causes irreversible dilation of these vessels (Solakovic et al., 2015). Dilation of these vessels prevents them from properly regulating peripheral vascular resistance and pressure when placed under steroid induced stress (Solakovic et al., 2015). However, the data collected based on this proposal was insignificant. Only 11 of the 35 individuals using anabolic steroids exhibited damage to each of the saphenous veins, whereas 6 of the 35 in the control group displayed the same type of dilating damage to vessels. In addition, they took into account the lipid deposition in the arterial system to help understand the cause of increased blood pressure from anabolic steroid use, but this will be discussed later.

In contrast to the study above, there have been other studies that do not show a statistically significant increases in blood pressure from anabolic steroid use. A study in 2003 conducted by Grace et al found there were no cardiovascular or morphological changes in the vasculature. This study used a small sample size of 32 to evaluate blood pressures taken manually with a sphygmomanometer and a stethoscope by means of auscultation. The same researcher throughout the study was used to take these blood pressures to help prevent intra-observer variability (Grace, Sculthorpe, Baker, & Davies, 2003). Throughout the duration of the study, systolic blood pressure showed minimal change from start to finish between the control group and experimental group. Systolic pressures ranged from 119 – 122 mmHg in the control and 119 – 124 mmHg in the individuals using steroids (Grace et al., 2003). Significant increases in diastolic pressure were seen during the study in subjects undergoing anabolic steroid use opposed to subjects not using. However, these numbers returned to baseline levels 6 to 8 weeks following drug cessation (Grace et al., 2003). The data therefore is inconsistent with stating that anabolic steroid use induces hypertension long-term. Acutely, steroid use can elevate diastolic blood pressure above normal, but systolic has no associated effects from steroid use (Grace et al., 2003).

A different approach was used in a study by Urhausen et al to evaluate steroid use by comparing prior steroid users against those who are currently using anabolic steroids (2004). Systolic blood pressure was found to be higher in current steroid users with a mean pressure of 140 mmHg compared to ex-users whose mean systolic pressure was 130 mmHg (A Urhausen, T Albers, & W Kindermann, 2004). Only 5 out of 17 current users displayed borderline hypertension with systolic pressures greater than 140 and diastolic pressures greater than 90, whereas 2 out of 15 non-users displayed these same levels as well (A Urhausen et al., 2004). Five months after discontinuing steroid intake, systolic blood pressure remained higher by 6 mmHg in steroid users compared to the control group who did not use anabolic steroids (A Urhausen et al., 2004). With these results it suggests that increases in blood pressure due to anabolic steroid use are minor and transient in nature. Blood pressure increases from baseline were minimal and short-lived once steroid use was discontinued.

Left Ventricular Hypertrophy due to AAS Use

Athletes who abuse anabolic androgenic steroids often develop and display left ventricular hypertrophy. Several studies have shown that left ventricular structure, function, and mass increase as result of exercise and anabolic-androgenic steroid use (Achar et al., 2010). In a retrospective study conducted by Kreig et al, 40 total male participants comprised of 14 anabolic-androgen steroid users, 11 nonuser athletes, and 15 age-related controls were utilized to evaluate echocardiographic findings related to interventricular septal wall thickness and left ventricular hypertrophy. Human subjects self-reported oral and injectable steroid use which was confirmed by luteinizing hormone, follicle-stimulating hormone, and testosterone ratios (Krieg, Scharhag, Albers, Kindermann, & Urhausen, 2007). Anabolic steroid users had significantly increased interventricular septal wall thickness and enlarged left ventricular muscle on echocardiograph when compared to non-users and controls (Krieg et al., 2007). As a result of this enlargement, there were significant differences in diastolic function that can be explained as result of myocardium thickening. Early diastolic filling was reduced in users compared to non-users and controls, which can be explained by impaired myocardium relaxation and decreased compliance secondary to myocardium enlargement (Krieg et al., 2007). Inefficient diastolic contractions can ultimately lead to heart failure if left untreated and appropriate management is not taken.

