1. Lifestyle Drugs
A
PROJECT REPORT ON
LIFESTYLE DRUGS
Submitted by
MR. DHAVAL SHAILESH WAGHELA
Roll no. 69
T.Y. B. pharmacy
2011-12
Under the guidance of
PROF. S.H. PAWAR
(M.Pharm)
Department of Pharmacology
Mahatma Gandhi Vidyamandir’s
Pharmacy College
Panchavati, Nashik-422003
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2. Lifestyle Drugs
Table of Contents
Sr no. Topic Page
no
1 Abstract 1
2 Introduction 2
3 Aims and Objectives 3
4 Background 4
5 Lifestyle drugs should not be interchanged with lifestyle medicine!!! 4
6 Why are lifestyle drugs booming? 6
7 Indian Prospective 7
8 An issue of Debate 11
9 Mood ,behaviour,cognition 17
10 The 2010 Lifestyle Medication List put up by BlueChoice HealthPlan of
South Carolina,Inc.
23
11 In depth analysis of Lifestyle Drugs
-Minoxidil
-Orlistat
-Anabolic Steroids
25
25
28
37
12 Lifestyle Drug Substitution 55
13 Conclusion 61
14 Expected Outcomes 62
15 References 63
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3. Lifestyle Drugs
List of Figures and Structures:
Fig
no.
Name Page
no.
A Structure of Minoxidil 25
B Structure of Orlistat 29
c Packaging of Orlistat (Xenical) 120 mg
capsules
30
D Crystallographic structure of human fatty acid synthase 34
E Structure of Testosterone 38
F A vial of injectable testosterone cypionate 40
G The human androgen receptor bound to
testosterone
42
h Various anabolic steroids and related
compounds
50
I Vials of injectable anabolic steroids 51
J Steroid pills intercepted by the US DEA 54
List of Tables:
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4. Lifestyle Drugs
Table
no.
Name of Table Page no.
I List of some Lifestyle Drugs and their
indications
5
II 2010 Lifestyle Medication List
by BlueChoice HealthPlan
23,24
II
I
Relative androgenic:anabolic
activity in animals
43
Abstract
4

