A basic pharmacology of Androgens

1. USMANU DANFODIYO UNIVERSITY SOKOTO
COLLEGE OF HEALTH SCIENCES
DEPARTMENT OF PHARMACOLOGY AND THERAPEUTICS
ANDROGENS
ALBASHIR TAHIR
22210708001
JUNE, 2023
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2. Introduction
• Also called male sex hormones, are substances which
cause development of secondary sex characters in the
castrated male.
• In humans, the most important androgen secreted by the
testis is testosterone.
• In men, approximately 8 mg of testosterone is produced
daily.
• About 95% is produced by the Leydig cells and only 5% by
the adrenals.
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3. Introduction…
• The testis also secretes small amounts of another potent androgen,
dihydrotestosterone, as well as androstenedione and
dehydroepiandrosterone, which are weak androgens.
• Pregnenolone and progesterone and their 17-hydroxylated derivatives
are also released in small amounts.
• Plasma levels of testosterone in males are about 0.6 mcg/dL after
puberty and appear to decline after age 50.
• Testosterone is also present in the plasma of women in concentrations
of approximately 0.03 mcg/dL and is derived in approximately equal
parts from the ovaries and adrenals and by the peripheral conversion of
other hormones.
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4. 4

5. Androgens Available For Therapeutic
Use
• Testosterone
• Testosterone Esters
• Testosterone enanthate/undecanoate/cypionate
• 17α-Alkylated Androgens
• Methyltestosterone, oxandrolone, stanozolol, fluoxymesterone, danazol
• Other
• 7α-Methyl-19-nortestosterone, tetrahydrogestrinone
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6. Physiologic Effects
• In the normal male, testosterone or its active metabolite 5α-
dihydrotestosterone is responsible for the many changes that occur in
puberty.
• In addition to the general growth-promoting properties of androgens
on body tissues, these hormones are responsible for penile and scrotal
growth.
• Changes in the skin include the appearance of pubic, axillary, and
beard hair.
• The sebaceous glands become more active, and the skin tends to
become thicker and oilier.
• The larynx grows and the vocal cords become thicker, leading to a
lower-pitched voice.
• Skeletal growth is stimulated and epiphysial closure accelerated.
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7. Physiologic Effects…
• Other effects include growth of the prostate and seminal vesicles,
darkening of the skin, and increased skin circulation.
• Androgens play an important role in stimulating and maintaining
sexual function in men.
• Androgens increase lean body mass and stimulate body hair growth
and sebum secretion.
• Metabolic effects include the reduction of hormone binding and other
carrier proteins and increased liver synthesis of clotting factors.
• They also stimulate renal erythropoietin secretion and decrease HDL
levels.
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8. Physiologic Effects…
• In women, androgens are capable of producing changes similar to
those observed in the prepubertal male.
• These include growth of facial and body hair, deepening of the
voice, enlargement of the clitoris, frontal baldness, and prominent
musculature.
• The administration of androgens reduces the excretion of
nitrogen into the urine, indicating an increase in protein synthesis
or a decrease in protein breakdown within the body.
• This effect is much more pronounced in women and children than
in normal men.
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9. Pharmacodynamics
• Like other steroids, testosterone acts intracellularly in target cells.
• In skin, prostate, seminal vesicles, and epididymis, it is converted to
5α- dihydrotestosterone by 5α-reductase.
• In these tissues, dihydrotestosterone is the dominant androgen.
• The distribution of this enzyme in the foetus is different and has
important developmental implications.
• Testosterone binds to the intracellular androgen receptor, forming a
complex that translocates to the nucleus, where it binds to and
regulates the transcription of various genes, leading to growth,
differentiation, and synthesis of a variety of enzymes and other
functional proteins.
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10. Pharmacokinetics
• Testosterone is inactive orally due to high first pass metabolism in liver.
• The duration of action after i.m. injection is also very short.
• Testosterone in circulation is 98% bound to sex hormone binding
globulin (SHBG) and to albumin.