In addition, a cross-sectional study conducted by Angell et al followed 13 strength trained athletes currently using anabolic steroids for more than 2 years and 8 strength trained athletes not using anabolic steroids by monitoring left ventricular mass and ejection fraction through cardiac magnetic resonance imaging and echocardiography. The study revealed that anabolic steroid users had a higher absolute ventricular mass compared to non-anabolic steroid users (P. Angell et al., 2014). As a result of the increase in left ventricular mass, the ejection fraction of the right ventricle was significantly less (51%) in anabolic steroid users compared to athletes not using anabolic steroids whose ejection fraction was 59% (P. Angell et al., 2014). When monitoring for left ventricle mass and ejection fractions, the study discovered that the peak left ventricular strain during diastole was much lower in athletes undergoing anabolic steroid use (P. Angell et al., 2014). All of these factors: elevated left ventricle mass, reduced ejection fraction, and increased strain placed on the myocardium during strength training in anabolic steroid users can be associated with the phenomenon of left ventricular hypertrophy.

Another small sample size evaluated 12 anabolic steroid users and 7 non-users for left ventricular hypertrophy through echocardiographic examination of left ventricular mass, tissue velocity or ejection fraction, and strain (Baggish et al., 2010). The study found that 6 anabolic steroid users and 5 non-users met criteria for LV hypertrophy. This suggests that non-users were at increased risk for left ventricular hypertrophy. However, anabolic steroid users differed greatly from non-users in many other interdependent systolic and diastolic functions. Left ventricular ejection fraction was less than 55 % in 10 of the anabolic steroid users and only one non-user had an ejection fraction of 54% (Baggish et al., 2010). Evidence of this was confirmed through echocardiographic imaging of diastolic filling where it revealed reduced early diastolic filling and increased late diastolic function, which is one hallmark sign for impaired left ventricular relaxation and function (Baggish et al., 2010). With an impaired diastolic filling, ventricle relaxation and compliance is decreased, which in turn causes lower left ventricular peak systolic strain and decreases the amount of blood forced out of the ventricle during systole (Baggish et al., 2010).

Increased Lipid Deposition from AAS

In this cross-sectional study conducted by Severo et al., they evaluated 10 athletes who were users of anabolic steroids confirmed by urine analysis and 12 non-using athletes. Both subject groups submitted to weekly blood draws to evaluate complete blood count (CBC), platelets, fibrinogen, lipid profile, C-reactive protein, follicle stimulating hormone, and testosterone levels (Severo et al., 2013). The area of importance to this study corresponds with the lipid profile due to the increased risk stratification cholesterol places on other components of the cardiovascular system such as blood pressure and vascular health. Results showed that HDL cholesterol was lower and LDL levels were elevated in anabolic steroid users (Severo et al., 2013). Similar findings were gathered from a study mentioned above that was conducted by Solakovic et al that found 19.4% of users had increased LDL, decreased HDL, and increased total cholesterol. This information was not statistically significant since there were 17.1% of non-anabolic steroid users with elevated LDL, reduced HDL, and increased total cholesterol (Solakovic et al., 2015). Therefore, findings within the literature are very conflicting and opposing, which makes interpreting the data very difficult.

Cardiac Arrhythmias and Myocardial Infarction Generated by AAS Use

Despairing evidence has linked anabolic steroid use with adverse cardiac events including but not limited to cardiac arrhythmias, myocardial infarction, and sudden death (Achar et al., 2010). Basic understanding into the mechanism for anabolic steroid use induced myocardial ischemia was evaluated in study by Major et al through comparison of electrocardiographic criterion before and after submaximal exercise between anabolic steroid users and non-anabolic steroid users. Anabolic steroid users were found to have a prolonged QT interval at rest and a significantly increased QT prolongation during the post-exercise period when compared to non-users (Maior et al., 2010). The prolongation of the QT interval is generally produced by slowed repolarization in the cardiac membrane due to reduced influx of potassium (K+) current into the cardiac tissue, which causes irregular ventricular contractions (Moss & Kass, 2005). Without proper ion channel control over ventricular contractions in cardiac tissue places individuals at increased risk for fatal cardiac events. One life-threatening associated arrhythmia seen from abnormal ventricular repolarization is ventricular fibrillation (Maior et al., 2010). This arrhythmia is often predicted by prolonged QT intervals, and can be utilized as a risk factor and preventive measure for limiting adverse cardiac events.