5. Lifestyle Drugs
Lifestyle drugs are the drugs which are used to treat certain disorders which are not
fatal to mankind, we may call these drugs as non essential drugs .The most
commonly accepted definition refers to a drug or medicine that is used to satisfy an
aspiration or a non health related goal. Summary of details of lifestyle drugs, like
their classifications ,mode of action ,adverse effects has been discussed here. Past
and present trends of these drugs in the market, and some controversies and debates
surrounding these drugs has been described. Besides this, highlight on 3 popular
lifestyle drugs- Minoxidal, Orlistat, Anabolic Steroids has been made here. A
subject called lifestyle drug substitution has been focused, which describes about
how people have started substituting alcohol with other lifestyle drugs like
diazepam to get euphoric state and to fulfill the addiction
Introduction
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6. Lifestyle Drugs
The term ’lifestyle drug’ is very difficult to define absolutely. Over the last few
decades, ‘lifestyle drugs’ and ‘lifestyle medicines’ have been used with increasing
frequency, but, no clear-cut definition and demarcation is ever suggested. Møldrup
et al., tried to evaluate the quality and quantity of such terms in scientific literature
and found no acceptable definition of these terms. The term is also used to describe
medicines that are used to treat ‘lifestyle illnesses’, that is to say diseases that arise
through ‘lifestyle choices’ such as smoking, alcoholism or overeating, and there are
many other shades of meaning as well. The general consensus is that a lifestyle
drug is one which can modify or change a non-medical or non-health related goal
or condition that is at the margin of health and well-being. It can be used to alter
not only the appearance, but also the physical and mental capabilities of the
individual. Let us know something about Lifestyle Diseases now, Lifestyle diseases
(also sometimes called diseases of longevity or diseases of civilization
interchangeably) are diseases that appear to increase in frequency as countries
become more industrialized and people live longer. They can include Alzheimer's
disease, atherosclerosis, asthma, cancer, chronic liver disease or cirrhosis, Chronic
Obstructive Pulmonary Disease, Type 2 diabetes, heart disease, metabolic
syndrome, nephritis or chronic renal failure, osteoporosis, acne ,stroke , depression
and obesity, some commenter’s maintain a distinction between diseases of
longevity, and diseases of civilization. Certain diseases, such as diabetes or asthma
appear at greater rates in young populations living in the "western" way; their
increased incidence is not related to age, so the terms cannot accurately be used
interchangeably for all diseases. So in short we can conclude that Lifestyle Drugs
are the drugs which are intended to improve lifestyle of an individual. [1]
Aims and Objectives
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7. Lifestyle Drugs
As we see that nowadays there are various disorders arising due improper lifestyle,
certain metabolic disorders and even due to various chemical agents present
around us. Lifestyle Drugs are tending to treat the disorders arising due to these 3
factors. So it is important to know more about these drugs-their type, their nature,
their mode of action, their toxic effects in order harness these drugs properly and
suitably for benefit of mankind and prevent its abuse. The lifestyle drugs market is
currently worth a phenomenal $29 billion from its starting value. The boom in the
growth of lifestyle drugs is suggested to be a complex interaction of vested interests
of pharmaceutical industries, surfacing of growing insecurities in the modern day
man and the availability of 24×7 telecasting tools of many media. A person in the
modern world seeks a very simplistic approach. Everybody tries to solve the
problem in a very reductionist, mechanical and biomedical way. They wish to
search the answer for every simple health problem in a pill. This bent of the human
psyche has further been exploited by some pharmaceutical industry, which
obviously has an interest in selling all sorts of pills. These pills may then be
dominated by quacks and other media. Hence it is important to know more about
these drugs to avoid abuse, dependence and overuse (e.g. alcohol and steroids) [2]
Background
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8. Lifestyle Drugs
Lifestyle has moved from being an indicator of the overall well being of an
individual to a cause of disease and now, "lifestyle" has itself become an object of
medical attention'. Alcohol has been used enormously as one of the oldest 'lifestyle'
drugs, and currently Sildenafil citrate (Viagra), the drug of choice for erectile
dysfunction, exemplifies a turning point in the era of modern lifestyle drugs. The
compound has transformed the lifestyle of millions and greatly increased the
revenue of many pharmaceutical companies. With the Indian economy growing
rapidly at the annual rate of 8- 9%, we have witnessed a new era of drug discovery
and development coupled with an enormous increase in the marketing of new
drugs. This has certainly made us vulnerable to issues related to lifestyle drugs.
There is a need to study the concept and impact of these drugs on Indian society,
particularly as the topic has already been discussed in other developed nations. [3]
Lifestyle drugs should not be interchanged with lifestyle medicine!!!
‘Lifestyle Medicine’ is an established branch of medicine where we discuss
lifestyle’s contribution to health in addition to non-pharmacological intervention in
the treatment and management of lifestyle diseases, such as exercise in diabetes
mellitus and weight management in obesity. Whereas, in the current scenario, the
most operational definition of ‘lifestyle drugs’ is as follows; Drugs that could
modify or change non-medical or non-health-related goal or conditions at the
margins of health and wellbeing. These can be used fashionably over the counter to
alter not only the appearance but also the physical and mental capabilities.
List of some Lifestyle Drugs and their indications:
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9. Lifestyle Drugs
Lifestyle Drugs Lifestyle Indications
Viagra (Sildenafil citrate) Impotency, Erectile dysfunction
Norethisterone Short / postpone menstruation
i-pills (levonorgesterol) Post-coital contraception
Hormone replacement therapy (HRT) Improving post-menopausal
problems
Anabolic steroids, clenbuterol Anabolic steroids, clenbuterol
Lipase inhibitor (Orlistat),
sibutramine
Weight Loss
Height increase pills Height
Benzodiazepines, SSRIs, Marijuana Mood-alteration, social anxiety
disorders
Nicotine Replacement Therapy,
bupropion
Cessation of smoking (nicotine)
Caffeine, amphetamine Memory loss, cognitive enhancers
Minoxidil, finasteride Baldness
Antioxidants, botulinum toxin Wrinkles and ageing / cosmetic
alterations
Melatonin Sleep remedy and jet lag remedy
Cyproheptadine Appetite enhancer
NSAIDs Work related fatigue
Food supplements, vitamins General wellbeing
Table - I
According to the WHO, counterfeit medicine is defined as those which have been
deliberately and fraudulently mislabeled with respect to identity and/or source.
Counterfeiting can apply to both branded and generic products; and counterfeit
products may include products with correct ingredients, wrong ingredients, without
active ingredients, with insufficient quantity of active ingredient or with fake
packaging. This definition as a consequence may includes all types of ‘spurious and
fake drugs’, ‘off labels drugs’ including ‘lifestyle drugs’. Thus, as a part of
counterfeit medicine strategy, lifestyle drugs should too be tackled as other
counterfeit medicines.[4][5][6][8][15]
Why are lifestyle drugs booming?
The boom is suggested to be a result of a complex interaction of vested interests by
pharmaceutical industries, surfacing of growing insecurities in the modern day
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10. Lifestyle Drugs
individual and the round the clock availability of media sources. In today's world a
lot of individuals try to solve their problems in a reductionist way and look for a
solution to every simple health problem in a pill. This bent of human psyche has
been exploited by pharmaceutical industry paving the way for lifestyle drugs.
Drug companies today, rather than addressing the healthcare problems of the
masses are more interested in catering to the need of a handful of people with
spending power. The old dictum of 'supply and demand' has been cleverly modified
by them and they, in fact, generate the demand first and then proceed to meet it.
They are actively involved in broadcasting the definition of diseases first and then
encouraging both prescribers and consumers to purchase their products. This has
been appropriately described by Moynihan et al as 'disease mongering'. 'Disease
mongering includes turning ordinary ailments into medical problems, seeing mild
symptoms as serious, treating personal problems as medical, seeing risks as
diseases and framing prevalence estimates to maximize potential markets.' Thus we
are now seeing an increase in the medicalisation of conditions i.e. conditions that
can be treated with behavioral modification are now moving along the continuum
toward 'medical necessity'. The latest example of medicalisation of a problem is
turning female sexual dysfunction into a disease and looking for Sildenafil citrate-
like alternatives to treat it. [15]
On the other hand there is a school of thought that supports lifestyle drugs in the
name of progress which is helping to delineate the exact definition of optimal
health. They contend that conditions such as obesity and smoking which are
currently outside the scope of treatment, will, in the future be treated with lifestyle
drugs. Clearly there is some ambiguity about this controversial topic. [5][6][7]
The Indian Perspective
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11. Lifestyle Drugs
The concept of increasing longevity with the help of drugs is not new. Our earliest
records reveal that, in an attempt to live forever and to enjoy the worldly pleasures
of life, deities used to drink Amrit or 'Nectar of Immortality'. This shows that even
in the absence of 'lifestyle drugs', these extraordinary mythological concepts were
born in the past.
The healthcare scenario in India has to face many challenges as we are lacking a
system like the National Health Scheme (NHS) of the United Kingdom or its
equivalent. While 14% and 4% of health care payments in India are borne by
government and insurance sectors respectively, 80% of the Indian population is
spending out-of-pocket money on the health sector. This could increase poverty by
2%.Whether the government and insurance companies should pay for lifestyle
drugs, or the individual, steering the way to poverty, is still debatable.
The use of lifestyle drugs is quite common amongst the affluent class, but of late
the great Indian middle class comprising of around 350 million people is
increasingly adopting the use of lifestyle drugs; opening up a huge market for
lifestyle drugs which has been largely untapped so far.
India is inhabited by around 600 million people below the age of 30 years. They are
the building blocks of India's future. With rampant direct to consumer advertising
(DTCA), young people are continually exposed to advertisements with claims of
products that will improve physical, mental and sexual performances. Lifestyle
drugs can have potentially devastating consequences on these vibrant and ambitious
people. The online supply of free samples of drugs such as anabolic steroids,
memory enhancers, emergency contraceptive pills and sildenafil is a matter of
serious psycho-sociological concern.
Advertising of products with limited efficacy, such as hair restoring agents, can
tempt impressionable minds and erode self esteem. The possibility of addiction
liability of such drugs and the long term negative affect on the overall health of the
nation cannot be denied.
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12. Lifestyle Drugs
These pills are widely available over the counter in India and are advertised
extensively. The 'Drugs and Magic Remedies Act' of 1954, India (amended in
1992) controls advertisements which are false or misleading and objectionable. In
these advertisements the law is clearly violated but no protest from anywhere has
been seen to date. Of greater concern is the uncertainty of the efficacy and adverse
effect profile of these pills, which opens a whole 'Pandora's Box'.
Many charlatans falsely claim to treat conditions like sexual dysfunction and
epilepsy with ayurvedic tablets, which in reality, may contain allopathic drugs. This
became evident with an article published by Gogtay et al, when they noticed that
ayurvedic tablets-which could successfully control patients' generalised tonicclonic
(GTC) epilepsy-when tested, were found to contain the combination of phenytoin
and phenobarbitone.
Two months after the launch, on December 26, 2005, Pfizer's Viagra exceeded its
targets by capturing 1.8% of the market, estimated to be worth USD $ 17 million
(approx.). 'We are excited with the response we have received for Viagra in India,'
said the Senior Director of Pfizer Pharmaceuticals Limited. Whether this
overwhelming response to Viagra is due to marketing initiatives in the urban
centers or have the multinationals managed to spread their reach to the small
villages of rural India remains to be seen"
The government and the editorial boards of national newspapers must recognize
this problem and ensure strict enforcement of the regulations for the overall interest
of society. The Indian government's initiative to ban television advertisements of
alcohol, tobacco and infant milk substitutes is commendable and a step forward but
a stronger political commitment will be required for the desired outcome. [5][6][7][8]
A case as an instance:
It’s a myth that taller people do better at sports, and height also plays an important
role in decisions related to employment, politics and choice of marital partners and
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13. Lifestyle Drugs
vice versa. Many companies are thus producing height increase pills worldwide. It
is publicized that height increase pills are essential for shorter persons! For the
same reasons height increasing pills are widely available in India as OTC products
and are widely advertised through advertisements in newspapers and TV channels.
These height increase pills or herbal products are assumed to be free from adverse
effects! Tall claims are made that these medicines increase height up to 4-5 inches
even after your 30th birthday? Such a common availability of dubious drugs lead to
many issues; whether these pills are really worth anything? For example, who
grows after puberty or 25 years of age? As per the laws of the Drugs and Magic
Remedies (Objectionable Advertisements) Act in India, no person can claim to
increase height using any medicine; it is punishable under the law. The efficacy of
these height increase pills is not known. Probably there might be some loopholes
which are being exploited. Indian lawmakers should consider these ineffective
“herbal” medicines and start protecting consumers’ interests, as consumers are
spending their valuable cash on these nonsense? .[5][6][7][8]
Implications:
Implications associated with labeling of indications and products sales of these
lifestyle drugs may be varied. Drugs can, over time, switch from ‘lifestyle’ to
‘mainstream’ use. For example, atropine was first used as a beauty aid based on its
ability to dilate the pupil. Cocaine was first described as a lifestyle drug in use by
the Indians in South America. It ’satisfies the hungry, gives new strength to the
weary and exhausted and makes the unhappy forget their sorrows’, so said
Garcilaso de la Vega in 1609. Subsequently assimilated into European medicine as
a local anaesthetic, it is now largely returned to lifestyle drug status and,
regrettably, is the basis of an illegal multimillion dollar international drugs
industry. Cannabis is another good example of a drug that has been considered (in
the west at least) as a purely recreational drug but which is now (as
tetrahydrocannabinol) in clinical trial for the relief of chronic pain and nausea.
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14. Lifestyle Drugs
Some of the other implications include, social and cultural, resulting from the use
of lifestyle drugs, which is changing the very social fabric of our culture. This
increase in their use raises the question of whether we are trying to homogenize the
society, consciously or subconsciously! Healthcare systems face an altogether
difficult challenge indeed! Should consumers not be protected from ineffective
medicines that cost money and distract them from real health problems? Most of
the lifestyle drugs are herbal products that are allowed for over-the-counter sales
without a prescription. Medical harm resulting from the indiscriminate use of
lifestyle drugs includes adverse effects, abuse potentialities and safety concerns. No
side-effects claim can also mean that these drugs might have no efficacy either?
