5.1.1 androgens and anabolic steroids

5.1.1 androgens and anabolic steroids

1. Androgens and
Anabolic Steroids

(AAS)

2. What are Steroids?

Endocrine hormones: chemical signals released into the
bloodstream which act upon target receptors far away from their
site of release.
Produced by body and made synthetically in the lab.
Classes of Steroids
— Naturally occurring
+ Androgens
* Corticoids
= Estrogens
* Progestogens
— Synthetic
+ Anabolic-Androgenic

* Medicinal versus performance enhancing

Dr. Muthuraman A. JSS College of Pharmacy, Mysuru

3. Definitions

* Androgen: Any hormone with testosterone -

like actions.

° Anabolism: Cellular synthesis of organic

molecules (including proteins).

Dr. Muthuraman A. JSS College of Pharmacy, Mysuru

4. « Testosterone discovered in 1935 by independent European
researchers.

* Anabolic steroids initially used in 2
— a condition in which testes produce abnormally
nw testosterone levels.

* Bodybuilders and weightlifters first used anabolic steroids in
1930s to increase skeletal muscle mass.

— Serving medicinal purposes (tre

).
Athletic manipule and taboo (prohibited or restricted by

social custom).

5. * Hypogonadism in adult males may alter certain
masculine physical characteristics and impair
normal reproductive function.

* Signs and symptoms may include:
Erectile dysfunction, Infertility,

Increase in body fat,

Decrease in beard and body hair growth,
Decrease in size or firmness of testicles,
Decrease in muscle mass,

Development of breast tissue,
Loss of bone mass (osteoporosis).

Dr. Muthuraman A.

6. Natural Steroid Derivatives:
Cholesterol and Testosterone

or Say

17 carbon atoms in a 4-ringed structure.

AS)

cyclopentanoperhydrophenanthrene

RU

Ho” TR

Cholesterol Testosterone

Dr. Muthuraman A. JSS College of Pharmacy, Mysuru

7. * The body uses hormones to maintain a stable
internal environment as well as perform long-
lasting communication.

* Because AAS are cholesterol derivates, they are
nonpolar and readily cross the plasma

membrane.

— However, they are insoluble in aqueous
environments and require plasma protein co-
transporters when circulating through blood .

8. Common Steroid Hormones

OH
Aldosterone
)

SIE oH
POLE
où

LK EN
HO NN

Estradiol

Progesterone

Dr. Muthuraman A. JSS College of Pharmacy, Mysuru

9. + At puberty, the pituitary gland signals the
production and release of testosterone.

— Deepening voice

— Development of facial, underarm & pubic hair

— Broadening shoulders

— Enlargement of external sex organs
— Testes to begin producing

— Increased muscular development

10. Androgens

(Primarily dehydroepiandrosterone)
— Enhance male characteristics and control growth

of hair follicles in the skin.

— Anabolic-Androgenic steroids are synthetic

formulations produced from testosterone, the male

hormone.

—Estimated use by 80 % of weightlifters &
bodybuilders

Dr. Muthuraman A. JSS College of Pharmacy, Mysuru

11. +» Manufacture by testis (initiated by luteinizing
hormone) and adrenal cortex, and to a lesser degree
by the ovaries.

* Androgen Receptor (AR) exists in reproductive as
well as non-reproductive tissue (i.c. skeletal muscle,
etc).

For example, prostate has 25X more AR than skeletal
muscle.

12. ° Medicinal: Therapeutic
of testosterone

effects
replacement

in
degenerative states, such as
hypogonadism, HIV-
related muscle wasting
conditions, sarcopenia

(age-related muscle loss).

Dr. Muthu

» Performance Enhancing
Effects

— Commonly self-
administered, therefore
little empirical evidence.

— Increased strength and
body weight due to
heightened skeletal muscle

— Numerous side effects.

13. Common Anabolic Adrogenic
Steroids

Lacks methyl group Ester as prodrug
OH

OR + OH
icHs
00 00 4
mo Ce de
o ?
o A
Testostero Nandrolone Ester

ne Oxymetholone (androle)

e
(R= CH3{CH2)gC0)

{Andro)

Dr. Muthuraman A. JSS College of Pharmacy, Mysuru

14. * AR exists in multiple tissue

* Functional domains: DNA À J j

binding domain, hinge =
domain and hormone |, )

binding domain.