Understanding the mechanism for which anabolic steroid use causes cardiac arrhythmias aids in the explanation of myocardial infarction (MI) and ventricular arrhythmias in young athletes with no cardiac risk factors. A study conducted by McNutt et discovered that an acute MI happened to a 22-year-old bodybuilder who openly discussed his anabolic steroid abuse in the absence of any cardiac risk factors. The patient above had elevated LDL and decreased HDL well out of the therapeutic range. A similar scenario happened to a 23-year-old wrestler who presented to the emergency department with crushing substernal chest pain (Poorzand et al., 2015). This patient had increased serum cardiac troponin markers in addition to ST-segment elevation on electrocardiograph, which classically indicates an acute myocardial infarction (Poorzand et al., 2015). Additional findings included an abnormal lipid profile and left ventricular enlargement. The patient did not have traditional cardiovascular risk factors such as smoking, diabetes, or hypertension.

Non-Human Animal Studies

With ethical and legal implications placed on anabolic steroid use and abuse in the human population, there have been more recent studies done on non-human subjects to evaluate time and dose-dependent relations corresponding to anabolic steroid use. A study conducted by Fotini Vasilaki et al looked at male rabbits over the course of 1 year under high (10mg/kg) and low doses (4mg/kg) of nandrolone decanoate with one control group receiving saline fluid. Rabbits under higher anabolic doses exhibited increased myocardial mass, reduced diastolic function, increased troponin cardiac biomarkers and focal fibrosis of cardiac tissue (Fotini Vasilaki et al., 2016). Subjects placed under low dose steroid injections saw these same changes but to a significantly less extent. During the wash-out period troponin levels continued to rise in subjects under high and low-dose steroids and BNP levels that were otherwise normal during the study, began to elevate during washout as well (Fotini Vasilaki et al., 2016).

Another dose-dependent approach to anabolic steroid administration was done in a study conducted by Pirompol et al which took male rats of similar weights, divided into equal groups of 4, and injected with different doses of testosterone propionate. One control group was used and injected with ethyl oleate. Evaluation of the cardiac parameters included but not limited to cardiac chamber size, septal wall thickness, and blood pressure. The study examined acute dysfunction of the cardiac parameters described above to determine whether steroid administration causes pathologic or physiologic impairment in time or dose-dependent fashion (Pirompol, Teekabut, Weerachatyanukul, Bupha-Intr, & Wattanapermpool, 2016). Significant findings of elevated cardiac muscle mass were found in all testosterone dosed rats compared to control (Pirompol et al., 2016). A time-dependent enlargement of the ventricular chamber was a significant finding in high-dose steroid using rats compared to low-dose steroid using rats and controls (Pirompol et al., 2016). Ventricular enlargement was found in the absence of increased septal and ventricular wall thickness, which implies a physiologic, time and dose-induced cardiac hypertrophy (Pirompol et al., 2016). In order to determine whether a pathologic induced cardiac hypertrophy occurred, the study conducted by Pirompol et al evaluated collagen deposition in the myocardium of each studied subject. There were no obvious deposits of collagen in the hearts of all rats using versus not using steroids regardless of steroid dose and exposure length. In regards to arterial blood pressures, there were no differences found between all studied subjects (Pirompol et al., 2016).
Discussion
The Research Issue
The history of anabolic steroid use is seen as early as the 1930’s when testosterone was converted into a synthetic form now known as anabolic-androgenic steroids. It was not long after that athletes and bodybuilders all over found the enhanced performance, increased muscle strength, and physical attractiveness that these drugs had to offer (Snyder, Matsumoto, & Fricker, 2017). As a result, anabolic-androgenic steroid use has become a major global health issue with recent studies showing a global prevalence rate of 3.3 percent (Snyder et al., 2017). More commonplace, anabolic steroid use is seen in men compared to women with 6.4 percent to 1.6 percent, respectively (Snyder et al., 2017). In the United States, it was found that nearly four out of five users of anabolic-androgenic steroids were recreational athletes and bodybuilders (Snyder et al., 2017). The foundation for anabolic steroid use in the elite athletic community is to help improve and boost performance. Athletes continue to use anabolic steroids despite the World Anti-Doping Agency (WADA) banning the use of these substances in all major competitive sports (Snyder et al., 2017). With the ban in place by WADA, it creates an ethical dilemma for athletes to openly report their misuse of these drugs. However, there are recent studies that look at anabolic steroid use and the associated cardiovascular and metabolic effects it poses to athlete’s health. Investigating the research to see how anabolic steroid use affects both cardiac and metabolic health can help clinicians and patients who use anabolic steroids understand the medical reasoning for using or not using androgenic-anabolic steroids.
The Risk Associated with AAS Use