These easily available ‘lifestyle drugs’ is revolutionizing the traditional relationship
of doctor and patient, and raise issues about the rights to, and limits of, self-
diagnosis, self-prescription, internet prescription, direct to consumer advertisement
(DTCA) and self-medication. Finally the implications to the regulatory system
include, evidence-based decision making, efficiency, ethics, laws and standards of
regulatory policy to name a few. Another major concern area for the regulatory is
the online “free samples” of ‘lifestyles drugs’ such as food supplements, vitamins
and drugs like sildanefil, which are directly supplied to consumers. [5][6][7][8]
Challenges ahead
In a country like India where issues such as high maternal and infant mortality rate,
malnourishment, rural health problems and communicable diseases need to be
addressed, we cannot afford to deride the country's growth by misplaced priorities.
India needs to be very clear about its drug policies and the pharmaceutical industry
should play a significant contribution in building the country's health infrastructure.
It should focus more on 'life-saving' and 'essential' medicines, rather than 'lifestyle
drugs'. In a free market system, profits may be an indicator of what we want as
individuals, but they may not be the best indication of what drugs we need as a
society. Indian drug regulators should not be influenced by approvals in the west,
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15. Lifestyle Drugs
where an image-conscious aging society is willing to pay high prices for such
products. To do so could have a devastating effect on India's growth. Are we ready
for it? [5][6][7][8]
An Issue of Debate
The past few years have witnessed the release of a number of highly publicized
"lifestyle" drugs, such as sildenafil for male erectile dysfunction and orlistat for
obesity. Other products have had their indications extended to include situations
that usually come under the rubric "lifestyle"; for example, finasteride may now be
prescribed for male pattern baldness. The appearance of these new products and the
new uses for established drugs have raised a series of issues for physicians, for the
health care system in terms of priorities for drug expenditures and for society in
general.
Many of the so-called lifestyle drugs are proving highly popular. For instance,
within the first 3 months after orlistat was launched in Canada, 78 200 prescriptions
for the drug had been written.As these drugs become more widely used, the scope
of the debate and its importance will also broaden: What exactly are lifestyle
drugs? What are the issues associated with prescribing them? Do they distract
attention from other forms of therapy? Are conducting research into lifestyle drugs
and including them in drug payment plans the most appropriate ways to be using
health care resources?
The first challenge lies in defining lifestyle drugs. Drug companies and patient
groups often object to this term on the grounds that it trivializes the conditions that
the drugs are designed to treat, although that is not usually the intent. To try to
clarify the meaning of the term, a recent report offered 2 definitions. First, the term
could be applied to any drug intended or used for a problem that falls into the
border zone between the medical and social definitions of health. From this point of
view, male pattern baldness could be dismissed as a problem outside the medical
sphere, and in this context finasteride would be considered a lifestyle drug. This
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16. Lifestyle Drugs
definition acknowledges that some men who are losing their hair may have a
concern but suggests that baldness should not be treated within the health care
system. According to the second definition,lifestyle drugs are those intended to
treat diseases that result from a person's lifestyle choices. For example, although
smoking has serious medical consequences, they are due to the lifestyle that the
smoker has chosen. Therefore, a drug such as bupropion for smoking cessation
would be classed as a lifestyle drug. According to this definition, such therapy
would be offered outside of the medical system, whereas treatment for the
consequences of smoking, such as respiratory diseases, would take place within the
medical system. Both of these perspectives raise questions that warrant further
examination.
The first definition forces us to consider how and where we draw the line between
the social and the medical dimensions of health. Last year, SmithKline Beecham
received approval to market paroxetine for the treatment of social phobia as defined
by the Diagnostic and Statistical Manual of Mental Disorders.This disorder can be
distressing and disabling for those who suffer from it, limiting their ability to
interact with the outside world. But what we now risk, given the cultural
acceptance of (and perhaps preference for) an extrovert norm, is an extension of the
definition of social phobia to include shyness: a normal character trait of some
people who have no psychiatric disease is turned into an abnormality that requires
treatment. In the United States a coalition of nonprofit groups, the Anxiety
Disorders Association of America (ADAA), which is partially funded by
SmithKline Beecham, has built a public awareness campaign for social phobia
around the slogan "Imagine Being Allergic to People." This campaign is being
orchestrated by SmithKline Beecham's public relations firm, some of the work
being done pro bono and the rest being paid for directly by the drug company. In
July 1999, as part of this public awareness campaign, the ADAA held a press
conference to publicize the findings of a study that purported to quantify the high
economic cost of anxiety disorders. The study in question was underwritten by a
group of drug manufacturers.
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17. Lifestyle Drugs
Expanding the definition of what constitutes a treatable medical problem will have
a variety of consequences. For example, there may be a change in how general
practitioners balance the risks and benefits of pharmacotherapy. No drug is without
side effects, but the acceptability of those side effects usually increases with the
severity of the illness being treated. What degree of side effects would be
acceptable in treating someone who feels too shy? Compared with the other
selective serotonin reuptake inhibitors, paroxetine causes significantly more sexual
dysfunction. Therefore, as the number of people undergoing pharmacologic
treatment for shyness rises, so too will the number with sexual problems. If we
redefine treatable medical problems to include normal variants in the population,
physicians and patients may become more willing to accept side effects (which
might themselves need treatment) that would otherwise be avoided.
On a more fundamental level we must ask whether doctors should even be trying to
define and prescribe "normality." In the past some physicians were quite willing to
take on this task. Medical journals from the 1960s and 1970s were filled with ads
for psychotropic medications showing young university women away from home
for the first time or housewives surrounded by giant vacuum cleaners. These ads
implied that the women were suffering from isolation and other forms of mental
distress that could be managed pharmacologically. Male doctors responded to the
ads and to prevailing societal views by prescribing mood-altering drugs for women,
justifying their decisions with comments such as "It's constitutional. The female's
nervous system is more sensitive... That's the way the Lord made them" and
"females have more time to indulge in neurosis than men." Perhaps prescribing
paroxetine for shyness is the new millennium's equivalent of prescribing diazepam
for the overwhelmed college student a quarter century ago.
Treating problems that are due to lifestyle choices also has consequences. It
appears that, when drug therapy is available, physicians are less willing to consider
nondrug treatments, even when there is no evidence that pharmacotherapy is
superior. One example is orlistat for the treatment of obesity. Although people
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18. Lifestyle Drugs
taking orlistat lose marginally more weight in the short term than those controlling
their dietary intake without pharmaceutical aids (from a starting weight of 100 kg,
about 8.9 kg with pharmaceutical aids v. 5.6 kg with placebo over 1 year), there is
no evidence that orlistat is any more effective than diet alone in reducing the
morbidity and mortality due to obesity. This abandonment of other types of therapy
may be due in part to pressure from the pharmaceutical industry in the form of
advertising directly to consumers. To continue with the example of orlistat, in 1999
Hoffman – La Roche spent over US$75 million promoting this drug to consumers
in the United States. Such levels of advertising are sure to affect patients' requests
to their physicians and hence physicians' prescribing practices. Treating conditions
such as obesity with drugs may also have negative psychological implications.
Some people have speculated that the use of medical interventions may be seen by
patients themselves and by others as a form of "cheating," an indication that the
person receiving treatment lacks the willpower to change her or his lifestyle.
Although it might be expected that such negative psychological connotations would
discourage the use of lifestyle drugs, the perceived lack of alternatives would
probably override any misgivings.
The increasing use of lifestyle drugs raises the question of whether we are trying to
homogenize society, consciously or subconsciously. For certain lifestyle problems,
medical treatment amounts to an attempt to make people more similar to one
another, to eradicate their differences. Remember, for example, the debate that
arose a few years ago when Prozac was being prescribed to make people feel "more
normal."
The question of whether it is acceptable to homogenize society arose in the late
1980s and early 1990s in considering which children should be treated with growth
hormone. When only pituitary-derived growth hormone was available and supplies
were therefore limited, treatment was by necessity restricted to children with
documented deficiency of growth hormone. However, once synthetic growth
hormone became available in the mid-1980s, consideration was given to
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19. Lifestyle Drugs
prescribing the hormone for normal children of short stature. This situation could
only have come about because there is a height bias in our society. Taller people do
better at sports, and height also plays an important role in decisions related to
employment, politics and choice of marital partners. Short children may be subject
to teasing and may have a negative self-image. Despite the difficulties posed by
discrimination on the basis of height, the question remains whether doctors have an
obligation to solve the problem through medication.
At a more general level, we must ask whether physicians should be trying to deal
with social injustices by prescribing drugs to render certain of their patients more
similar to the norm (with the net effect of homogenizing the human population) or
whether it is up to society to eliminate injustice while retaining the population's
heterogeneity. I will use an extreme example to illustrate. Suppose there was a pill
that could make everybody's skin colour exactly the same. If everyone took the
medication, discrimination on the basis of skin colour would certainly be
eliminated. Yet having the "wrong" skin colour can hardly be considered a
"lifestyle problem," and eliminating discrimination by erasing our differences can
be expected to have profound effects on other aspects of human society.
In terms of economic considerations, there is a real worry that research into
lifestyle problems is being driven in a single direction — drug therapy — because
that is where the profits lie. At present, the pharmaceutical industry is the single
largest direct funder of medical research in both Canada and the United States. For
example, in Canada the industry contributed $880 million to the total of $2.1 billion
in 1998. Through its financial support, the pharmaceutical industry is, to a large
extent, determining research priorities, and because of the nature of the industry,
research into drug therapy is the type most likely to be funded. To return to the
example of social phobia, some research has shown that cognitive behavioural
therapy for this condition is just as effective as pharmacotherapy in the short term
and probably more effective in the long term. Yet it is unlikely that research funds
will be made available to study behavioural therapy. And if researchers know that
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20. Lifestyle Drugs
there is no money to answer certain questions, they may not even bother to ask
them. Furthermore, drug companies are heavily promoting products for use in
lifestyle problems. In 1999 alone, almost US$325 million was spent advertising just
4 lifestyle drugs (Propecia [finasteride], Viagra [sildenafil], Xenical [orlistat] and
Zyban [bupropion]) to US consumers. If research is mainly confined to drug
treatment, and drugs are the only form of therapy being publicized through ads,
seminars and other publicity, the chances are slim that alternative modalities such
as behavioural therapy will be as widely used as they should be.
The issue of which topics receive research funding is only part of the broader
question of how society makes decisions about health care priorities. Drug
companies have identified lifestyle drugs as a "growth market." The problems these
drugs are designed to treat are easily self- diagnosed — we can all see if we are
bald or fat — and as the baby boomer generation ages, the number of people
looking for these drugs will continue to increase. Drug companies, driven by profit,
go where the money is, and the money is not to be found in drugs for diseases of
the poor, in either developed or developing countries. For example, during the 25
years before 1998, no new drug treatments for tuberculosis were introduced in the
United States. A total of 1223 new chemical entities were commercialized between
1975 and 1997, but only 13 were specifically for tropical diseases and only 4 of
these (0.3% of the total) could be considered to have resulted directly from research
and development activity of the pharmaceutical industry. Until the World Health
Organization initiated its Roll Back Malaria campaign, not 1 of the 24 largest drug
companies maintained an in-house research program for this disease, and only 2
had expressed even minimal interest in primary research on malaria.
Because of the potential size of the market for lifestyle drugs, paying for them in
unlimited quantities will be very expensive. For example, in June to September
1999, in the first 3 months after orlistat was launched, $7.2 million worth of the
drug was sold in Canada. The resources available for health care are limited, so
decisions must be made as to where those resources should best be spent. How are
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21. Lifestyle Drugs
those decisions going to be made and by whom? If we as a society decide that
lifestyle drugs should be covered through the health care system, then other
treatments may not get funded or at least will not get as much funding as they
otherwise would have. Decisions will also be needed about who will get the drugs
(since almost everyone will want one or more of them) and whether they will be
available in unlimited supply.
The need for decisions on how to spend research dollars and on whether lifestyle
drugs, especially the expensive ones, should be funded through the health care
system may create the impetus we need to start a serious debate on these issues. I
would argue that these questions should not be answered only by the
pharmaceutical companies, who are looking for profits, or by the medical
profession, which is focused on finding solutions to the problems of individual
patients, or by the baby boomers, who are looking for their lost youth. We need to
find mechanisms whereby all elements of society — government, industry, health
care professionals, patients and consumers — can participate in the decisions.
In the near future an increasing number of lifestyle drugs can be expected to reach
the marketplace. The debate over how to use and pay for them is going to intensify.
A coherent long-term strategy to manage lifestyle drugs entails coming to terms
with the issues raised here. [4][6][7][8]
Mood, Behaviour, Cognition
The controversy about lifestyle drugs was stimulated mainly by the use of
fluoxetine (Prozac) and sildenafil (Viagra). In the case of fluoxetine, the issue was
its use in people who did not fulfill the criteria for a psychiatric disorder. However,
although paroxetine (Paxil), another selective serotonin reuptake inhibitor (SSRI),
is not usually considered a lifestyle drug when it is used to treat depression, the
popular press has certainly written about it as a lifestyle drug when it is used to
21

