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Physiologic Effects of Anabolic Steroid Abuse
Part 1
Mark W. Rodacker, MD PhD and Lawrence Maile, PhD
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The purpose of this limited review will be to examine the physiologic mechanisms of disease and pathology produced by androgenic anabolic steroid (AAS) abuse. Though the legitimate medical uses for anabolic steroids are few, they are widely abused by an ever-increasing cross section of society. The side effects produced when AAS are used at physiologic levels for legitimate medical purposes are typically minimal. However, those seen in abusers range from purely cosmetic to potentially fatal. Because the more serious side effects often take years to develop (though not necessarily), they are commonly dismissed altogether or down-played by athletes and black market distributors and steroid "gurus". Furthermore, in recent years, there has been increased ease and anonymity in obtaining these compounds with the advent of offshore pharmacies (see figures 1 and 2) and over the counter preparations available even to minors.
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Figure 1. Mexican Pharmacy, AAS…a la carte
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Figure 2. Some commercially available AAS
Figure 3. Testosterone and Estrogen production
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The fact that AAS produce an advantage to the abuser in sport has long been obvious to the athletes if not the medical community (Boje, 1939). This long overdue public reckoning on the part of the medical community, in this author's opinion, discredited medical educators in the eyes of the typical abuser and placed a barrier to productive discourse. In addition, AAS are very commonly included as only one (albeit critical) ingredient in an athlete's pharmaceutical arsenal. In fact, the number of other compounds abused, especially notorious among top-level body builders, is staggering to the imagination (Evans, 1997). This poly-pharmaceutical milieu no doubt adds to the physiological derangements all to often seen in modern athletes. The solution to AAS abuse, we believe, is a multi-fold approach. Steps in this process include, but are not limited to, better public education including the inclusion of AAS abuse awareness beginning in health sciences curricula of middle school and high school, increased governmental regulation of the "supplement" industry, better and more universal doping control with increased out of meet testing for athletes, continued research which yields effective and safe ergogenic supplements such as creatine monohydrate (rather than expensive ripoffs), and stiff legal ramifications for convictions.
Anabolic androgenic steroids are synthetic derivatives of the male sex hormone testosterone (T), a 19 carbon-4 ring molecule. T is normally produced from a building block molecule of cholesterol by the testes and in far lesser quantities by the adrenal glands and ovaries, see figure 3.
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These compounds were originally discovered in the 1930s and have been refined ever since. They are androgenic because they produce the secondary sex characteristics of male body habitus, hair distribution, deepening of voice, etc. They are anabolic because they promote tissue growth (positive nitrogen balance), see figure 4.
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Because the virilizing effects of steroids are not always the sought after clinical effect (or desired effect of the abuser), but rather the anabolic effects are desired, chemists have altered the chemical makeup to enhance the anabolic effects and diminish androgenic effects. This is accomplished by substitutions of different chemical groups at the 17-carbon position (see figure 5).
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Figure 4. Normal androgen effects on tissues through T and DHT. |
However, it has not thus far been possible to completely divorce one property from the other, but only to change the relative ratios of their effects. In general, the more anabolic a compound, the more it will retain androgenic effects as well. Unfortunately, the more androgenic a compound is, the more toxic it tends to be as well. It should be noted that far from affecting only muscle, AAS have effects (and consequences) on virtually every organ system of the body including altered mental functions (see psychology of AAS use in this series). This occurs through the binding of testosterone, or through it's conversion to Dihydrotestosterone (DHT), to intracellular receptors that bind to chromosomes and guide increased protein synthesis. Given orally, approximately 50% of T is metabolized as it passes through the liver. Thus, huge doses are required for therapeutic use. Chemically altering the group at 17-carbon position allows compounds such as methyl testosterone and oxandralone to have acceptable oral activity. Injectable steroids are also metabolized by the liver but are released from the tissues slowly so that the dose is not so great at one time and thus less toxic.
Testicular (and to a lesser extent, ovarian) production of T is under the influence of trophic pituitary hormones, namely follicle stimulating hormone (FSH) and luteinizing hormone (LH), see figures 7 and 8.
Figure 6. The OH group is at carbon 17 in the T molecule and can be manipulated to make different synthetic AAS such as Dianabol and Winstrol shown right.
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Figure 5. The testosterone molecule with an OH group at the 17-carbon.
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Figure 7. The Endocrine Organ System exerts its effects throughout the whole body by sending chemical messengers called hormones to maintain homeostasis (balance) in the body. Some of the hormones are proteins (peptides such as insulin) and some are steroids such as cortisol and progesterone.
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| Figure 8. The gonads (testes and ovaries) as well as many other hormone systems have a check and balance (feedback) system with the pituitary and hypothalamus to regulate hormone levels within homeostatic (normal) levels.
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FSH and LH were originally named for their stimulating and ovulation inducing properties on the ovarian follicle in which a mature egg is produced. When an adequate quantity of T is produced, this negatively feeds back to influence the hypothalamus and the pituitary gland such that less FSH and LH are produced. In this way, much like many other endocrine hormones, T production is finely regulated to keep its serum concentration within physiologic levels. It has traditionally been held that as we age, after about 40 years, the average male loses approximately 1% testosterone production per year. A recent study has shown that approximately 20% of males aged 60-80 have free T levels below normal (Synder, 1998). It is estimated that approximately 6 mg of T are produced daily by the typical young male (Karch, 1996) giving rise to urine testosterone to epitestosterone ratio (T:E) of 1:1. Thus no more than 50 mg of T are produced weekly. Because giving synthetic T (see figure 9) in doses of 100-200 mg weekly may not cause an athlete to exceed the IOC's screening test cutoff of T:E > 6:1, AAS doping is a serious potential problem (Dehennin and Matsumoto, 1992 and Shackleton, et al., 1997).
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Figure 9. Testosterone cypionate, a commonly abused injectable AAS
Of course, AAS are illegal to own or sell without a physician's prescription and supervision (controlled substances act 1991, schedule class III). The legitimate uses of AAS (in patients without contraindications) are the following (Karch, 1996 and Nasrollah, 2001):
1. T replacement for individuals who cannot make it in sufficient quantities, e.g., males who do not undergo puberty.
2. Elderly males with documented T deficiency and clinical indications such as osteoporosis, loss of libido and fatigue.
3. Some forms of severe anemia (now rare).
4. Severe catabolic states such as burns or AIDS (rarely indicated).
5. Hereditary angioedema (rare).
6. Women with metastatic breast cancer to bone (rare).
7. Methyl testosterone in estrogen preparations for menopause.
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The pathophysiologic effects of steroid abuse will be discussed in the next issue.
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