Many of the studies available on anabolic steroid use and associated cardiovascular and metabolic effects is lacking due to adverse ethical implications and small epidemiological sample size linked with anabolic steroid use (P. J. Angell et al., 2012). With the studies available despite limitations, many reports link anabolic steroid use with elevated blood pressure, left ventricular hypertrophy, and myocardial infarction. Lipid profile has been one metabolic component that is tightly regulated with promoting cardiovascular health.

The relationship between anabolic steroid use and hypertension was very controversial in the past. Some studies correlate a link between anabolic steroid use and an increase in blood pressure whereas others show no association between the two. Recent literature and the analysis of studies in this review would point towards a positive correlation between anabolic steroid use and hypertension. One explanation for this is a dose-response trend. As studied subjects receive much higher doses, their blood pressure can increase much greater than subjects who receive a much lower dose of anabolic steroids (Achar et al., 2010). It also displayed a correlation between length of time using AAS. In two separate studies that underwent a three-month course of AAS, subjects had a significantly less increase in their blood pressure compared to studied individuals who underwent a six-month period of AAS use (A Urhausen et al., 2004; Achar et al., 2010). During the washout period, when AAS use had been discontinued, studied subjects had a return of their blood pressure to levels prior to the start of their study. In another retrospective that followed bodybuilders over the course of three years, they found that blood pressures would increase acutely, but pressures plateaued after six months of use. After discontinuation of AAS, blood pressures returned to previous levels recorded prior to the start of the study. This finding is significant because it shows that hypertension in AAS use is prevalent, but considered transient in nature. The effect of AAS during the acute stage of AAS use can induce hypertension, but if AAS use is discontinued then blood pressures should be expected to return to normal.
Left ventricular hypertrophy associated to AAS use was one of the more widely studied correlations in past studies. It was also found to be significant in the current literature as several studies analyzed LVH through echocardiographic measures. In a study by Krieg et al and Chung et al, both similar studies follow a small sample size with no underlying cardiac conditions and found that interventricular septal wall thickness increases over the course of AAS use. Subjects who receive higher doses of steroid injections exhibit a decrease in diastolic function as a result (Krieg et al., 2007). However, results of the study show no association due to length of time using AAS. Those who receive a shorter course of AAS in comparison to those who use for a longer duration still experience increases in left ventricular mass and a reduction in diastolic function. Findings between all studies show conclusive evidence that left ventricular function was reduced from AAS use. Not only can it affect cardiac performance, but also it can lead to poor outcomes. One case report conducted by Sabzi found that LVH induces a thrombus in the left ventricular outflow tract. This was seen in an autopsy report for the individual who was using AAS and suffered a myocardial infarction (Sabzi & Faraji, 2017). With this being an isolated incidence in the general population, future studies need to be done on non-human subjects in order to fully understand the mechanism on how AAS induces thrombus formation.
Myocardial infarction and arrhythmias associated to AAS use…… needs finished
This review investigated the association between anabolic steroid use and the affect it has on the lipid profile. There was a significant link between anabolic steroid consumption and elevated plasma LDL levels (P. J. Angell et al., 2012). Total cholesterol was noted to be increased as a result of elevated LDL levels, but with LDL levels taken into account there was no significant finding associated with steroid use and total cholesterol (P. J. Angell et al., 2012). Triglyceride levels were not seen to be affected by low or high dose steroid use as well. Prior studies found that HDL was not affected from increased doses of steroid administration. However, in the 4 studies reviewed, there was clear and concise evidence that displayed elevated LDL levels and decreased HDL levels. Two studies displayed increased triglyceride levels in high dose steroid administration. Decreased HDL levels from AAS use contributes to new findings within recent literature. Elevated LDL levels with decreased HDL levels together can contribute to increased lipid deposition into vessels (Severo et al., 2013). With increased lipid deposition, this would suggest that anabolic steroid use can increase the risk of arterial disease (Severo et al., 2013). In a study conducted by Gheshlaghi et al., researchers explored the association between abnormal cholesterol in accordance with blood pressure and found that AAS users with poor lipid profiles had increases in blood pressures as well. This is a significant finding for clinicians moving forward in educating patients about AAS use and adverse effects associated.
Implications for the Clinician
There is a major challenge for clinicians moving forward in identifying patients who use AAS, since these individuals are likely to hide this information. It is extremely important for healthcare providers to obtain an in depth medical history for all patients suspected of abusing hormone replacement, especially in regards to AAS. If clinicians are aware of the potential patient population of athletes who are in major athletic sports or bodybuilding, then adequate information and education can be provided in order to prevent future AAS misuse. The American Academy of Family Physicians, American Medical Association, and American Academy of Pediatrics recommend that healthcare providers discuss the dangers of drug abuse in all children, adolescents, and adults as a part of routine medical visits (Snyder et al., 2017). In order to recognize potential abuse in patient’s, there are a few key characteristics to look for when interviewing a patient.