22. Lifestyle Drugs
treat social anxiety disorder. Obviously, social anxiety disorder is not considered to
be on par with disorders such as depression or schizophrenia. This is despite the
fact that social anxiety disorder is clearly defined, is closely related to other anxiety
disorders and can cause considerable disability.
Lexchin addressed some of the controversies surrounding lifestyle drugs and
discussed 2 definitions of lifestyle drugs offered in a recent report. The first is any
drug intended or used for a condition that falls into the border zone between
medical and social definitions of health. The second is any drug intended to treat a
disease that results from a person's lifestyle choices. The second definition certainly
does not fit with the way the term is typically used — baldness and social anxiety
disorder are not the result of lifestyle choices. The first definition is better, but not
entirely satisfactory. Attempts to treat baldness and enhance mental agility are not
matters of health, but preference.
Two factors seem to be important when the term “lifestyle drug” is used. The
person taking the drug perceives that it will increase her or his happiness, and the
person using the term, or a significant portion of society, does not consider the
target symptom or symptoms to be a “real” disease or disorder. This raises the issue
of what is and is not considered a disease. In a survey reported in the British
Medical Journal in 1979, various groups were asked whether they considered
certain conditions to be diseases. The percentages of medical academics who did
not consider schizophrenia, alcoholism and depression to be diseases were about
20%, 40% and 50%, respectively. However, attitudes have probably changed over
the past 2 decades, particularly in relation to depression. More recently, the British
Medical Journal ran a vote on bmj.com to identify the “top 10 non-diseases.” The
top 6 were aging, work, boredom, bags under the eyes, ignorance and baldness.
Unhappiness came in at number 14 and loneliness at 20. Although most would
agree that unhappiness and loneliness are not diseases, they are feelings that most
people would prefer not to have and can predispose to diseases. But to what extent
should unhappiness, as opposed to clinical depression, be something that is treated
with a drug?
22

