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Androgens & Antiandrogens

Androgens & Antiandrogens. Munir Gharaibeh, MD, PhD, MHPE Faculty of Medicine The Jordan University April 2014. Androgens. The testes have two major functions: 1. Spermatogenesis occurring within the seminiferous tubules 2. Production of androgenic hormones. Androgens.

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Androgens & Antiandrogens

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  1. Androgens & Antiandrogens Munir Gharaibeh, MD, PhD, MHPE Faculty of Medicine The Jordan University April 2014

  2. Androgens The testes have two major functions: 1. Spermatogenesis occurring within the seminiferous tubules 2. Production of androgenic hormones

  3. Androgens Naturally occurring androgenic hormones are: 1. Testosterone, the principal androgenic hormone, is mainly produced by the Leydig cells of testes. 2. Dehydroepiandrosterone (DHEA) is produced by adrenal cortex. 3. Androstenedione The testes also produce other hormones: Estradiol Inhibin( feedback inhibits FSH) Activin

  4. Testosterone synthesis DEDeh Cholesterol Pregnenolone Progesterone Hyd Testosterone AndrostenedioneHydroxyprog. 5α-reductase 5α-dihydrotestosterone Munir Gharaibeh, MD, PhD, MHPE

  5. GnRH - ↓ LH; FSH - ↓ Testosterone; spermatogenesis Munir Gharaibeh, MD, PhD, MHPE

  6. Transport & MOA of androgens: • 65% is bound to SHBG, 2% is free, rest bound to albumin. 5α-reductase Testosterone 5α-dihydrotestosterone (sex organs) (skeletal muscles) cytosloic; nuclear receptors increase transcription of a specific protein androgen effects DHT is 10 times more potent than testosterone and mediates the effects of testosterone on skin and sexual apparatus (prostate; seminal vesicle, epididymis…) Munir Gharaibeh, MD, PhD, MHPE

  7. Pharmacological effects • Virilizing=musculinizing effect 1° & 2° sexual characteristics • Spermatogenesis • Erythropoiesis • Anabolic or growth promoting effect (bone; skeletal muscles) Munir Gharaibeh, MD, PhD, MHPE

  8. Clinical Uses • Testosterone deficiency Hypogonadism; impotence; ↓ libido; aging; infertility. • Anemia; leukemia; lymphoma • Endometriosis (Danazol is particularly used) Munir Gharaibeh, MD, PhD, MHPE

  9. Clinical Uses • Antiestrogenic effect: Breast cancer. • Anabolic effect. Osteoporosis Abused by athletes. Munir Gharaibeh, MD, PhD, MHPE

  10. Testosterone preparations For androgen replacement: • Testosterone I.M; S.C • Testosterone propionate I.M, S.L • Testosterone cypionate I.M; depo I.M • Methyltestosterone O; S.L • Fluoxymestrone O For breast cancer: Testolactone (progesterone derivative and aromatase inhibitor) O Munir Gharaibeh, MD, PhD, MHPE

  11. Testosterone preparations For anabolism (osteoporosis): Androgen:anabolic ratio=1:2 or 1:3 (promote + ve anabolism and muscular growth but little effect on sex) • Ethylestrenol O • Stanozolol O • Oxandrolone O • Nandrolonedecanoate I.M • Methandienone O Munir Gharaibeh, MD, PhD, MHPE

  12. Side Effects of Testosterone • Virilization (musculinization) Hirsutism; acne; menstrual disorders in ♀’s • Precocious puberty & hirsutism in children • Salt & water retention • Jaundice; gall bladder stones (methyltestosterone) • Enlargement of prostate • ? Liver cancer Munir Gharaibeh, MD, PhD, MHPE

  13. Antiandrogens • Estrogens: Diethylstilbesterol; mestranol... • Progestins: Cyproterone acetate • GnRHsuperagonists (Leuprolide acetate); GnRH antagonists (Ganirelix) Flutamide; Bicalutamide and Nilutamide • 5α- reductase inhibitors: Finasteride • Ketoconazole • Spironolactone • Gossypol Munir Gharaibeh, MD, PhD, MHPE

  14. Gossypol Munir Gharaibeh, MD, PhD, MHPE Cottonseed derivative, China. Destroys elements of the seminifrous epithelium, but does not affect the endocrine function of the testes. Irreversible if continued more than 2 years. Can cause hypokalemia and paralysis. Not used in western medicine.

  15. Clinical Uses of Antiandrogens • Ca prostate • Benign hyperplasia of the prostate (Finasteride) • Severe acne and hirsutism in ♀’s (Spironolactone; Cyproterone acetate) • Precocious puberty • ♂ antifertility agents (♂ contraceptive) (Gossypol) • ♂ baldness (Cyoctol=topical antiandrogen; Finasteride) Munir Gharaibeh, MD, PhD, MHPE

  16. Side Effects of Antiandrogens Munir Gharaibeh, MD, PhD, MHPE ↓ Libido Impotence ↓ Spermatogenesis ↓ Ejaculate

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