Male Sex hormones & Drugs use in Erectile dysfunction(ED)

1. presented By
Dr. Manoj Kumar
Assistant Professor
Department of Pharmacology
Adesh Medical College & Hospital Ambala Can’t

2.  Male
 Androgens
 Anti-androgens
 Female
 Oestrogens
 Anti-oestrogen
 Progestin
 Anti-progestin
2

3.  Testes – 8-12 mg testosterone androgens
are synthesize from cholesterol
 5 alpha reducates – Dihydrotestosterone
in extra glandular tissue.
 Adrenal cortex – Dihydrotestosterone,
androstenedione ( weak androgens)
 Ovary – small amount testosterone
3

4. Testosterone
 Source: Leydig Cells (interstitial cells) of testes
under influence of LH of anterior pituitary
Androgens: 2 types
 Natural: Testosterone, Dihydrotestosterone
 Synthetic: Methyltestosterone, testosterone
undecanoate
4

5. 5
Hypothalamus
Anterior Pituitary
Paracrine
Effect
Testosterone Inhibin
Leydig
Cells
Sertoli
Cells
Systemic
Effects
Gn-RH
FSH
LH

6. Androgenic effects
 Development of male secondary sexual
characters
 Breast development at puberty in female
 Growth spurt
 Regression of facial & body hair growth
 Oily sebaceous secretions
 Predilection for acne
 Laryngeal growth  Deepening of voice
 Maturation of reproductive organs
 Improve libido 6

7. Anabolic effects
 Increase in mass & strength of skeletal muscle
 Erythropoiesis
7
 .

8. 8

10. Testosterone Estrogen
Aromatase
Testosterone DHT
5α-reductase
10

11.  When given orally
 High pre-systemic elimination
 Extensive metabolism in liver
 Converted to dihydrotestosterone in skin, prostrate,
seminal vesicles
 Preferred route: IM
 Well absorbed from skin & mucosa
 Available in topical gel
 Precautions for factory workers
 Scrotal patches available
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12.  Therapeutic uses
 Replacement therapy in hypogonadism
 Senile osteoporosis in males
 Undescended testes, delayed puberty
 Adverse effects
 Sodium & water retention edema
 Weight gain
 Jaundice
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13. In females
Hirsutism, menstrual irregularities, breast
atrophy, acne, deepening of voice
 In children
 Impairment of growth due to premature closure of
epiphysis
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14.  Anabolic steroids
 Promote protein synthesis
 Increase muscle mass
 Weight gain
 Lesser androgenic action
 Greater anabolic action
 Nandrolone (IM), oxandrolone (oral),
stanozolol (oral), ethylestrenol (oral)
14

15. 15
Androgen Biosynthesis
Cholesterol
Pregnenolone
17-OH
Pregnenolone
DHEA
Androstenedione
Corticosteroid pathway
17-OH
Progesterone
Progesterone
Testosterone

16.  Chronic illness
 To improve appetite & feeling of well being
 Recovery from prolonged illness, surgery, burns,
trauma
 Breast cancer
 Postmenopausal , senile osteoporosis
 Aplastic anemia
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17.  Adverse effects
 Same as testosterone
 Abused by athletes to increase muscle strength,
performance
 Cholestatic jaundice, increased risk of CAD,
sudden death, testicular atrophy, sterility,
gynaecomastia
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18.  Physiological antagonist of androgen
 Oestrogen
 Decrease androgen levels by inhibiting gonadotropin
secretion
 Testosterone synthesis inhibitors
 Ketoconazole, spironolactone, danazol
 Androgen receptor blockers
 Flutamide, cyproterone, spironolactone, Nilutamide
 5α-reductase inhibitors: Finasteride, Dutasteride
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19. Testes
Testosterone
Dihydrotestosterone
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5α-reductase
-
Finasteride
-
Ketoconazole
Androgen receptors blocker
-
Flutamide

