Anabolic Steriods – Lowdown – Pharmacology

ANABOLIC STEROIDS

Androgens are steroids that have masculinizing effects or anabolic effects associated with proteins building in muscle and bones of both males as well females. Testosterone are the most important androgen present in humans which is synthesized by testes in males, by the ovary of the females and by the adrenal gland in both genders. Other androgens secreted by the testes in small amounts are dihydrotestosterone, androstenedione, and dehydroepiandrosterone. In adult males, testosterone secretion is controlled by gonadotropin-releasing hormone from the hypothalamus, which stimulates the anterior pituitary gland to secrete Follicle Stimulating Hormones and Luteinizing Hormone. Testosterone or its active metabolite Dihydrotestosterone, regulates testosterone production by inhibits production of these specific hormones through a negative feedback.

The androgens are required for

• Normal maturation in the male
• Sperm production
• Increased synthesis of muscle proteins and hemoglobin
• Decreased bone resorption.

The structure of androgens are designed synthetically to modify solubility and susceptibility to enzymatic breakdown which prolongs the half-life of the hormone and to separate anabolic and androgenic effects.

Classification of Anabolic Steroids

Danazol

Fluoxymesterone

Nandrolone

Mesterolone

oxymetholone

Oxandrolone

Testosterone cypionate

Testosterone enanthate

Chemical Structures

Modifications in the structure of testosterone can be done to maximize the anabolic effect and minimize the androgenic effect.

 Mechanism of Action of Anabolic Steroids

Anabolic steroids bind to a specific nuclear receptor in a target cell. Although testosterone itself is the active ligand in muscle and liver but in other tissues, it must be metabolized to active derivatives, such as Dihydrotestosterone. Testosterone is converted by 5α-reductase to DHT after diffusing into the cells of the prostate, seminal vesicles, epididymis, and skin that binds to the receptor.  Testosterone is biotransformed to estradiol by cytochrome P450 aromatase in the brain, liver, and adipose tissue. The synthesis of specific RNAs and proteins is stimulated by the formation of hormone-receptor complex binds to DNA. Testosterone derivatives that cannot be converted to DHT have less effect on the reproductive system than they do on the skeletal musculature.

Antianabolic activity

There is a gain in muscle mass and strength when anabolic steroids are administered to healthy women and children due to the anabolic effect. There is a downregulation of receptors in the skeletal muscle when androgen receptor population is saturated with testosterone in the adult men during puberty. The mycotrophic effect could be through anticatabolic mechanism rather than a direct anabolic effect from the administration of anabolic steroids to men. The upregulation may occur with the administration of androgens by converting muscles that normally have a minor or no response to muscles with enhanced response to androgen.

Behavioural mechanisms

The behavioural effects of androgens/anabolic steroids include sexual behaviour, cognitive abilities, aggression and mood. Androgens are important in the human male sexual behaviour and they can also enhance female sexual desire and arousal as well. Testosterone also plays an important role in cognitive functioning like attention and alertness, memory and spatial skills. Major mood syndromes can arise with use of anabolic steroid such as mania or hypomania. Anabolic steroids also increase aggression, especially when used in high doses.

Therapeutic Indications

The administration of these drugs for clinical purposes can be of therapeutically effective and reasonably safe, with the physician making objective decisions based on the benefit/ risk ratio in relation to the condition of a patient.

Androgenic effects:

Androgenic steroids are used for males in which androgen secretion is inadequate. Androgen therapy is indicated in hypogonadism which can be caused by testicular dysfunction i.e. primary hypogonadism or due to failure of the hypothalamus or pituitary i.e. secondary hypogonadism.

Anabolic effects:

Anabolic steroids can be used to treat senile osteoporosis associated with human immunodeficiency virus or cancer. They can also be used in severe burns and to speed up recovery from surgery or chronic debilitating diseases.

Endometriosis:

Danazol is a mild androgen which is commonly used in the treatment of fibrocystic breast disease and ectopic growth of the endometrium. Although it has no effect on the aromatase but it inhibits release of FSH and LH.

Unapproved use:

Anabolic steroids are used to increase lean body mass, strengthen the muscle, and to improve endurance in athletes and bodybuilders. DHEA is a precursor of testosterone and estrogen, is used as the anti-aging hormone and also to improve performance.

