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Male sex hormones

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Title: Male sex hormones


1
Male sex hormones
By C.Adithan
2
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

3
Androgens
  • Includes testosterone, DHT androstenedione
  • - Testosterone serves as a prohormone for
  • Dihydrotestosterone (DHT)
  • Oestradiol

4
Cholesterol
Oestriol
17-a- Hydroxy pregnenolone
Dehydro-epi androsterone
Pregnenolone
Progesterone
17- Hydroxy progesterone
Andro-stenedione
Oestrone
TESTOSTERONE
OESTRADIOL
5
Regulation of secretion
  • Oestrogen similar to Testosterone
  • Inhibin inhibits FSH secretion at A.P level

6
cytoplasm
Nucleus
R
T- R
T- R
10
90
T
DHT
DHT- R
R
5-?reductase
7
Testosterone DHT
8
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9
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

10
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

11
Adverse effects of testosterone
  • Virilization (female)
  • Feminizing side effects (male)
  • Precocious puberty stunted growth
  • Cholestatic jaundice
  • Enlargement of prostate
  • Atherosclerosis
  • Hepatic carcinoma
  • Oedema

12
Anabolic steroids
13
(No Transcript)
14
Uses of anabolic steroids
  • Osteoporosis
  • Catabolic states
  • Short stature
  • Anaemia (refractory)
  • Athletic performance

15
Anti-androgens
  • Danazol
  • Cyproterone acetate
  • Flutamide
  • Finasteride

16
Danazol
  • FSH LH release in both sexes
  • Binding of steroids to receptors
  • Enzymes needed for steroid synthesis
  • Weak androgenic, anabolic, progestational
    glucocorticoid action

17
Cyproterone acetate
  • Block androgen receptors
  • secretion of gonadotropins
  • Uses
  • Acne
  • Male pattern of baldness
  • hirusitism
  • Ca. of prostate
  • Virilizing syndrome
  • Precocious puberty
  • Inappropriate behaviour

18
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.

19
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.
20
SILDENAFIL
21
Hypothalamus
ANS
Parasympathetic
Sympathetic
Noradrenaline
Acetyl choline
vasoconstriction
Muscarinic Receptors
Penile flaccidity
Penile erection
22
Muscarinic Receptors
? VP
? NO
ATP
AC
GC
GTP
cGMP
cAMP
PDE V
? Ca
5 GMP
Vasodilatation
Penile Erection
23
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
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