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Periodic (every six months) X-ray examinations of bone age should be made during treatment of pre-pubertal males to determine the rate of bone maturation and the effects of androgen therapy on the epiphyseal centers. Hemoglobin and hematocrit should be checked periodically for polycythemia in patients who are receiving high doses of androgens. When administered concurrently, the following drugs may interact with androgens: Anticoagulants, oral ‘ C-17 substituted derivatives of testosterone, such as methandrostenolone, have been reported to decrease the anticoagulant requirement. Patients receiving oral anticoagulant therapy require close monitoring especially when androgens are started or stopped. Antidiabetic drugs and insulin ‘ In diabetic patients, the metabolic effects of androgens may decrease blood glucose and insulin requirements. ACTH and corticosteroids ‘ Enhanced tendency toward edema. Use caution when giving these drugs together, especially in patients with hepatic or cardiac disease. Oxyphenbutazone ‘ Elevated serum levels of oxyphenbutazone may result. Androgens may decrease levels of thyroxine-binding globulin, resulting in decreased total T 4 serum levels and increased resin uptake of T 3 and T 4. Free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction. Testosterone has been tested by subcutaneous injection and implantation in mice and rats. The implant induced cervical-uterine tumors in mice, which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats. There are rare reports of hepatocellular carcinoma in patients receiving long-term therapy with androgens in high doses. Withdrawal of the drugs did not lead to regression of the tumors in all cases. Geriatric patients treated with androgens may be at an increased risk for the development of prostatic hypertrophy and prostatic carcinoma. It is not known whether androgens are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from androgens, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Androgen therapy should be used very cautiously in pediatric patients and only by specialists who are aware of the adverse effects on bone maturation, anabolic steroids muscle cramps. Skeletal maturation must be monitored every six months by an X-ray of the hand and wrist (see INDICATIONS AND USAGE and WARNINGS ). Endocrine and Urogenital, Female ‘ The most common side effects of androgen therapy are amenorrhea and other menstrual irregularities, inhibition of gonadotropin secretion, and virilization, including deepening of the voice and clitoral enlargement. The latter usually is not reversible after androgens are discontinued. When administered to a pregnant woman, androgens cause virilization of the external genitalia of the female fetus. Male ‘ Gynecomastia, and excessive frequency and duration of penile erections.
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