This document discusses androgens and anabolic steroids. It begins by defining androgens as male sex hormones such as testosterone that are produced in the testes and adrenal cortex. It then covers the production, actions, and mechanisms of androgens. The document also discusses the uses, side effects, and classifications of androgens and anabolic steroids. It concludes by examining antiandrogens and drugs that inhibit androgen synthesis.

1. ANDROGENS AND ANABOLIC STEROIDS
Praveen Kumar.s
M.pharm2nd semester
Department of pharmacology
PSG College of pharmacy.
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ANDROGEN AND ANABOLIC STERIODS

2. CONTENTS
■ Introduction of androgen
■ Production and synthesis of male sex hormone
■ Classification of androgen and related drugs.
■ Actions of androgen
■ Mechanism of action
■ Side effects and uses
■ Anabolic steroids
■ Antiandrogens
■ Drugs for erectile dysfunction.
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ANDROGEN AND ANABOLIC STERIODS

3. ANDROGENS
Androgen - Male sex hormones
■ Androgen are produced chiefly in the testis and small amounts in the adrenal cortex.
■ In the females,small amounts of androgens are produced in the ovary and adrenal cortex.
■ Androgens are synthesized from cholesterol.
■ Androgen are the substance which cause development of secondary sex characters in the castrated
male.
■ Its endocrine function was established by berthold in 1849. Testosterone was isolated as the
testicular hormone,and it was synthetically prepared by the year 1935.
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ANDROGEN AND ANABOLIC STERIODS

4. Natural androgen is testosterone.
Testes of adult male produce 5-12mg of testosterone daily.
Which is converted in extraglandular tissues to more active dihydrotestosterone (DHT) by
enzyme 5 alpha reductase.
Cholesterol is a starting material.
Adrenal cortex produce small quantity of dehyroepiandrosterone and androstenedione.
Testosteron
e
Dihydrotestosterone
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ANDROGEN AND ANABOLIC STERIODS

5. Synthesis of testosterone
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ANDROGEN AND ANABOLIC STERIODS
Image source: tctmd.com

6. Hormonal regulation and secretion
Image source: principles of anatomy and physiology by Gerard j.tortora, Bryan
derrickson. 6
ANDROGEN AND ANABOLIC STERIODS

7. Actions of testosterone
1. Sex organs and secondary sex characters (androgenic)
■ Testosterone is responsible for all the changes that occur in a boy at puberty:
■ Growth of genitals- penis, scrotum,seminal vesicles, prostate.
■ Growth of hair- pubic, axillary,beard,moustache, body hair.
■ Thickening of skin which becomes greasy due to proliferation and increased
sabaceous gland especially on the face.
■ Subcutaneous fat is lost and vein looks prominent.
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ANDROGEN AND ANABOLIC STERIODS

8. Cont…
■ Larynx grows and voice
deepens.
■ Behavioural effects – increased
physical vigour,aggressiveness,penile
erections.
■ Testosterone is also important
for the intrauterine development of
the male phenotype.
■ Relatively large amounts of
testosterone are produced by foetal
testes during the first half of
intrauterine life.
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ANDROGEN AND ANABOLIC STERIODS

9. 2.Testes
■ Moderately large doses cause testicular atrophy by inhibiting Gn secretion from
pituitary.
■ Testosterone is needed for normal spermatogenesis and maturation of spermatozoa.
■ High concentration of testosterone is attained locally in the spermatogenic tubules by
diffuse from the leydig cells and stimulate spermatogenesis.
3.Erythropoiesis
■ Testosterone is accelerates erythropoiesis by increasing erythropoietin production and
probably direct action on haeme synthesis.
■ Men have higher hematocrit than women.
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ANDROGEN AND ANABOLIC STERIODS

10. 4. Skeleton and skeletal muscles
■ Testosterone is responsible for the pubertal spurt of growth in boys and to a smaller
extent in girls.
■ There is rapid bone growth,both in thickness as well as in length.
■ Estradiol produced from testosterone . Moreover, estradiol largely mediates the
effect of testosterone on bone mineralization.
■ Stimulation of anabolism. Androgens are anabolic hormones; that is, they stimulate
protein synthesis. This effect is obvious in the heavier muscle and bone mass of most men
as compared to women.
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ANDROGEN AND ANABOLIC STERIODS

11. Androgen Drug classification
Image source:student file
Medical pharmacology kd Tripathi
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ANDROGEN AND ANABOLIC STERIODS

12. Mechanism of action of androgens
Image source: research gate.in
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ANDROGEN AND ANABOLIC STERIODS