23. Lifestyle Drugs
Attempts to increase happiness through pharmacology go back to our earliest
history with the use of alcohol, the cannabinoids and other naturally occurring
compounds. The extensive use of drugs of abuse is, in part, a short-sighted attempt
to increase happiness. The future will see increasing demand for drugs that increase
happiness and do not have the adverse effects of the older drugs. The debate about
the use of fluoxetine in people without a DSM disorder will pale in comparison
with the debates that will ensue with the discovery of drugs that raise mood in
mentally healthy people, with limited or no side effects. Will such drugs really be
discovered? The idea that a single compound could raise mood; decrease blood
pressure, cortisol and subjective responses to acute psychological stress; and
increase the frequency of sexual intercourse in healthy young adults (particularly in
women) without any important side effects is one that invites skepticism. However,
if results in recent issues of Psychopharmacology and Biological Psychiatry are to
be believed, such a compound already exists. It is high-dose (3 g/d) ascorbic acid.
There is also accumulating evidence that the omega-3 fatty acids in fish oils have
beneficial effects on mood and behaviour that may not be limited to the treatment
of psychopathology. If ascorbic acid and fish oils can have these effects, surely
other more effective but still nontoxic compounds will be discovered.
The debate about lifestyle drugs that influence the brain is caused in part by the
continuum in some areas between normal and abnormal functioning. This is an
issue that psychiatry has grappled with for a long time — for example, in debates
about the boundaries of an adjustment disorder and the extent to which
bereavement precludes the diagnosis of depression. Many people now accept that
those suffering the extremes of depressed mood have a disorder for which treatment
might be appropriate. However, the characterization of paroxetine as a lifestyle
drug when it is used to treat social anxiety disorder suggests that there is less
acceptance of the idea that extreme shyness is a disorder. Once there is acceptance
of the need for treatment of conditions at the extremes of the distribution curve,
there is often debate about those that deviate less from the norm. As society accepts
increasingly that depression is a disorder for which pharmacological treatment is
often appropriate, the debate moves on to the degree of unhappiness for which a
23

24. Lifestyle Drugs
pharmacological intervention is appropriate. The next step is to consider if or when
it is appropriate to use chemicals to change a neutral mood to happiness or increase
the degree of happiness. A similar debate has already started in the area of memory
and cognition. A recent review in Nature Reviews Neuroscience entitled “Smart
Drugs: Do they work? Are they ethical? Will they be legal?” lists 9 classes of drugs
that are currently under investigation as cognitive enhancers and discusses some of
the issues related to the use of such drugs by people whose cognitive abilities are in
the normal range.
The development of drugs that healthy people may take to enhance their mental
state creates considerable problems for regulatory agencies. Even for one of the
original lifestyle drugs, alcohol, there is little agreement on how it should be
regulated. Some countries use total prohibition, and others place limits on where it
can be sold, the age of those who can buy it and when and where it can be drunk or
increase taxation to decrease the amount sold. In some situations, regulations owe
more to tradition than to rational consideration of risk and benefit. Current
governmental regulations permit a 9-year-old who is about to take an exam to buy
and ingest a mixture of 2 compounds, both of which may enhance exam
performance. The mixture comes in the form of a cola, and the 2 compounds are
caffeine and glucose. Caffeine can enhance arousal and attention, but can also
enhance anxiety and, in excess, can cause insomnia and a variety of other
symptoms. Caffeine dependence can occur, although withdrawal symptoms are
relatively mild. If caffeine was not used traditionally and it was proposed as a
cognitive enhancer today, the chances of it being approved for use in children
would be small. The memory-enhancing effect of glucose in humans is now well
established. Glucose intake can decrease the intake of micronutrients and is
associated with obesity and diabetes. It also would not likely be approved as a
cognitive enhancer in children. Caffeine, like alcohol, certainly seems to fit some of
the definitions of a lifestyle drug, even if it is not usually considered one. People
have a strong attachment to these drugs; attempts are often made to overcome the
regulations concerning alcohol, and any attempt to regulate the use of caffeine
would be unthinkable. When drugs are developed that provide the benefits of these
24

25. Lifestyle Drugs
compounds and none of their adverse effects, people will acquire them by legal or
illegal means. There needs to be a debate on an appropriate regulatory framework
for the use of mood and cognitive enhancers by healthy people.
As far as regulatory policy is concerned, there are likely to be 4 different types of
lifestyle drugs.
· Drugs approved for specific indications (e.g., baldness or social anxiety
disorder). They are classified as lifestyle drugs because of a feeling in society, that
may or may not be justified, that pharmacotherapy for these types of problems is in
some way frivolous.
· Drugs, approved for specific indications, that are used for other purposes. At
the moment, the main examples of this are the SSRIs, which are sometimes used in
people who do not have a DSM disorder. However, in the future, this class will
probably include other drugs approved for the treatment of mood or cognitive
disorders but used by those anywhere in the normal range to enhance their mood or
cognitive ability. They will be used in this way because some physicians will be
willing to write prescriptions for these drugs, even for people who do not have a
disorder. They will also be taken by people who obtain them through illegal means.
· Drugs that have been used traditionally and are therefore not usually thought of
as lifestyle drugs but are taken for the purpose of altering mood or social behaviour
in people who may or may not be mentally healthy. This includes illegal drugs of
abuse, as well as those that are legally sanctioned, such as alcohol and caffeine.
· Natural products. Potential examples of this category include ascorbic acid and
fish oils, but also include a wide range of other products, such as herbal extracts.
These are minimally regulated by governments unless they are clearly toxic or
specific claims are made by the manufacturer about their actions. Use of this type
of product depends on information, sometimes correct, about their actions that is
distributed by anyone other than the manufacturer. Overall, the regulations are
based more on factors such as traditional patterns of use and whether the product is
synthesized by living organisms or by drug companies than on consideration of the
implications of the use of lifestyle drugs for the individual and society.
25

26. Lifestyle Drugs
Before a rational and consistent policy for the regulation of lifestyle drugs is
developed, there has to be much more consideration of the desirability of enhancing
mental states to please the individual. Currently, the main focus is on the adverse
effects of drugs of abuse, because those are the main drugs taken to alter mental
state in those without psychopathology. However, with the development of
compounds that enhance normal mood or cognition, but have limited or no adverse
effects, the potential positive aspects have to be considered. One issue that has been
raised is whether the increasing use of lifestyle drugs is an attempt to homogenize
society. Should those who are less smart or less happy accept the mental state
allocated to them by their genes and environment, or should they be allowed to take
compounds that will move them toward the upper half of the distribution curve? Is
popping a pill for mild dysphoria an abrogation of personal responsibility? Is taking
a pill to move mood from mildly happy to euphoric acceptable in any
circumstances, if the pill has no direct adverse effects? Should parents be allowed
to help their children gain a university education in part through pharmacology if
the only adverse effect to the parents and child is financial? Or should society be
paying for all children to take cognitive enhancers if ones without side effects or
adverse effects are ever developed?
Society has not to any great extent attempted to come to grips with issues such as
these. Meanwhile, there are increasing signs that more effective and less toxic
lifestyle drugs will be developed long before there is any broad agreement that will
enable rational and consistent regulation of them. This is a sharp contrast with some
other areas of research, such as genetics and reproductive technologies, where the
ethical and societal implications of research developments, as well as proposals for
keeping regulations responsive to new discoveries, have been widely discussed.[4][7]
[9]
The 2010 Lifestyle Medication List put up by BlueChoice HealthPlan of South
Carolina,Inc. BlueChoice HealthPlan is an independent licensee of the Blue Cross
and Blue Shield Association
.
26

27. Lifestyle Drugs
Category Active Constituent Market Product
Anti Obesity Agents Benzphetamine
diethylpropion (various)
Didrex
Phendimetrazine (various) Brontil PDM
Brontil Slow Release
Phentermine (various) Adipex-P
Sibutramine Meredia
Contraceptive Agents
or Products
Injectables Medroxyprogesterone
Acetate
Depo-Provera
Oral Contraceptives Progestin only
Nor-QD
Ortho Micronor
Estrogen/Progestin
Combinations
Apri Nordette
Brevicon Norinyl
Ogestrel
Desogen Ortho-Cept
Ortho-Cyclen
Ortho-Novum
Levora Ortho-TriCyclen
Lo/Oral Ortho-TriCyclen Lo
Low-Ogestrel Ovcon
Mircette Tri-Norinyl
Modicon Trivora
Necon Zovia
Cosmetic
Eflornithine Vaniqa
Tazarotene Avage
Tretinoin,emollient Renova
Erectile Dysfunction
Agent
Alprostadil Caverject
Edex
Muse
Sildenafil Viagra
Tadalafil Cialis
Vardenafil Levitra
Male Pattern Finasteride Propecia
27

28. Lifestyle Drugs
Baldness
Skin Depigmenting
Agent
Hydroquinone Eldoquin Forte
Eldopaque Forte
Lustra
Melpaque HP
Melquin-3
Melquin HP
Hydroquinone/Sunscreen Alphaquin HP
Nuqin HP
Solaquin Forte
Smoking Cessation
Agents
Nicotine Nasal/Oral
Inhalation
Zyban (Brand Only)
Nicotrol NS
Nicotrol
Table - II
Anti-Obesity Agents Cosmetic
In depth Analysis of Lifestyle Drug
Let us now focus on Minoxidil,a drug used in treatment of alopecia(Hair loss),
Minoxidil is an antihypertensive vasodilator medication which also slows or stops
hair loss and promotes hair regrowth. Now off-patent, it is available over-the-
counter for the treatment of androgenic alopecia. Minoxidil must be used
indefinitely for continued support of existing hair follicles and the maintenance of
any experienced hair regrowth. It is marketed under many trade names, including
Rogaine/Regaine, Vanarex, Mintop and Loniten (oral), and Avacor Physician's
Formulation (Avacor also produce a number of hair loss treatments that do not
include minoxidil). [10][11]
28

29. Lifestyle Drugs
Fig- a
IUPAC name: 6-piperidin-1-ylpyrimidine-2,4-diamine 3-oxide
Trade names: Rogaine
Legal status: P(UK) for topical use, otherwise POM. Cannot be prescribed on the
NHS.
Routes: Oral / topical
Pharmacokinetic data-
Metabolism: Primarily hepatic
Half-life:4.2 hours
Excretion: renal
Chemical data-
Formula: C9H15N5O
Mol. Mass: 209.251 g/m
History
Minoxidil was first used exclusively as an oral drug (with the trade name 'Loniten')
to treat high blood pressure. However, it was discovered to have an interesting side
effect: Minoxidil may cause increased growth or darkening of fine body hairs, or in
29