AAS use can be suspect in patients who participate in any competitive sport or activity associated with exogenous steroid use (Snyder et al., 2017). Typically, these sports are associated with collegiate and professional athletes, but AAS use has been seen within high school athletes as well. When suspecting AAS use in athletes, often times these patients will have significant behavior changes such as depression, irritability, and elevated aggression (Snyder et al., 2017). Upon physical examination for male patients, they will display increased muscle strength, tone, and mass. Androgenic physical exam components consist of gynecomastia, acne, and hypogonadism (Snyder et al., 2017). If these patients have been over exerting themselves during workouts, then it is not uncommon for them to have tendon and ligament ruptures (Snyder et al., 2017). AAS use in women, although not as common as men, is still prevalent and should be considered in females who suddenly develop irregular menstrual cycles, acne, hirsutism, deep voice, and increases in muscle mass (Snyder et al., 2017).

To further evaluate these patients, appropriate lab work should be completed in order to better understand the extent of their AAS use. Hormone levels to consider in evaluation include serum luteinizing hormone and sex hormone-binding globulin (Snyder et al., 2017). Hematocrit may be useful to evaluate in a serum complete blood count since AAS can increase these levels (Snyder et al., 2017). Other means of evaluation include looking at growth factors such as insulin-like growth factor-1 (IGF-1), which is a new method for athletes to use (Snyder et al., 2017). When the patient admits to using any anabolic-androgenic steroids or performance enhancing drugs, then it is up to the clinician to educate the associated risks. There is no legal obligation to report this finding to any major affiliates regardless of patient’s age (Snyder et al., 2017). However, the World Anti-Doping Agency may require healthcare providers to complete forms on patient’s suspected of AAS use (Snyder et al., 2017). If the clinician finds a positive test result, they must report this information to the World Anti-Doping Agency, otherwise they can be held liable for falsifying medical records.

As a clinician, it should be a priority to educate all patients who use AAS on the potential risks associated with its use. Many times patients who abuse AAS are unwilling to discontinue the use of these drugs in order to maintain a high level of performance. Expressing the potential harmful and dangerous side effects associated with the use of these medications is extremely important. It should not be our job to force discontinuation of these illegal drugs, but rather to provide pertinent information so that the patient can make the most informed decision.
Conclusion

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