13. Uses
1. Catabolic states:
Anabolic steroids may benefit patients following surgery, trauma, prolonged illness and
debilitating conditions. the negative nitrogen balance is corrected, appetite improves and there
is a feeling of well-being.
2. Testicular failure:
■ It may be primary,is noticed during childhood, and results in delayed puberty.
■ Treatment with parentral Testosterone esters or transdermal
Testosterone/dihydrotestosterone in course of 4-6months at a time may achieve satisfactory
results.
■ Secondary testicular failure (hypogonadism) occuring later in life.mainly in loss of libido,
muscle mass and energy,feminization mild anaemia and impotence.
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ANDROGEN AND ANABOLIC STERIODS

14. 3.Hypopituitarism
Hypogonadism is one of the features of hypopituitarism.androgen are added at the time of
puberty in boys to other hormonal replacement.
4.Growth stimulation in children:
Anabolic steroids promote linear growth in prepubertal boys particularly in delayed
puberty. They may be used only for short periods--but actual benefit on final height is not
established.
5.AIDS related muscle wasting
Testosterone therapy has been shown to improve weakness and muscle wasting in AIDS
patients with low testosterone levels.
6.Hereditary angioneurotic edema
This is a genetic disorder. The attacks can be prevented by 17a-alkylated androgens
(methyltestosterone, stanozolol, danazol) but not by testosterone. These drugs act by increasing
the synthesis of complement (C1) esterase inhibitor.
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ANDROGEN AND ANABOLIC STERIODS

15. Side effects
1. Administered to women, androgens can cause
virilization, excess body hair and menstrual
irregularities. Many effects, e.g. voice change
may be permanent after prolonged therapy.
2. Acne: In both males and females.
3. Frequent, sustained and often painful erec
tions in males in the beginning of therapy;
subside spontaneously after sometime.
4. Oligozoospermia can occur with moderate
doses given for a few weeks to men with normal
testosterone levels. Prolonged use may produce
testicular atrophy.
Image source:www.shecares.com
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ANDROGEN AND ANABOLIC STERIODS

16. Cont..
5. Salt retention and edema:
especially when large doses are given to patients with heart or kidney disease. This is rare
with the doses used for hypogonadism.
6.Cholestatic jaundice:
occurs with methyltestosterone and other 17 alkyl substituted derivatives as(fluoxymesterone
and anabolic steroids like oxymetholone,stanozolol) the jaundice is reversible on discontinuation.
7.Hepatic carcinoma:
Incidence is higher in patients who have received long term methyl-testosterone or other
oral androgens.
8.Gynaecomastia:
May occur, especially in children and in patients with liver disease.this is due to peripheral
conversion of testosterone to estrogens.
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ANDROGEN AND ANABOLIC STERIODS

17. Image source:Frontiersin.org
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ANDROGEN AND ANABOLIC STERIODS

18. Anabolic steroids
These are synthetic androgens with supposedly higher anabolic and lower androgenic activity.
Drugs are Nandrolone, oxymetholone,stanozolol and methandienone.
■ Abuse in Athletes
■ Arabolic steroids enjoy a reputation for improving athletic performance. When combined
with adequate exercise, the muscle mass increases.
■ But the dose used by athletes is very high and is associated with serious adverse effects like
testicular atrophy, sterility and gynaecomastia in men and virilizing effects in women; increased
aggressiveness, psychotic symptoms and increased risk of coronary heart disease in both sexes.
■ Hence the use of anabolic steroids by athletes has been banned and is medically not
recommended.
Contraindications for the use of androgens:
1. Pregnancy
2. Carcinoma of Prostate / breast ichlidren
3. Infants and cchlidren
4. Renal / cardiac /liver disease.
Image source:tctmd.com
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ANDROGEN AND ANABOLIC STERIODS

19. Antiandrogens
■ Cyproterone acetate :a derivative of progesterone competitively bind to androgen receptors
and thus blocks the action of androgens.it also has progestational activity.is used for,
1. To treat hypersexuality in males
2. In carcinoma prostate and
3. In female hirsutism –used along with an estrogen.
■ Flutamide :Are potent competitive antagonist at androgen receptors.
It’s active metabolite 2-hydroxyflutamide competitively block androgen action on
accessory sex organ as well as on pituitary.Thus,it increases LH secretion by blocking feedback
inhibition.
plasma Testosterone levels increase in males which partially overcome the direct
antiandrogens action.
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ANDROGEN AND ANABOLIC STERIODS

