Chapter 65 Androgens 1

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

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

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

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

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

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

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

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

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

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