• The major metabolic products of testosterone are androsterone and
etiocholanolone which are excreted in urine, mostly as conjugates with
glucuronic acid and sulfate.
• Small quantities of estradiol are also produced from testosterone by
aromatization in extraglandular tissues (liver, fat, hypothalamus).
• Plasma t½ of testosterone is 10–20 min.
• Methyltestosterone , Fluoxymesterone, Danazol, Nadrolone.
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11. Clinical Uses
Androgen Replacement Therapy in Men
• Androgens are used to replace or augment endogenous androgen secretion in
hypogonadal men.
Gynecologic Disorders
• Androgens have been used to reduce breast engorgement during the
postpartum period, usually in conjunction with estrogens.
• Androgens are sometimes given in combination with estrogens for
replacement therapy in the postmenopausal period in an attempt to
eliminate the endometrial bleeding that may occur when only estrogens are
used and to enhance libido.
• They have been used for chemotherapy of breast tumours in premenopausal
women.
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12. Clinical Uses…
Hypopituitarism
• Androgens are added at the time of puberty to other hormonal replacement.
AIDS related muscle wasting
• Testosterone therapy has been shown to improve weakness and muscle
wasting in AIDS patients with low testosterone levels.
Hereditary angioneurotic oedema
• The attacks can be prevented by 17α-alkylated androgens
(methyltestosterone, stanozolol, danazol) but not by testosterone.
• These drugs act by increasing synthesis of complement (C1) esterase
inhibitor.
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13. Clinical Uses…
Ageing
• Because testosterone levels decline in old age, it has been
administered to elderly males to improve bone mineralization and
muscle mass.
• However, safety of such therapy in terms of metabolic,
cardiovascular and prostatic complications is not known.
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14. Side Effects
• Virilization, excess body hair and menstrual irregularities in
women.
• Many effects, e.g. voice change may be permanent after prolonged
therapy.
• Acne: in males and females.
• Frequent, sustained and often painful erections in males in the
beginning of therapy; subside spontaneously after sometime.
• Oligozoospermia can occur with moderate doses given for a few
weeks to men with normal testosterone levels.
• Prolonged use may produce testicular atrophy.
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15. Side Effects…
• Precocious puberty, premature sexual behaviour, and stunting of
stature due to early closure of epiphysis—if testosterone is given
continuously to young boys for increasing stature.
• Salt retention and edema: especially when large doses are used in
patients with heart or kidney disease.
• Cholestatic jaundice: occurs with methyltestosterone and other
17-alkyl substituted derivatives (fluoxymesterone) and some
anabolic steroids likeoxymetholone, stanozolol).
• Jaundice is reversible on discontinuation.
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16. Side Effects…
• Hepatic carcinoma: incidence is higher in patients who have
received long-term methyltestosterone or other oral androgens.
• Gynaecomastia: may occur, especially in children and in patients
with liver disease.
• This is due to peripheral conversion of testosterone to estrogens.
• Dihydrotestosterone does not cause gynaecomastia because it is not
converted to estradiol.
• Lowering of HDL and rise in LDL levels, especially with 17α-
alkylated analogues.
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17. Contraindications
• Carcinoma of prostate and male breast
• Liver and kidney disease
• During pregnancy (masculinization of female foetus).
• They should not be given to men aged >65 years, and to those
with coronary artery disease or CHF.
• Androgen therapy can worsen sleep apnoea, migraine and
epilepsy.
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18. References
• Basic and Clinical Pharmacology, 14th Edition by Bertram G.
Katzung, Anthony J. Trevor, and Marieke Knuidering-Hall.
• Essentials of Medical Pharmaclogy, 7th Edition by KD Tripathi.
• Goodman and Gilman's The Pharmacological Basis of
Therapeutics, 13th Edition by Laurence Brunton, Bjorn Knollman,
and Randa Hilal-Dandan.
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19. THANK YOU
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