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Chapter: Modern Pharmacology with Clinical Applications: Androgens, Antiandrogens, and Anabolic Steroids

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Androgens: Adverse Effects

As a class, the androgens are relatively safe and non-toxic. However, in inappropriate doses or for inappro-priate reasons, their use can result in significant toxicity.

ADVERSE EFFECTS

 

As a class, the androgens are relatively safe and non-toxic. However, in inappropriate doses or for inappro-priate reasons, their use can result in significant toxicity.

 

Toxicity in Men

 

The administration of androgens to sexually mature hy-pogonadal men is associated with few untoward effects. However, prepuberal or hypogonadal males never ex-posed to testosterone show enhanced sensitivity to ad-ministered androgens, and many do not like the effects. Testosterone administration can cause irritability, agita-tion, or aggressive behavior. Androgen administration to normal males inhibits the release of the pituitary go-nadotropins FSH, LH, and as a consequence, endoge-nous testicular production of testosterone is reduced. Spermatogenesis is also reduced, and if administration is continued, azoospermia and infertility may result. Peripheral aromatization of androgens to estrogens can cause gynecomastia. Cessation of exogenous androgen treatment in normal males usually results in restoration of normal sperm levels over a 6-month period. Finally, androgen replacement therapy in elderly men should be monitored closely. Men at this age are at risk for devel-oping prostatic neoplasms (benign and malignant), and use of androgens in this setting is contraindicated be-cause of the likelihood of stimulating growth of these tumors.

 

 

Toxicity in Women

 

Although masculinization is a desired action of andro-gens in the treatment of men with testicular deficien-cies, these effects can be quite distressing to women. The degree of virilization in women will vary with the dosage, duration of therapy, and particular androgen preparation used. In women receiving high doses of an- drogen for any reason, facial hair growth may progress to total body hair growth, baldness may develop, breasts may shrink, and the voice may deepen. In addition, cli-toral hypertrophy, uterine atrophy, and menstrual irreg-ularities may develop. Although some of the symptoms are reversible and disappear upon cessation of therapy, several effects—baldness, growth of facial hair, clitoral enlargement, and deepening of the voice—are com-monly irreversible. Steroids taken by women during pregnancy may cause pseudohermaphroditism in the genetically female fetus and may even cause its death.

 

Toxicity in Either Sex

 

Androgen administration to male or female adults, es-pecially at high dosages, results in erythrocytosis and polycythemia, fluid retention, and it may produce or ex-acerbate edema. This can be serious when associated with congestive heart failure, cirrhosis of the liver, or nephrotic syndrome. Since androgens stimulate the ac-tivity of sebaceous glands, oily skin and acne are found in some individuals who are receiving androgen ther-apy. A change in cholesterol levels can result from an-drogen therapy, such as decreased levels of high-density lipoprotein cholesterol and increased levels of low-density lipoprotein cholesterol. This change in the distri-bution of cholesterol may contribute to increased risk of atherosclerosis and coronary artery disease, espe-cially in athletes who are exposed for long periods to high levels of anabolic steroids.

 

Oral androgen preparations that have the 17-methyl substitution on the steroid molecule are associated with the development of liver disorders, including hyper-bilirubinemia, and elevated liver function tests. As many as 80% of individuals who take these compounds have been shown to develop liver problems. Although these changes are usually reversed if steroid treatment is dis-continued, use of the oral preparations is also associ-ated with the development of benign liver tumors and a rare liver disorder involving the development of blood-filled sacs (peliosis hepatis). Finally, worsening of sleep apnea and precipitation of superior sagittal sinus thrombosis—seizures, facial palsy, hemiplegia, stupor, and coma—have been associated with androgen therapy.

 

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