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.
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.
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.
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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