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Anabolic steroids

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Anabolic-androgenic steroids ('anabolic steroids') are structurally related to testosterone.

They have in common the removal of a C19 methyl group from the androgen structure; this accentuates the effect of increasing muscle bulk at the expense of virilization.

  • anabolic-androgenic steroids ('anabolic steroids') are structurally related to testosterone (1,2,3)
  • all anabolic steroids resemble testosterone in their pharmacological actions, but they vary in the ratio of anabolic (tissue-building) to androgenic (masculinising) properties
  • some preparations are active when taken orally (e.g. oxymetholone, stanozolol); others have to be injected to avoid extensive first-pass metabolism in the liver (e.g. nandrolone decanoate, testosterone enantate)
  • international studies reported an overall lifetime prevalence of AAS use for men of 3-4 % and of 1.6 % for women (3)

  • AAS use among male gym attendees is estimated to be as high as 15-25 %, depending on the country and with an increasing prevalence (3)

They promote weight gain and bone mineralization. To this end, they are occasionally used in patients in a hypercatabolic state e.g. chronic debilitating illness, malignancy.

However, the effect of anabolic steroids on muscle growth and activity has lead to their abuse by 'body builders' and athletes. Illicit use is associated with dangerous side effects ranging from cholestatic jaundice to death

  • when taken for several weeks, with a carefully controlled diet and exercise regimen, supraphysiological doses of testosterone (around 5-10 times the recommended replacement dose for male hypogonadism) increase fat-free body mass, muscle size and strength in healthy adult males, when compared with placebo plus diet and exercise
    • body-builders and other gym-users sometimes use even bigger doses to increase muscle mass and strength, heighten aggression, and facilitate harder, more vigorous training

  • metabolic and endocrine adverse effects include:
    • moderate increases in liver transaminase levels are common in people taking anabolic steroids; occasionally cholestatic jaundice and severe hepatotoxicity occur
      • rare effects include peliosis hepatis (a cystic haemorrhagic degeneration), and benign and malignant liver tumours
    • risk of liver toxicity is greatest with chronic administration of large doses of orally active C-17a alkylated steroids such as methandienone, methyltestosterone or stanozolol
    • androgenic effects of anabolic steroids that occur commonly in both men and women are oily skin and hair
    • in men, use of anabolic steroids suppresses pituitary gonadotrophin secretion, impairs spermatogenesis and leads to decreased fertility
      • prolonged use of anabolic steroids causes testicular atrophy (which some men try to prevent by self-administering human chorionic gonadotrophin); also may also lead to prostatic enlargement and decreased urinary flow.
      • recovery is usual after stopping the drugs but can take several months
    • fluctuations in libido mirror cycles on and off steroids
    • conversion of anabolic steroids to oestrogens in the liver may lead to gynaecomastia.
    • in women, anabolic steroids commonly cause menstrual disorders, breast atrophy, virilisation and increased libido
      • virilising effects, notably hirsutism, male-pattern baldness, enlargement of the clitoris and deepening of the voice, are not reversed by stopping the steroids
      • if taken during pregnancy, anabolic steroids can cause masculinisation of the female fetus
    • if taken in adolescence, they may cause premature epiphyseal closure, and permanent stunting of linear growth

  • cardiovascular adverse effects include:
    • increase the blood concentration of low-density-lipoprotein (LDL) cholesterol and decrease that of high-density-lipoprotein (HDL) cholesterol
    • when taken in high doses, they activate the haemostatic system and increase the haematocrit, and so could increase the likelihood of thrombotic events
    • plasma fibrinogen concentration falls during chronic use, a potentially protective effect
    • blood pressure may rise, however this is not a consistent finding

Notes:

  • note that there are two types of androgen doping:
    • direct and indirect
      • Direct doping involves exogenous administration of both natural and synthetic androgens
        • Natural androgens
          • to circumvent the detection of synthetic androgens, athletes have resorted to doping with testosterone. Hence, the detection of illegal use depends upon distinguishing between endogenous and exogenous testosterone
        • Synthetic androgens
      • availability of synthetic androgens has not only provided more options for the athletes but at the same time circumvents their detection by the doping authorities because chemical signatures of many of these compounds are not readily available Norbolethone has been credited as the first designer androgen that was identified in the 1960s
      • Indirect doping refers to strategies employed by athletes that result in a sustained increase in endogenous testosterone production
        • these strategies include:
          • 1) estrogen blockers such as estrogen receptor antagonists (antiestrogens) or aromatase inhibitors
            • original antiestrogens were the nonsteroidal drugs like clomiphene and tamoxifen that bind to both estrogen receptor alpha and beta
            • aromatase is an enzyme that is a product of CYP19 gene and is responsible for converting testosterone to estradiol
              • aromatase inhibitors completely and irreversibly inhibit this enzyme, which results in a decrease in estradiol synthesis
                • aminoglutethimide was the first steroidal drug in this class. Since then, more specific and potent steroidal aromatase inhibitors have become available such as testolactone, atamestane, and exemestane. The nonsteroidal aromatase inhibitors include anastrozole, letrozole, and vorozole
          • 2) androgen precursors such as dehydroepiandrosterone (DHEA) and androstenedione; and
          • 3) gonadotropins

Reference:


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