Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 65 Androgens

2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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

3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Androgens  Primary clinical application is management of androgen deficiency in males  Principal adverse effects are virilization and hepatotoxicity

4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig. 65–1. Structural formulas of representative androgens.

5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Testosterone  Biosynthesis and secretion  Males: testosterone  Females: preandrogens  Effects on sex characteristics in males  Pubertal transformation  Spermatogenesis

6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Testosterone  Effects on sex characteristics in females  Clitoral growth  Anabolic effects  Skeletal muscle  Erythropoietic effects  Synthesis of erythropoietin  Men have greater hematocrit than women

7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Clinical Pharmacology of the Androgens  Two basic categories  Testosterone and testosterone esters  17-Alpha-alkylated compounds

8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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  Anemias

9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Clinical Pharmacology of the Androgens  Adverse effects  Virilization  Premature epiphyseal closure  Hepatotoxicity  Effects on cholesterol levels  Use in pregnancy  Prostate cancer  Edema  Gynecomastia  Abuse potential (athletic performance)

10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Clinical Pharmacology of the Androgens  Androgen preparations for male patients  Hypogonadism Oral androgens Oral androgens Intramuscular testosterone ester Intramuscular testosterone ester Transdermal testosterone patches Transdermal testosterone patches Transdermal testosterone gels Transdermal testosterone gels Implantable testosterone pellets Implantable testosterone pellets Testosterone buccal tablets Testosterone buccal tablets

11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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  Renal damage  Psychologic effects Mentally healthy: minimal impact Mentally healthy: minimal impact Psychologically unbalanced: could intensify aggression Psychologically unbalanced: could intensify aggression