30. Lifestyle Drugs
some cases, significant hair growth. When the medication is discontinued, the hair
loss will return to normal rate within 30 to 60 days. Upjohn Corporation produced a
topical solution that contained 2% minoxidil to be used to treat baldness and hair
loss, under the brand name Rogaine in the United States and Canada, and Regaine
in Europe and the Asia-Pacific. Treatments usually include a 5% concentration
solution that is designed for men, whereas the 2% concentration solutions are
designed for women. The patent on minoxidil expired February 11, 1996. While the
drug is available in the United Kingdom, it cannot be prescribed on the NHS, so
patients must either buy it over-the-counter or have a private prescription for it.
In 2007, a new foam-based formulation of 5% minoxidil, which is claimed to be as
effective as the liquid-based formulation, was introduced by Upjohn and marketed
under the brand name Rogaine/Regaine Foam.
In 2011, it was announced that a generic version of minoxidil foam would be
available beginning in March 2012. [10][11]
Mechanism
The mechanism by which minoxidil promotes hair growth is not fully understood.
Minoxidil contains the nitric oxide chemical moiety and may act as a nitric oxide
agonist. Similarly, minoxidil is a potassium channel opener, causing
hyperpolarization of cell membranes. Minoxidil is less effective when there is a
large area of hair loss. In addition, its effectiveness has largely been demonstrated
in younger men who have experienced hair loss for less than 5 years. Minoxidil use
is indicated for central (vertex) hair loss only. Minoxidil is also a vasodilator.
Hypothetically, by widening blood vessels and opening potassium channels, it
allows more oxygen, blood, and nutrients to the follicle. This may cause follicles in
30

31. Lifestyle Drugs
the telogen phase to shed, which are then replaced by thicker hairs in a new anagen
phase. [10][11]
Side effects
Common side effects of minoxidil include burning or irritation of the eye, itching,
redness or irritation at the treated area, as well as unwanted hair growth elsewhere
on the body. Users should stop treatment and seek medical attention right away if
they experience any of the following serious side effects: Severe allergic reactions
(rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the
mouth, face, lips, or tongue); chest pain; dizziness; fainting; fast heartbeat; sudden,
unexplained weight gain; swollen hands or feet.
Alcohol present in topical preparations may dry the scalp, resulting in dandruff.
Side effects of oral minoxidil may include swelling of the face and extremities,
rapid and irregular heartbeat, lightheadedness, cardiac lesions, and focal necrosis of
the papillary muscle and subendocardial areas of the left ventricle.There have been
cases of allergic reactions to minoxidil or the non-active ingredient propylene
glycol, which is found in some topical minoxidil formulations. Pseudoacromegaly
is an extremely rare side effect reported with large doses of oral
minoxidil.Paradoxically, hair loss is a common side effect of minoxidil treatment.
Manufacturers note that minoxidil-induced hair loss is a common side effect and
describe the process as "shedding". Although this phenomenon demonstrates that
minoxidil is indeed affecting hair follicles, manufacturers offer no guarantee that
the new hair loss will be replaced with hair growth. The speculated reason for this
shedding is the encouragement of hairs already in the telogen phase to shed early,
before often beginning a fresh, healthier anagen phase.Minoxidil is highly toxic to
cats and may cause death with inadvertent skin contact. [10][11]
Application
31

32. Lifestyle Drugs
Minoxidil needs to be applied once or the recommended twice daily, and may be
used indefinitely for continued support of existing hair follicles and the
maintenance of any experienced hair regrowth. To achieve maximum effect, the
solution should be in contact with the scalp for at least 4 hours before allowing hair
to get wet.Minoxidil stimulates hair follicles and growth, but does not reduce DHT
or the enzyme responsible for its accumulation around the hair follicle, 5-alpha
reductase, which is the primary mediator of male pattern baldness in genetically
susceptible individuals.Therefore, when treatment is stopped, the DHT has its
expected effect of shrinking and ultimately destroying the genetically predisposed
hair follicles.
Minoxidil solutions are sold under many brand names. Many high priced as well as
generic brands of minoxidil regrowth solutions exist and do not differ in their
active ingredient or concentration. Minoxidil products involve contact with hair
strands which may cause problems with hair styling as minoxidil must be in an
alcohol-based solution. If the solution does not pose any issues, hair styling
products may be applied after it has dried. [10][11]
Another drug that we will now focus is Orlistat, (marketed as a prescription under
the trade name Xenical by Roche in most countries, or over-the-counter as Alli by
GlaxoSmithKline in the United Kingdom and the United States), also known as
tetrahydrolipstatin, is a drug designed to treat obesity. Its primary function is
preventing the absorption of fats from the human diet, thereby reducing caloric
intake. It is intended for use in conjunction with a physician-supervised reduced-
calorie diet. Orlistat is the saturated derivative of lipstatin, a potent natural inhibitor
of pancreatic lipases isolated from the bacterium Streptomyces toxytricini.
However, due to simplicity and stability, orlistat rather than lipstatin was developed
into an anti-obesity drug.
The effectiveness of orlistat in promoting weight loss is definite, though modest.
Pooled data from clinical trials suggest that people given orlistat in addition to
lifestyle modifications, such as diet and exercise, lose about 2–3 kilograms (4.4–6.6
32

33. Lifestyle Drugs
lb) more than those not taking the drug over the course of a year. Orlistat also
modestly reduces blood pressure, and appears to prevent the onset of type 2
diabetes, whether due to weight loss itself or to other effects; in a large randomized
controlled trial, orlistat was found to reduce the incidence of diabetes by nearly
40% in obese people.
Orlistat is notorious for its gastrointestinal side effects (sometimes referred to as
treatment effects), which can include steatorrhea (oily, loose stools). These
decrease with time, however, and are the most frequently reported adverse effects
of the drug.
In the United States, the European Union, and Australia, orlistat is
available for sale without a prescription. Over-the-counter approval was
controversial in the United States, with consumer advocacy group Public Citizen
repeatedly opposing it on safety and efficacy grounds. [12][13][14]
Fig- b: Structure of Orlistat
33

34. Lifestyle Drugs
Fig- c: Packaging of Orlistat (Xenical) 120 mg capsules, as sold in Canada.
IUPAC name: (S)-((S)-1-((2S,3S)-3-hexyl-4-oxooxetan-2-yl)tridecan-2-yl) 2-
formamido-4-methylpentanoate
Clinical data
Trade names: Xenical, Alli
Legal status: Pharmacist Only (S3) (AU) P (UK) OTC (US)
Routes: Oral
Pharmacokinetic data
Bioavailability: Negligible
Protein binding: >99%
Metabolism: In the GI tract
34

35. Lifestyle Drugs
Half-life: 1 to 2 hours
Excretion: Fecal
Chemical data
Formula: C29H53NO5
Mol. Mass: 495.735 g/mol
Medical uses
Orlistat is used for the treatment of obesity. The amount of weight loss achieved
with orlistat varies. In one-year clinical trials, between 35.5% and 54.8% of
subjects achieved a 5% or greater decrease in body mass, although not all of this
mass was necessarily fat. Between 16.4% and 24.8% achieved at least a 10%
decrease in body mass. After orlistat was stopped, a significant number of subjects
regained weight—up to 35% of the weight they had lost.
The incidence of type 2 diabetes in an obese population over four years is
decreased with orlistat (6.2%) compared to placebo (9.0%). Long-term use of
orlistat also leads to a modest reduction in blood pressure (mean reductions of 2.5
and 1.9 mmHg in systolic and diastolic blood pressure respectively). [12][13][14]
Contraindications
Orlistat is contraindicated in:
• Malabsorption
• Hypersensitivity to orlistat
• Reduced gallbladder function (e.g. after cholecystectomy)
• Pregnancy and breastfeeding
• Use caution with: obstructed bile duct, impaired liver function, and pancreatic
disease
35

36. Lifestyle Drugs
Side effects
The primary side effects of the drug are gastrointestinal-related, and include
steatorrhea (oily, loose stools with excessive flatus due to unabsorbed fats reaching
the large intestine), fecal incontinence and frequent or urgent bowel movements.
GlaxoSmithKline recommends that all users be cautious of the possible side effects
until they "have a sense of any treatment effects". To minimize these effects, foods
with high fat content should be avoided; the manufacturer advises consumers to
follow a low-fat, reduced-calorie diet. Oily stools and flatulence can be controlled
by reducing the dietary fat content to somewhere in the region of 15 grams per
meal. The manual for Alli makes it clear that orlistat treatment involves aversion
therapy, encouraging the user to associate eating fat with unpleasant treatment
effects.
According to Roche, side effects are most severe when beginning therapy and may
decrease in frequency with time; this is supported by the results of the XENDOS
study, which found that only 36% of people had gastrointestinal adverse effects
during their fourth year of taking orlistat, whereas 91% of study subjects had
experienced at least one GI-related side effect during the first year of treatment. It
has also been suggested that the decrease in side effects over time may be
associated with long-term compliance with a low-fat diet.
The side effect profile of orlistat led US consumer group Prescription Access
Litigation (PAL) to award its first 2007 "Bitter Pill Award" to GlaxoSmithKline—
the 'With Allies Like This, Who Needs Enemas?' Award.
On May 26, 2010, the U.S. Food and Drug Administration (FDA) has approved a
revised label for Xenical to include new safety information about cases of severe
liver injury that have been reported rarely with the use of this medication.
36

37. Lifestyle Drugs
An analysis of over 900 orlistat users in Ontario showed that their rate of acute
kidney injury was more than triple that of non-users. The putative mechanism for
this effect is postulated to be excessive oxalate absorption from the gut and its
subsequent deposition in the kidney, with excessive oxalate absorption being a
known consequence of fat malabsorption. [12][13][14]
Long-term
Despite a higher incidence of breast cancer amongst those taking orlistat in early,
pooled clinical trial data—the analysis of which delayed FDA review of orlistat—a
two-year study published in 1999 found similar rates between orlistat and placebo
(0.54% versus 0.51%), and evidence that tumors predated treatment in 3 of the 4
participants who had them. There is evidence from an in vitro study to suggest that
the introduction of specific varied preparations containing orlistat, namely the
concurrent administration of orlistat and the monoclonal antibody trastuzumab, can
induce cell death in breast cancer cells and block their growth.
A 2006 animal study linked orlistat with aberrant crypt foci (ACF), lesions found in
the colon which are believed to be one of the earliest precursors of colon cancer. [12]
[13][14]
Precautions
Absorption of fat-soluble vitamins and other fat-soluble nutrients is inhibited by the
use of orlistat. A multivitamin tablet containing vitamins A, D, E, K, and beta-
carotene should be taken once a day, at bedtime, when using orlistat.
On June 4, 2009, the U.S. Food and Drug Administration released its quarterly list
of drugs that are under investigation for potential safety issues or new safety
information. Orlistat was included in the list as having a "Potential Signal of
Serious Risk" of liver toxicity, meaning that a potential risk of liver toxicity was
identified based on reports to the FDA Adverse Event Reporting System between
October and December 2008. Isolated cases of orlistat-associated liver problems
37