A

15. * AR activity is contingent upon ligand binding, AR
mic 22 and

of target
genes.
= al ef s such as increased skeletal muscle mass
and siremeth occur due to heightened ability to fixate
nitrogen, facilitating protein synthesis, as well as
erythropoiesis (production of red blood cells).

16. AR Competition: Anti-androgens

Dr. Muthuraman A. JSS College of Pharmacy, Mysuru

17. Androgen antagonists
Method of action

Suppr

include

prostate cancer, benign
prostatic hyperplasia,
hypersexuality and others;
counteracts androgen-
caused diseases.

Cyproterone (4)

18. Performance
Enhancing Drugs

19. « Administration of AAS may occur through multiple routes
and often in combination (stacking).
— Intramuscular injection, orally, and in gels or creams
that are rubbed on the skin.
* Self-administration is common and often occurs in a
regimented pattern.
— User cycles may last between 4 and 12 weeks, with “off-
cycles” occuring between using periods.

+ AAS may be used in

20. n Type Effects
Increased growth of :

— prostate gland
— Body/facial hair
— Oil production
Deepening voice

Increased sexual interest
and desire

Enhancement of abstract
thinking

Increased aggression

: Type Effects
« Increased:

—Organ and skeletal
muscle mass

— Calcium in bones
— Retention of nitrogen

— Hemoglobin
concentration

— Protein synthesis

21. * Most common reason: Improve athletic performance.

* Also, to g a] and uscle > and/or
in an effort to ys

in addition to initial physical
gains, Andragen receptors in the brain stimulate feelings
of euphoria and increased aggressiveness.
— Additional use is perpetuated as one becomes less
receptive to outside opinion and resorts to aggressive
behavior to continue the cycle.

* AAS reduce recovery time between periods of st
ty, but evidence remains minimal.

* No proven effect on endurance or stamina.

A.

22. — increased sexual drive, acne, increased body hair
and baldness, aggressive behavior (13).
> interferes with ability to naturally
produce testosterone in the face of withdrawl.
due to chronic abuse also
include hypertension, atherosclerosis, blood clotting,
jaundice, hepatic carcinoma, tendon damage, and
reduced fertility in males.
side effects include heart

attacks and liver cancer.

Dr. Muthuraman A. JSS College of Pharmacy, Mysuru

23. Females
— Oily skin acne
— Decrease

+ breast size,
ovulation, lactation,
menstruation

— Hoarse / deep voice

— Clitoral enlargement

— Unusual hair growth
+/- male patterned
baldness

« Males

— Increase penis size, #
of erections, &
secondary male
characteristics

— Priapism (continuing
erections)

— Gynecomastia
(increased breast size)

— Testicular atrophy,

— impotence

Dr. Muthuraman A.

JSS College of Pharmacy, Mysuru

24. ADR in Both Genders

Gastric ulcers

Liver Complications

Hyperglycemia
Reduction in HDL

Increased platelet
aggregation with increased

risk of CV disorders

Dr. Muthuraman A.

Hypercalcemia

Edema

Urinary calculi

Insomnia

Iron deficiency anemia
Nausea, vomiting, anorexia,
stomach pains

JSS College of Pharmacy, Mysuru

25. » International Olympic Committee placed anabolic
steroids on their list of banned substances in 1975.

+ AAS put on list of Schedule III Controlled Substances
in 1990, making it available only by prescription.
However, recent studies indicate that use may be on the
rise .

1999 survey amongst middle school and high school
students showed an increase in lifetime use by 10%
graders, alongside a decr s

26. ¢ Enhancing / understanding medical treatments
—Fracture healing, soft tissue healing, postoperative
rehabilitation.

« Efforts must be made to eradicate athletic use through
education.

¢ Long-term effects are currently under investigation,
and adverse effects of AAS on cardiovascular, hepatic,
endocrine / reproductive, behavioral, dermatologic
systems are being studied.

27. Thank you

Dr. Muthuraman A. JSS College of Pharmacy, Mysuru