Testosterone and other androgens may give rise to adverse effects related to their androgenic or anabolic activities. These include increased retention of sodium and water, oedema, hypercalcaemia, and impaired glucose tolerance. Other effects include increased low density- lipoprotein cholesterol, decreased high-density- lipoprotein cholesterol, increased haematocrit, and suppression of clotting factors. Androgens may cause headache, depression, and gastrointestinal bleeding. It has been suggested that androgens may induce sleep apnoea in susceptible patients. Abnormal liver function tests may occur and there have been reports of liver toxicity including jaundice and cholestatic hepatitis. There have also been reports of peliosis hepatis and hepatic tumours in patients who have received high doses over prolonged periods. These adverse hepatic effects have occurred primarily with the 17α-alkylated derivatives (. methyltestosterone, stanozolol). In men, large doses suppress spermatogenesis and cause testicular atrophy. Epididymitis and bladder irritability can occur. Priapism is a sign of excessive dosage and may occur especially in elderly males. Gynaecomastia may occur. Androgens may cause prostatic hyperplasia and accelerate the growth of malignant neoplasms of the prostate. Continued use produces symptoms of virilism, such as hirsutism or male-pattern baldness, deepening of the voice, atrophy of the breasts and endometrial tissue, oily skin, acne, and hypertrophy of the clitoris. Virilisation may not be reversible, even after stopping therapy. Large and repeated doses in early puberty may cause closure of the epiphyses and stop linear growth. Children may experience symptoms of virilisation: in boys there may be precocious sexual development with phallic enlargement and increased frequency of erection, and in girls, clitoral enlargement. Gynaecomastia may also occur in boys. Masculinisation of the external genitalia of the female fetus may occur if androgens are given during pregnancy. After transdermal application of testosterone, skin reactions may include irritation, erythema, allergic contact dermatitis, and sometimes burn-like lesions. Skin reactions are more common with patches that contain permeation enhancers. The anabolic steroids, because they generally retain some androgenic activity, share the adverse effects of the androgens described above, but their virilising effects, especially in women, are usually less. There have been reports of adverse psychiatric effects in athletes taking large doses to try and improve performance.