20.  Ketoconazole
 Antifungal agent
 Inhibits adrenal & gonadal steroid synthesis
 Spironolactone
 Aldosterone antagonist
 Inhibits testosterone synthesis
20

21.  Weak androgenic, progestational, antioestrogenic
anabolic actions
 Inhibits spermatogenesis
 Ovulation in females
 Inhibits testosterone secretion
 Inhibits synthesis, release of gonadotropins
 Uses
 Endometriosis
 Hereditary angioneurotic edema
 Gynaecomastia
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23.  Flutamide, cyproterone
 Block action of androgens on target cell
 Prevent binding of DHT to Androgen receptors
 Uses
 Carcinoma of prostrate
 Acne
 Hirsutism in females
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24.  Adverse effects
 Impotence,
 Hot flushes,
 Gynaecomastia,
 Decreased spermatogenesis,
 Hepatic damage,
 GI effects (nausea, vomiting, diarrhoea)
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25. Finasteride
 Decrease conversion of Testosterone into DHT
 Used orally
 Benign hypertrophy of prostrate
 ↓ size & ↑ outflow
 Baldness
 Acne
 Prostrate cancer
 Adverse effects
 Impotence, skin rashes,  libido
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26. 26

27.  Erectile dysfunction(ED) and benign prostatic
hyperplasia(BPH) are the common urological
disorders in male.
 ED is the inability to maintain penile erection for
the successful performance of sexual activity.
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28.  Loss of stimulation.
 poor nerve input to penis.
 poor blood flow to penis.
 Hardening of penis tissue.
 Inability to contain blood.
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29.  Age
 Family history
 vascular disease
 Smoking
 Diabetes
 Medication,
 Depression, sedentary
lifestyle
 Hormone changes
 Prostatic surgery
 Injury of penis
 High blood pressure
 Obesity
 Performance anxiety
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30.  Lifestyle changes.
 Psychotherapy
 Adjust medications
 Pills
 Creams and gels
 Vacuum devices
 Injection
 Surgery
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31.  Stop smoking
 Regular exercise
 Weight loss
 Increase dietary habits & breakfast
 Relationship changes
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32.  Sildenafil(viagra)
 Tadalafil(cialis)
 Vardenafil(levitra, staxyn)
 All the above drugs are phosphodiesterase-5
inhibitors.
 Increase blood flow into penile blood vessels.
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33.  Block enzyme phosphodiesterase-5 inhibitors (PDE -5)
 Enhances normal erection response.
 Improves blood flow into penis.
 PED-5 inhibitor do not increase sex drive.
 Pills will not produce an erection without normal
sexual stimulation.
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34. Onset Duration
(frequency )
Notes
Sildenafil(viagra) 20 – 60
minutes
24 Hours Avoid fatty food,
alcohol
Tadalafil(cialis)
20 – 60
minutes
24 Hours _
Vardenafil(levitra,
staxyn)
20 – 60
minutes
36 Hours _
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35. TABLETS USUAL DOSE
Sildenafil(viagra) 25 mg
50 mg
100 mg
100 mg
Tadalafil(cialis)
10 mg
20 mg
20 mg
Vardenafil(levitra, staxyn)
5 mg
10 mg
20 mg
20 mg
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36. Headache
Flushing
Dyspepsia
Heartburn or indigestion
Nasal congestion
Allergy reaction
Myalgia
Loose motion
Disturbances of color vision(loss of blue/green
discrimination) may occur with PDE5 inhibitors.
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37.  Absorbed orally and half-life is 4 Hrs
 Inhibits PDE5 in the corpus cavernosa of the
penis 50 mg 1 h before sexual activity
 Potentiate nitrate’s hypotension activity
 Ketoconazole, erythromycin, Verapamil
increases its level – due to CYP3A4 inhibition
 Renal & hepatic disease increases its
level
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38. 38

39. Headache,
Flushing,
Dyspepsia,
Myalgia,
Loose motion
Other Uses:
Pulmonary hypertension
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