Androgens (Anabolic Steroids)

Androgens (Anabolic Steroids)

Examples include testosterone, testosterone esters (propio-nate, enanthoate, and cypionate), danazol, fluoxymesterone, methyltestosterone, oxandrolone, nandrolone, stanozolol, ethylestrenol, oxymetholone, methandrostenolone, mester-olone, and boldenone. Testosterone is secreted by the testis and is the main androgen in the plasma of men. In women, testosterone (in small amounts) is secreted by the ovary and adrenal glands. Many of the androgens are modified forms of testosterone (to circumvent rapid degradation in the body) or synthetic testosterone-like drugs.

Anabolic steroids cause a retention of nitrogen which may result in weight gain and a feeling of well-being. There is also retention of potassium, sodium, phosphorus and chloride asso-ciated with a gain in weight, which could be accounted for by the water held in association with the retained salts and protein. Anabolic steroids are thought to promote the improved use of proteins by contributing to the reversal of catabolic processes. Increased protein synthesis has been noted in skeletal muscle cells. They have been used in the treatment of hypogonadism, hereditary angioneurotic oedema, osteoporosis due to androgen deficiency, and also for enhancement of athletic performance, for stimulation of erythropoiesis in refractory anaemias, and enhancement of stature (controversial).

Testosterone is readily absorbed on oral administration, but is virtually ineffective since it is absorbed into the portal circulation and metabolised by the liver before reaching the systemic circulation. Injected testosterone also is metabolised and excreted too quickly for the androgenic effect to manifest. In order to retard the rate of absorption, testosterone esters in oil are used which are less polar than the free steroid, and when injected intramuscularly are slowly absorbed. Testosterone is metabolised mainly in the liver, at first to androstenedione, and later to androsterone or etiocholanolone. Dihydrotestosterone is metabolised to androsterone, androstenedione and andro-stanediol. Esters of testosterone are hydrolysed to free testos-terone and subsequently metabolised in the manner described. Excretion occurs principally in the urine and minimally in the faeces.

Adverse Effects

·              Virilising effects—Results in masculinisation when taken by women, characterised by hirsutism, acne, deepening of the voice, menstrual irregularities, male pattern baldness,prominent musculature, and hypertrophy of clitoris.

·              Feminising effects—Seen in men who receive androgens,* and is characterised by gynaecomastia. This is because of conversion (by aromatisation) of the androgen to oestrogen in extraglandular tissues.

·              Administration of anabolic steroids during gestation may result in masculinisation of the urogenital sinus and clitoral hypertrophy. Premature bone maturation and decreased birthweight have been reported.

·              Growing children may develop pre-mature fusion of the epiphyses of long bones, leading to permanent short stature.

·              Cystic acne, sebaceous cysts, furunculosis, and seborrheic dermatitis have occurred in persons using anabolic steroids.

Toxic Effects

·              Oedema—Retention of water and sodium chloride leads to

·              weight gain and oedema.

·              Jaundice—Results from stasis and accumulation of bile inbiliary capillaries of the central portion of hepatic lobuleswithout obstruction in the larger ducts. Peliosis hepatis is

·              common: formation of blood-filled sacks in the peripheral zones of hepatic lobules. There is elevation of plasma levels of bilirubin, aspartate aminotransferase, and alkaline phos- phatase. An increased predisposition to hepatic carcinoma has been reported. Hepatotoxicity is however rare with testosterone esters.

·              CVS effects—Hypertension and thrombotic complications (stroke, myocardial infarction).

·              Endocrine effects—Testicular atrophy, low sperm count, sterility, gynaecomastia. In women, masculinising effects occur (vide supra). Decreased testicular size is a common complaint among users, and a common finding in chronic users at autopsy.

·              Behavioural changes—Increased aggressiveness, iritability, psychosis. Increased aggression known as “roid rage”, delusional grandiosity, and acts of violent crime including homicide have been described as a result of anabolic steroid abuse by athletes. Psychotic symptoms have been described in bodybuilders and football players during periods of anabolic steroid abuse. Patients who chronically misuse anabolic steroids may experience a withdrawal reaction. Anorexia, depression, fatigue, insomnia, decreased sex drive, and dissatisfaction with body image have all been reported.

·              Anabolic steroid use parallel with exercise may lead to dysplasia of collagen fibrils, decreased tendon strength, and increased likelihood of rupture under stress. Several cases of unusual tendon rupture have been reported among steroid users, including that of triceps, extensor pollicis longus, and rectus femoris.

Treatment

·              Blood anabolic steroid levels are not clinically useful.

·              Withdrawal of androgen. Steroid withdrawal needs to be treated as other drug withdrawals, including detoxification, support in denial phase, short-term rehabilitation/recovery therapy, and long-term aftercare recovery.

·              Natriuresis for treatment of oedema.

·              Supportive and symptomatic measures. In acute single overdosage, toxicity is unlikely. Gastrointestinal decon- tamination is generally not needed after acute ingestion unless another toxic coingestant is involved.

·              Liver-specific isoenzymes (alkaline phosphatase, lactate dehydrogenase) should be used to monitor liver function in athletes.

·              Some of the effects resulting from long-term administration are irreversible.

Forensic Issues: Abuse of anabolic steroids by athletesto enhance performance has attained epidemic proportions in recent times. Athletes often take doses of androgens in 100 to 1000-fold excess over physiologic doses. In spite of such widespread conviction about the “beneficial” effects of anabolic steroids in relation to athletic performance, it is not yet clear as to whether these agents really do work (except for increasing muscle mass). The tragic part is that several athletes have died in their prime due to the adverse effects of such abuse. Testing for anabolic steroids in athletes is now mandatory during the course of competitive athletic events. Testosterone abuse may be detected by checking the ratio of testosterone to epitestos-terone. If this ratio exceeds 6 to 1, it is an indication of exog-enous testosterone use. The International Olympic Committee has issued strict guidelines in this regard, and suggests that gas chromatography-mass spectrometry (GC-MS) is the best method for drug testing in urine samples. Oral products can be detected for 2 to 14 days after the last use, and injectables for up to a month. Nandrolone decanoate injections can be detected up to 12 months.