Androgens & Antiandrogens CPPS307 2025

Learning Objectives

• Understand the different sources androgens, routes of administration, and the definitions and impacts of anabolic steroids.
• Describe anti-androgens: sites of action, pharmacological mechanisms (leuprolide, ganirelix, spironolactone, flutamide, finasteride, cyproterone acetate).
• Recognize the therapeutic uses of anti-androgens.

Overview of Male Reproductive System Control

• The hypothalamus releases Gonadotropin-Releasing Hormone (GnRH) influencing the anterior pituitary.
• Anterior pituitary releases LH (Interstitial Cell-Stimulating Hormone - ICSH) and FSH:
  • FSH: Maintains seminiferous tubules; aids in gametogenesis via Sertoli cells.
  • LH (ICSH): Stimulates Leydig's cells to synthesize testosterone; initiates at puberty.

Primary Functions of Testosterone

• Maintains spermatogenesis and fertility through Sertoli cells.
• Facilitates maturation of spermatozoa in epididymis and vas deferens.
• Feedback regulates pituitary sensitivity to GnRH, influencing LH/ICSH secretion.
• Anabolic effects: promotes muscle growth, bone development, and causes epiphyseal closure post-puberty.

Natural Androgens

• Testosterone: Main natural androgen, synthesized primarily (95%) in Leydig cells.
• Converted to Dihydrotestosterone (DHT) by 5α-reductase at various target sites.
• Intermediary androgens: Androstenedione and Dehydroepiandrosterone (DHEA).
• Natural testosterone is ineffective orally; formulated alternatives can be administered.

Synthetic Androgens

• 17α-methyl testosterone: Available in oral/sublingual forms.
• Testosterone propionate and enantate: Administered parenterally (subcutaneously/intramuscularly).
• Stanozolol: Synthetic anabolic steroid with reduced androgenic and heightened anabolic activity.

Androgen Actions

• Androgenic Effects:

  • Maturation of male reproductive organs.
  • Increased sebaceous gland function & acne.
  • Enhanced body weight, muscle mass, and male-pattern hair distribution (axillary, pubic, facial).
  • Potential for increased libido and overall physical vigor.
  • Note: Hirsutism in females.

• Adverse Effects of Androgens:

  • Suppressed gonadotropin release, leading to infertility.
  • Edema due to salt and water retention.
  • Risk of liver tumors and impaired growth in children.

• Anabolic Effects:

  • Notable in cachexia and prolonged illness.
  • Misuse among athletes and potential adverse effects include liver dysfunction and cardiovascular risks.

Therapeutic Uses of Testosterone

• Combat hypogonadism, stimulate secondary sex characteristics, and aid in osteoporosis treatment.
• Useful in trauma recovery and management of intractable anemia.

Antiandrogens and Their Mechanisms

GnRH Analogs & Antagonists

• Control gonadotropin secretion and have therapeutic applications in hormone-sensitive conditions (prostate cancer, endometriosis).
• Danazol: Inhibits GnRH release and reduces estrogen production in women; reduces androgen synthesis in men.

Mechanism of Action of Specific Antiandrogens

1. Leuprolide: GnRH agonist used for prostate cancer; inhibits FSH/LH production after initial overstimulation.
2. Ganirelix: GnRH antagonist; does not cause initial flare; reduces testosterone levels for prostate cancer management.
3. Flutamide: Non-steroidal antiandrogen; hepatotoxic; blocks DHT receptor actions in prostate cancer therapy.
4. Cyproterone Acetate: Effective for hirsutism and behavioral control in offenders; combines potent progestin and antiandrogen properties.
5. Finasteride: Inhibits 5α-reductase, reducing DHT levels; indicated for hirsutism and prostate cancer management.
6. Spironolactone: Aldosterone antagonist with weak antiandrogenic effects; used as a K+-sparing diuretic and for hirsutism treatment.

Summary of Drug Mechanisms and Uses