Male sex hormones

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1. Androgens

Types: 1. Natural androgens: – Androsterone and testosterone

2. Synthetic androgens: – Testosterone propionate. – Anabolic steroids: Danazol

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Uses: • Hypogonadism: as hormonal replacement therapy.• For Anabolic effects: –Osteoporosis– Severe burns – To increase lean body mass, muscle strength

• Breast cancer • Hereditary angioedema

1. Natural androgens • Testosterone• Converted to dihydrotestosterone (DHT) in skin,

prostate, seminal vesicles, and epididymus.• I.M. testosterone is used to treat androgen deficiency • Effects: – At puberty 2° sexual characteristics in male.– It increase protein synthesis (anabolism), which

increase muscle and bone mass and strength, affect development of male 2° characteristics.

– They increase hair growth and libido in women. Excessive secretion: masculine effects in women.

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2. Synthetic androgensA. Anabolic steroids• Greater anabolic:androgenic activity• Oxandrolone (anabolic: androgenic=3:1-13-1)

Adverse drug reactions:• Infertility: due to suppressed FSH and LH – Decreased testicular size and function

• Masculinization in women: Hirsutism, deepening of voice, menstrual irregularities

• Hepatic dysfunction, Cholestatic jaundice• Psychotic symptoms

Contraindications:1. Benign prostatic hyperplasia and cancer

prostate.2. Pregnancy.3. Children.4. Liver diseases.

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B. Danazol

Mechanism of action: • Danazol is a synthetic steroid analogue with strong

antigonadotropic activity (inhibits pituitary LH and FSH) and weak androgenic action.

• Inhibits CYP450 enzymes involved in gonadal hormone synthesis

Uses:– Endometriosis– Fibrocystic breast disease– Hereditary angioedema (It occurs due to deficiency of

C1- esterase inhibitor)

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Adverse effects– Acne– Hirsutism–Menstrual irregularities– Hepatotoxicity– Thromboembolism– Teratogenic

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2. Antiandrogens

A. Gonadotropin release inhibitors

B. 5a-reductase inhibitorC. Androgen synthesis

inhibitorsD. Androgen Receptor

blockers

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A. Gonadotropin release inhibitors

• Long acting GnRH analogs– Leuprolide–Goserelin–Nafarelin

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B. 5a-reductase inhibitor• In the prostate, testosterone is converted into

dihydrotestosterone (DHT) by the action of 5a-reductase

• DHT acts on prostate cells to stimulate new growth• Finastride: synthetic testosterone derivative• It inhibits the synthesis of Dihydrotestosterone (DHT)

by inhibiting 5a-reductaseTherapeutic uses:• Benign prostatic hyperplasia• Male pattern baldness

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C. Androgen synthesis inhibitors

• Ketoconazole• It is an antifungal agent.Mechanism of action: • It inhibits gonadal & adrenal steroid synthesis by

inhibiting cholesterol side chain cleavage (inhibits P450SCC).

Adverse effects:• Gynecomastia• hepatotoxicity

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D. Androgen Receptor blockers1. Flutamide, BicalutamideMechanism of action: • They block the action of dihydrotestosterone on testosterone

receptors and inhibit the synthesis of new proteins in prostate and prostate cancer cells.

Uses: • Combined with GnRH analogs to treat inoperable prostate Ca.Adverse effects:– Gynecomastia or nipple tenderness– Diarrhea– Hepatotoxicity – Impotence

2. Cyproterone acetate: – It is a competitive blocker of testosterone receptors. – It is used in male hypersexuality, hirsutism, acne,

male baldness, and cancer prostate.

Good luck