1. Chapter 65
Androgens 1

2. Androgens Produced by the testes, ovaries, and adrenal cortex
Major endogenous androgen is testosterone
Noted most for their ability to promote expression of male sex characteristics
Significant physiologic and pharmacologic effects unrelated to sex 2

3. Androgens
Primary clinical application is management of androgen deficiency in males
Principal adverse effects are virilization and hepatotoxicity (see 17-alpha alkylated androgens on next slide) 3

4. Fig. 65–1. Structural formulas of representative androgens.4

5. Testosterone Biosynthesis and secretion
Males: testosterone
Females: preandrogens
Effects on sex characteristics in males
Pubertal transformation
Spermatogenesis 5

6. Testosterone Effects on sex characteristics in females
Clitoral growth
Anabolic effects
Skeletal muscle
Erythropoietic effects
Synthesis of erythropoietin
Men have greater hematocrit than women- has more impact in women 6

7. Clinical Pharmacology of the Androgens
Two basic categories
Testosterone and testosterone esters
17-Alpha-alkylated compounds (methyltestosterone, fluoxymesterone) 7

8. Clinical Pharmacology of the Androgens
Therapeutic uses
Male hypogonadism
Replacement therapy
Delayed puberty
Breast cancer
Replacement therapy in menopausal women
Wasting in patients with AIDS 8

9. Clinical Pharmacology of the Androgens
Adverse effects
Virilization
Premature epiphyseal closure- we check wrist xrays on children every 6 months
Hepatotoxicity- with 17-alpha alkylated compounds
Effects on cholesterol levels- adverse effects
Use in pregnancy
Prostate cancer- promote growth of existing cancer
Edema- sodium and water retention, HTN, worsening of heart failiure
Gynecomastia
Abuse potential (athletic performance) 9

10. Clinical Pharmacology of the Androgens
Androgen preparations for male patients
Hypogonadism
Oral androgens
Intramuscular testosterone ester
Transdermal testosterone patches
Transdermal testosterone gels
Implantable testosterone pellets
Testosterone buccal tablets 10

11. Androgen (Anabolic Steroid) Abuse by Athletes
Many athletes use to enhance athletic performance
Significant risks
Hypertension, suppression of release of LH and FSH, testicular shrinkage, sterility, gynecomastia, acne, reduction in HDL and increase in LDL
Hepatotoxicity with 17-alpha-alkylated compounds
Psychologic effects
Mentally healthy: minimal impact
Psychologically unbalanced: could intensify aggression 11