38. Lifestyle Drugs
have been reported before. On August 24, the FDA reported that it would
investigate 30 cases of liver damage reported between 1999 and October 2008 in
patients taking orlistat, including six cases of liver failure. [12][13][14]
Interactions
Orlistat may reduce plasma levels of ciclosporin (also known as "cyclosporin" or
"cyclosporine", trade names Sandimmune, Gengraf, Neoral, etc.), an
immunosuppressive drug frequently used to prevent transplant rejection; the two
drugs should therefore not be administered concomitantly. Orlistat can also impair
absorption of the antiarrhythmic amiodarone. [12][13][14]
Mechanism of action
Fig- d
Crystallographic structure of human fatty acid synthase (rainbow color, N-terminus
= blue, C-terminus = red) inhibited by orlistat (space-filling model; carbon = grey,
oxygen = red, nitrogen = blue).
Orlistat works by inhibiting gastric and pancreatic lipases, the enzymes that break
down triglycerides in the intestine. When lipase activity is blocked, triglycerides
from the diet are not hydrolyzed into absorbable free fatty acids, and are excreted
undigested instead. Only trace amounts of orlistat are absorbed systemically; the
primary effect is local lipase inhibition within the GI tract after an oral dose. The
primary route of elimination is through the feces.
38

39. Lifestyle Drugs
At the standard prescription dose of 120 mg three times daily before meals, orlistat
prevents approximately 30% of dietary fat from being absorbed, and about 25% at
the standard over-the-counter dose of 60 mg. Higher doses do not produce more
potent effects. [12][13][14]
Society and culture
Legal status
Orlistat has historically been available by prescription only, and this situation
continues in Canada. In Australia, the European Union, and the United States,
certain formulations of orlistat have been approved for sale without a prescription.
In 2009, Roche began recruiting in Russia for a clinical trial of Xenical in obese
teenagers between the ages of 12 and 14.
Australia and New Zealand
In Australia and New Zealand, orlistat is currently available over-the-counter in
120 mg size (84 capsules to the pack). Initially available only with a prescription, it
was reclassified as a "Pharmacist Only Medicine" in October 2003. In late 2006,
the Australian Consumers' Association complained that Roche was inappropriately
advertising the drug to teenagers, and Roche was forced to withdraw its ads. The
Association filed further complaints with the Therapeutic Goods Administration—
TGA, Australia's regulatory authority for healthcare products—and the TGA's
Scheduling Committee agreed to convene on February 20, 2007, to discuss possible
revoking of orlistat's over-the-counter status. The Committee ultimately decided to
keep orlistat as a Schedule 3 drug, but withdrew its authorization of direct-to-
consumer Xenical advertising, stating this "increased pressure on pharmacists to
provide orlistat to consumers...this in turn had the potential to result in
inappropriate patterns of use". Xenical has recently began being advertised direct-
to-customers again. [12][13][14]]
39

40. Lifestyle Drugs
United States
On January 23, 2006, a U.S. Food and Drug Administration advisory panel voted
11 to 3 to recommend the approval of an OTC formulation of orlistat, to be
marketed under the name alli by GlaxoSmithKline. Approval was granted on
February 7, 2007, and alli became the first weight loss drug officially sanctioned by
the U.S. government for over-the-counter use. Consumer advocacy organization
Public Citizen, through its Health Research Group, opposed over-the-counter
approval for orlistat, calling it "the height of recklessness" and "a dangerous
mistake" due to questionable benefits and possible adverse effects. Public Citizen
had already called for a ban of orlistat in April 2006.
Alli became available in the U.S. in June 2007. It is sold as 60 mg capsules—half
the dosage of prescription orlistat. [12][13][14]
European Union
On January 21, 2009, the European Medicines Agency granted approval for the sale
of orlistat without a prescription.
Generic formulations
As of September 2009, no generic formulations of orlistat are legally available in
the United States. U.S. patent protection for Xenical, originally to end on June 18,
2004, was extended by five years (until 2009) by the U.S. Patent and Trademark
Office. The extension was granted on July 20, 2002, and expired on June 18, 2009.
Generic orlistat is available in India, under the brands Olistat, Obelit, Orlica and
Reeshape.
In Russia orlistat is available under the brand Orsoten. [12][13][14]
40