Pharmacokinetics

Absorption

Testosterone and its C17-esters (for example, testosterone cypionate or enanthate) are administered intramuscularly and are rapidly absorbed. Testosterone is therapeutically ineffective after oral administration because of inactivation by first-pass metabolism. Testosterone derivatives such as Fluoxymesterone and Oxandrolone are hormones that are effective when administered orally. Topical gels, buccal tablets and transdermal patches of testosterone are also available.

Metabolism and Elimination

Anabolic steroids are metabolized to relatively or completely inactive compounds that are excreted primarily in the urine. The hormone becomes more lipid-soluble by addition of esterified lipid, which results in increase in its duration of action.

Anabolic steroid such as fluoxymesterone have a longer half-life in the body than that of the naturally occurring androgens.

 Adverse Drug Effects

In females:

Androgens can cause masculinization, deepening of the voice, male pattern baldness, with acne, growth of facial hair, excessive muscle development and menstrual irregularities. Testosterone is contraindicated in pregnant women because it may cause virilization of the female fetus.

In males:

Excessive androgens may leads to impotence, decreased spermatogenesis, priapism, and gynecomastia. Changes that occur in females, may also occur in males as well. Growth of the prostate can also be stimulated by Androgens.

In children:

 Androgens may leads to growth disturbances and sexual maturation.

General effects:

Androgens increase serum Low-Density Lipoproteins and lower serum High-Density Lipoproteins levels. Therefore, significantly increase the risk for premature coronary heart disease. Androgens can also cause edema because of fluid retention.

In athletes:

Use of anabolic steroids such as DHEA or nandrolone by athletes, stunts the growth of long bones and interrupts development. The high doses taken by these young athletes may result in hepatic abnormalities, increased aggression, and reduction of testicular size, major mood disorders, and the other common adverse effects in males.

References

Antonio J, Wilson JD, George FW (1999). Effects of castration and androgen treatment on androgen-receptor levels in rat skeletal muscles. J Appl Physiol 87: 2016–2019.

Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J et al. (1996). The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med 335: 1–7.

Catlin DH, Ahrens BD, Kucherova Y (2002). Detection of norbolethone, an anabolic steroid never marketed, in athletes’ urine. Rapid Commun Mass Spectrom 16: 1273–1275.

Catlin DH, Sekera MH, Ahrens BD, Starcevic B, Chang YC, Hatton CK (2004). Tetrahydrogestrinone: discovery, synthesis, and detectionin urine. Rapid Commun Mass Spectrom 18: 1245–1249.

FDA (2004). White Paper. 11 March 2004. Health Effects of Androstenedione. Food and Drug Administration: Rockville, MD.

Feldkoren BI, Andersson S (2005). Anabolic–androgenic steroid interaction with rat androgen receptor in vivo and in vitro: a comparative study. J Steroid Biochem Mol Biol 94: 481–487.

Labrie F, Luu-The V, Calvo E, Martel C, Cloutier J, Gauthier S. et al. (2005).

Tetrahydrogestrinone induces a genomic signature typical of a potent anabolic steroid. J Endocrinol 184: 427–433.

James VHT, Kicman AT (2004). Medical aspects of drug use in the gym. Drug Ther Bull 42: 1–5.

Jasuja R, Catlin DH, Miller A, Chang YC, Herbst KL, Starcevic B et al. (2005).

Tetrahydrogestrinone is an androgenic steroid that stimulates androgen receptor-mediated, myogenic differentiation in C3H10T1/2 multipotent mesenchymal cells and promotes muscle accretion in orchidectomized male rats. Endocrinology 146: 4472–4478.

Olsen EA, Hordinsky M, Whiting D, Stough D, Hobbs S, Ellis ML et al. (2006). The importance of dual 5 alpha-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride. J Am Acad Dermatol 55: 1014–1023.

Wolf SS, Obendorf M (2004). Selective androgen receptor modulators. In: Nieschlag E, Behre HM (eds). Testosterone, 3rd edn. Cambridge University Press: UK, pp 623–640.

Woodhouse LJ, Reisz-Porszasz S, Javanbakht M, Storer TW, Lee M, Zerounian H et al. (2003). Development of models to predict anabolic response to testosterone administration in healthy young men. Am J Physiol Endocrinol Metab 284: E1009–E1017.

Read More:

Alcohol Use in Men What You Need to Know

Legal Disclaimer

Caution: Content on this site is for entertainment purposes and is not intended to substitute for advice given by a licensed health-care professional.  You should not use this information as self-diagnosis or for treating a health problem.  Contact your health-care provider immediately if you suspect that you have a medical problem.