Male sex hormones

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Male sex hormones
By C.Adithan
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Male sex hormones

• Androgens
• Synthesis secretion
• Regulation
• Pharmacological actions
• Pharmacokinetics
• Preparations
• Therapeutic uses
• Adverse effects

• Anabolic steroids
• Differ from androgens?
• Preparations
• Therapeutic uses
• Adverse effects
• Anti-androgens
• Danazole
• Cyproterone acetate
• Flutamide
• Finasteride
• Sildenafil

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Androgens

• Includes testosterone, DHT androstenedione
• - Testosterone serves as a prohormone for
• Dihydrotestosterone (DHT)
• Oestradiol

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Cholesterol
Oestriol
17-a- Hydroxy pregnenolone
Dehydro-epi androsterone
Pregnenolone
Progesterone
17- Hydroxy progesterone
Andro-stenedione
Oestrone
TESTOSTERONE
OESTRADIOL
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Regulation of secretion

• Oestrogen similar to Testosterone
• Inhibin inhibits FSH secretion at A.P level

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cytoplasm
Nucleus
R
T- R
T- R
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90
T
DHT
DHT- R
R
5-?reductase
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Testosterone DHT
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Pharmacokinetics

• Absorption undergoes high first pass metabolism.
  Therefore i.m. injections or synthetic
  preparations are used.
• Transport highly protein bound
• (98, SHBG,albumin)
• Metabolism
• by liver enzymes androsterone
  etiocholanolone
• excretion by urine after conjugation
• small quantity of oestrogen also produced from
  testosterone

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Clinical uses of testosterone

• Testicular failure Primary Secondary
• Chronic illness
• Burns
• Osteoporosis
• Long term corticosteroid therapy
• Pituitary dwarfism
• Carcinoma of breast
• Hereditary angioneurotic oedema
• Anaemia (refractory)
• Menopausal syndrome

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Adverse effects of testosterone

• Virilization (female)
• Feminizing side effects (male)
• Precocious puberty stunted growth
• Cholestatic jaundice
• Enlargement of prostate
• Atherosclerosis
• Hepatic carcinoma
• Oedema

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Anabolic steroids
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Uses of anabolic steroids

• Osteoporosis
• Catabolic states
• Short stature
• Anaemia (refractory)
• Athletic performance

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Anti-androgens

• Danazol
• Cyproterone acetate
• Flutamide
• Finasteride

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Danazol

• FSH LH release in both sexes
• Binding of steroids to receptors
• Enzymes needed for steroid synthesis
• Weak androgenic, anabolic, progestational
  glucocorticoid action

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Cyproterone acetate

• Block androgen receptors
• secretion of gonadotropins
• Uses
• Acne
• Male pattern of baldness
• hirusitism
• Ca. of prostate
• Virilizing syndrome
• Precocious puberty
• Inappropriate behaviour

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Flutamide

• Non-steroidal anti-inflammatory
• Antagonise androgens
• Accessory sex organs
• Pituitary
• Uses
• Cancer of prostate along with GnRH agonist
• Female hirusitism
• Dose 250 mg tds.

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5 ? reductase inhibitors
Finasteride
Prostate volume Symptom score Peak urine flow
rate DHT level in prostate

• Orally active
• DHT levels
• Benign prostatic
• hyperplasia
• Dose 5mg/day

Also used for prevention of hair loss
Side effects Loss of libido impotence in 5
pts.
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SILDENAFIL
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Hypothalamus
ANS
Parasympathetic
Sympathetic
Noradrenaline
Acetyl choline
vasoconstriction
Muscarinic Receptors
Penile flaccidity
Penile erection
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Muscarinic Receptors
? VP
? NO
ATP
AC
GC
GTP
cGMP
cAMP
PDE V
? Ca
5 GMP
Vasodilatation
Penile Erection
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Sildenafil

• Inhibits PDE5 in the corpus cavernosa of the
  penis
• 50mg, p.o. 1 h before sexual activity
• potentiate nitrates hypotension activity
• ketoconazole erythromycin increases its level
• renal hepatic disease increases its level
• Side effects
• headache, flushing, dyspepsia, myalgia