41. Lifestyle Drugs
Counterfeit products
In January 2010, the United States Food and Drug Administration issued an alert
stating that some counterfeit versions of Alli sold over the Internet contain no
orlistat, and instead contain the weight-loss drug sibutramine. The concentration of
sibutramine in these counterfeit products is at least twice the amount recommended
for weight loss. [12][13][14]
Another popular lifestyle drug is Anabolic steroids, technically known as
anabolic-androgen steroids (AAS) or colloquially as "steroids" (or even "roids"),
are drugs that mimic the effects of testosterone and dihydrotestosterone in the body.
They increase protein synthesis within cells, which results in the buildup of cellular
tissue (anabolism), especially in muscles. Anabolic steroids also have androgenic
and virilizing properties, including the development and maintenance of masculine
characteristics such as the growth of the vocal cords, testicles, and body hair
(secondary sexual characteristics). The word anabolic comes from the Greek
anabole, "that which is thrown up, mound", and the word androgenic from the
Greek andros, "of a man" -genes, "born".
Anabolic steroids were first isolated, identified, and synthesized in the 1930s, and
are now used therapeutically in medicine to stimulate bone growth and appetite,
induce male puberty, and treat chronic wasting conditions, such as cancer and
AIDS. The American College of Sports Medicine acknowledges that AAS, in the
presence of adequate diet, can contribute to increases in body weight, often as lean
mass increases, and that the gains in muscular strength achieved through high-
intensity exercise and proper diet can be additionally increased by the use of AAS
in some individuals.
Health risks can be produced by long-term use or excessive doses of anabolic
steroids. These effects include harmful changes in cholesterol levels (increased
low-density lipoprotein and decreased high-density lipoprotein), acne, high blood
pressure, liver damage (mainly with oral steroids), dangerous changes in the
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42. Lifestyle Drugs
structure of the left ventricle of the heart. Conditions pertaining to hormonal
imbalances such as gynecomastia and testicular atrophy may also be caused by
anabolic steroids.
Ergogenic uses for anabolic steroids in sports, racing, and bodybuilding are
controversial because of their adverse effects and the potential to gain an advantage
conventionally considered "cheating." Their use is referred to as doping and banned
by all major sporting bodies. For many years, AAS have been by far the most
detected doping substances in IOC-accredited laboratories. In countries where AAS
are controlled substances, there is often a black market in which smuggled,
clandestinely manufactured, or even counterfeit drugs are sold to users. [21]
History
Isolation of gonadal AAS
Fig- e
Chemical structure of the natural anabolic hormone testosterone, 17β-hydroxy-4-
androsten-3-one
The use of gonadal steroids pre-dates their identification and isolation. Medical use
of testicle extract began in the late 19th century while its effects on strength were
still being studied. The isolation of gonadal steroids can be traced back to 1931,
when Adolf Butenandt, a chemist in Marburg, purified 15 milligrams of the male
hormone androstenone from tens of thousands of litres of urine. This steroid was
subsequently synthesized in 1934 by Leopold Ruzicka, a chemist in Zurich.
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43. Lifestyle Drugs
In the 1930s, it was already known that the testes contain a more powerful
androgen than androstenone, and three groups of scientists, funded by competing
pharmaceutical companies in the Netherlands, Germany, and Switzerland, raced to
isolate it. This hormone was first identified by Karoly Gyula David, E.
Dingemanse, J. Freud and Ernst Laqueur in a May 1935 paper "On Crystalline
Male Hormone from Testicles (Testosterone)." They named the hormone
testosterone, from the stems of testicle and sterol, and the suffix of ketone. The
chemical synthesis of testosterone was achieved in August that year, when
Butenandt and G. Hanisch published a paper describing "A Method for Preparing
Testosterone from Cholesterol." Only a week later, the third group, Ruzicka and A.
Wettstein, announced a patent application in a paper "On the Artificial Preparation
of the Testicular Hormone Testosterone (Androsten-3-one-17-ol)."Ruzicka and
Butenandt were offered the 1939 Nobel Prize in Chemistry for their work, but the
Nazi government forced Butenandt to decline the honor, although he accepted the
prize after the end of World War II.
Clinical trials on humans, involving either oral doses of methyltestosterone or
injections of testosterone propionate, began as early as 1937. Testosterone
propionate is mentioned in a letter to the editor of Strength and Health magazine in
1938; this is the earliest known reference to an anabolic steroid in a U.S.
weightlifting or bodybuilding magazine himself.[21][22]
Development of synthetic AAS
The development of muscle-building properties of testosterone was pursued in the
1940s, in the Soviet Union and in Eastern Bloc countries such as East Germany,
where steroid programs were used to enhance the performance of Olympic and
other amateur weight lifters. In response to the success of Russian weightlifters, the
U.S. Olympic Team physician Dr. John Ziegler worked with synthetic chemists to
develop an anabolic steroid with reduced androgenic effects. Ziegler's work
resulted in the production of methandrostenolone, which Ciba Pharmaceuticals
marketed as Dianabol. The new steroid was approved for use in the U.S. by the
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44. Lifestyle Drugs
Food and Drug Administration (FDA) in 1958. It was most commonly
administered to burn victims and the elderly. The drug's off-label users were mostly
bodybuilders and weight lifters. Although Ziegler prescribed only small doses to
athletes, he soon discovered that those having abused Dianabol suffered from
enlarged prostates and atrophied testes. AAS were placed on the list of banned
substances of the IOC in 1976, and a decade later the committee introduced 'out-of-
competition' doping tests because many athletes used AAS in their training period
rather than during competition.
Three major ideas governed modifications of testosterone into a multitude of AAS:
Alkylation at 17-alpha position with methyl or ethyl group created orally active
compounds because it slows the degradation of the drug by the liver; esterification
of testosterone and nortestosterone at the 17-beta position allows the substance to
be administered parenterally and increases the duration of effectiveness because
agents soluble in oily liquids may be present in the body for several months; and
alterations of the ring structure were applied for both oral and parenteral agents to
seeking to obtain different anabolic to androgenic effect ratios. [21]
Pharmacology
Routes of administrations
Fig- f: A vial of injectable testosterone cypionate
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45. Lifestyle Drugs
There are four common forms in which anabolic steroids are administered: oral
pills, injectable steroids, creams/gels for topical application, and skin patches. Oral
administration is the most convenient. Testosterone administered by mouth is
rapidly absorbed, but it is largely converted to inactive metabolites, and only about
1/6 is available in active form. In order to be sufficiently active when given by
mouth, testosterone derivatives are alkylated at the 17 position, e.g.
methyltestosterone and fluoxymesterone. This modification reduces the liver's
ability to break down these compounds before they reach the systemic circulation.
Testosterone can be administered parenterally, but it has more irregular prolonged
absorption time and greater activity in propionate, enanthate, undecanoate, or
cypionate ester form. These derivatives are hydrolyzed to release free testosterone
at the site of injection; absorption rate (and thus injection schedule) varies among
different esters, but medical injections are normally done anywhere between semi-
weekly to once every 12 weeks. A more frequent schedule may be desirable in
order to maintain a more constant level of hormone in the system.]
Injectable
steroids are typically administered into the muscle, not into the vein, to avoid
sudden changes in the amount of the drug in the bloodstream. In addition, because
estered testosterone is dissolved in oil, intravenous injection has the potential to
cause a dangerous embolism (clot) in the bloodstream.
Transdermal patches (adhesive patches placed on the skin) may also be used to
deliver a steady dose through the skin and into the bloodstream. Testosterone-
containing creams and gels that are applied daily to the skin are also available, but
absorption is inefficient (roughly 10%, varying between individuals) and these
treatments tend to be more expensive. Individuals who are especially physically
active and/or bathe often may not be good candidates, since the medication can be
washed off and may take up to six hours to be fully absorbed. There is also the risk
that an intimate partner or child may come in contact with the application site and
inadvertently dose himself or herself; children and women are highly sensitive to
testosterone and can suffer unintended masculinization and health effects, even
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46. Lifestyle Drugs
from small doses. Injection is the most common method used by individuals
administering anabolic steroids for non-medical purposes.
The traditional routes of administration do not have differential effects on the
efficacy of the drug. Studies indicate that the anabolic properties of anabolic
steroids are relatively similar despite the differences in pharmacokinetic principles
such as first-pass metabolism. However, the orally available forms of AAS may
cause liver damage in high doses. [20][22]
Mechanism of action
Fig- g
The human androgen receptor bound to testosterone .The protein is shown as a
ribbon diagram in red, green, and blue, with the steroid shown in white.
The pharmacodynamics of anabolic steroids are unlike peptide hormones. Water-
soluble peptide hormones cannot penetrate the fatty cell membrane and only
indirectly affect the nucleus of target cells through their interaction with the cell’s
surface receptors. However, as fat-soluble hormones, anabolic steroids are
membrane-permeable and influence the nucleus of cells by direct action. The
pharmacodynamic action of anabolic steroids begin when the exogenous hormone
penetrates the membrane of the target cell and binds to an androgen receptor
located in the cytoplasm of that cell. From there, the compound hormone-receptor
diffuses into the nucleus, where it either alters the expression of genes or activates
processes that send signals to other parts of the cell. Different types of anabolic
steroids bind to the androgen receptor with different affinities, depending on their
chemical structure. Some anabolic steroids such as methandrostenolone bind
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47. Lifestyle Drugs
weakly to this receptor in vitro, but still exhibit androgenic effects in vivo. The
reason for this discrepancy is not known.
The effect of anabolic steroids on muscle mass is caused in at least two ways: first,
they increase the production of proteins; second, they reduce recovery time by
blocking the effects of stress hormone cortisol on muscle tissue, so that catabolism
of muscle is greatly reduced. It has been hypothesized that this reduction in muscle
breakdown may occur through anabolic steroids inhibiting the action of other
steroid hormones called glucocorticoids that promote the breakdown of muscles.
Anabolic steroids also affect the number of cells that develop into fat-storage cells,
by favouring cellular differentiation into muscle cells instead. Anabolic steroids can
also decrease fat by increasing basal metabolic rate (BMR), since an increase in
muscle mass increases BMR.[19][21][22]
Anabolic and androgenic effects
Relative androgenic:anabolic
activity in animals
Preparation Ratio
Testosterone 1:1
Methyltestosterone 1:1
Fluoxymesterone 1:2
Oxymetholone 1:3
Oxandrolone 1:3–1:13
Nandrolone decanoate 1:2.5–1:4
Table-III
As the name suggests, anabolic-androgenic steroids have two different, but
overlapping, types of effects: anabolic, meaning that they promote anabolism (cell
growth), and androgenic (or virilising), meaning that they affect the development
and maintenance of masculine characteristics.
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48. Lifestyle Drugs
Some examples of the anabolic effects of these hormones are increased protein
synthesis from amino acids, increased appetite, increased bone remodeling and
growth, and stimulation of bone marrow, which increases the production of red
blood cells. Through a number of mechanisms anabolic steroids stimulate the
formation of muscle cells and hence cause an increase in the size of skeletal
muscles, leading to increased strength.
The androgenic effects of AAS are numerous. Processes affected include pubertal
growth, sebaceous gland oil production, and sexuality (especially in fetal
development). Some examples of virilizing effects are growth of the clitoris in
females and the penis in male children (the adult penis does not grow even when
exposed to high doses of androgens), increased growth of androgen-sensitive hair
(pubic, beard, chest, and limb hair), increased vocal cord size, deepening the voice,
increased libido, suppression of natural sex hormones, and impaired production of
sperm.
The androgenic:anabolic ratio of an AAS is an important factor when determining
the clinical application of these compounds. Compounds with a high ratio of
androgenic to a anabolic effects are the drug of choice in androgen-replacement
therapy (e.g., treating hypogonadism in males), whereas compounds with a reduced
androgenic:anabolic ratio are preferred for anemia and osteoporosis, and to reverse
protein loss following trauma, surgery, or prolonged immobilization. Determination
of androgenic:anabolic ratio is typically performed in animal studies, which has led
to the marketing of some compounds claimed to have anabolic activity with weak
androgenic effects. This disassociation is less marked in humans, where all
anabolic steroids have significant androgenic effects.
A commonly used protocol for determining the androgenic:anabolic ratio, dating
back to the 1950s, uses the relative weights of ventral prostate (VP) and levator ani
muscle (LA) of male rats. The VP weight is an indicator of the androgenic effect,
while the LA weight is an indicator of the anabolic effect. Two or more batches of
rats are castrated and given no treatment and respectively some AAS of interest.
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49. Lifestyle Drugs
The LA/VP ratio for an AAS is calculated as the ratio of LA/VP weight gains
produced by the treatment with that compound using castrated but untreated rats as
baseline: (LAc,t–LAc)/(VPc,t–VPc). The LA/VP weight gain ratio from rat
experiments is not unitary for testosterone (typically 0.3–0.4), but it is normalized
for presentation purposes, and used as basis of comparison for other AAS, which
have their androgenic:anabolic ratios scaled accordingly (as shown in the table
above). In the early 2000s, this procedure was standardized and generalized
throughout OECD in what is now known as the Hershberger assay. [19][21]
Body composition and strength improvements
A review spanning more than three decades of experimental studies in men found
that body weight may increase by 2–5 kg as a result of short-term (<10 weeks)
AAS use, which may be attributed mainly to an increase of lean mass. Animal
studies also found that fat mass was reduced, but most studies in humans failed to
elucidate significant fat mass decrements. The effects on lean body mass have been
shown to be dose-dependent. Both muscle hypertrophy and the formation of new
muscle fibers have been observed. The hydration of lean mass remains unaffected
by AAS use, although small increments of blood volume cannot be ruled out.
The upper region of the body (thorax, neck, shoulders, and upper arm) seems to be
more susceptible for AAS than other body regions because of predominance of
androgen receptors in the upper body. The largest difference in muscle fiber size
between AAS users and non-users was observed in type I muscle fibers of the
vastus lateralis and the trapezius muscle as a result of long-term AAS self-
administration. After drug withdrawal, the effects fade away slowly, but may
persist for more than 6–12 weeks after cessation of AAS use.
The same review observed strength improvements in the range of 5-20% of
baseline strength, depending largely on the drugs and dose used as well as the
administration period. Overall, the exercise where the most significant
improvements were observed is the bench press. For almost two decades, it was
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50. Lifestyle Drugs
assumed that AAS exerted significant effects only in experienced strength athletes,
particularly based on the studies of Hervey and coworkers. In 1996, a randomized
controlled trial published in the New England Journal of Medicine demonstrated,
however, that even in novice athletes a 10-week strength training program
accompanied by testosterone enanthate at 600 mg/week may improve strength
more than training alone does. The same study found that dose to be sufficient to
significantly improve lean muscle mass relative to placebo even in subjects that did
not exercise at all. A 2001 study by the same first author, showed that the anabolic
effects of testosterone enanthate were highly dose dependent. [21][22]
Adverse effects
Anabolic steroids can cause many adverse effects. Most of these side-effects are
dose-dependent, the most common being elevated blood pressure, especially in
those with pre-existing hypertension, and harmful changes in cholesterol levels:
Some steroids cause an increase in LDL "bad" cholesterol and a decrease in HDL
"good" cholesterol. Anabolic steroids have been shown to alter fasting blood sugar
and glucose tolerance tests. Anabolic steroids such as testosterone also increase the
risk of cardiovascular disease or coronary artery disease. Acne is fairly common
among anabolic steroid users, mostly due to stimulation of the sebaceous glands by
increased testosterone levels. Conversion of testosterone to dihydrotestosterone
(DHT) can accelerate the rate of premature baldness for males genetically
predisposed, but testosterone itself can produce baldness in females.
High doses of oral anabolic steroid compounds can cause liver damage, as the
steroids are metabolized (17α-alkylated) in the digestive system to increase their
bioavailability and stability.
There are also sex-specific side-effects of anabolic steroids. Development of breast
tissue in males, a condition called gynecomastia (which is usually caused by high
levels of circulating estradiol), may arise because of increased conversion of
testosterone to estradiol by the enzyme aromatase. Reduced sexual function and
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51. Lifestyle Drugs
temporary infertility can also occur in males. Another male-specific side-effect that
can occur is testicular atrophy, caused by the suppression of natural testosterone
levels, which inhibits production of sperm (most of the mass of the testes is
developing sperm). This side-effect is temporary: The size of the testicles usually
returns to normal within a few weeks of discontinuing anabolic steroid use as
normal production of sperm resumes. Female-specific side-effects include increases
in body hair, permanent deepening of the voice, enlarged clitoris, and temporary
decreases in menstrual cycles. When taken during pregnancy, anabolic steroids can
affect fetal development by causing the development of male features in the female
fetus and female features in the male fetus.
A number of severe side-effects can occur if adolescents use anabolic steroids.
For example, the steroids may prematurely stop the lengthening of bones
(premature epiphyseal fusion through increased levels of estrogen metabolites),
resulting in stunted growth. Other effects include, but are not limited to, accelerated
bone maturation, increased frequency and duration of erections, and premature
sexual development. Anabolic steroid use in adolescence is also correlated with
poorer attitudes related to health.
Other side-effects can include alterations in the structure of the heart, such as
enlargement and thickening of the left ventricle, which impairs its contraction and
relaxation. Possible effects of these alterations in the heart are hypertension, cardiac
arrhythmias, congestive heart failure, heart attacks, and sudden cardiac death.
These changes are also seen in non-drug-using athletes, but steroid use may
accelerate this process. However, both the connection between changes in the
structure of the left ventricle and decreased cardiac function, as well as the
connection to steroid use have been disputed. [17][19][20][21][22]
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52. Lifestyle Drugs
Psychiatric effects
A 2005 review in CNS Drugs determined that "significant psychiatric symptoms
including aggression and violence, mania, and less frequently psychosis and suicide
have been associated with steroid abuse. Long-term steroid abusers may develop
symptoms of dependence and withdrawal on discontinuation of AAS". High
concentrations of AAS, comparable to those likely sustained by many recreational
AAS users, produce apoptotic effects on neurons, raising the specter of possibly
irreversible neuropsychiatric toxicity. Recreational AAS use appears to be
associated with a range of potentially prolonged psychiatric effects, including
dependence syndromes, mood disorders, and progression to other forms of
substance abuse, but the prevalence and severity of these various effects remains
poorly understood. There is no evidence that steroid dependence develops from
therapeutic use of anabolic steroids to treat medical disorders, but instances of
AAS dependence have been reported among weightlifters and bodybuilders who
chronically administered supraphysiologic doses. Mood disturbances (e.g.
depression, [hypo-]mania, psychotic features) are likely to be dose- and drug-
dependent, but AAS dependence or withdrawal effects seem to occur only in a
small number of AAS users.
Large-scale long-term studies of psychiatric effects on AAS users are not currently
available. In 2003, the first naturalistic long-term study on ten users, seven of
which having completed the study, found a high incidence of mood disorders and
substance abuse, but few clinically relevant changes in physiological parameters or
laboratory measures were noted throughout the study, and these changes were not
clearly related to periods of reported AAS use. A 13-month study, which was
published in 2006 and which involved 320 body builders and athletes suggests that
the wide range of psychiatric side-effects induced by the use of AAS is correlated
to the severity of abuse. [17][19][20][21][22]
Aggression and hypomania
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53. Lifestyle Drugs
From the mid-1980s onward, the popular press has been reporting "roid rage" as a
side-effect of AAS (the term being a play on the more established phenomenon of
road rage).
A 2005 review determined that some, but not all, randomized controlled studies
have found that anabolic steroid use correlates with hypomania and increased
aggressiveness, but pointed out that attempts to determine whether AAS use
triggers violent behaviour have failed, primarily because of high rates of non-
participation. A 2008 study on a nationally representative sample of young adult
males in the United States found an association between lifetime and past-year self-
reported anabolic-androgenic steroid use and involvement in violent acts.
Compared with individuals that did not use steroids, young adult males that used
anabolic-androgenic steroids reported greater involvement in violent behaviors
even after controlling for the effects of key demographic variables, previous violent
behavior, and polydrug use.A 1996 review examining the blind studies available at
that time also found that these had demonstrated a link between aggression and
steroid use, but pointed out that with estimates of over one million past or current
steroid users in the United States at that time, an extremely small percentage of
those using steroids appear to have experienced mental disturbance severe enough
to result in clinical treatments or medical case reports.
A 2006 study of two pairs of identical twins, in which one twin used anabolic
steroids and the other did not, found that in both cases the steroid-using twin
exhibited high levels of aggressiveness, hostility, anxiety, and paranoid ideation not
found in the "control" twin. A small-scale study of 10 AAS users found that cluster
B personality disorders were confounding factors for aggression. [23][26][27][28]
Depression and suicide
The relationship between AAS use and depression is inconclusive. There have been
anecdotal reports of depression and suicide in teenage steroid users, but little
systematic evidence. A 1992 review found that anabolic-androgenic steroids may
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54. Lifestyle Drugs
both relieve and cause depression, and that cessation or diminished use of anabolic-
androgenic steroids may also result in depression, but called for additional studies
due to disparate data. [17][20][21][22]
Addiction potential
In an animal study, male rats developed a conditioned place preference to
testosterone injections into the nucleus accumbens, an effect blocked by dopamine
antagonists, which suggests that androgen reinforcement is mediated by the brain.
Moreover, testosterone appears to act through the mesolimbic dopamine system, a
common substrate for drugs of abuse. Nonetheless, androgen reinforcement is not
comparable to that of cocaine, nicotine, or heroin. Instead, testosterone resembles
other mild reinforcers, such as caffeine, or benzodiazepines. The potential for
androgen addiction remains to be determined. [17][20][21][22]
Medical and ergogenic uses
Medical uses
Fig-h : Various anabolic steroids and related compounds
Since the discovery and synthesis of testosterone in the 1930s, anabolic steroids
have been used by physicians for many purposes, with varying degrees of success,
for the treatment of:
• Bone marrow stimulation: For decades, anabolic steroids were the mainstay of
therapy for hypoplastic anemias due to leukemia or kidney failure, especially
aplastic anemia. Anabolic steroids have largely been replaced in this setting by
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55. Lifestyle Drugs
synthetic protein hormones (such as epoetin alfa) that selectively stimulate growth
of blood cell precursors.
• Growth stimulation: Anabolic steroids can be used by pediatric endocrinologists
to treat children with growth failure. However, the availability of synthetic growth
hormone, which has fewer side effects, makes this a secondary treatment.
• Stimulation of appetite and preservation and increase of muscle mass: Anabolic
steroids have been given to people with chronic wasting conditions such as cancer
and AIDS.
• Induction of male puberty: Androgens are given to many boys distressed about
extreme delay of puberty. Testosterone is now nearly the only androgen used for
this purpose and has been shown to increase height, weight, and fat-free mass in
boys with delayed puberty.
• Male contraception, in the form of testosterone enanthate; potential for use in
the near-future as a safe, reliable, and reversible male contraceptive.
• Stimulation of lean body mass and prevention of bone loss in elderly men, as
some studies indicate. However, a 2006 placebo-controlled trial of low-dose
testosterone supplementation in elderly men with low levels of testosterone found
no benefit on body composition, physical performance, insulin sensitivity, or
quality of life.
• Hormone replacement for men with low levels of testosterone; also effective in
improving libido for elderly males.
• Gender Identity Disorder, by producing secondary male characteristics, such as
a deeper voice, increased bone and muscle mass, facial hair, increased levels of red
blood cells, and clitoral enlargement in female-to-male patients.[17][20][21][22]
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56. Lifestyle Drugs
Ergogenic use and abuse
Fig-i : Numerous vials of injectable anabolic steroids
Between 1 million and 3 million people (1% of the population) are thought to have
misused AAS in the United States. Studies in the United States have shown that
anabolic steroid users tend to be mostly middle-class heterosexual men with a
median age of about 25 who are noncompetitive bodybuilders and non-athletes and
use the drugs for cosmetic purposes. Another study found that non-medical use of
AAS among college students was at or less than 1%. According to a recent survey,
78.4% of steroid users were noncompetitive bodybuilders and non-athletes, while
about 13% reported unsafe injection practices such as reusing needles, sharing
needles, and sharing multidose vials, though a 2007 study found that sharing of
needles was extremely uncommon among individuals using anabolic steroids for
non-medical purposes, less than 1%. Another 2007 study found that 74% of non-
medical anabolic steroid users had secondary college degrees and more had
completed college and less had failed to complete high school than is expected
from the general populace. The same study found that individuals using anabolic
steroids for non-medical purposes had a higher employment rate and a higher
household income than the general population. Anabolic steroid users tend to
research the drugs they are taking more than other controlled-substance users;
however, the major sources consulted by steroid users include friends, non-medical
handbooks, internet-based forums, blogs, and fitness magazines, which can provide
questionable or inaccurate information.
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57. Lifestyle Drugs
Anabolic steroid users tend to be disillusioned by the portrayal of anabolic steroids
as deadly in the media and in politics. According to one study, AAS users also
distrust their physicians and in the sample 56% had not disclosed their AAS use to
their physicians. Another 2007 study had similar findings, showing that, while 66%
of individuals using anabolic steroids for non-medical purposes were willing to
seek medical supervision for their steroid use, 58% lacked trust in their physicians,
92% felt that the medical community's knowledge of non-medical anabolic steroid
use was lacking, and 99% felt that the public has an exaggerated view of the side-
effects of anabolic steroid use. A recent study has also shown that long term AAS
users were more likely to have symptoms of muscle dysmorphia and also showed
stronger endorsement of more conventional male roles.
Anabolic steroids have been used by men and women in many different kinds of
professional sports to attain a competitive edge or to assist in recovery from injury.
These sports include bodybuilding, weightlifting, shot put and other track and field,
cycling, baseball, wrestling, mixed martial arts, boxing, football, and cricket. Such
use is prohibited by the rules of the governing bodies of most sports. Anabolic
steroid use occurs among adolescents, especially by those participating in
competitive sports. It has been suggested that the prevalence of use among high-
school students in the U.S. may be as high as 2.7%. Male students used anabolic
steroids more frequently than female students and, on average, those that
participated in sports used steroids more often than those that did not.[17][20][21]
Legal and sport restrictions
The use of anabolic steroids is banned by all major sporting bodies, including the
International Olympic Committee, United States Olympic Committee, Major
League Baseball, the National Football League, the National Basketball
Association, the National Hockey League, the International Cricket Council,
Ultimate Fighting Championship, ITF, FIFA, FINA, UEFA, the European Athletic
Association, and the Brazilian Football Confederation.[21]
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