20. ■ Bicalutamide:
This more potent and long acting (t1/2 6days). Given once daily and more hepatotoxic
than flutamide. When used along with GnRH agonist or castration,50mg OD affords marked relief
in bone pain and other symptoms to metastasis.
■ Nilutamide is simliar to bicalutamide ,but appears to produce more adverse effects than it . It’s
used following surgical castration.
■ Enzalutamide is pure androgen receptor antagonist with higher affinity for it.
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ANDROGEN AND ANABOLIC STERIODS

21. 5 –alpha reductase inhibitor
■ Finasteride inhibits the enzyme 5-alpha reductase (type II isozyme) and thus inhibits the
convertion of testosterone to its active metabolite dihydrotestosterone which acts mainly in
the male urogenital tract.
■ Finasteride is used in benign prostatic hypertrophy (BPH) to reduce the prostate size. The
symptoms of obstruction also decrease and there is an Improvement in the urine flow.
■ It may beCombined with tamsulosin or other alpha blockers for synergistic effect.
■ Finasteride is also tried in the treatment of male pattern baldness with fairly good results but it
requires continued use as the effect may be reversed in 5—12 months after stopping the drug.
■ Side effects include decreased libido and impotence.
■ Finasteride may be used along with estrogen and cyproterone in the androgen treatment of
hirsutism.
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ANDROGEN AND ANABOLIC STERIODS

22. Inhibitors of androgen synthesis
Image source:nature.com
• Gonadotropin releasing hormone or Its
agonist like leuprolide when given
continuously inhibits LH and testosterone
secretion resulting in pharmacological
castration –used in men with prostatic
cancer.
• Danazol is a derivative of ethisterone
(17alpha ethinyl testosterone)is primarily
used in the treatment of endometrosis also
used in menorrhagia,fibrocystic disease of
the breast,gynaecomastia,angioodema,
Christmas disease.
• Ketoconazole also inhibits steroid hormone
synthesis and there by inhibit androgen
synthesis.
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ANDROGEN AND ANABOLIC STERIODS

23. Male contraceptive
■ The requirement of a safe and effective chemical contraceptive in men has not been fulfilled
largely because it is difficult to totally suppress spermatogenesis.
■ Various compounds including testosterone with progestin, estrogens with progestins,
antiandrogens like cyproterone acetate have been tried, but are neither reliable nor safe.
■ GnRH agonists and antagonists along with estosterone inhibit gonadotrophin secretion and are
being studied.
■ Gossypol, a cotton seed derivative, has ilts shown to produce oligozoospermia and ay mpair
sperm motility in Chinese studies.
■ This the effect is reversible in a few months. nd Hypokalaemia is the major adverse effect.
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ANDROGEN AND ANABOLIC STERIODS

24. Drug used for erectile dysfunction
■ Sexual impotence is the inability of a man to have satisfactory sexual intercourse due to
inability to have and maintain an erection.
■ During erection, there is of the nonvascular smooth muscle of the corpora covernosa.
■ As a result blood flows into the sinuses of the cavernosa at a high pressure which is
responsible for erection.
■ Several drugs have been tried including testosterone, yohimbine, papaverine and
antidepressants.
■ The recent introduction sildenafil has been a success in a large rostatic percentage of them.
■ Nitric oxide is released which activates guanylyl cyclase leading to increased inhibits synthesis
of cGMP resulting in smooth muscle hereby relaxation.
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25. Sildenafil (Viagra)
■ Sildenafil is the first agent to be effective orally for the treatment of erectile dysfunction.
■ Sildenafil inhibits the enzyme phospho diesterase in the penis and thus prolongs the life of
cyclic GMP.
■ This causes relaxation of smooth muscle in the corpus cavernosum and vasodilation--both
resulting in cavernosal enlargement and penile erection.
■ Sildenafil is given orally.
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ANDROGEN AND ANABOLIC STERIODS

26. Adverse effects of sildenafil
Image source:Aioway.com
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ANDROGEN AND ANABOLIC STERIODS

27. ■ Alprostadil:
■ Alprostadil is PGE, analog that can be injected directly, into the cavernosa.
■ It can also be used as a minisuppository placed in the urethra and it diffuses into the
cavernosal tissue.
■ Alprostadil is used in patients who do not respond to sildenafil or in whom sildenafil cannot
be used.
■ Phentolamine,
■ An alpha blocker, can also be injected into the cavernosa with or without papaverine—called
phentolamine/papa verine induced penile erection (PIPE therapy),
■ However, it is not preferred because of the inconvenience of the route of administration and
complications.
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28. References
■ Principles of anatomy and physiology by Gerard J. Tortora / Bryan derrickson 14TH
EDITION.
■ Essentials of medical pharmacology kd tripathi.
■ Medical pharmacology padmaja uday kumar
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