Androgen production falls with age in men and may contribute to the decline in muscle mass, strength, and libido. Preliminary studies of androgen replacement in aging males with low androgen levels show an increase in lean body mass and hematocrit and a decrease in bone turnover. However, many factors other than deficient androgen production contribute to these effects of aging. Longer studies will be required to assess the usefulness of this therapy.
The adverse effects of these compounds are due largely to their masculinizing actions and are most noticeable in women and prepubertal children. In women, the administration of more than 200–300 mg of testosterone per month is usually associated with hirsutism, acne, amenorrhea, clitoral enlargement, and deepening of the voice. These effects may occur with even smaller doses in some women. Some of the androgenic steroids exert progestational activity, leading to endometrial bleeding upon discontinuation. These hormones also alter serum lipids and could conceivably increase susceptibility to atherosclerotic disease in women.
Except under the most unusual circumstances, androgens should not be used in infants. Recent studies in animals suggest that administration of androgens in early life may have profound effects on maturation of central nervous system centers governing sexual development, particularly in the female. Administration of these drugs to pregnant women may lead to masculinization or undermasculinization of the external genitalia in the female and male fetus, respectively. Although the above-mentioned effects may be less marked with the anabolic agents, they do occur.
Sodium retention and edema are not common but must be carefully watched for in patients with heart and kidney disease.
Most of the synthetic androgens and anabolic agents are 17-alkyl-substituted steroids. Administration of drugs with this structure is often associated with evidence of hepatic dysfunction. Hepatic dysfunction usually occurs early in the course of treatment, and the degree is proportionate to the dose. Bilirubin levels may increase until clinical jaundice is apparent. The cholestatic jaundice is reversible upon cessation of therapy, and permanent changes do not occur. In older males, prostatic hyperplasia may develop, causing urinary retention.
Replacement therapy in men may cause acne, sleep apnea, erythrocytosis, gynecomastia, and azoospermia. Supraphysiologic doses of androgens produce azoospermia and decrease in testicular size, both of which may take months to recover after cessation of therapy. The alkylated androgens in high doses can produce peliosis hepatica, cholestasis, and hepatic failure. They lower plasma HDL and may increase LDL. Hepatic adenomas and carcinomas have also been reported. Behavioral effects include psychological dependence, increased aggressiveness, and psychotic symptoms.
The use of androgenic steroids is contraindicated in pregnant women or women who may become pregnant during the course of therapy.
Androgens should not be administered to male patients with carcinoma of the prostate or breast. Until more is known about the effects of these hormones on the central nervous system in developing children, they should be avoided in infants and young children.
Special caution is required in giving these drugs to children to produce a growth spurt. In most patients, the use of somatotropin is more appropriate (see Chapter 37).
Care should be exercised in the administration of these drugs to patients with renal or cardiac disease predisposed to edema. If sodium and water retention occurs, it will respond to diuretic therapy.
Methyltestosterone therapy is associated with creatinuria, but the significance of this finding is not known.
Caution: Several cases of hepatocellular carcinoma have been reported in patients with aplastic anemia treated with androgen anabolic therapy. Erythropoietin and colony-stimulating factors (see Chapter 33) should be used instead.