Male sex hormones

2 1. Androgens Types: 1.Natural androgens: – Androsterone and testosterone 2.Synthetic androgens: – Testosterone propionate. – Anabolic steroids: Danazol

3 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.

5 2. Synthetic androgens A. 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.

7 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 C 1 - esterase inhibitor)

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

9 2. Antiandrogens A.Gonadotropin release inhibitors B.5  -reductase inhibitor C. Androgen synthesis inhibitors D. Androgen Receptor blockers

10 A. Gonadotropin release inhibitors Long acting GnRH analogs – Leuprolide – Goserelin – Nafarelin

11 B. 5  -reductase inhibitor In the prostate, testosterone is converted into dihydrotestosterone (DHT) by the action of 5  - reductase DHT acts on prostate cells to stimulate new growth Finastride: synthetic testosterone derivative It inhibits the synthesis of Dihydrotestosterone (DHT) by inhibiting 5  -reductase Therapeutic uses: Benign prostatic hyperplasia Male pattern baldness

12 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 P450 SCC ). Adverse effects: Gynecomastia hepatotoxicity

13 D. Androgen Receptor blockers 1.Flutamide, Bicalutamide Mechanism 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.

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